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International Consensus Criteria

2022-01-10T19:06:53Z

Kmdenmark:Citation

[[File:What-is-Myalgic-Encephalomyelitis-ME-ICC.png|frameless|upright=0.75|right|Simplified ME International Consensus Criteria symptoms.]]
The [[myalgic encephalomyelitis|Myalgic Encephalomyelitis]] (ME) '''International Consensus Criteria''' (ICC)<ref name="icc">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> is a medical case definition that can accurately diagnose [[myalgic encephalomyelitis]] (ME), is a chronic, [[Inflammation|inflammatory]], physically and [[Nervous system|neurologically]] disabling disease. For pediatric and adult cases a diagnosis should be made immediately; there is no need to wait up to 6 months.

==Authors==
[[Bruce Carruthers]], [[Marjorie van de Sande]], [[Kenny de Meirleir]], [[Nancy Klimas]], [[Gordon Broderick]], [[Terry Mitchell]], [[Donald Staines]], [[A C Peter Powles]], [[Nigel Speight]], [[Rosamund Vallings]], [[Lucinda Bateman]], [[Barbara Baumgarten-Austrheim]], [[David Bell]], [[Nicoletta Carlo-Stella]], [[John Chia]], [[Austin Darragh]], [[Daehyun Jo]], [[Donald Lewis]], [[Alan Light]], [[Sonya Marshall-Gradisnik]], [[Ismael Mena]], [[Judy Mikovits]], [[Kunihisa Miwa]], [[Modra Murovska]], [[Martin Pall]], and [[Staci Stevens]]<ref name="icc" />

==Criteria==
A patient will meet the criteria for [[myalgic encephalomyelitis|Myalgic Encephalomyelitis]] if they have:

'''A''' - [[Postexertional neuroimmune exhaustion]]

'''B''' - at least ONE '''[[Nervous system|neurological]] impairment''' symptom from THREE categories:

# Neurocognitive Impairments
# [[Pain]]          
# [[Sleep dysfunction|Sleep Disturbance]]      
# [[:Category:Cognitive signs and symptoms|Neurosensory]], [[perceptual distortion|Perceptual]] and [[motor problems|Motor Disturbances]]

'''C''' - at least ONE '''[[Immune system|immune]]/[[Gastrointestinal|gastro-intestinal]]/genitourinary impairment''' from THREE categories:
# [[Flu-like symptoms]] may be recurrent or chronic and typically activate or worsen with [[exertion]]
# [[susceptibility to viruses|Susceptibility to viral infections]] with prolonged recovery periods
# [[Gastrointestinal system|Gastro-intestinal]] tract
# [[:Category:Genitourinary signs and symptoms|Genitourinary]]    
# [[Hypersensitivity|Sensitivities]] to [[Food intolerance|food]], [[Medicine sensitivities|medications]], [[Odor sensitivities|odors]] or [[multiple chemical sensitivity|chemicals]], and

'''D''' - at least ONE '''[[Metabolic|energy metabolism]]/[[Ion transportation|ion transport]] impairment''' symptom.
# [[Cardiovascular system|Cardiovascular]]  
# [[Breathing problems in ME/CFS|Respiratory]]    
# [[thermostatic instability|Loss of thermostatic stability]]
# [[Temperature sensitivity|Intolerance of extremes of temperature]]  
<hr />

{| class="wikitable left"
|-
| style="background-color: peachpuff;color:black;text-shadow:none" |
|<h3>[[Postexertional neuroimmune exhaustion]] (PENE pen’-e): Compulsory</h3>
|-
| style="background-color: peachpuff;color:black;text-shadow:none" |A.
|
This cardinal feature is a pathological [[inability to produce sufficient energy on demand]] with prominent symptoms primarily in the neuroimmune regions. Characteristics are as follows:

: 1. Marked, rapid physical and/or cognitive [[post-exertional fatigue|fatigability in response to exertion]], which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
: 2. [[Postexertional symptom exacerbation]]: e.g. acute [[flu-like symptoms]], pain and worsening of other symptoms.
: 3. [[Postexertional exhaustion]] may occur immediately after activity or be delayed by hours or days.
: 4. [[Prolonged recovery after exertion|Recovery period is prolonged]], usually taking 24h or longer. A relapse can last days, weeks or longer.
: 5. [[Lack of stamina|Low threshold of physical and mental fatigability]] (lack of stamina) results in a [[Greatly lowered ability to do activities that were usual before the illness|substantial reduction in pre-illness activity level]].

Operational notes: ''For a diagnosis of ME, symptom severity must result in a significant reduction of a patient’s premorbid activity level. [[Mild myalgic encephalomyelitis or chronic fatigue syndrome|Mild]] (an approximate 50% reduction in pre-illness activity level), [[Moderate myalgic encephalomyelitis or chronic fatigue syndrome|moderate]] (mostly housebound), [[severe myalgic encephalomyelitis or chronic fatigue syndrome|severe]] (mostly bedridden) or [[very severe myalgic encephalomyelitis or chronic fatigue syndrome|very severe]] (totally bedridden and need help with basic functions). There may be marked fluctuation of symptom severity and hierarchy from day to day or hour to hour. Consider activity, context and interactive effects. Recovery time: e.g. Regardless of a patient’s recovery time from reading for ½ hour, it will take much longer to recover from grocery shopping for ½ hour and even longer if repeated the next day – if able. Those who rest before an activity or have adjusted their activity level to their limited energy may have shorter recovery periods than those who do not pace their activities adequately. Impact: e.g. An outstanding athlete could have a [[substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities|50% reduction in his/her pre-illness activity level]] and is still more active than a sedentary person.''
|-
| style="background-color: palegreen;color:black;text-shadow:none" |
|<h3>Neurological impairments</h3>
|-
| style="background-color: palegreen;color:black;text-shadow:none" |B.
|
At least one symptom from three of the following four symptom categories

<h4>1. Neurocognitive impairments</h4>

:a. [[difficulty thinking|Difficulty processing information]]: [[slowed thought]], [[attention deficit|impaired concentration]] e.g. [[confusion]], [[disorientation]], cognitive overload, difficulty with making decisions, [[slowed speech]], acquired or exertional [[dyslexia]]
:b. [[Memory problems|Short-term memory loss]]: e.g. difficulty remembering what one wanted to say, what one was saying, [[word-finding problems|retrieving words]], recalling information, [[poor working memory]]

<h4>2. [[Pain]]</h4>

:a. [[Headache]]s: e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; [[migraine]]; [[tension-type headache|tension headaches]]
:b. Significant pain can be experienced in [[myalgia|muscles]], muscle-tendon junctions, [[arthralgia|joints]], [[abdominal pain|abdomen]] or [[chest pain|chest]]. It is noninflammatory in nature and often migrates. e.g. generalized [[hyperalgesia]], widespread pain (may meet fibromyalgia criteria), [[myofascial pain|myofascial]] or radiating pain

<h4>3. [[Sleep disturbance]]</h4>

: a. Disturbed sleep patterns: e.g. [[insomnia]], [[hypersomnia|prolonged sleep including naps]], [[sleep reversal|sleeping most of the day and being awake most of the night]], frequent awakenings, [[early waking|awaking much earlier]] than before illness onset, [[vivid dreams|vivid dreams/nightmares]]
: b. [[unrefreshing sleep|Unrefreshed sleep]]: e.g. awaken feeling exhausted regardless of duration of sleep, [[daytime sleepiness|day-time sleepiness]]

<h4>4. Neurosensory, perceptual and motor disturbances</h4>

: a. Neurosensory and perceptual: e.g. [[inability to focus vision]], [[photophobia|sensitivity to light]], [[Hyperacusis|noise]], vibration, odour, taste and touch; [[impaired depth perception]]
: b. Motor: e.g. [[paresis|muscle weakness]], [[fasciculation|twitching]], [[poor coordination]], feeling unsteady on feet, [[ataxia]]

Notes: ''Neurocognitive impairments, reported or observed, become more pronounced with fatigue. [[Overload phenomena]] may be evident when [[difficulty multi-tasking|two tasks are performed simultaneously]]. Abnormal accommodation responses of the pupils are common. Sleep disturbances are typically expressed by prolonged sleep, sometimes extreme, in the acute phase and often evolve into marked sleep reversal in the chronic stage. Motor disturbances may not be evident in mild or moderate cases but [[abnormal tandem gait]] and [[Romberg test|positive Romberg test]] may be observed in severe cases.''
|-
| style="background-color: thistle;color:black;text-shadow:none;border: none" |
|<h3>Immune, gastro-intestinal and genitourinary impairments</h3>
|-
| style="background-color: thistle;color:black;text-shadow:none; " |C.
|
At least one symptom from three of the following five symptom categories

: 1. [[Flu-like illness|Flu-like symptoms]] may be recurrent or chronic and typically activate or [[Symptoms worsening with exertion|worsen with exertion]] e.g. [[sore throat]], [[sinusitis]], cervical and/or axillary [[swollen lymph nodes|lymph nodes may enlarge]] or be tender on palpitation
: 2. [[Susceptibility to viruses|Susceptibility to viral infections]] with prolonged recovery periods
: 3. Gastro-intestinal tract: e.g. [[nausea]], [[abdominal pain]], [[bloating]], [[irritable bowel syndrome]]
: 4. Genitourinary: e.g. urinary urgency or [[Urinary frequency|frequency]], [[nocturia]]
: 5. [[Development of new sensitivities|Sensitivities]] to [[Food sensitivities|food]], [[Medicine sensitivities|medications]], [[Odor sensitivities|odours]] or [[multiple chemical sensitivity|chemicals]]

Notes: ''Sore throat, tender lymph nodes, and flu-like symptoms obviously are not specific to ME but their activation in reaction to exertion is abnormal. The throat may feel sore, dry and scratchy. Faucial injection and crimson crescents may be seen in the tonsillar fossae, which are an indication of immune activation.''
|-
| style="background-color: lightsteelblue;color:black;text-shadow:none" |
|<h3>Energy production/transportation impairments: At least one symptom</h3>
|-
| style="background-color: lightsteelblue;color:black;text-shadow:none" |D.
|
: 1. Cardiovascular: e.g. inability to tolerate an upright position - [[orthostatic intolerance]], [[neurally mediated hypotension]], [[postural orthostatic tachycardia syndrome]], [[Heart palpitation|palpitations]] with or without [[arrhythmia|cardiac arrhythmias]], [[light-headedness]]/[[dizziness]]
: 2. [[Breathing problems in ME/CFS|Respiratory]]: e.g. [[air hunger]], [[laboured breathing]], [[fatigue of chest wall muscles]]
: 3. [[thermostatic instability|Loss of thermostatic stability]]: e.g. [[subnormal body temperature]], marked [[diurnal fluctuation]]s; [[excessive sweating|sweating episodes]], recurrent feelings of feverishness with or without [[low-grade fever|low grade fever]], [[cold hands and feet|cold extremities]]
: 4. [[Temperature sensitivity|Intolerance of extremes of temperature]]

Notes: ''[[Orthostatic intolerance]] may be delayed by several minutes. Patients who have orthostatic intolerance may exhibit mottling of extremities, extreme pallor or [[Raynaud's syndrome|Raynaud's Phenomenon]]. In the chronic phase, moons of finger nails may recede.''
|-
| colspan="2" |<h3>Paediatric considerations</h3>
|-
| colspan="2" |''Symptoms may progress more slowly in children than in teenagers or adults. In addition to [[postexertional neuroimmune exhaustion]], the most prominent symptoms tend to be neurological: [[headache]]s, [[cognitive impairment]]s, and [[sleep disturbance]]s.''

:* '''[[Headache]]s:''' Severe or chronic headaches are often debilitating. [[Migraine]] may be accompanied by a rapid drop in temperature, shaking, [[vomiting]], [[diarrhoea]] and severe weakness.
:* '''Neurocognitive impairments:''' [[inability to focus vision|Difficulty focusing eyes]] and reading are common. Children may become [[dyslexia|dyslexic]], which may only be evident when fatigued. [[Slow processing of information]] makes it difficult to follow auditory instructions or take notes. All cognitive impairments worsen with physical or mental exertion. Young people [[unable to go to school full-time|will not be able to maintain a full school program]].
:* '''[[Pain]]''' may seem erratic and migrate quickly. '''[[Hypermobility|Joint hypermobility]]''' is common.

'''''Notes:''''' ''Fluctuation and severity hierarchy of numerous prominent symptoms tend to vary more rapidly and dramatically.''
|-
| colspan="2" class="left" style="text-align: left" |<h3 class="center">Classification</h3>

——— '''Myalgic encephalomyelitis'''

——— '''Atypical myalgic encephalomyelitis:'''<br />
meets criteria for [[postexertional neuroimmune exhaustion]] but has a limit of two less than required of the remaining criterial symptoms. [[Pain]] or [[sleep disturbance]] may be absent in rare cases.
|-
| colspan="2" |<h3>Exclusions</h3>
|-
| colspan="2" |As in all diagnoses, exclusion of alternate explanatory diagnoses is achieved by the patient’s history, physical examination, and laboratory/biomarker testing as indicated. It is possible to have more than one disease but it is important that each one is identified and treated. [[:Category:mental disorders|Primary psychiatric disorders]], [[somatoform disorder]] and [[substance abuse]] are excluded. Paediatric: [[school phobia|'primary' school phobia]].
|-
| colspan="2" |<h3>Comorbid entities</h3>
|-
| colspan="2" |[[Fibromyalgia]], [[myofascial pain syndrome]], [[temporomandibular joint syndrome]], [[irritable bowel syndrome]], [[interstitial cystitis]], [[Raynaud's syndrome|Raynaud’s phenomenon]], [[prolapsed mitral valve]], [[migraine]]s, [[allergy|allergies]], [[multiple chemical sensitivity|multiple chemical sensitivities]], [[Hashimoto's thyroiditis]], [[Sicca syndrome]], [[depression#Reactive_depression|reactive depression]]. [[Migraine]] and [[irritable bowel syndrome]] may precede ME but then become associated with it. [[Fibromyalgia]] overlaps.
|}

==Background and purpose==

The 2012 ICC is very clear on the topic of names:

Problem

The label ‘chronic fatigue syndrome’ (CFS), coined in the 1980s, has persisted due to lack of knowledge of its etiologic agents and pathophysiology. Misperceptions have arisen because the name ‘CFS’ and its hybrids ME/CFS, CFS/ME and CFS/CF have been used for widely diverse conditions. Patient sets can include those who are seriously ill with ME, many bedridden and unable to care for themselves, to those who have general fatigue or, under the Reeves criteria, patients are not required to have any physical symptoms. There is a poignant need to untangle the web of confusion caused by mixing diverse and often overly inclusive patient populations in one heterogeneous, multi-rubric pot called ‘chronic fatigue syndrome’. We believe this is the foremost cause of diluted and inconsistent research findings, which hinders progress, fosters scepticism, and wastes limited research monies.

Solution

The rationale for the development of the ICC was to utilize current research knowledge to identify objective, measurable and reproducible abnormalities that directly reflect the interactive, regulatory components of the underlying pathophysiology of ME. Specifically, the ICC select patients who exhibit explicit multi-systemic neuropathology, and have a pathological low threshold of physical and mental fatigability in response to exertion. Cardiopulmonary exercise test- retest studies have confirmed many post-exertional abnormalities. Criterial symptoms are compulsory and identify patients who have greater physical, cognitive and functional impairments. The ICC advance the successful strategy of the Canadian Consensus Criteria (CCC) of grouping coordinated patterns of symptom clusters that identify areas of pathology. The criteria are designed for both clinical and research settings.

1. Name: Myalgic encephalomyelitis, a name that originated in the 1950s, is the most accurate and appropriate name because it reflects the underlying multi-system pathophysiology of the disease. Our panel strongly recommends that only the name ‘myalgic encephalomyelitis’ be used to identify patients meeting the ICC because a distinctive disease entity should have one name. Patients diagnosed using broader or other criteria for CFS or its hybrids (Oxford, Reeves, London, Fukuda, CCC, etc.) should be reassessed with the ICC. Those who fulfill the criteria have ME; those who do not would remain in the more encompassing CFS classification. (bold emphasis mine)

2. Remove patients who satisfy the ICC from the broader category of CFS. The purpose of diagnosis is to provide clarity. The criterial symptoms, such as the distinctive abnormal responses to exertion can differentiate ME patients from those who are depressed or have other fatiguing conditions. Not only is it common sense to extricate ME patients from the assortment of conditions assembled under the CFS umbrella, it is compliant with the WHO classification rule that a disease cannot be classified under more than one rubric. The panel is not dismissing the broad components of fatiguing illnesses, but rather the ICC are a refinement of patient stratification. As other identifiable patient sets are identified and supported by research, they would then be removed from the broad CFS/CF category.

Research on ME: The logical way to advance science is to select a relatively homogeneous patient set that can be studied to identify biopathological mechanisms, biomarkers and disease process specific to that patient set, as well as comparing it to other patient sets. It is counterproductive to use inconsistent and overly inclusive criteria to glean insight into the pathophysiology of ME if up to 90% of the research patient sets may not meet its criteria (Jason 2009). Research on other fatiguing illnesses, such as cancer and multiple sclerosis (MS), is done on patients who have those diseases. There is a current, urgent need for ME research using patients who actually have ME. (bold emphasis mine)

4. Research confirmation: When research is applied to patients satisfying the ICC, previous findings based on broader criteria will be confirmed or refuted. Validation of ME being a differential diagnosis, as is multiple sclerosis (MS), or a subgroup of chronic fatigue syndrome, will then be verified.

5. Focus on treatment efficacy: With enhanced understanding of biopathological mechanisms, biomarkers and other components of pathophysiology specific to ME, more focus and research emphasis can target expanding and augmenting treatment efficacy.

==International Consensus Primer (ICP)==

Problem

Overly inclusive criteria have created misperceptions, fostered cynicism and have had a major negative impact on how ME is viewed by the medical community, patients, their families, as well as the general public. Some medical schools do not include ME in their curriculum with the result that very significant scientific advances and appropriate diagnostic and treatment protocols have not reached many busy medical practitioners. Some doctors may be unaware of the complexity and serious nature of ME. Patients may go undiagnosed and untreated; they may be shunned or isolated.<ref name="ICP2011primer">{{citation
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Bell | first12= DS | authorlink12= David Bell
| last13 = Carlo-Stella | first13= N | authorlink13= Nicoletta Carlo-Stella
| last14 = Chia | first14= J | authorlink14= John Chia
| last15 = Darragh | first15= A | authorlink15= Austin Darragh
| last16 = Gerken | first16= A | authorlink16= Anne Gerken
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Light | first20= KC | authorlink20= Kathleen Light
| last21 = Marshall-Gradisnik | first21= S | authorlink21= Sonya Marshall-Gradisnik
| last22 = McLaren-Howard | first22= J | authorlink22= John McLaren-Howard
| last23 = Mena | first23= I | authorlink23= Ismael Mena
| last24 = Miwa | first24= K | authorlink24= Kunihisa Miwa
| last25 = Murovska | first25= M | authorlink25= Modra Murovska
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners
| date = 2012
| isbn = 978-0-9739335-3-6
| url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf
}}</ref>

==World Health Organisation==
The World Health Organisation (WHO) lists ME and post viral fatigue syndrome under neurological conditions. The diagnostic code is G93.3<ref>[http://apps.who.int/classifications/icd10/browse/2016/en#/G93.3 WHO Classifications G93.3 - 2016]</ref> Importantly, it doesn’t include chronic fatigue syndrome there, or ME/CFS or CFS/ME. Fatigue syndromes are listed in "Other neurotic disorders."<ref>[http://apps.who.int/classifications/icd10/browse/2016/en#/F48.0 WHO Classifications F48.0 - 2016]</ref>

==Comparison with other criteria==
[[File:Individuals_referred_by_medical_specialists_in_CFS_and_ME-CFS_.png|right|450px|thumb|M.E. and CFS are different but partially overlapping (Twisk, 2015)]]
*Norwegian researchers compare the main criteria ([[Oxford criteria]], [[Fukuda criteria]], [[Canadian Consensus Criteria]], International Consensus Criteria and [[SEID]]). They say "it is important to distinguish between myalgic encephalomyelitis and chronic fatigue syndrome” to improve understanding of the disease, treatment and patients’ lives, as using incorrect criteria can lead to incorrect treatment.<ref name="Egeland2015" />

*'Scientists must agree on classifying patients’ Leonard Jason<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=McManimen|first2=Stephanie|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Furst|first5=Jacob|last6=Newton|first6=Julia L.|last7=Strand|first7=Elin Bolle|date=2016-01-02|title=Case definitions integrating empiric and consensus perspectives|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1124520?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=4|issue=1|pages=1–23|doi=10.1080/21641846.2015.1124520|issn=2164-1846|pmc=4831204|pmid=27088059}}</ref>

*Frank Twisk explains that ME and CFS are "distinct, partially overlapping, clinical entities such as ME and CFS" Frank Twisk 2016<ref>{{Cite journal|last=Twisk|first=Frank NM|date=2015-06-26|title=Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482824/|journal=World Journal of Methodology|volume=5|issue=2|pages=68–87|doi=10.5662/wjm.v5.i2.68|issn=2222-0682|pmc=4482824|pmid=26140274}}</ref>

==Diagram of ME ICC symptoms ==
[[File:What-is-Myalgic-Encephalomyelitis-ME-ICC.png|550px|thumb|center|Simplified diagram of the main myalgic encephalomyelitis international consensus criteria symptoms]]

== Tool to determine if you meet ICC criteria ==
The following online questionnaire was developed by [[Schweizerische Gesellschaft für ME & CFS]], a patient association in Switzerland, to help you determine whether the diagnosis of ME (Myalgic Encephalomyelitis) according to the International Consensus Criteria (ICC) is applicable to you. English and Dutch versions are available.<ref>{{Cite web|url=https://sgme.ch/icc/en/|title=Do I Have ME?|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=|archive-url=|archive-date=|url-status=|access-date=Jan 10, 2022}}</ref>

[https://sgme.ch/icc/en/ Questionnaire in English]

[https://sgme.ch/icc/de/ Questionnaire in German]

==See also==

*[[Definitions of ME and CFS]]
*[[Canadian Consensus Criteria]]
*[[List_of_symptoms_in_ME_CFS|List of symptoms in ME/CFS]]
*[[Common_symptoms_in_ME_CFS|Common symptoms]]
*[[Differential diagnosis]]

=== Generally accepted criteria for diagnosing ME and ME/CFS ===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*International Consensus Criteria (ICC)<ref name="icc" /> This criterion will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|url-status=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegria|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==

*[http://www.meadvocacy.org/the_international_consensus_criteria_what_is_it_do_i_fit_the_criteria MEAdvocacy - The International Consensus Criteria: What is it? Do I fit the criteria?]

*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf International Consensus Primer for Medical Practioners]

==References==
<references>
<ref name="Egeland2015">{{citation
| last1 = Egeland | first1 = T | authorlink1 = Torstein Egeland
| last2 = Angelsen | first2 = A | authorlink2 = Arild Angelsen
| last3 = Haug | first3 = R | authorlink3 = Ruth Haug
| last4 = Henriksen | first4 = JO | authorlink4 = Jan-Olave Henriksen
| last5 = Lea | first5 = TE | authorlink5 = Tor Erling Lea
| last6 = Saugstad | first6 = OD | authorlink6 = Ola Didrik Saugstad
| title = What exactly is myalgic encephalomyelitis?
| type = Perspectives
| journal = Tidsskr Nor Legeforen | volume = 2015 | issue = 135 | page = 1756–9
| date = Oct 2015
| doi = 10.4045/tidsskr.15.0089
| url = http://tidsskriftet.no/article/3404849/en_GB
| lay-url = http://www.meaction.net/2015/12/10/norwegian-researchers-ask-what-exactly-is-m-e/
}}</ref>
</references>

[[Category:Definitions]]
[[Category:Secondary sources]]

International Consensus Criteria

2022-01-10T19:02:08Z

Kmdenmark:Copy edit and corrected error

[[File:What-is-Myalgic-Encephalomyelitis-ME-ICC.png|frameless|upright=0.75|right|Simplified ME International Consensus Criteria symptoms.]]
The [[myalgic encephalomyelitis|Myalgic Encephalomyelitis]] (ME) '''International Consensus Criteria''' (ICC)<ref name="icc">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> is a medical case definition that can accurately diagnose [[myalgic encephalomyelitis]] (ME), is a chronic, [[Inflammation|inflammatory]], physically and [[Nervous system|neurologically]] disabling disease. For pediatric and adult cases a diagnosis should be made immediately; there is no need to wait up to 6 months.

==Authors==
[[Bruce Carruthers]], [[Marjorie van de Sande]], [[Kenny de Meirleir]], [[Nancy Klimas]], [[Gordon Broderick]], [[Terry Mitchell]], [[Donald Staines]], [[A C Peter Powles]], [[Nigel Speight]], [[Rosamund Vallings]], [[Lucinda Bateman]], [[Barbara Baumgarten-Austrheim]], [[David Bell]], [[Nicoletta Carlo-Stella]], [[John Chia]], [[Austin Darragh]], [[Daehyun Jo]], [[Donald Lewis]], [[Alan Light]], [[Sonya Marshall-Gradisnik]], [[Ismael Mena]], [[Judy Mikovits]], [[Kunihisa Miwa]], [[Modra Murovska]], [[Martin Pall]], and [[Staci Stevens]]<ref name="icc" />

==Criteria==
A patient will meet the criteria for [[myalgic encephalomyelitis|Myalgic Encephalomyelitis]] if they have:

'''A''' - [[Postexertional neuroimmune exhaustion]]

'''B''' - at least ONE '''[[Nervous system|neurological]] impairment''' symptom from THREE categories:

# Neurocognitive Impairments
# [[Pain]]          
# [[Sleep dysfunction|Sleep Disturbance]]      
# [[:Category:Cognitive signs and symptoms|Neurosensory]], [[perceptual distortion|Perceptual]] and [[motor problems|Motor Disturbances]]

'''C''' - at least ONE '''[[Immune system|immune]]/[[Gastrointestinal|gastro-intestinal]]/genitourinary impairment''' from THREE categories:
# [[Flu-like symptoms]] may be recurrent or chronic and typically activate or worsen with [[exertion]]
# [[susceptibility to viruses|Susceptibility to viral infections]] with prolonged recovery periods
# [[Gastrointestinal system|Gastro-intestinal]] tract
# [[:Category:Genitourinary signs and symptoms|Genitourinary]]    
# [[Hypersensitivity|Sensitivities]] to [[Food intolerance|food]], [[Medicine sensitivities|medications]], [[Odor sensitivities|odors]] or [[multiple chemical sensitivity|chemicals]], and

'''D''' - at least ONE '''[[Metabolic|energy metabolism]]/[[Ion transportation|ion transport]] impairment''' symptom.
# [[Cardiovascular system|Cardiovascular]]  
# [[Breathing problems in ME/CFS|Respiratory]]    
# [[thermostatic instability|Loss of thermostatic stability]]
# [[Temperature sensitivity|Intolerance of extremes of temperature]]  
<hr />

{| class="wikitable left"
|-
| style="background-color: peachpuff;color:black;text-shadow:none" |
|<h3>[[Postexertional neuroimmune exhaustion]] (PENE pen’-e): Compulsory</h3>
|-
| style="background-color: peachpuff;color:black;text-shadow:none" |A.
|
This cardinal feature is a pathological [[inability to produce sufficient energy on demand]] with prominent symptoms primarily in the neuroimmune regions. Characteristics are as follows:

: 1. Marked, rapid physical and/or cognitive [[post-exertional fatigue|fatigability in response to exertion]], which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
: 2. [[Postexertional symptom exacerbation]]: e.g. acute [[flu-like symptoms]], pain and worsening of other symptoms.
: 3. [[Postexertional exhaustion]] may occur immediately after activity or be delayed by hours or days.
: 4. [[Prolonged recovery after exertion|Recovery period is prolonged]], usually taking 24h or longer. A relapse can last days, weeks or longer.
: 5. [[Lack of stamina|Low threshold of physical and mental fatigability]] (lack of stamina) results in a [[Greatly lowered ability to do activities that were usual before the illness|substantial reduction in pre-illness activity level]].

Operational notes: ''For a diagnosis of ME, symptom severity must result in a significant reduction of a patient’s premorbid activity level. [[Mild myalgic encephalomyelitis or chronic fatigue syndrome|Mild]] (an approximate 50% reduction in pre-illness activity level), [[Moderate myalgic encephalomyelitis or chronic fatigue syndrome|moderate]] (mostly housebound), [[severe myalgic encephalomyelitis or chronic fatigue syndrome|severe]] (mostly bedridden) or [[very severe myalgic encephalomyelitis or chronic fatigue syndrome|very severe]] (totally bedridden and need help with basic functions). There may be marked fluctuation of symptom severity and hierarchy from day to day or hour to hour. Consider activity, context and interactive effects. Recovery time: e.g. Regardless of a patient’s recovery time from reading for ½ hour, it will take much longer to recover from grocery shopping for ½ hour and even longer if repeated the next day – if able. Those who rest before an activity or have adjusted their activity level to their limited energy may have shorter recovery periods than those who do not pace their activities adequately. Impact: e.g. An outstanding athlete could have a [[substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities|50% reduction in his/her pre-illness activity level]] and is still more active than a sedentary person.''
|-
| style="background-color: palegreen;color:black;text-shadow:none" |
|<h3>Neurological impairments</h3>
|-
| style="background-color: palegreen;color:black;text-shadow:none" |B.
|
At least one symptom from three of the following four symptom categories

<h4>1. Neurocognitive impairments</h4>

:a. [[difficulty thinking|Difficulty processing information]]: [[slowed thought]], [[attention deficit|impaired concentration]] e.g. [[confusion]], [[disorientation]], cognitive overload, difficulty with making decisions, [[slowed speech]], acquired or exertional [[dyslexia]]
:b. [[Memory problems|Short-term memory loss]]: e.g. difficulty remembering what one wanted to say, what one was saying, [[word-finding problems|retrieving words]], recalling information, [[poor working memory]]

<h4>2. [[Pain]]</h4>

:a. [[Headache]]s: e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; [[migraine]]; [[tension-type headache|tension headaches]]
:b. Significant pain can be experienced in [[myalgia|muscles]], muscle-tendon junctions, [[arthralgia|joints]], [[abdominal pain|abdomen]] or [[chest pain|chest]]. It is noninflammatory in nature and often migrates. e.g. generalized [[hyperalgesia]], widespread pain (may meet fibromyalgia criteria), [[myofascial pain|myofascial]] or radiating pain

<h4>3. [[Sleep disturbance]]</h4>

: a. Disturbed sleep patterns: e.g. [[insomnia]], [[hypersomnia|prolonged sleep including naps]], [[sleep reversal|sleeping most of the day and being awake most of the night]], frequent awakenings, [[early waking|awaking much earlier]] than before illness onset, [[vivid dreams|vivid dreams/nightmares]]
: b. [[unrefreshing sleep|Unrefreshed sleep]]: e.g. awaken feeling exhausted regardless of duration of sleep, [[daytime sleepiness|day-time sleepiness]]

<h4>4. Neurosensory, perceptual and motor disturbances</h4>

: a. Neurosensory and perceptual: e.g. [[inability to focus vision]], [[photophobia|sensitivity to light]], [[Hyperacusis|noise]], vibration, odour, taste and touch; [[impaired depth perception]]
: b. Motor: e.g. [[paresis|muscle weakness]], [[fasciculation|twitching]], [[poor coordination]], feeling unsteady on feet, [[ataxia]]

Notes: ''Neurocognitive impairments, reported or observed, become more pronounced with fatigue. [[Overload phenomena]] may be evident when [[difficulty multi-tasking|two tasks are performed simultaneously]]. Abnormal accommodation responses of the pupils are common. Sleep disturbances are typically expressed by prolonged sleep, sometimes extreme, in the acute phase and often evolve into marked sleep reversal in the chronic stage. Motor disturbances may not be evident in mild or moderate cases but [[abnormal tandem gait]] and [[Romberg test|positive Romberg test]] may be observed in severe cases.''
|-
| style="background-color: thistle;color:black;text-shadow:none;border: none" |
|<h3>Immune, gastro-intestinal and genitourinary impairments</h3>
|-
| style="background-color: thistle;color:black;text-shadow:none; " |C.
|
At least one symptom from three of the following five symptom categories

: 1. [[Flu-like illness|Flu-like symptoms]] may be recurrent or chronic and typically activate or [[Symptoms worsening with exertion|worsen with exertion]] e.g. [[sore throat]], [[sinusitis]], cervical and/or axillary [[swollen lymph nodes|lymph nodes may enlarge]] or be tender on palpitation
: 2. [[Susceptibility to viruses|Susceptibility to viral infections]] with prolonged recovery periods
: 3. Gastro-intestinal tract: e.g. [[nausea]], [[abdominal pain]], [[bloating]], [[irritable bowel syndrome]]
: 4. Genitourinary: e.g. urinary urgency or [[Urinary frequency|frequency]], [[nocturia]]
: 5. [[Development of new sensitivities|Sensitivities]] to [[Food sensitivities|food]], [[Medicine sensitivities|medications]], [[Odor sensitivities|odours]] or [[multiple chemical sensitivity|chemicals]]

Notes: ''Sore throat, tender lymph nodes, and flu-like symptoms obviously are not specific to ME but their activation in reaction to exertion is abnormal. The throat may feel sore, dry and scratchy. Faucial injection and crimson crescents may be seen in the tonsillar fossae, which are an indication of immune activation.''
|-
| style="background-color: lightsteelblue;color:black;text-shadow:none" |
|<h3>Energy production/transportation impairments: At least one symptom</h3>
|-
| style="background-color: lightsteelblue;color:black;text-shadow:none" |D.
|
: 1. Cardiovascular: e.g. inability to tolerate an upright position - [[orthostatic intolerance]], [[neurally mediated hypotension]], [[postural orthostatic tachycardia syndrome]], [[Heart palpitation|palpitations]] with or without [[arrhythmia|cardiac arrhythmias]], [[light-headedness]]/[[dizziness]]
: 2. [[Breathing problems in ME/CFS|Respiratory]]: e.g. [[air hunger]], [[laboured breathing]], [[fatigue of chest wall muscles]]
: 3. [[thermostatic instability|Loss of thermostatic stability]]: e.g. [[subnormal body temperature]], marked [[diurnal fluctuation]]s; [[excessive sweating|sweating episodes]], recurrent feelings of feverishness with or without [[low-grade fever|low grade fever]], [[cold hands and feet|cold extremities]]
: 4. [[Temperature sensitivity|Intolerance of extremes of temperature]]

Notes: ''[[Orthostatic intolerance]] may be delayed by several minutes. Patients who have orthostatic intolerance may exhibit mottling of extremities, extreme pallor or [[Raynaud's syndrome|Raynaud's Phenomenon]]. In the chronic phase, moons of finger nails may recede.''
|-
| colspan="2" |<h3>Paediatric considerations</h3>
|-
| colspan="2" |''Symptoms may progress more slowly in children than in teenagers or adults. In addition to [[postexertional neuroimmune exhaustion]], the most prominent symptoms tend to be neurological: [[headache]]s, [[cognitive impairment]]s, and [[sleep disturbance]]s.''

:* '''[[Headache]]s:''' Severe or chronic headaches are often debilitating. [[Migraine]] may be accompanied by a rapid drop in temperature, shaking, [[vomiting]], [[diarrhoea]] and severe weakness.
:* '''Neurocognitive impairments:''' [[inability to focus vision|Difficulty focusing eyes]] and reading are common. Children may become [[dyslexia|dyslexic]], which may only be evident when fatigued. [[Slow processing of information]] makes it difficult to follow auditory instructions or take notes. All cognitive impairments worsen with physical or mental exertion. Young people [[unable to go to school full-time|will not be able to maintain a full school program]].
:* '''[[Pain]]''' may seem erratic and migrate quickly. '''[[Hypermobility|Joint hypermobility]]''' is common.

'''''Notes:''''' ''Fluctuation and severity hierarchy of numerous prominent symptoms tend to vary more rapidly and dramatically.''
|-
| colspan="2" class="left" style="text-align: left" |<h3 class="center">Classification</h3>

——— '''Myalgic encephalomyelitis'''

——— '''Atypical myalgic encephalomyelitis:'''<br />
meets criteria for [[postexertional neuroimmune exhaustion]] but has a limit of two less than required of the remaining criterial symptoms. [[Pain]] or [[sleep disturbance]] may be absent in rare cases.
|-
| colspan="2" |<h3>Exclusions</h3>
|-
| colspan="2" |As in all diagnoses, exclusion of alternate explanatory diagnoses is achieved by the patient’s history, physical examination, and laboratory/biomarker testing as indicated. It is possible to have more than one disease but it is important that each one is identified and treated. [[:Category:mental disorders|Primary psychiatric disorders]], [[somatoform disorder]] and [[substance abuse]] are excluded. Paediatric: [[school phobia|'primary' school phobia]].
|-
| colspan="2" |<h3>Comorbid entities</h3>
|-
| colspan="2" |[[Fibromyalgia]], [[myofascial pain syndrome]], [[temporomandibular joint syndrome]], [[irritable bowel syndrome]], [[interstitial cystitis]], [[Raynaud's syndrome|Raynaud’s phenomenon]], [[prolapsed mitral valve]], [[migraine]]s, [[allergy|allergies]], [[multiple chemical sensitivity|multiple chemical sensitivities]], [[Hashimoto's thyroiditis]], [[Sicca syndrome]], [[depression#Reactive_depression|reactive depression]]. [[Migraine]] and [[irritable bowel syndrome]] may precede ME but then become associated with it. [[Fibromyalgia]] overlaps.
|}

==Background and purpose==

The 2012 ICC is very clear on the topic of names:

Problem

The label ‘chronic fatigue syndrome’ (CFS), coined in the 1980s, has persisted due to lack of knowledge of its etiologic agents and pathophysiology. Misperceptions have arisen because the name ‘CFS’ and its hybrids ME/CFS, CFS/ME and CFS/CF have been used for widely diverse conditions. Patient sets can include those who are seriously ill with ME, many bedridden and unable to care for themselves, to those who have general fatigue or, under the Reeves criteria, patients are not required to have any physical symptoms. There is a poignant need to untangle the web of confusion caused by mixing diverse and often overly inclusive patient populations in one heterogeneous, multi-rubric pot called ‘chronic fatigue syndrome’. We believe this is the foremost cause of diluted and inconsistent research findings, which hinders progress, fosters scepticism, and wastes limited research monies.

Solution

The rationale for the development of the ICC was to utilize current research knowledge to identify objective, measurable and reproducible abnormalities that directly reflect the interactive, regulatory components of the underlying pathophysiology of ME. Specifically, the ICC select patients who exhibit explicit multi-systemic neuropathology, and have a pathological low threshold of physical and mental fatigability in response to exertion. Cardiopulmonary exercise test- retest studies have confirmed many post-exertional abnormalities. Criterial symptoms are compulsory and identify patients who have greater physical, cognitive and functional impairments. The ICC advance the successful strategy of the Canadian Consensus Criteria (CCC) of grouping coordinated patterns of symptom clusters that identify areas of pathology. The criteria are designed for both clinical and research settings.

1. Name: Myalgic encephalomyelitis, a name that originated in the 1950s, is the most accurate and appropriate name because it reflects the underlying multi-system pathophysiology of the disease. Our panel strongly recommends that only the name ‘myalgic encephalomyelitis’ be used to identify patients meeting the ICC because a distinctive disease entity should have one name. Patients diagnosed using broader or other criteria for CFS or its hybrids (Oxford, Reeves, London, Fukuda, CCC, etc.) should be reassessed with the ICC. Those who fulfill the criteria have ME; those who do not would remain in the more encompassing CFS classification. (bold emphasis mine)

2. Remove patients who satisfy the ICC from the broader category of CFS. The purpose of diagnosis is to provide clarity. The criterial symptoms, such as the distinctive abnormal responses to exertion can differentiate ME patients from those who are depressed or have other fatiguing conditions. Not only is it common sense to extricate ME patients from the assortment of conditions assembled under the CFS umbrella, it is compliant with the WHO classification rule that a disease cannot be classified under more than one rubric. The panel is not dismissing the broad components of fatiguing illnesses, but rather the ICC are a refinement of patient stratification. As other identifiable patient sets are identified and supported by research, they would then be removed from the broad CFS/CF category.

Research on ME: The logical way to advance science is to select a relatively homogeneous patient set that can be studied to identify biopathological mechanisms, biomarkers and disease process specific to that patient set, as well as comparing it to other patient sets. It is counterproductive to use inconsistent and overly inclusive criteria to glean insight into the pathophysiology of ME if up to 90% of the research patient sets may not meet its criteria (Jason 2009). Research on other fatiguing illnesses, such as cancer and multiple sclerosis (MS), is done on patients who have those diseases. There is a current, urgent need for ME research using patients who actually have ME. (bold emphasis mine)

4. Research confirmation: When research is applied to patients satisfying the ICC, previous findings based on broader criteria will be confirmed or refuted. Validation of ME being a differential diagnosis, as is multiple sclerosis (MS), or a subgroup of chronic fatigue syndrome, will then be verified.

5. Focus on treatment efficacy: With enhanced understanding of biopathological mechanisms, biomarkers and other components of pathophysiology specific to ME, more focus and research emphasis can target expanding and augmenting treatment efficacy.

==International Consensus Primer (ICP)==

Problem

Overly inclusive criteria have created misperceptions, fostered cynicism and have had a major negative impact on how ME is viewed by the medical community, patients, their families, as well as the general public. Some medical schools do not include ME in their curriculum with the result that very significant scientific advances and appropriate diagnostic and treatment protocols have not reached many busy medical practitioners. Some doctors may be unaware of the complexity and serious nature of ME. Patients may go undiagnosed and untreated; they may be shunned or isolated.<ref name="ICP2011primer">{{citation
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Bell | first12= DS | authorlink12= David Bell
| last13 = Carlo-Stella | first13= N | authorlink13= Nicoletta Carlo-Stella
| last14 = Chia | first14= J | authorlink14= John Chia
| last15 = Darragh | first15= A | authorlink15= Austin Darragh
| last16 = Gerken | first16= A | authorlink16= Anne Gerken
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Light | first20= KC | authorlink20= Kathleen Light
| last21 = Marshall-Gradisnik | first21= S | authorlink21= Sonya Marshall-Gradisnik
| last22 = McLaren-Howard | first22= J | authorlink22= John McLaren-Howard
| last23 = Mena | first23= I | authorlink23= Ismael Mena
| last24 = Miwa | first24= K | authorlink24= Kunihisa Miwa
| last25 = Murovska | first25= M | authorlink25= Modra Murovska
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners
| date = 2012
| isbn = 978-0-9739335-3-6
| url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf
}}</ref>

==World Health Organisation==
The World Health Organisation (WHO) lists ME and post viral fatigue syndrome under neurological conditions. The diagnostic code is G93.3<ref>[http://apps.who.int/classifications/icd10/browse/2016/en#/G93.3 WHO Classifications G93.3 - 2016]</ref> Importantly, it doesn’t include chronic fatigue syndrome there, or ME/CFS or CFS/ME. Fatigue syndromes are listed in "Other neurotic disorders."<ref>[http://apps.who.int/classifications/icd10/browse/2016/en#/F48.0 WHO Classifications F48.0 - 2016]</ref>

==Comparison with other criteria==
[[File:Individuals_referred_by_medical_specialists_in_CFS_and_ME-CFS_.png|right|450px|thumb|M.E. and CFS are different but partially overlapping (Twisk, 2015)]]
*Norwegian researchers compare the main criteria ([[Oxford criteria]], [[Fukuda criteria]], [[Canadian Consensus Criteria]], International Consensus Criteria and [[SEID]]). They say "it is important to distinguish between myalgic encephalomyelitis and chronic fatigue syndrome” to improve understanding of the disease, treatment and patients’ lives, as using incorrect criteria can lead to incorrect treatment.<ref name="Egeland2015" />

*'Scientists must agree on classifying patients’ Leonard Jason<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=McManimen|first2=Stephanie|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Furst|first5=Jacob|last6=Newton|first6=Julia L.|last7=Strand|first7=Elin Bolle|date=2016-01-02|title=Case definitions integrating empiric and consensus perspectives|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1124520?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=4|issue=1|pages=1–23|doi=10.1080/21641846.2015.1124520|issn=2164-1846|pmc=4831204|pmid=27088059}}</ref>

*Frank Twisk explains that ME and CFS are "distinct, partially overlapping, clinical entities such as ME and CFS" Frank Twisk 2016<ref>{{Cite journal|last=Twisk|first=Frank NM|date=2015-06-26|title=Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482824/|journal=World Journal of Methodology|volume=5|issue=2|pages=68–87|doi=10.5662/wjm.v5.i2.68|issn=2222-0682|pmc=4482824|pmid=26140274}}</ref>

==Diagram of ME ICC symptoms ==
[[File:What-is-Myalgic-Encephalomyelitis-ME-ICC.png|550px|thumb|center|Simplified diagram of the main myalgic encephalomyelitis international consensus criteria symptoms]]

== Tool to determine if you meet ICC criteria ==
The following online questionnaire was developed by [[Schweizerische Gesellschaft für ME & CFS]], a patient association in Switzerland, to help you determine whether the diagnosis of ME (Myalgic Encephalomyelitis) according to the International Consensus Criteria (ICC) is applicable to you. English and Dutch versions are available.

[https://sgme.ch/icc/en/ Questionnaire in English]

[https://sgme.ch/icc/de/ Questionnaire in German]

==See also==

*[[Definitions of ME and CFS]]
*[[Canadian Consensus Criteria]]
*[[List_of_symptoms_in_ME_CFS|List of symptoms in ME/CFS]]
*[[Common_symptoms_in_ME_CFS|Common symptoms]]
*[[Differential diagnosis]]

=== Generally accepted criteria for diagnosing ME and ME/CFS ===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*International Consensus Criteria (ICC)<ref name="icc" /> This criterion will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|url-status=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegria|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==

*[http://www.meadvocacy.org/the_international_consensus_criteria_what_is_it_do_i_fit_the_criteria MEAdvocacy - The International Consensus Criteria: What is it? Do I fit the criteria?]

*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf International Consensus Primer for Medical Practioners]

==References==
<references>
<ref name="Egeland2015">{{citation
| last1 = Egeland | first1 = T | authorlink1 = Torstein Egeland
| last2 = Angelsen | first2 = A | authorlink2 = Arild Angelsen
| last3 = Haug | first3 = R | authorlink3 = Ruth Haug
| last4 = Henriksen | first4 = JO | authorlink4 = Jan-Olave Henriksen
| last5 = Lea | first5 = TE | authorlink5 = Tor Erling Lea
| last6 = Saugstad | first6 = OD | authorlink6 = Ola Didrik Saugstad
| title = What exactly is myalgic encephalomyelitis?
| type = Perspectives
| journal = Tidsskr Nor Legeforen | volume = 2015 | issue = 135 | page = 1756–9
| date = Oct 2015
| doi = 10.4045/tidsskr.15.0089
| url = http://tidsskriftet.no/article/3404849/en_GB
| lay-url = http://www.meaction.net/2015/12/10/norwegian-researchers-ask-what-exactly-is-m-e/
}}</ref>
</references>

[[Category:Definitions]]
[[Category:Secondary sources]]

International Consensus Criteria

2022-01-08T20:50:20Z

Kmdenmark:Added questionnaire/tool

[[File:What-is-Myalgic-Encephalomyelitis-ME-ICC.png|frameless|upright=0.75|right|Simplified ME International Consensus Criteria symptoms.]]
The [[myalgic encephalomyelitis|Myalgic Encephalomyelitis]] (ME) '''International Consensus Criteria''' (ICC)<ref name=":0">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> is a medical case definition that can accurately diagnose [[myalgic encephalomyelitis]] (ME), is a chronic, [[Inflammation|inflammatory]], physically and [[Nervous system|neurologically]] disabling disease. For pediatric and adult cases a diagnosis should be made immediately; there is no need to wait up to 6 months.

==Authors==
[[Bruce Carruthers]], [[Marjorie van de Sande]], [[Kenny de Meirleir]], [[Nancy Klimas]], [[Gordon Broderick]], [[Terry Mitchell]], [[Donald Staines]], [[A C Peter Powles]], [[Nigel Speight]], [[Rosamund Vallings]], [[Lucinda Bateman]], [[Barbara Baumgarten-Austrheim]], [[David Bell]], [[Nicoletta Carlo-Stella]], [[John Chia]], [[Austin Darragh]], [[Daehyun Jo]], [[Donald Lewis]], [[Alan Light]], [[Sonya Marshall-Gradisnik]], [[Ismael Mena]], [[Judy Mikovits]], [[Kunihisa Miwa]], [[Modra Murovska]], [[Martin Pall]], and [[Staci Stevens]]<ref name=":0" />

==Criteria==
A patient will meet the criteria for [[myalgic encephalomyelitis|Myalgic Encephalomyelitis]] if they have:

'''A''' - [[Postexertional neuroimmune exhaustion]]

'''B''' - at least ONE '''[[Nervous system|neurological]] impairment''' symptom from THREE categories:

# Neurocognitive Impairments
# [[Pain]]          
# [[Sleep dysfunction|Sleep Disturbance]]      
# [[:Category:Cognitive signs and symptoms|Neurosensory]], [[perceptual distortion|Perceptual]] and [[motor problems|Motor Disturbances]]

'''C''' - at least ONE '''[[Immune system|immune]]/[[Gastrointestinal|gastro-intestinal]]/genitourinary impairment''' from THREE categories:
# [[Flu-like symptoms]] may be recurrent or chronic and typically activate or worsen with [[exertion]]
# [[susceptibility to viruses|Susceptibility to viral infections]] with prolonged recovery periods
# [[Gastrointestinal system|Gastro-intestinal]] tract
# [[:Category:Genitourinary signs and symptoms|Genitourinary]]    
# [[Hypersensitivity|Sensitivities]] to [[Food intolerance|food]], [[Medicine sensitivities|medications]], [[Odor sensitivities|odors]] or [[multiple chemical sensitivity|chemicals]], and

'''D''' - at least ONE '''[[Metabolic|energy metabolism]]/[[Ion transportation|ion transport]] impairment''' symptom.
# [[Cardiovascular system|Cardiovascular]]  
# [[Breathing problems in ME/CFS|Respiratory]]    
# [[thermostatic instability|Loss of thermostatic stability]]
# [[Temperature sensitivity|Intolerance of extremes of temperature]]  
<hr />

{| class="wikitable left"
|-
| style="background-color: peachpuff;color:black;text-shadow:none" |
|<h3>[[Postexertional neuroimmune exhaustion]] (PENE pen’-e): Compulsory</h3>
|-
| style="background-color: peachpuff;color:black;text-shadow:none" |A.
|
This cardinal feature is a pathological [[inability to produce sufficient energy on demand]] with prominent symptoms primarily in the neuroimmune regions. Characteristics are as follows:

: 1. Marked, rapid physical and/or cognitive [[post-exertional fatigue|fatigability in response to exertion]], which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
: 2. [[Postexertional symptom exacerbation]]: e.g. acute [[flu-like symptoms]], pain and worsening of other symptoms.
: 3. [[Postexertional exhaustion]] may occur immediately after activity or be delayed by hours or days.
: 4. [[Prolonged recovery after exertion|Recovery period is prolonged]], usually taking 24h or longer. A relapse can last days, weeks or longer.
: 5. [[Lack of stamina|Low threshold of physical and mental fatigability]] (lack of stamina) results in a [[Greatly lowered ability to do activities that were usual before the illness|substantial reduction in pre-illness activity level]].

Operational notes: ''For a diagnosis of ME, symptom severity must result in a significant reduction of a patient’s premorbid activity level. [[Mild myalgic encephalomyelitis or chronic fatigue syndrome|Mild]] (an approximate 50% reduction in pre-illness activity level), [[Moderate myalgic encephalomyelitis or chronic fatigue syndrome|moderate]] (mostly housebound), [[severe myalgic encephalomyelitis or chronic fatigue syndrome|severe]] (mostly bedridden) or [[very severe myalgic encephalomyelitis or chronic fatigue syndrome|very severe]] (totally bedridden and need help with basic functions). There may be marked fluctuation of symptom severity and hierarchy from day to day or hour to hour. Consider activity, context and interactive effects. Recovery time: e.g. Regardless of a patient’s recovery time from reading for ½ hour, it will take much longer to recover from grocery shopping for ½ hour and even longer if repeated the next day – if able. Those who rest before an activity or have adjusted their activity level to their limited energy may have shorter recovery periods than those who do not pace their activities adequately. Impact: e.g. An outstanding athlete could have a [[substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities|50% reduction in his/her pre-illness activity level]] and is still more active than a sedentary person.''
|-
| style="background-color: palegreen;color:black;text-shadow:none" |
|<h3>Neurological impairments</h3>
|-
| style="background-color: palegreen;color:black;text-shadow:none" |B.
|
At least one symptom from three of the following four symptom categories

<h4>1. Neurocognitive impairments</h4>

:a. [[difficulty thinking|Difficulty processing information]]: [[slowed thought]], [[attention deficit|impaired concentration]] e.g. [[confusion]], [[disorientation]], cognitive overload, difficulty with making decisions, [[slowed speech]], acquired or exertional [[dyslexia]]
:b. [[Memory problems|Short-term memory loss]]: e.g. difficulty remembering what one wanted to say, what one was saying, [[word-finding problems|retrieving words]], recalling information, [[poor working memory]]

<h4>2. [[Pain]]</h4>

:a. [[Headache]]s: e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; [[migraine]]; [[tension-type headache|tension headaches]]
:b. Significant pain can be experienced in [[myalgia|muscles]], muscle-tendon junctions, [[arthralgia|joints]], [[abdominal pain|abdomen]] or [[chest pain|chest]]. It is noninflammatory in nature and often migrates. e.g. generalized [[hyperalgesia]], widespread pain (may meet fibromyalgia criteria), [[myofascial pain|myofascial]] or radiating pain

<h4>3. [[Sleep disturbance]]</h4>

: a. Disturbed sleep patterns: e.g. [[insomnia]], [[hypersomnia|prolonged sleep including naps]], [[sleep reversal|sleeping most of the day and being awake most of the night]], frequent awakenings, [[early waking|awaking much earlier]] than before illness onset, [[vivid dreams|vivid dreams/nightmares]]
: b. [[unrefreshing sleep|Unrefreshed sleep]]: e.g. awaken feeling exhausted regardless of duration of sleep, [[daytime sleepiness|day-time sleepiness]]

<h4>4. Neurosensory, perceptual and motor disturbances</h4>

: a. Neurosensory and perceptual: e.g. [[inability to focus vision]], [[photophobia|sensitivity to light]], [[Hyperacusis|noise]], vibration, odour, taste and touch; [[impaired depth perception]]
: b. Motor: e.g. [[paresis|muscle weakness]], [[fasciculation|twitching]], [[poor coordination]], feeling unsteady on feet, [[ataxia]]

Notes: ''Neurocognitive impairments, reported or observed, become more pronounced with fatigue. [[Overload phenomena]] may be evident when [[difficulty multi-tasking|two tasks are performed simultaneously]]. Abnormal accommodation responses of the pupils are common. Sleep disturbances are typically expressed by prolonged sleep, sometimes extreme, in the acute phase and often evolve into marked sleep reversal in the chronic stage. Motor disturbances may not be evident in mild or moderate cases but [[abnormal tandem gait]] and [[Romberg test|positive Romberg test]] may be observed in severe cases.''
|-
| style="background-color: thistle;color:black;text-shadow:none;border: none" |
|<h3>Immune, gastro-intestinal and genitourinary impairments</h3>
|-
| style="background-color: thistle;color:black;text-shadow:none; " |C.
|
At least one symptom from three of the following five symptom categories

: 1. [[Flu-like illness|Flu-like symptoms]] may be recurrent or chronic and typically activate or [[Symptoms worsening with exertion|worsen with exertion]] e.g. [[sore throat]], [[sinusitis]], cervical and/or axillary [[swollen lymph nodes|lymph nodes may enlarge]] or be tender on palpitation
: 2. [[Susceptibility to viruses|Susceptibility to viral infections]] with prolonged recovery periods
: 3. Gastro-intestinal tract: e.g. [[nausea]], [[abdominal pain]], [[bloating]], [[irritable bowel syndrome]]
: 4. Genitourinary: e.g. urinary urgency or [[Urinary frequency|frequency]], [[nocturia]]
: 5. [[Development of new sensitivities|Sensitivities]] to [[Food sensitivities|food]], [[Medicine sensitivities|medications]], [[Odor sensitivities|odours]] or [[multiple chemical sensitivity|chemicals]]

Notes: ''Sore throat, tender lymph nodes, and flu-like symptoms obviously are not specific to ME but their activation in reaction to exertion is abnormal. The throat may feel sore, dry and scratchy. Faucial injection and crimson crescents may be seen in the tonsillar fossae, which are an indication of immune activation.''
|-
| style="background-color: lightsteelblue;color:black;text-shadow:none" |
|<h3>Energy production/transportation impairments: At least one symptom</h3>
|-
| style="background-color: lightsteelblue;color:black;text-shadow:none" |D.
|
: 1. Cardiovascular: e.g. inability to tolerate an upright position - [[orthostatic intolerance]], [[neurally mediated hypotension]], [[postural orthostatic tachycardia syndrome]], [[Heart palpitation|palpitations]] with or without [[arrhythmia|cardiac arrhythmias]], [[light-headedness]]/[[dizziness]]
: 2. [[Breathing problems in ME/CFS|Respiratory]]: e.g. [[air hunger]], [[laboured breathing]], [[fatigue of chest wall muscles]]
: 3. [[thermostatic instability|Loss of thermostatic stability]]: e.g. [[subnormal body temperature]], marked [[diurnal fluctuation]]s; [[excessive sweating|sweating episodes]], recurrent feelings of feverishness with or without [[low-grade fever|low grade fever]], [[cold hands and feet|cold extremities]]
: 4. [[Temperature sensitivity|Intolerance of extremes of temperature]]

Notes: ''[[Orthostatic intolerance]] may be delayed by several minutes. Patients who have orthostatic intolerance may exhibit mottling of extremities, extreme pallor or [[Raynaud's syndrome|Raynaud's Phenomenon]]. In the chronic phase, moons of finger nails may recede.''
|-
| colspan="2" |<h3>Paediatric considerations</h3>
|-
| colspan="2" |''Symptoms may progress more slowly in children than in teenagers or adults. In addition to [[postexertional neuroimmune exhaustion]], the most prominent symptoms tend to be neurological: [[headache]]s, [[cognitive impairment]]s, and [[sleep disturbance]]s.''

:* '''[[Headache]]s:''' Severe or chronic headaches are often debilitating. [[Migraine]] may be accompanied by a rapid drop in temperature, shaking, [[vomiting]], [[diarrhoea]] and severe weakness.
:* '''Neurocognitive impairments:''' [[inability to focus vision|Difficulty focusing eyes]] and reading are common. Children may become [[dyslexia|dyslexic]], which may only be evident when fatigued. [[Slow processing of information]] makes it difficult to follow auditory instructions or take notes. All cognitive impairments worsen with physical or mental exertion. Young people [[unable to go to school full-time|will not be able to maintain a full school program]].
:* '''[[Pain]]''' may seem erratic and migrate quickly. '''[[Hypermobility|Joint hypermobility]]''' is common.

'''''Notes:''''' ''Fluctuation and severity hierarchy of numerous prominent symptoms tend to vary more rapidly and dramatically.''
|-
| colspan="2" class="left" style="text-align: left" |<h3 class="center">Classification</h3>

——— '''Myalgic encephalomyelitis'''

——— '''Atypical myalgic encephalomyelitis:'''<br />
meets criteria for [[postexertional neuroimmune exhaustion]] but has a limit of two less than required of the remaining criterial symptoms. [[Pain]] or [[sleep disturbance]] may be absent in rare cases.
|-
| colspan="2" |<h3>Exclusions</h3>
|-
| colspan="2" |As in all diagnoses, exclusion of alternate explanatory diagnoses is achieved by the patient’s history, physical examination, and laboratory/biomarker testing as indicated. It is possible to have more than one disease but it is important that each one is identified and treated. [[:Category:mental disorders|Primary psychiatric disorders]], [[somatoform disorder]] and [[substance abuse]] are excluded. Paediatric: [[school phobia|'primary' school phobia]].
|-
| colspan="2" |<h3>Comorbid entities</h3>
|-
| colspan="2" |[[Fibromyalgia]], [[myofascial pain syndrome]], [[temporomandibular joint syndrome]], [[irritable bowel syndrome]], [[interstitial cystitis]], [[Raynaud's syndrome|Raynaud’s phenomenon]], [[prolapsed mitral valve]], [[migraine]]s, [[allergy|allergies]], [[multiple chemical sensitivity|multiple chemical sensitivities]], [[Hashimoto's thyroiditis]], [[Sicca syndrome]], [[depression#Reactive_depression|reactive depression]]. [[Migraine]] and [[irritable bowel syndrome]] may precede ME but then become associated with it. [[Fibromyalgia]] overlaps.
|}

==Background and purpose==

The 2012 ICC is very clear on the topic of names:

Problem

The label ‘chronic fatigue syndrome’ (CFS), coined in the 1980s, has persisted due to lack of knowledge of its etiologic agents and pathophysiology. Misperceptions have arisen because the name ‘CFS’ and its hybrids ME/CFS, CFS/ME and CFS/CF have been used for widely diverse conditions. Patient sets can include those who are seriously ill with ME, many bedridden and unable to care for themselves, to those who have general fatigue or, under the Reeves criteria, patients are not required to have any physical symptoms. There is a poignant need to untangle the web of confusion caused by mixing diverse and often overly inclusive patient populations in one heterogeneous, multi-rubric pot called ‘chronic fatigue syndrome’. We believe this is the foremost cause of diluted and inconsistent research findings, which hinders progress, fosters scepticism, and wastes limited research monies.

Solution

The rationale for the development of the ICC was to utilize current research knowledge to identify objective, measurable and reproducible abnormalities that directly reflect the interactive, regulatory components of the underlying pathophysiology of ME. Specifically, the ICC select patients who exhibit explicit multi-systemic neuropathology, and have a pathological low threshold of physical and mental fatigability in response to exertion. Cardiopulmonary exercise test- retest studies have confirmed many post-exertional abnormalities. Criterial symptoms are compulsory and identify patients who have greater physical, cognitive and functional impairments. The ICC advance the successful strategy of the Canadian Consensus Criteria (CCC) of grouping coordinated patterns of symptom clusters that identify areas of pathology. The criteria are designed for both clinical and research settings.

1. Name: Myalgic encephalomyelitis, a name that originated in the 1950s, is the most accurate and appropriate name because it reflects the underlying multi-system pathophysiology of the disease. Our panel strongly recommends that only the name ‘myalgic encephalomyelitis’ be used to identify patients meeting the ICC because a distinctive disease entity should have one name. Patients diagnosed using broader or other criteria for CFS or its hybrids (Oxford, Reeves, London, Fukuda, CCC, etc.) should be reassessed with the ICC. Those who fulfill the criteria have ME; those who do not would remain in the more encompassing CFS classification. (bold emphasis mine)

2. Remove patients who satisfy the ICC from the broader category of CFS. The purpose of diagnosis is to provide clarity. The criterial symptoms, such as the distinctive abnormal responses to exertion can differentiate ME patients from those who are depressed or have other fatiguing conditions. Not only is it common sense to extricate ME patients from the assortment of conditions assembled under the CFS umbrella, it is compliant with the WHO classification rule that a disease cannot be classified under more than one rubric. The panel is not dismissing the broad components of fatiguing illnesses, but rather the ICC are a refinement of patient stratification. As other identifiable patient sets are identified and supported by research, they would then be removed from the broad CFS/CF category.

Research on ME: The logical way to advance science is to select a relatively homogeneous patient set that can be studied to identify biopathological mechanisms, biomarkers and disease process specific to that patient set, as well as comparing it to other patient sets. It is counterproductive to use inconsistent and overly inclusive criteria to glean insight into the pathophysiology of ME if up to 90% of the research patient sets may not meet its criteria (Jason 2009). Research on other fatiguing illnesses, such as cancer and multiple sclerosis (MS), is done on patients who have those diseases. There is a current, urgent need for ME research using patients who actually have ME. (bold emphasis mine)

4. Research confirmation: When research is applied to patients satisfying the ICC, previous findings based on broader criteria will be confirmed or refuted. Validation of ME being a differential diagnosis, as is multiple sclerosis (MS), or a subgroup of chronic fatigue syndrome, will then be verified.

5. Focus on treatment efficacy: With enhanced understanding of biopathological mechanisms, biomarkers and other components of pathophysiology specific to ME, more focus and research emphasis can target expanding and augmenting treatment efficacy.

==International Consensus Primer (ICP)==

Problem

Overly inclusive criteria have created misperceptions, fostered cynicism and have had a major negative impact on how ME is viewed by the medical community, patients, their families, as well as the general public. Some medical schools do not include ME in their curriculum with the result that very significant scientific advances and appropriate diagnostic and treatment protocols have not reached many busy medical practitioners. Some doctors may be unaware of the complexity and serious nature of ME. Patients may go undiagnosed and untreated; they may be shunned or isolated.<ref name="ICP2011primer">{{citation
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Bell | first12= DS | authorlink12= David Bell
| last13 = Carlo-Stella | first13= N | authorlink13= Nicoletta Carlo-Stella
| last14 = Chia | first14= J | authorlink14= John Chia
| last15 = Darragh | first15= A | authorlink15= Austin Darragh
| last16 = Gerken | first16= A | authorlink16= Anne Gerken
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Light | first20= KC | authorlink20= Kathleen Light
| last21 = Marshall-Gradisnik | first21= S | authorlink21= Sonya Marshall-Gradisnik
| last22 = McLaren-Howard | first22= J | authorlink22= John McLaren-Howard
| last23 = Mena | first23= I | authorlink23= Ismael Mena
| last24 = Miwa | first24= K | authorlink24= Kunihisa Miwa
| last25 = Murovska | first25= M | authorlink25= Modra Murovska
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners
| date = 2012
| isbn = 978-0-9739335-3-6
| url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf
}}</ref>

==World Health Organisation==
The World Health Organisation (WHO) lists ME and post viral fatigue syndrome under neurological conditions. The diagnostic code is G93.3<ref>[http://apps.who.int/classifications/icd10/browse/2016/en#/G93.3 WHO Classifications G93.3 - 2016]</ref> Importantly, it doesn’t include chronic fatigue syndrome there, or ME/CFS or CFS/ME. Fatigue syndromes are listed in "Other neurotic disorders."<ref>[http://apps.who.int/classifications/icd10/browse/2016/en#/F48.0 WHO Classifications F48.0 - 2016]</ref>

==Comparison with other criteria==
[[File:Individuals_referred_by_medical_specialists_in_CFS_and_ME-CFS_.png|right|450px|thumb|M.E. and CFS are different but partially overlapping (Twisk, 2015)]]
*Norwegian researchers compare the main criteria ([[Oxford criteria]], [[Fukuda criteria]], [[Canadian Consensus Criteria]], International Consensus Criteria and [[SEID]]). They say "it is important to distinguish between myalgic encephalomyelitis and chronic fatigue syndrome” to improve understanding of the disease, treatment and patients’ lives, as using incorrect criteria can lead to incorrect treatment.<ref name="Egeland2015" />

*'Scientists must agree on classifying patients’ Leonard Jason<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=McManimen|first2=Stephanie|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Furst|first5=Jacob|last6=Newton|first6=Julia L.|last7=Strand|first7=Elin Bolle|date=2016-01-02|title=Case definitions integrating empiric and consensus perspectives|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1124520?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=4|issue=1|pages=1–23|doi=10.1080/21641846.2015.1124520|issn=2164-1846|pmc=4831204|pmid=27088059}}</ref>

*Frank Twisk explains that ME and CFS are "distinct, partially overlapping, clinical entities such as ME and CFS" Frank Twisk 2016<ref>{{Cite journal|last=Twisk|first=Frank NM|date=2015-06-26|title=Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482824/|journal=World Journal of Methodology|volume=5|issue=2|pages=68–87|doi=10.5662/wjm.v5.i2.68|issn=2222-0682|pmc=4482824|pmid=26140274}}</ref>

==Diagram of ME ICC symptoms ==
[[File:What-is-Myalgic-Encephalomyelitis-ME-ICC.png|550px|thumb|center|Simplified diagram of the main myalgic encephalomyelitis international consensus criteria symptoms]]

== Tool to determine if you meet ICC criteria ==
The following online questionnaire was developed by Schweizerische Gesellschaft für ME & CFS, a patient association in Switzerland, to help you determine whether the diagnosis of ME (Myalgic Encephalomyelitis) according to the International Consensus Criteria (ICC) is applicable to you. English and Dutch versions are available.

[https://sgme.ch/icc/en/ Questionnaire in English]

[https://sgme.ch/icc/de/ Questionnaire in Dutch]

==See also==

*[[Definitions of ME and CFS]]
*[[Canadian Consensus Criteria]]
*[[List_of_symptoms_in_ME_CFS|List of symptoms in ME/CFS]]
*[[Common_symptoms_in_ME_CFS|Common symptoms]]
*[[Differential diagnosis]]

=== Generally accepted criteria for diagnosing ME and ME/CFS ===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*International Consensus Criteria (ICC)<ref name=":0" /> This criterion will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|url-status=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegria|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==

*[http://www.meadvocacy.org/the_international_consensus_criteria_what_is_it_do_i_fit_the_criteria MEAdvocacy - The International Consensus Criteria: What is it? Do I fit the criteria?]

*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf International Consensus Primer for Medical Practioners]

==References==
<references>
<ref name="Egeland2015">{{citation
| last1 = Egeland | first1 = T | authorlink1 = Torstein Egeland
| last2 = Angelsen | first2 = A | authorlink2 = Arild Angelsen
| last3 = Haug | first3 = R | authorlink3 = Ruth Haug
| last4 = Henriksen | first4 = JO | authorlink4 = Jan-Olave Henriksen
| last5 = Lea | first5 = TE | authorlink5 = Tor Erling Lea
| last6 = Saugstad | first6 = OD | authorlink6 = Ola Didrik Saugstad
| title = What exactly is myalgic encephalomyelitis?
| type = Perspectives
| journal = Tidsskr Nor Legeforen | volume = 2015 | issue = 135 | page = 1756–9
| date = Oct 2015
| doi = 10.4045/tidsskr.15.0089
| url = http://tidsskriftet.no/article/3404849/en_GB
| lay-url = http://www.meaction.net/2015/12/10/norwegian-researchers-ask-what-exactly-is-m-e/
}}</ref>
</references>

[[Category:Definitions]]
[[Category:Secondary sources]]

Acetylcholine

2021-10-07T20:40:01Z

Kmdenmark:fixed error in ref

'''Acetylcholine''' is a [[neurotransmitter]] that is thought to play a role in many human diseases including [[Myalgic encephalomyelitis|myalgic encephalomyelitis]] and [[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]].

== Function ==
Acetylcholine is used in the [[autonomic nervous system]], both as an internal transmitter for the [[sympathetic nervous system]] and as the final product released by the [[parasympathetic nervous system]]. It plays an important role in regulating the [[inflammation|inflammatory]] response and is used at the neuromuscular junction by motor neurons in order to activate muscles.

In the [[central nervous system]], acetylcholine modulates arousal and [[temperature]] regulation, is important for attention, memory and motivation, and may play a role in [[central fatigue]].

=== General Function Summary ===
As a neurotransmitter, acetylcholine is produced in nerve cells. Any cell that produces or is affected by acetylcholine is called cholinergic. In the nervous system, acetylcholine typically travels from the axon to the dendrite of the next nerve cell across the synaptic cleft. In muscle cells, it travels to the receptors on the muscle fiber, called the motor end plate. Acetylcholine can activate receptors, such as the [[nicotonic]] receptors or [[Muscarinic acetylcholine receptor|muscarinic]] receptors. These receptors can also be activated by, or blocked by, other molecules such as nicotine and muscarine. Muscarinic receptors are typically found in the parasypathetic nervous system, whereas nicotonic receptors are found in the [[central nervous system]], [[peripheral nervous system]], and [[Neuromuscular junction|neuromuscular]] junctions. Nicotonic receptors are classified as ligand-gated [[Ion channel|ion channels]] - when activated they open and allow ions like K+, Na+, and Ca+ to move in or out of the cell. Muscarinic receptors exert their effects on cells via a secondary messenger system.

Closing of the gate is completed by [[Acetylcholinesterase]] ( AChE) which catalyzes the breakdown of acetylcholine into [[choline]] and acetic acid, which allows the ion gate to close. Each molecule of AChE can degrade about 25,000 molecules of acetylcholine (ACh) per second. If the AChE molecule is blocked, breakdown of ACh will not be completed and the gate will remain open. If the AChE is blocked on a muscle fiber, the fiber will remain contracted.<ref>{{Cite book|title=Concepts of Biology – 1st Canadian Edition|pages=Chapter 19.4|isbn=|edition=1|volume=1|language=English|title-link=|url=ttps://opentextbc.ca/biology/chapter/19-4-muscle-contraction-and-locomotion/|access-date=2020-05-28|date=June 13, 2019|publisher=B.C. Open Textbook Collection|last=Molnar|first=Charles|author-link=|last2=Gair|first2=Jane|author-link2=|last3=|first3=|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|author-link7=|last8=|first8=|author-link8=|last9=|first9=|author-link9=|veditors=|others=|doi=|oclc=|quote=|archive-url=|archive-date=|location=|editor-last=|editor-first=|editor1-link=|editor-last2=|editor-first2=}}</ref> Various duration and strength AChE blockers exist. Short-duration or reversible AChE blockers have been developed as medications, as short-term blocking of AChE can allow the ion gates to stay open longer and increase ACh availability. Long-duration and irreversible AChE blockers, including Nerve Gas, can cause various symptoms up to and including paralysis and death. <ref>{{Cite journal|last=Čolović|first=Mirjana B|last2=Krstić|first2=Danijela Z|last3=Lazarević-Pašti|first3=Tamara D|last4=Bondžić|first4=Aleksandra M|last5=Vasić|first5=Vesna M|date=May 2013|title=Acetylcholinesterase Inhibitors: Pharmacology and Toxicology|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648782/|journal=Current Neuropharmacology|volume=11|issue=3|pages=315–335|doi=10.2174/1570159X11311030006|issn=1570-159X|pmc=3648782|pmid=24179466|quote=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

==Immune system==

The [[vagus nerve]] speaks directly to the [[immune system]] via acetylcholine.<ref>{{Cite news|url=https://www.sciencedaily.com/releases/2007/10/071024083630.htm|title=Direct Route From The Brain To The Immune System Discovered|work=ScienceDaily|access-date=2018-08-10|language=en}}</ref><ref>{{Cite news|url=http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-2-2015-14-16-10|title=Scientists uncover new role for neurotransmitter that helps fight infection {{!}} Imperial News {{!}} Imperial College London|work=Imperial News|access-date=2018-08-10|language=en-GB}}</ref><ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref>

Acetylcholine plays a role in [[innate immune system|innate immunity]] through nicotinic [[acetylcholine receptors]] and in the [[adaptive immune system|adaptive immune response]] via M3 muscarinic acetylcholine receptors (M3R).<ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref>

===Muscarinic receptors===

Knockout mice, that is mice lacking the gene that encodes for M3R, had impaired response to bacterial infection, while normal mice given a muscarinic [[agonist]] (to increase the activity of M3R) had enhanced production of [[Interleukin 13|IL-13]] and [[IFN-γ]].<ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref> Another study used a muscarinic agonist and an [[antagonist]] (reduce activity) and found antagonist suppressed the immune response while the agonist exaggerated it.<ref>{{Cite journal|last=Razani-Boroujerdi|first=Seddigheh|last2=Behl|first2=Muskaan|last3=Hahn|first3=Fletcher F.|last4=Pena-Philippides|first4=Juan Carlos|last5=Hutt|first5=Julie|last6=Sopori|first6=Mohan L.|date=Feb 2008|title=Role of muscarinic receptors in the regulation of immune and inflammatory responses|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323336/|journal=Journal of neuroimmunology|volume=194|issue=1-2|pages=83–88|doi=10.1016/j.jneuroim.2007.11.019|issn=0165-5728|pmid=18190972}}</ref>

===Mast cells===

Several studies suggest a relationship between [[autonomic nervous system]] dysfunction and [[mast cell]] activation via acetylcholine.

One study found that acetylcholine via muscarinic receptors strongly inhibited the release of [[histamine]] in [[mucosal]] mast cells.<ref>{{Cite journal|title=Acetylcholine via Muscarinic Receptors Inhibits Histamine Release from Human Isolated Bronchi|url=http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.2.96-12079#.V7vo-ZMrLMV|journal =American Journal of Respiratory and Critical Care Medicine|volume =|issue =|pages =|language=en|doi=10.1164/ajrccm.156.2.96-12079#.v7vo-zmrlmv}}</ref> The activity of [[acetylcholinesterase]], an enzyme that breaks down acetylcholine, was found to be significantly increased in 64% of patients experiencing flares of [[ulcerative colitis]].<ref>https://www.myknowtions.com/portfolio/autonomic-nervous-alterations-and-mast-cell-degranulation-in-the-exacerbation-of-ulcerative-colitis</ref>

==In human disease==

===Myasthenia Gravis===

Autoantibodies to acetylcholine receptors alpha subunit have been found in patients with [[myasthenia gravis]]. These cross react with [[herpesvirus]] glycoprotein D.<ref>{{cite book|last1=Angelini|first1=Lucia|last2=Bardare|first2=Maria|last3=Martini|first3=Alberto|year=2002|title=Immune-mediated Disorders of the Central Nervous System in Children|url=https://books.google.com/books?id=5trQOK8hcZUC&pg=PA7&lpg=PA7&dq=coxsackie+b+acetylcholine&source=bl&ots=zhup8ZXq68&sig=CxDwQCHO8-OMBYkcp4EayjnDKnw&hl=en&sa=X&ved=0ahUKEwjflpmqg9fOAhWBeSYKHSR4Dh0Q6AEIMTAD#v=onepage&q=coxsackie%20b%20acetylcholine&f=false}}</ref> Antibodies to acetylcholine receptor and [[HSV-1]] antigens crossreact.<ref>{{Cite journal|last=Gebhardt|first=B. M.|date=2000-06-26|title=Evidence for antigenic cross-reactivity between herpesvirus and the acetylcholine receptor|url=http://www.ncbi.nlm.nih.gov/pubmed/10742556|journal=Journal of Neuroimmunology|volume=105|issue=2|pages=145–153|issn=0165-5728|pmid=10742556}}</ref>

[[B cell]]s from myasthenia gravis patient stimulated ''in vitro'' by [[Epstein-Barr virus]] (EBV) produced acetylcholine autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=http://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> Ongoing EBV infection of the [[thymus]] has been posited as a causative agent for the production of aceytlcholine receptor autoantibodies in myasthenia gravis.<ref>{{Cite journal|last=Kaminski|first=Henry J.|last2=Janos|first2=Minarovits|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134}}</ref><ref>{{Cite web|url=http://journals.lww.com/neurologynow/_layouts/15/oaks.journals.mobile/post.aspx?blogId=2&postId=10|title=Official Brain & Life Home Page|website=journals.lww.com|language=en|access-date=2018-08-10}}</ref>

===Sjögren's syndrome===

Autoantibodies against muscarinic acetylcholine receptor on exocrine glands were found in patients with [[Sjögren's syndrome]].<ref>http://www.omicsonline.org/open-access/autoantibodies-against-muscarinic-acetylcholine-receptor-on-exocrine-glands-in-sjgren-syndrome-2161-1122.1000265.pdf</ref>

===Chronic fatigue syndrome===

Since at least the 1990s it has been theorized that CFS might be associated with abnormalities of acetylcholine neurotransmission. To test this hypothesis, a provocation study was performed using the acetylcholinesterase inhibitor [[pyridostigmine]]. The results did indicate that CFS patients' hypothalamuses are hypersensitive to cholinergic stimulation relative to matched healthy controls. <ref>{{Cite journal|last=Chaudhuri|first=A.|last2=Majeed|first2=T.|last3=Dinan|first3=T.|last4=Behan|first4=P. O.|date=Jan 1997|title=Chronic Fatigue Syndrome: A Disorder of Central Cholinergic Transmission|url=http://www.tandfonline.com/doi/full/10.1300/J092v03n01_02|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=3|issue=1|pages=3–16|doi=10.1300/J092v03n01_02|issn=1057-3321}}</ref> These results mirror similar, highly replicated findings showing that CFS patients' hypothalamuses are hypersensitive to serotonergic stimulation as well (see [[Buspirone challenge test]]).

A 2003 study of 60 CFS patients found that 53.3% had detectable autoantibodies against the M1 muscarinic acetylcholine receptor. <ref>{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=2003-08-01|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=http://www.spandidos-publications.com/10.3892/ijmm.12.2.225|journal=International Journal of Molecular Medicine|doi=10.3892/ijmm.12.2.225|issn=1107-3756}}</ref> In 2015, a large German study found 29% of [[ME/CFS]] patients had elevated autoantibodies to M3 and M4 [[muscarinic acetylcholine receptor]]s, as well as ß2 [[adrenergic receptor]]s.<ref>{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref><ref>{{Cite web|url=http://www.meaction.net/2015/09/26/antibodies-found-in-subset-of-cfs-patients/|title=Autoantibodies found in subset of CFS patients {{!}} #MEAction|website=[[MEAction]]|language=en-US|access-date=2018-08-10}}</ref> A 2016 Australian study found that ME/CFS patients had significantly greater numbers of [[single nucleotide polymorphism]]s associated with the gene encoding for M3 muscarinic acetylcholine receptors.<ref>{{Cite journal|last=Marshall-Gradisnik|first=Sonya|last2=Smith|first2=Peter|last3=Nilius|first3=Bernd|last4=Staines|first4=Donald R.|date=2015-01-01|title=Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients|url=https://doi.org/10.4137/III.S25105|journal=Immunology and Immunogenetics Insights|language=en|volume=7|pages=III.S25105|doi=10.4137/III.S25105|issn=1178-6345}}</ref>

Several small clinical trials have been performed to assess the benefit of treatment with acetylcholinesterase inhibitors in CFS; one using pyridostigmine <ref>{{Cite journal|last=Kawamura|first=Yasuo|last2=Kihara|first2=Mikihiro|last3=Nishimoto|first3=Kazuhiro|last4=Taki|first4=Mayumi|date=May 2003|title=Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports|url=https://linkinghub.elsevier.com/retrieve/pii/S0928468003000075|journal=Pathophysiology|language=en|volume=9|issue=3|pages=189–194|doi=10.1016/S0928-4680(03)00007-5}}</ref> and another using galantamine. <ref>{{Cite journal|last=Snorrason|first=Ernir|last2=Geirsson|first2=Arni|last3=Stefansson|first3=Kari|date=Jan 1996|title=Trial of a Selective Acetylcholinesterase Inhibitor, Galanthamine Hydrobromide, in the Treatment of Chronic Fatigue Syndrome|url=http://www.tandfonline.com/doi/full/10.1300/J092v02n02_04|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=2|issue=2-3|pages=35–54|doi=10.1300/J092v02n02_04|issn=1057-3321}}</ref> Both trials showed improvement of symptoms on the treatment. The exact mechanism or mechanisms by which AChE inhibition might help in CFS are unclear due to how widely represented acetylcholine-responsive tissues are in the brain, (neuro)musculature, cranial and pre-ganglionic spinal autonomic nerves, vasculature, and peripheral C-fibers. Additionally, AChE inhibitors such as [[pyridostigmine]] are able to stimulate growth hormone secretion, and both CFS and POTS patients have been shown to have disturbed growth hormone levels. <ref>{{Cite journal|last=Berwaerts|first=J.|last2=Moorkens|first2=G.|last3=Abs|first3=R.|date=Apr 1998|title=Secretion of growth hormone in patients with chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1096637498800361|journal=Growth Hormone & IGF Research|language=en|volume=8|pages=127–129|doi=10.1016/S1096-6374(98)80036-1}}</ref><ref>{{Cite journal|last=Moorkens|first=G.|last2=Wynants|first2=H.|last3=Abs|first3=R.|date=Apr 1998|title=Effect of growth hormone treatment in patients with chronic fatigue syndrome: A preliminary study|url=https://linkinghub.elsevier.com/retrieve/pii/S1096637498800373|journal=Growth Hormone & IGF Research|language=en|volume=8|pages=131–133|doi=10.1016/S1096-6374(98)80037-3}}</ref><ref>{{Cite journal|last=Johansson|first=Madeleine|last2=Ricci|first2=Fabrizio|last3=Schulte|first3=Janin|last4=Persson|first4=Margaretha|last5=Melander|first5=Olle|last6=Sutton|first6=Richard|last7=Hamrefors|first7=Viktor|last8=Fedorowski|first8=Artur|date=2021-04-21|title=Circulating levels of growth hormone in postural orthostatic tachycardia syndrome|url=https://www.nature.com/articles/s41598-021-87983-5|journal=Scientific Reports|language=en|volume=11|issue=1|pages=8575|doi=10.1038/s41598-021-87983-5|issn=2045-2322}}</ref>

Anecdotally, some ME/CFS patients have tried pyridostigmine (trade name [[Mestinon]]), with some success.<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/06/17/mestinon-chronic-fatigue-vagus-nerve-stimulation-exercise/|title=A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise - Health Rising|date=2016-06-17|work=Health Rising|access-date=2018-08-10|language=en-US}}</ref> A work in progress study of [[exercise intolerance]] in [[preload failure]] found that Mestinon improved exercise tolerance, but the study has not yet been published.<ref>{{Cite journal|last=Oliveira|first=R.K.|date=2016|title=Pyridostigmine for Exercise Intolerance Treatment in Preload Failure|url=https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2016.193.1_MeetingAbstracts.A5664|journal=American Journal of Respiratory and Critical Care Medicine|volume=|pages=|via=}}</ref>

===Postural orthostatic tachycardia===
A small study of [[postural orthostatic tachycardia syndrome]] in children found that 24.39% of patients had acetylcholine receptor autoantibodies.<ref>{{Cite journal|last=Li|first=Jiawei|last2=Zhang|first2=Qingyou|last3=Liao|first3=Ying|last4=Zhang|first4=Chunyu|last5=Hao|first5=Hongjun|last6=Du|first6=Junbao|date=2014-08-03|title=The Value of Acetylcholine Receptor Antibody in Children with Postural Tachycardia Syndrome|url=https://link.springer.com/article/10.1007/s00246-014-0981-8|journal=Pediatric Cardiology|language=en|volume=36|issue=1|pages=165–170|doi=10.1007/s00246-014-0981-8|issn=0172-0643}}</ref> A small study of adult patients found elevated α1, β1 and β2 adrenergic receptor autoantibodies.<ref>{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde‐Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-01-27|title=Autoimmune Basis for Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/abs/10.1161/JAHA.113.000755|journal=Journal of the American Heart Association|language=EN|volume=3|issue=1|doi=10.1161/jaha.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref> A small randomized crossover design trial found that patients with postural orthostatic tachychardia improved with Mestinon.<ref>{{Cite journal|last=Raj|first=S. R.|date=2005-05-31|title=Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/pdf/10.1161/circulationaha.104.497594|journal=Circulation|volume=111|issue=21|pages=2734–2740|doi=10.1161/circulationaha.104.497594|issn=0009-7322}}</ref>

== Increasing and decreasing acetylcholine ==
Many classes of drugs including [[Benzodiazepine|benzodiazepines]], [[Opiod|opiods]], anesthetics, and some [[Antihistimane|antihistimanes]] such as [[Benadryl]] are anticholinergic.{{Citation needed}} During [[exercise]], levels of acetylcholine drop.<ref>Conlay, L. A., Sabournjian, L. A., and Wurtman, R. J. Exercise and neuromodulators: choline and acetylcholine in marathon runners.Int. J. Sports Med. 13(Suppl. 1):S141-142, 1992</ref>

=== Acetylcholinesterase inhibitors ===
[[Acetylcholinesterase]] is an enzyme that breaks down acetylcholine. Acetylcholinesterase inhibitors block or downregulate the activity of acetylcholinesterase; in turn, because there is less enzyme breaking down acetylcholine, the amount of circulating acetylcholine increases.

The following compounds are acetylcholinesterase inhibitors:
* [[pyridostigmine]] (Mestinon) - A peripheral AChE inhibitor, pyridostigmine is unable to cross the blood brain barrier due to its chemical structure. <ref>{{Cite journal|last=Anderson|first=Tim|last2=Pope|first2=Carey N.|date=2017|title=Pyridostigmine ☆|journal==J. Med. Chem.|url=https://linkinghub.elsevier.com/retrieve/pii/B978012801238397627X|language=en|publisher=Elsevier|pages=B978012801238397627X|doi=10.1016/b978-0-12-801238-3.97627-x|isbn=978-0-12-801238-3}}</ref>
* [[huperzine A]] (crosses blood-brain barrier){{Citation needed}}
* galantamine - A central/peripheral AChE inhibitor. While prescription only in some countries, galantamine is available over the counter in the United States.
* blueberries<ref>{{Cite journal|last=Papandreou|first=Magdalini A.|last2=Dimakopoulou|first2=Andriana|last3=Linardaki|first3=Zacharoula I.|last4=Cordopatis|first4=Paul|last5=Klimis-Zacas|first5=Dorothy|last6=Margarity|first6=Marigoula|last7=Lamari|first7=Fotini N.|date=2009-03-17|title=Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity|url=https://www.ncbi.nlm.nih.gov/pubmed/19056430|journal=Behavioural Brain Research|volume=198|issue=2|pages=352–358|doi=10.1016/j.bbr.2008.11.013|issn=1872-7549|pmid=19056430}}</ref>

== Research studies related to ME/CFS ==
* 2004, Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome<ref>{{Cite journal|last=Spence|first=V.A|author-link=Vance Spence|last2=Khan|first2=F|author-link2=Faisel Khan|last3=Kennedy|first3=G|author-link3=|last4=Abbot|first4=N.C|author-link4=|last5=Belch|first5=J.J.F|author-link5=|date=Apr 2004|title=Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0952327804000134|journal=Prostaglandins, Leukotrienes and Essential Fatty Acids|language=en|volume=70|issue=4|pages=403–407|doi=10.1016/j.plefa.2003.12.016|quote=|via=}}</ref> - [[pubmed:15041034|(Abstract)]]

== See also ==
*[[Autoantibody]]
*[[Vagus nerve]]
*[[Vagus nerve infection hypothesis]]
==Learn more==

*2003, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/ The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation], Molecular Medicine, 2003 May-Aug; 9(5-8): 125–134.
*2011, [https://www.youtube.com/watch?v=n8j3BWeMOuo Video - "Is acetylcholine toxicity the cause of CFS?"]
*24 February 2015, [http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-2-2015-14-16-10 Scientists uncover new role for neurotransmitter that helps fight infection], Imperial College London News

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]

Acetylcholine

2021-10-07T20:37:06Z

Kmdenmark:added journal name

'''Acetylcholine''' is a [[neurotransmitter]] that is thought to play a role in many human diseases including [[Myalgic encephalomyelitis|myalgic encephalomyelitis]] and [[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]].

== Function ==
Acetylcholine is used in the [[autonomic nervous system]], both as an internal transmitter for the [[sympathetic nervous system]] and as the final product released by the [[parasympathetic nervous system]]. It plays an important role in regulating the [[inflammation|inflammatory]] response and is used at the neuromuscular junction by motor neurons in order to activate muscles.

In the [[central nervous system]], acetylcholine modulates arousal and [[temperature]] regulation, is important for attention, memory and motivation, and may play a role in [[central fatigue]].

=== General Function Summary ===
As a neurotransmitter, acetylcholine is produced in nerve cells. Any cell that produces or is affected by acetylcholine is called cholinergic. In the nervous system, acetylcholine typically travels from the axon to the dendrite of the next nerve cell across the synaptic cleft. In muscle cells, it travels to the receptors on the muscle fiber, called the motor end plate. Acetylcholine can activate receptors, such as the [[nicotonic]] receptors or [[Muscarinic acetylcholine receptor|muscarinic]] receptors. These receptors can also be activated by, or blocked by, other molecules such as nicotine and muscarine. Muscarinic receptors are typically found in the parasypathetic nervous system, whereas nicotonic receptors are found in the [[central nervous system]], [[peripheral nervous system]], and [[Neuromuscular junction|neuromuscular]] junctions. Nicotonic receptors are classified as ligand-gated [[Ion channel|ion channels]] - when activated they open and allow ions like K+, Na+, and Ca+ to move in or out of the cell. Muscarinic receptors exert their effects on cells via a secondary messenger system.

Closing of the gate is completed by [[Acetylcholinesterase]] ( AChE) which catalyzes the breakdown of acetylcholine into [[choline]] and acetic acid, which allows the ion gate to close. Each molecule of AChE can degrade about 25,000 molecules of acetylcholine (ACh) per second. If the AChE molecule is blocked, breakdown of ACh will not be completed and the gate will remain open. If the AChE is blocked on a muscle fiber, the fiber will remain contracted.<ref>{{Cite book|title=Concepts of Biology – 1st Canadian Edition|pages=Chapter 19.4|isbn=|edition=1|volume=1|language=English|title-link=|url=ttps://opentextbc.ca/biology/chapter/19-4-muscle-contraction-and-locomotion/|access-date=2020-05-28|date=June 13, 2019|publisher=B.C. Open Textbook Collection|last=Molnar|first=Charles|author-link=|last2=Gair|first2=Jane|author-link2=|last3=|first3=|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|author-link7=|last8=|first8=|author-link8=|last9=|first9=|author-link9=|veditors=|others=|doi=|oclc=|quote=|archive-url=|archive-date=|location=|editor-last=|editor-first=|editor1-link=|editor-last2=|editor-first2=}}</ref> Various duration and strength AChE blockers exist. Short-duration or reversible AChE blockers have been developed as medications, as short-term blocking of AChE can allow the ion gates to stay open longer and increase ACh availability. Long-duration and irreversible AChE blockers, including Nerve Gas, can cause various symptoms up to and including paralysis and death. <ref>{{Cite journal|last=Čolović|first=Mirjana B|last2=Krstić|first2=Danijela Z|last3=Lazarević-Pašti|first3=Tamara D|last4=Bondžić|first4=Aleksandra M|last5=Vasić|first5=Vesna M|date=May 2013|title=Acetylcholinesterase Inhibitors: Pharmacology and Toxicology|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648782/|journal=Current Neuropharmacology|volume=11|issue=3|pages=315–335|doi=10.2174/1570159X11311030006|issn=1570-159X|pmc=3648782|pmid=24179466|quote=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

==Immune system==

The [[vagus nerve]] speaks directly to the [[immune system]] via acetylcholine.<ref>{{Cite news|url=https://www.sciencedaily.com/releases/2007/10/071024083630.htm|title=Direct Route From The Brain To The Immune System Discovered|work=ScienceDaily|access-date=2018-08-10|language=en}}</ref><ref>{{Cite news|url=http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-2-2015-14-16-10|title=Scientists uncover new role for neurotransmitter that helps fight infection {{!}} Imperial News {{!}} Imperial College London|work=Imperial News|access-date=2018-08-10|language=en-GB}}</ref><ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref>

Acetylcholine plays a role in [[innate immune system|innate immunity]] through nicotinic [[acetylcholine receptors]] and in the [[adaptive immune system|adaptive immune response]] via M3 muscarinic acetylcholine receptors (M3R).<ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref>

===Muscarinic receptors===

Knockout mice, that is mice lacking the gene that encodes for M3R, had impaired response to bacterial infection, while normal mice given a muscarinic [[agonist]] (to increase the activity of M3R) had enhanced production of [[Interleukin 13|IL-13]] and [[IFN-γ]].<ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref> Another study used a muscarinic agonist and an [[antagonist]] (reduce activity) and found antagonist suppressed the immune response while the agonist exaggerated it.<ref>{{Cite journal|last=Razani-Boroujerdi|first=Seddigheh|last2=Behl|first2=Muskaan|last3=Hahn|first3=Fletcher F.|last4=Pena-Philippides|first4=Juan Carlos|last5=Hutt|first5=Julie|last6=Sopori|first6=Mohan L.|date=Feb 2008|title=Role of muscarinic receptors in the regulation of immune and inflammatory responses|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323336/|journal=Journal of neuroimmunology|volume=194|issue=1-2|pages=83–88|doi=10.1016/j.jneuroim.2007.11.019|issn=0165-5728|pmid=18190972}}</ref>

===Mast cells===

Several studies suggest a relationship between [[autonomic nervous system]] dysfunction and [[mast cell]] activation via acetylcholine.

One study found that acetylcholine via muscarinic receptors strongly inhibited the release of [[histamine]] in [[mucosal]] mast cells.<ref>{{Cite journal|title=Acetylcholine via Muscarinic Receptors Inhibits Histamine Release from Human Isolated Bronchi|url=http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.2.96-12079#.V7vo-ZMrLMV|journal =American Journal of Respiratory and Critical Care Medicine|volume =|issue =|pages =|language=en|doi=10.1164/ajrccm.156.2.96-12079#.v7vo-zmrlmv}}</ref> The activity of [[acetylcholinesterase]], an enzyme that breaks down acetylcholine, was found to be significantly increased in 64% of patients experiencing flares of [[ulcerative colitis]].<ref>https://www.myknowtions.com/portfolio/autonomic-nervous-alterations-and-mast-cell-degranulation-in-the-exacerbation-of-ulcerative-colitis</ref>

==In human disease==

===Myasthenia Gravis===

Autoantibodies to acetylcholine receptors alpha subunit have been found in patients with [[myasthenia gravis]]. These cross react with [[herpesvirus]] glycoprotein D.<ref>{{cite book|last1=Angelini|first1=Lucia|last2=Bardare|first2=Maria|last3=Martini|first3=Alberto|year=2002|title=Immune-mediated Disorders of the Central Nervous System in Children|url=https://books.google.com/books?id=5trQOK8hcZUC&pg=PA7&lpg=PA7&dq=coxsackie+b+acetylcholine&source=bl&ots=zhup8ZXq68&sig=CxDwQCHO8-OMBYkcp4EayjnDKnw&hl=en&sa=X&ved=0ahUKEwjflpmqg9fOAhWBeSYKHSR4Dh0Q6AEIMTAD#v=onepage&q=coxsackie%20b%20acetylcholine&f=false}}</ref> Antibodies to acetylcholine receptor and [[HSV-1]] antigens crossreact.<ref>{{Cite journal|last=Gebhardt|first=B. M.|date=2000-06-26|title=Evidence for antigenic cross-reactivity between herpesvirus and the acetylcholine receptor|url=http://www.ncbi.nlm.nih.gov/pubmed/10742556|journal=Journal of Neuroimmunology|volume=105|issue=2|pages=145–153|issn=0165-5728|pmid=10742556}}</ref>

[[B cell]]s from myasthenia gravis patient stimulated ''in vitro'' by [[Epstein-Barr virus]] (EBV) produced acetylcholine autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=http://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> Ongoing EBV infection of the [[thymus]] has been posited as a causative agent for the production of aceytlcholine receptor autoantibodies in myasthenia gravis.<ref>{{Cite journal|last=Kaminski|first=Henry J.|last2=Janos|first2=Minarovits|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134}}</ref><ref>{{Cite web|url=http://journals.lww.com/neurologynow/_layouts/15/oaks.journals.mobile/post.aspx?blogId=2&postId=10|title=Official Brain & Life Home Page|website=journals.lww.com|language=en|access-date=2018-08-10}}</ref>

===Sjögren's syndrome===

Autoantibodies against muscarinic acetylcholine receptor on exocrine glands were found in patients with [[Sjögren's syndrome]].<ref>http://www.omicsonline.org/open-access/autoantibodies-against-muscarinic-acetylcholine-receptor-on-exocrine-glands-in-sjgren-syndrome-2161-1122.1000265.pdf</ref>

===Chronic fatigue syndrome===

Since at least the 1990s it has been theorized that CFS might be associated with abnormalities of acetylcholine neurotransmission. To test this hypothesis, a provocation study was performed using the acetylcholinesterase inhibitor [[pyridostigmine]]. The results did indicate that CFS patients' hypothalamuses are hypersensitive to cholinergic stimulation relative to matched healthy controls. <ref>{{Cite journal|last=Chaudhuri|first=A.|last2=Majeed|first2=T.|last3=Dinan|first3=T.|last4=Behan|first4=P. O.|date=Jan 1997|title=Chronic Fatigue Syndrome: A Disorder of Central Cholinergic Transmission|url=http://www.tandfonline.com/doi/full/10.1300/J092v03n01_02|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=3|issue=1|pages=3–16|doi=10.1300/J092v03n01_02|issn=1057-3321}}</ref> These results mirror similar, highly replicated findings showing that CFS patients' hypothalamuses are hypersensitive to serotonergic stimulation as well (see [[Buspirone challenge test]]).

A 2003 study of 60 CFS patients found that 53.3% had detectable autoantibodies against the M1 muscarinic acetylcholine receptor. <ref>{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=2003-08-01|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=http://www.spandidos-publications.com/10.3892/ijmm.12.2.225|journal=International Journal of Molecular Medicine|doi=10.3892/ijmm.12.2.225|issn=1107-3756}}</ref> In 2015, a large German study found 29% of [[ME/CFS]] patients had elevated autoantibodies to M3 and M4 [[muscarinic acetylcholine receptor]]s, as well as ß2 [[adrenergic receptor]]s.<ref>{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref><ref>{{Cite web|url=http://www.meaction.net/2015/09/26/antibodies-found-in-subset-of-cfs-patients/|title=Autoantibodies found in subset of CFS patients {{!}} #MEAction|website=[[MEAction]]|language=en-US|access-date=2018-08-10}}</ref> A 2016 Australian study found that ME/CFS patients had significantly greater numbers of [[single nucleotide polymorphism]]s associated with the gene encoding for M3 muscarinic acetylcholine receptors.<ref>{{Cite journal|last=Marshall-Gradisnik|first=Sonya|last2=Smith|first2=Peter|last3=Nilius|first3=Bernd|last4=Staines|first4=Donald R.|date=2015-01-01|title=Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients|url=https://doi.org/10.4137/III.S25105|journal=Immunology and Immunogenetics Insights|language=en|volume=7|pages=III.S25105|doi=10.4137/III.S25105|issn=1178-6345}}</ref>

Several small clinical trials have been performed to assess the benefit of treatment with acetylcholinesterase inhibitors in CFS; one using pyridostigmine <ref>{{Cite journal|last=Kawamura|first=Yasuo|last2=Kihara|first2=Mikihiro|last3=Nishimoto|first3=Kazuhiro|last4=Taki|first4=Mayumi|date=May 2003|title=Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports|url=https://linkinghub.elsevier.com/retrieve/pii/S0928468003000075|journal=Pathophysiology|language=en|volume=9|issue=3|pages=189–194|doi=10.1016/S0928-4680(03)00007-5}}</ref> and another using galantamine. <ref>{{Cite journal|last=Snorrason|first=Ernir|last2=Geirsson|first2=Arni|last3=Stefansson|first3=Kari|date=Jan 1996|title=Trial of a Selective Acetylcholinesterase Inhibitor, Galanthamine Hydrobromide, in the Treatment of Chronic Fatigue Syndrome|url=http://www.tandfonline.com/doi/full/10.1300/J092v02n02_04|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=2|issue=2-3|pages=35–54|doi=10.1300/J092v02n02_04|issn=1057-3321}}</ref> Both trials showed improvement of symptoms on the treatment. The exact mechanism or mechanisms by which AChE inhibition might help in CFS are unclear due to how widely represented acetylcholine-responsive tissues are in the brain, (neuro)musculature, cranial and pre-ganglionic spinal autonomic nerves, vasculature, and peripheral C-fibers. Additionally, AChE inhibitors such as [[pyridostigmine]] are able to stimulate growth hormone secretion, and both CFS and POTS patients have been shown to have disturbed growth hormone levels. <ref>{{Cite journal|last=Berwaerts|first=J.|last2=Moorkens|first2=G.|last3=Abs|first3=R.|date=Apr 1998|title=Secretion of growth hormone in patients with chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1096637498800361|journal=Growth Hormone & IGF Research|language=en|volume=8|pages=127–129|doi=10.1016/S1096-6374(98)80036-1}}</ref><ref>{{Cite journal|last=Moorkens|first=G.|last2=Wynants|first2=H.|last3=Abs|first3=R.|date=Apr 1998|title=Effect of growth hormone treatment in patients with chronic fatigue syndrome: A preliminary study|url=https://linkinghub.elsevier.com/retrieve/pii/S1096637498800373|journal=Growth Hormone & IGF Research|language=en|volume=8|pages=131–133|doi=10.1016/S1096-6374(98)80037-3}}</ref><ref>{{Cite journal|last=Johansson|first=Madeleine|last2=Ricci|first2=Fabrizio|last3=Schulte|first3=Janin|last4=Persson|first4=Margaretha|last5=Melander|first5=Olle|last6=Sutton|first6=Richard|last7=Hamrefors|first7=Viktor|last8=Fedorowski|first8=Artur|date=2021-04-21|title=Circulating levels of growth hormone in postural orthostatic tachycardia syndrome|url=https://www.nature.com/articles/s41598-021-87983-5|journal=Scientific Reports|language=en|volume=11|issue=1|pages=8575|doi=10.1038/s41598-021-87983-5|issn=2045-2322}}</ref>

Anecdotally, some ME/CFS patients have tried pyridostigmine (trade name [[Mestinon]]), with some success.<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/06/17/mestinon-chronic-fatigue-vagus-nerve-stimulation-exercise/|title=A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise - Health Rising|date=2016-06-17|work=Health Rising|access-date=2018-08-10|language=en-US}}</ref> A work in progress study of [[exercise intolerance]] in [[preload failure]] found that Mestinon improved exercise tolerance, but the study has not yet been published.<ref>{{Cite journal|last=Oliveira|first=R.K.|date=2016|title=Pyridostigmine for Exercise Intolerance Treatment in Preload Failure|url=https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2016.193.1_MeetingAbstracts.A5664|journal=American Journal of Respiratory and Critical Care Medicine|volume=|pages=|via=}}</ref>

===Postural orthostatic tachycardia===
A small study of [[postural orthostatic tachycardia syndrome]] in children found that 24.39% of patients had acetylcholine receptor autoantibodies.<ref>{{Cite journal|last=Li|first=Jiawei|last2=Zhang|first2=Qingyou|last3=Liao|first3=Ying|last4=Zhang|first4=Chunyu|last5=Hao|first5=Hongjun|last6=Du|first6=Junbao|date=2014-08-03|title=The Value of Acetylcholine Receptor Antibody in Children with Postural Tachycardia Syndrome|url=https://link.springer.com/article/10.1007/s00246-014-0981-8|journal=Pediatric Cardiology|language=en|volume=36|issue=1|pages=165–170|doi=10.1007/s00246-014-0981-8|issn=0172-0643}}</ref> A small study of adult patients found elevated α1, β1 and β2 adrenergic receptor autoantibodies.<ref>{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde‐Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-01-27|title=Autoimmune Basis for Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/abs/10.1161/JAHA.113.000755|journal=Journal of the American Heart Association|language=EN|volume=3|issue=1|doi=10.1161/jaha.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref> A small randomized crossover design trial found that patients with postural orthostatic tachychardia improved with Mestinon.<ref>{{Cite journal|last=Raj|first=S. R.|date=2005-05-31|title=Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/pdf/10.1161/circulationaha.104.497594|journal=Circulation|volume=111|issue=21|pages=2734–2740|doi=10.1161/circulationaha.104.497594|issn=0009-7322}}</ref>

== Increasing and decreasing acetylcholine ==
Many classes of drugs including [[Benzodiazepine|benzodiazepines]], [[Opiod|opiods]], anesthetics, and some [[Antihistimane|antihistimanes]] such as [[Benadryl]] are anticholinergic.{{Citation needed}} During [[exercise]], levels of acetylcholine drop.<ref>Conlay, L. A., Sabournjian, L. A., and Wurtman, R. J. Exercise and neuromodulators: choline and acetylcholine in marathon runners.Int. J. Sports Med. 13(Suppl. 1):S141-142, 1992</ref>

=== Acetylcholinesterase inhibitors ===
[[Acetylcholinesterase]] is an enzyme that breaks down acetylcholine. Acetylcholinesterase inhibitors block or downregulate the activity of acetylcholinesterase; in turn, because there is less enzyme breaking down acetylcholine, the amount of circulating acetylcholine increases.

The following compounds are acetylcholinesterase inhibitors:
* [[pyridostigmine]] (Mestinon) - A peripheral AChE inhibitor, pyridostigmine is unable to cross the blood brain barrier due to its chemical structure. <ref>{{Cite journal=J. Med. Chem.|last=Anderson|first=Tim|last2=Pope|first2=Carey N.|date=2017|title=Pyridostigmine ☆|url=https://linkinghub.elsevier.com/retrieve/pii/B978012801238397627X|language=en|publisher=Elsevier|pages=B978012801238397627X|doi=10.1016/b978-0-12-801238-3.97627-x|isbn=978-0-12-801238-3}}</ref>
* [[huperzine A]] (crosses blood-brain barrier){{Citation needed}}
* galantamine - A central/peripheral AChE inhibitor. While prescription only in some countries, galantamine is available over the counter in the United States.
* blueberries<ref>{{Cite journal|last=Papandreou|first=Magdalini A.|last2=Dimakopoulou|first2=Andriana|last3=Linardaki|first3=Zacharoula I.|last4=Cordopatis|first4=Paul|last5=Klimis-Zacas|first5=Dorothy|last6=Margarity|first6=Marigoula|last7=Lamari|first7=Fotini N.|date=2009-03-17|title=Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity|url=https://www.ncbi.nlm.nih.gov/pubmed/19056430|journal=Behavioural Brain Research|volume=198|issue=2|pages=352–358|doi=10.1016/j.bbr.2008.11.013|issn=1872-7549|pmid=19056430}}</ref>

== Research studies related to ME/CFS ==
* 2004, Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome<ref>{{Cite journal|last=Spence|first=V.A|author-link=Vance Spence|last2=Khan|first2=F|author-link2=Faisel Khan|last3=Kennedy|first3=G|author-link3=|last4=Abbot|first4=N.C|author-link4=|last5=Belch|first5=J.J.F|author-link5=|date=Apr 2004|title=Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0952327804000134|journal=Prostaglandins, Leukotrienes and Essential Fatty Acids|language=en|volume=70|issue=4|pages=403–407|doi=10.1016/j.plefa.2003.12.016|quote=|via=}}</ref> - [[pubmed:15041034|(Abstract)]]

== See also ==
*[[Autoantibody]]
*[[Vagus nerve]]
*[[Vagus nerve infection hypothesis]]
==Learn more==

*2003, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/ The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation], Molecular Medicine, 2003 May-Aug; 9(5-8): 125–134.
*2011, [https://www.youtube.com/watch?v=n8j3BWeMOuo Video - "Is acetylcholine toxicity the cause of CFS?"]
*24 February 2015, [http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-2-2015-14-16-10 Scientists uncover new role for neurotransmitter that helps fight infection], Imperial College London News

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]

Acetylcholine

2021-10-07T20:31:00Z

Kmdenmark:CS1 error- date

'''Acetylcholine''' is a [[neurotransmitter]] that is thought to play a role in many human diseases including [[Myalgic encephalomyelitis|myalgic encephalomyelitis]] and [[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]].

== Function ==
Acetylcholine is used in the [[autonomic nervous system]], both as an internal transmitter for the [[sympathetic nervous system]] and as the final product released by the [[parasympathetic nervous system]]. It plays an important role in regulating the [[inflammation|inflammatory]] response and is used at the neuromuscular junction by motor neurons in order to activate muscles.

In the [[central nervous system]], acetylcholine modulates arousal and [[temperature]] regulation, is important for attention, memory and motivation, and may play a role in [[central fatigue]].

=== General Function Summary ===
As a neurotransmitter, acetylcholine is produced in nerve cells. Any cell that produces or is affected by acetylcholine is called cholinergic. In the nervous system, acetylcholine typically travels from the axon to the dendrite of the next nerve cell across the synaptic cleft. In muscle cells, it travels to the receptors on the muscle fiber, called the motor end plate. Acetylcholine can activate receptors, such as the [[nicotonic]] receptors or [[Muscarinic acetylcholine receptor|muscarinic]] receptors. These receptors can also be activated by, or blocked by, other molecules such as nicotine and muscarine. Muscarinic receptors are typically found in the parasypathetic nervous system, whereas nicotonic receptors are found in the [[central nervous system]], [[peripheral nervous system]], and [[Neuromuscular junction|neuromuscular]] junctions. Nicotonic receptors are classified as ligand-gated [[Ion channel|ion channels]] - when activated they open and allow ions like K+, Na+, and Ca+ to move in or out of the cell. Muscarinic receptors exert their effects on cells via a secondary messenger system.

Closing of the gate is completed by [[Acetylcholinesterase]] ( AChE) which catalyzes the breakdown of acetylcholine into [[choline]] and acetic acid, which allows the ion gate to close. Each molecule of AChE can degrade about 25,000 molecules of acetylcholine (ACh) per second. If the AChE molecule is blocked, breakdown of ACh will not be completed and the gate will remain open. If the AChE is blocked on a muscle fiber, the fiber will remain contracted.<ref>{{Cite book|title=Concepts of Biology – 1st Canadian Edition|pages=Chapter 19.4|isbn=|edition=1|volume=1|language=English|title-link=|url=ttps://opentextbc.ca/biology/chapter/19-4-muscle-contraction-and-locomotion/|access-date=2020-05-28|date=June 13, 2019|publisher=B.C. Open Textbook Collection|last=Molnar|first=Charles|author-link=|last2=Gair|first2=Jane|author-link2=|last3=|first3=|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|author-link7=|last8=|first8=|author-link8=|last9=|first9=|author-link9=|veditors=|others=|doi=|oclc=|quote=|archive-url=|archive-date=|location=|editor-last=|editor-first=|editor1-link=|editor-last2=|editor-first2=}}</ref> Various duration and strength AChE blockers exist. Short-duration or reversible AChE blockers have been developed as medications, as short-term blocking of AChE can allow the ion gates to stay open longer and increase ACh availability. Long-duration and irreversible AChE blockers, including Nerve Gas, can cause various symptoms up to and including paralysis and death. <ref>{{Cite journal|last=Čolović|first=Mirjana B|last2=Krstić|first2=Danijela Z|last3=Lazarević-Pašti|first3=Tamara D|last4=Bondžić|first4=Aleksandra M|last5=Vasić|first5=Vesna M|date=May 2013|title=Acetylcholinesterase Inhibitors: Pharmacology and Toxicology|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648782/|journal=Current Neuropharmacology|volume=11|issue=3|pages=315–335|doi=10.2174/1570159X11311030006|issn=1570-159X|pmc=3648782|pmid=24179466|quote=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

==Immune system==

The [[vagus nerve]] speaks directly to the [[immune system]] via acetylcholine.<ref>{{Cite news|url=https://www.sciencedaily.com/releases/2007/10/071024083630.htm|title=Direct Route From The Brain To The Immune System Discovered|work=ScienceDaily|access-date=2018-08-10|language=en}}</ref><ref>{{Cite news|url=http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-2-2015-14-16-10|title=Scientists uncover new role for neurotransmitter that helps fight infection {{!}} Imperial News {{!}} Imperial College London|work=Imperial News|access-date=2018-08-10|language=en-GB}}</ref><ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref>

Acetylcholine plays a role in [[innate immune system|innate immunity]] through nicotinic [[acetylcholine receptors]] and in the [[adaptive immune system|adaptive immune response]] via M3 muscarinic acetylcholine receptors (M3R).<ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref>

===Muscarinic receptors===

Knockout mice, that is mice lacking the gene that encodes for M3R, had impaired response to bacterial infection, while normal mice given a muscarinic [[agonist]] (to increase the activity of M3R) had enhanced production of [[Interleukin 13|IL-13]] and [[IFN-γ]].<ref>{{Cite journal|last=Darby|first=Matthew|last2=Schnoeller|first2=Corinna|last3=Vira|first3=Alykhan|last4=Culley|first4=Fiona|last5=Bobat|first5=Saeeda|last6=Logan|first6=Erin|last7=Kirstein|first7=Frank|last8=Wess|first8=Jürgen|last9=Cunningham|first9=Adam F.|date=2015-01-28|title=The M3 Muscarinic Receptor Is Required for Optimal Adaptive Immunity to Helminth and Bacterial Infection|url=http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004636|journal=PLOS Pathogens|language=en|volume=11|issue=1|pages=e1004636|doi=10.1371/journal.ppat.1004636|issn=1553-7374|pmid=25629518}}</ref> Another study used a muscarinic agonist and an [[antagonist]] (reduce activity) and found antagonist suppressed the immune response while the agonist exaggerated it.<ref>{{Cite journal|last=Razani-Boroujerdi|first=Seddigheh|last2=Behl|first2=Muskaan|last3=Hahn|first3=Fletcher F.|last4=Pena-Philippides|first4=Juan Carlos|last5=Hutt|first5=Julie|last6=Sopori|first6=Mohan L.|date=Feb 2008|title=Role of muscarinic receptors in the regulation of immune and inflammatory responses|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323336/|journal=Journal of neuroimmunology|volume=194|issue=1-2|pages=83–88|doi=10.1016/j.jneuroim.2007.11.019|issn=0165-5728|pmid=18190972}}</ref>

===Mast cells===

Several studies suggest a relationship between [[autonomic nervous system]] dysfunction and [[mast cell]] activation via acetylcholine.

One study found that acetylcholine via muscarinic receptors strongly inhibited the release of [[histamine]] in [[mucosal]] mast cells.<ref>{{Cite journal|title=Acetylcholine via Muscarinic Receptors Inhibits Histamine Release from Human Isolated Bronchi|url=http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.2.96-12079#.V7vo-ZMrLMV|journal =American Journal of Respiratory and Critical Care Medicine|volume =|issue =|pages =|language=en|doi=10.1164/ajrccm.156.2.96-12079#.v7vo-zmrlmv}}</ref> The activity of [[acetylcholinesterase]], an enzyme that breaks down acetylcholine, was found to be significantly increased in 64% of patients experiencing flares of [[ulcerative colitis]].<ref>https://www.myknowtions.com/portfolio/autonomic-nervous-alterations-and-mast-cell-degranulation-in-the-exacerbation-of-ulcerative-colitis</ref>

==In human disease==

===Myasthenia Gravis===

Autoantibodies to acetylcholine receptors alpha subunit have been found in patients with [[myasthenia gravis]]. These cross react with [[herpesvirus]] glycoprotein D.<ref>{{cite book|last1=Angelini|first1=Lucia|last2=Bardare|first2=Maria|last3=Martini|first3=Alberto|year=2002|title=Immune-mediated Disorders of the Central Nervous System in Children|url=https://books.google.com/books?id=5trQOK8hcZUC&pg=PA7&lpg=PA7&dq=coxsackie+b+acetylcholine&source=bl&ots=zhup8ZXq68&sig=CxDwQCHO8-OMBYkcp4EayjnDKnw&hl=en&sa=X&ved=0ahUKEwjflpmqg9fOAhWBeSYKHSR4Dh0Q6AEIMTAD#v=onepage&q=coxsackie%20b%20acetylcholine&f=false}}</ref> Antibodies to acetylcholine receptor and [[HSV-1]] antigens crossreact.<ref>{{Cite journal|last=Gebhardt|first=B. M.|date=2000-06-26|title=Evidence for antigenic cross-reactivity between herpesvirus and the acetylcholine receptor|url=http://www.ncbi.nlm.nih.gov/pubmed/10742556|journal=Journal of Neuroimmunology|volume=105|issue=2|pages=145–153|issn=0165-5728|pmid=10742556}}</ref>

[[B cell]]s from myasthenia gravis patient stimulated ''in vitro'' by [[Epstein-Barr virus]] (EBV) produced acetylcholine autoantibodies.<ref>{{Cite journal|last=Brenner|first=T.|last2=Timore|first2=Y.|last3=Wirguin|first3=I.|last4=Abramsky|first4=O.|last5=Steinitz|first5=M.|date=Oct 1989|title=In vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr virus-stimulated B-lymphocytes derived from patients with myasthenia gravis|url=http://www.ncbi.nlm.nih.gov/pubmed/2553772|journal=Journal of Neuroimmunology|volume=24|issue=3|pages=217–222|issn=0165-5728|pmid=2553772}}</ref> Ongoing EBV infection of the [[thymus]] has been posited as a causative agent for the production of aceytlcholine receptor autoantibodies in myasthenia gravis.<ref>{{Cite journal|last=Kaminski|first=Henry J.|last2=Janos|first2=Minarovits|title=Epstein-barr virus: Trigger for autoimmunity?|url=http://www.academia.edu/20258853/Epstein-barr_virus_Trigger_for_autoimmunity/|journal=Annals of Neurology|language=en|issn=0364-5134}}</ref><ref>{{Cite web|url=http://journals.lww.com/neurologynow/_layouts/15/oaks.journals.mobile/post.aspx?blogId=2&postId=10|title=Official Brain & Life Home Page|website=journals.lww.com|language=en|access-date=2018-08-10}}</ref>

===Sjögren's syndrome===

Autoantibodies against muscarinic acetylcholine receptor on exocrine glands were found in patients with [[Sjögren's syndrome]].<ref>http://www.omicsonline.org/open-access/autoantibodies-against-muscarinic-acetylcholine-receptor-on-exocrine-glands-in-sjgren-syndrome-2161-1122.1000265.pdf</ref>

===Chronic fatigue syndrome===

Since at least the 1990s it has been theorized that CFS might be associated with abnormalities of acetylcholine neurotransmission. To test this hypothesis, a provocation study was performed using the acetylcholinesterase inhibitor [[pyridostigmine]]. The results did indicate that CFS patients' hypothalamuses are hypersensitive to cholinergic stimulation relative to matched healthy controls. <ref>{{Cite journal|last=Chaudhuri|first=A.|last2=Majeed|first2=T.|last3=Dinan|first3=T.|last4=Behan|first4=P. O.|date=Jan 1997|title=Chronic Fatigue Syndrome: A Disorder of Central Cholinergic Transmission|url=http://www.tandfonline.com/doi/full/10.1300/J092v03n01_02|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=3|issue=1|pages=3–16|doi=10.1300/J092v03n01_02|issn=1057-3321}}</ref> These results mirror similar, highly replicated findings showing that CFS patients' hypothalamuses are hypersensitive to serotonergic stimulation as well (see [[Buspirone challenge test]]).

A 2003 study of 60 CFS patients found that 53.3% had detectable autoantibodies against the M1 muscarinic acetylcholine receptor. <ref>{{Cite journal|last=Tanaka|first=Susumu|last2=Kuratsune|first2=Hirohiko|last3=Hidaka|first3=Yoh|last4=Hakariya|first4=Yukiko|last5=Tatsumi|first5=Ke-Ita|last6=Takano|first6=Toru|last7=Kanakura|first7=Yuzuru|last8=Amino|first8=Nobuyuki|date=2003-08-01|title=Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome|url=http://www.spandidos-publications.com/10.3892/ijmm.12.2.225|journal=International Journal of Molecular Medicine|doi=10.3892/ijmm.12.2.225|issn=1107-3756}}</ref> In 2015, a large German study found 29% of [[ME/CFS]] patients had elevated autoantibodies to M3 and M4 [[muscarinic acetylcholine receptor]]s, as well as ß2 [[adrenergic receptor]]s.<ref>{{Cite journal|last=Loebel|first=Madlen|last2=Grabowski|first2=Patricia|last3=Heidecke|first3=Harald|last4=Bauer|first4=Sandra|last5=Hanitsch|first5=Leif G.|last6=Wittke|first6=Kirsten|last7=Meisel|first7=Christian|last8=Reinke|first8=Petra|last9=Volk|first9=Hans-Dieter|date=Feb 2016|title=Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref><ref>{{Cite web|url=http://www.meaction.net/2015/09/26/antibodies-found-in-subset-of-cfs-patients/|title=Autoantibodies found in subset of CFS patients {{!}} #MEAction|website=[[MEAction]]|language=en-US|access-date=2018-08-10}}</ref> A 2016 Australian study found that ME/CFS patients had significantly greater numbers of [[single nucleotide polymorphism]]s associated with the gene encoding for M3 muscarinic acetylcholine receptors.<ref>{{Cite journal|last=Marshall-Gradisnik|first=Sonya|last2=Smith|first2=Peter|last3=Nilius|first3=Bernd|last4=Staines|first4=Donald R.|date=2015-01-01|title=Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients|url=https://doi.org/10.4137/III.S25105|journal=Immunology and Immunogenetics Insights|language=en|volume=7|pages=III.S25105|doi=10.4137/III.S25105|issn=1178-6345}}</ref>

Several small clinical trials have been performed to assess the benefit of treatment with acetylcholinesterase inhibitors in CFS; one using pyridostigmine <ref>{{Cite journal|last=Kawamura|first=Yasuo|last2=Kihara|first2=Mikihiro|last3=Nishimoto|first3=Kazuhiro|last4=Taki|first4=Mayumi|date=May 2003|title=Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports|url=https://linkinghub.elsevier.com/retrieve/pii/S0928468003000075|journal=Pathophysiology|language=en|volume=9|issue=3|pages=189–194|doi=10.1016/S0928-4680(03)00007-5}}</ref> and another using galantamine. <ref>{{Cite journal|last=Snorrason|first=Ernir|last2=Geirsson|first2=Arni|last3=Stefansson|first3=Kari|date=Jan 1996|title=Trial of a Selective Acetylcholinesterase Inhibitor, Galanthamine Hydrobromide, in the Treatment of Chronic Fatigue Syndrome|url=http://www.tandfonline.com/doi/full/10.1300/J092v02n02_04|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=2|issue=2-3|pages=35–54|doi=10.1300/J092v02n02_04|issn=1057-3321}}</ref> Both trials showed improvement of symptoms on the treatment. The exact mechanism or mechanisms by which AChE inhibition might help in CFS are unclear due to how widely represented acetylcholine-responsive tissues are in the brain, (neuro)musculature, cranial and pre-ganglionic spinal autonomic nerves, vasculature, and peripheral C-fibers. Additionally, AChE inhibitors such as [[pyridostigmine]] are able to stimulate growth hormone secretion, and both CFS and POTS patients have been shown to have disturbed growth hormone levels. <ref>{{Cite journal|last=Berwaerts|first=J.|last2=Moorkens|first2=G.|last3=Abs|first3=R.|date=Apr 1998|title=Secretion of growth hormone in patients with chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S1096637498800361|journal=Growth Hormone & IGF Research|language=en|volume=8|pages=127–129|doi=10.1016/S1096-6374(98)80036-1}}</ref><ref>{{Cite journal|last=Moorkens|first=G.|last2=Wynants|first2=H.|last3=Abs|first3=R.|date=Apr 1998|title=Effect of growth hormone treatment in patients with chronic fatigue syndrome: A preliminary study|url=https://linkinghub.elsevier.com/retrieve/pii/S1096637498800373|journal=Growth Hormone & IGF Research|language=en|volume=8|pages=131–133|doi=10.1016/S1096-6374(98)80037-3}}</ref><ref>{{Cite journal|last=Johansson|first=Madeleine|last2=Ricci|first2=Fabrizio|last3=Schulte|first3=Janin|last4=Persson|first4=Margaretha|last5=Melander|first5=Olle|last6=Sutton|first6=Richard|last7=Hamrefors|first7=Viktor|last8=Fedorowski|first8=Artur|date=2021-04-21|title=Circulating levels of growth hormone in postural orthostatic tachycardia syndrome|url=https://www.nature.com/articles/s41598-021-87983-5|journal=Scientific Reports|language=en|volume=11|issue=1|pages=8575|doi=10.1038/s41598-021-87983-5|issn=2045-2322}}</ref>

Anecdotally, some ME/CFS patients have tried pyridostigmine (trade name [[Mestinon]]), with some success.<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/06/17/mestinon-chronic-fatigue-vagus-nerve-stimulation-exercise/|title=A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise - Health Rising|date=2016-06-17|work=Health Rising|access-date=2018-08-10|language=en-US}}</ref> A work in progress study of [[exercise intolerance]] in [[preload failure]] found that Mestinon improved exercise tolerance, but the study has not yet been published.<ref>{{Cite journal|last=Oliveira|first=R.K.|date=2016|title=Pyridostigmine for Exercise Intolerance Treatment in Preload Failure|url=https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2016.193.1_MeetingAbstracts.A5664|journal=American Journal of Respiratory and Critical Care Medicine|volume=|pages=|via=}}</ref>

===Postural orthostatic tachycardia===
A small study of [[postural orthostatic tachycardia syndrome]] in children found that 24.39% of patients had acetylcholine receptor autoantibodies.<ref>{{Cite journal|last=Li|first=Jiawei|last2=Zhang|first2=Qingyou|last3=Liao|first3=Ying|last4=Zhang|first4=Chunyu|last5=Hao|first5=Hongjun|last6=Du|first6=Junbao|date=2014-08-03|title=The Value of Acetylcholine Receptor Antibody in Children with Postural Tachycardia Syndrome|url=https://link.springer.com/article/10.1007/s00246-014-0981-8|journal=Pediatric Cardiology|language=en|volume=36|issue=1|pages=165–170|doi=10.1007/s00246-014-0981-8|issn=0172-0643}}</ref> A small study of adult patients found elevated α1, β1 and β2 adrenergic receptor autoantibodies.<ref>{{Cite journal|last=Li|first=Hongliang|last2=Yu|first2=Xichun|last3=Liles|first3=Campbell|last4=Khan|first4=Muneer|last5=Vanderlinde‐Wood|first5=Megan|last6=Galloway|first6=Allison|last7=Zillner|first7=Caitlin|last8=Benbrook|first8=Alexandria|last9=Reim|first9=Sean|date=2014-01-27|title=Autoimmune Basis for Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/abs/10.1161/JAHA.113.000755|journal=Journal of the American Heart Association|language=EN|volume=3|issue=1|doi=10.1161/jaha.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref> A small randomized crossover design trial found that patients with postural orthostatic tachychardia improved with Mestinon.<ref>{{Cite journal|last=Raj|first=S. R.|date=2005-05-31|title=Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/pdf/10.1161/circulationaha.104.497594|journal=Circulation|volume=111|issue=21|pages=2734–2740|doi=10.1161/circulationaha.104.497594|issn=0009-7322}}</ref>

== Increasing and decreasing acetylcholine ==
Many classes of drugs including [[Benzodiazepine|benzodiazepines]], [[Opiod|opiods]], anesthetics, and some [[Antihistimane|antihistimanes]] such as [[Benadryl]] are anticholinergic.{{Citation needed}} During [[exercise]], levels of acetylcholine drop.<ref>Conlay, L. A., Sabournjian, L. A., and Wurtman, R. J. Exercise and neuromodulators: choline and acetylcholine in marathon runners.Int. J. Sports Med. 13(Suppl. 1):S141-142, 1992</ref>

=== Acetylcholinesterase inhibitors ===
[[Acetylcholinesterase]] is an enzyme that breaks down acetylcholine. Acetylcholinesterase inhibitors block or downregulate the activity of acetylcholinesterase; in turn, because there is less enzyme breaking down acetylcholine, the amount of circulating acetylcholine increases.

The following compounds are acetylcholinesterase inhibitors:
* [[pyridostigmine]] (Mestinon) - A peripheral AChE inhibitor, pyridostigmine is unable to cross the blood brain barrier due to its chemical structure. <ref>{{Cite journal|last=Anderson|first=Tim|last2=Pope|first2=Carey N.|date=2017|title=Pyridostigmine ☆|url=https://linkinghub.elsevier.com/retrieve/pii/B978012801238397627X|language=en|publisher=Elsevier|pages=B978012801238397627X|doi=10.1016/b978-0-12-801238-3.97627-x|isbn=978-0-12-801238-3}}</ref>
* [[huperzine A]] (crosses blood-brain barrier){{Citation needed}}
* galantamine - A central/peripheral AChE inhibitor. While prescription only in some countries, galantamine is available over the counter in the United States.
* blueberries<ref>{{Cite journal|last=Papandreou|first=Magdalini A.|last2=Dimakopoulou|first2=Andriana|last3=Linardaki|first3=Zacharoula I.|last4=Cordopatis|first4=Paul|last5=Klimis-Zacas|first5=Dorothy|last6=Margarity|first6=Marigoula|last7=Lamari|first7=Fotini N.|date=2009-03-17|title=Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity|url=https://www.ncbi.nlm.nih.gov/pubmed/19056430|journal=Behavioural Brain Research|volume=198|issue=2|pages=352–358|doi=10.1016/j.bbr.2008.11.013|issn=1872-7549|pmid=19056430}}</ref>

== Research studies related to ME/CFS ==
* 2004, Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome<ref>{{Cite journal|last=Spence|first=V.A|author-link=Vance Spence|last2=Khan|first2=F|author-link2=Faisel Khan|last3=Kennedy|first3=G|author-link3=|last4=Abbot|first4=N.C|author-link4=|last5=Belch|first5=J.J.F|author-link5=|date=Apr 2004|title=Acetylcholine mediated vasodilatation in the microcirculation of patients with chronic fatigue syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0952327804000134|journal=Prostaglandins, Leukotrienes and Essential Fatty Acids|language=en|volume=70|issue=4|pages=403–407|doi=10.1016/j.plefa.2003.12.016|quote=|via=}}</ref> - [[pubmed:15041034|(Abstract)]]

== See also ==
*[[Autoantibody]]
*[[Vagus nerve]]
*[[Vagus nerve infection hypothesis]]
==Learn more==

*2003, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430829/ The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation], Molecular Medicine, 2003 May-Aug; 9(5-8): 125–134.
*2011, [https://www.youtube.com/watch?v=n8j3BWeMOuo Video - "Is acetylcholine toxicity the cause of CFS?"]
*24 February 2015, [http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-2-2015-14-16-10 Scientists uncover new role for neurotransmitter that helps fight infection], Imperial College London News

==References==
{{Reflist}}

[[Category:Neurotransmitters and hormones]]

Andrew Bretherton

2021-10-07T19:44:50Z

Kmdenmark:added categories

'''Andrew Bretherton''' is a passionate human rights advocate and unionist. Andrew has worked with a number of organisations including 88 Days And Counting, Tom & Mia’s legacy, Migrant Workers Hub and the Migrant Workers Centre actively fighting against modern slavery and for the improvement of migrant workers rights. He gave evidence to the [https://www.aph.gov.au/modernslavery Australian modern slavery inquiry 2016]<ref>https://www.aph.gov.au/modernslavery</ref> and cross examined for the [https://www.fwc.gov.au/awards-and-agreements/awards/award-modernisation/variation-applications/AM2020/104 inquiry into the horticulture award]<ref>https://www.fwc.gov.au/awards-and-agreements/awards/award-modernisation/variation-applications/AM2020/104</ref>
Andrew became an advocate for people with ME when he himself was diagnosed in 2015. Andrew is actively campaigning for better conditions and to stop the abuse of people living with ME. He has spoken for various ME organisations in Australia and in the UK.

Andrew is currently leading a [https://chng.it/mNbnkz9ZSN Call For Change petition]<ref>https://chng.it/mNbnkz9ZSN</ref> to submit to the Australian Disability Royal Commission and Australian Parliament to investigate the violence, neglect, abuse and exploitation currently occurring in the ME and CFS community due to outdated guidelines, policies and research.

== '''Illness''' ==
Andrew was studying a B.A. of Psychology and Sport Science, working professionally and heavily involved in his local community when he caught glandular fever (EBV) and shingles and was struck down with the condition. He attended hospital fatigue clinic and an exercise health clinic in Melbourne where the therapies recommended to him GET/CBT and high doses of amphetamines which he found exploitative, abusive and reduced his functionality to the point where he was housebound and could no longer work or study. He later attended Dr [[Donald Lewis]] clinic CFS discovery where he received proper medical care before it closed in 2019.

Andrew experienced many cases of diagnosis discrimination found the process of applying for social supports (housing, national disability insurance scheme, disability support pension) in Australia discriminatory simply because services excluded him from support because he had the “ME or CFS” label.

In 2019 his apartment complex flooded and through no fault of his own Andrew found himself homeless and was admitted to hospital where he experienced further medical abuse where the hospital tried to “cure” his ME with psychiatric treatments (e.g. more GET/CBT and antidepressants)

It took Andrew 3 years to access the DSP and NDIS. Andrew believes had he had early access to appropriate services then he would be much less impaired then he is now and could have possibly avoided what happened to him.

== '''Advocacy''' ==
Andrew has publicly called for more biomedical funding and [https://www.abc.net.au/triplej/programs/hack/what-its-like-living-with-chronic-fatigue/9046886 said that having ME was like a “living death” - Triple J hack - 2017] he said that recommending graded exercise therapy and cognitive behaviour therapy for the condition is “just garbage” - Insight - 2018 on the insight program he said “It’s not often you get a chance to confront your abuser, so it was therapeutic for me in that sense. I only regret that they focused more on outdated modes of practice, but we do need people to stand up and put forward the message of real science and show that these dinosaur practices of treatment (graded exercise therapy and cognitive behavioural therapy) are harmful to patients.” ME Australia - 2018

In 2018 Andrew gave evidence to the Inquiry into establishing a [https://www.legislation.gov.au/Details/C2018A00153 Modern Slavery Act] in Australia on behalf of Tom & Mia’s legacy and his partner at the time.

'''''Andrew’s statement:'''''

“My partner is currently working on a farm for her second year visa. She's Chinese. When we were discussing her coming here, I told her that Australia has workplace and safety laws that can protect her. Even utilising and knowing these services and procedures myself, it has been extremely hard to get her fair pay and conditions, and my partner is currently still being exploited. I would love to tell you more, but my partner and her workmates are petrified that if I speak to you today not only will they lose their opportunity to stay in Australia but they'll also be at risk of physical harm. (For context her room was knocked on late at night and they were demanding which “backpackers boyfriend” called the farm and company and got the union involved) What was said earlier about Asian workers versus European workers being harder or better is (just an example of) cultural exploitation. Farmers, hostels and contractors are (actively) taking advantage of backpackers of Asian backgrounds. There's a saying in China that “the nail that sticks out gets hammered down”, so traditionally it is not part of their culture to speak out against their employer. When I spoke to my partner about coming to Australia, she was surprised by all our working and safety rights that we have here, as they do not exist in her country, (China) unlike in Australia and Europe.

I'd also like to address some other issues with you today, the first being piece rates. Piece rates are being used as a legal loophole to exploit women and backpackers out of decent pay conditions. At the moment, backpackers' employers decide what the average competent worker is and then off this decide what the rate of pay will be. I would call for this to be abolished or at the very least government regulated rather than farm regulated, as it is currently in other working sectors. In Australia we regard ourselves as giving equal pay to women, but with piece rates, women are consistently earning less than men. I understand that this is because of the physical nature of the work, but keep in mind these women are working the same hours and same conditions as the men on the farms.

The other issue I'd like to bring up is the myth Australians don't want to work on farms or are too lazy for farm work. When looking for work for my partner's second year visa, which took almost six months, I also believed this myth that farmers are desperate for Australian workers, so I would call these farms myself as an Australian looking for work, and then the farmer or contractor would say that there is no work available. My partner would then call the same place after me this time as a backpacker asking for the same work, and automatically she was offered the job! But well under the award wages. At the community meeting yesterday I also spoke to a local resident who also had trouble obtaining work here in the area (Mildura) . He believes he was turned down for the same reason, and I believe he's still looking for work.

There are two avenues to find farm work in Australia. One is legitimate sources like the government harvest trail website, Seek and the other job networks online. These seem to have very few regional farming jobs available, but then there are the unregulated social media or apps, in which there are literally hundreds of farming jobs available (for backpackers). Australia regards itself as the land of the fair go, but, having personally experienced what my partner is going through, and through working with Rosie, I can honestly say I no longer believe this to be true.”

In 2021 Andrew was acknowledged in the book “[https://www.penguin.com.au/books/far-from-home-9780143796398 Far From Home]” - by Rosie Ayliffe.<ref>https://www.penguin.com.au/books/far-from-home-9780143796398</ref>

Andrew also actively participated on behalf of 88 days and counting into variation of the Horticultural Award 2020 <ref>https://www.fwc.gov.au/awards-and-agreements/awards/award-modernisation/variation-applications/AM2020/104</ref> cross examining witnesses and providing statements on behalf of temporary migrant workers in Australia.

== '''Positions held:''' ==

Community Engagement officer - Emerge Australia 2017

Video media and live streaming - Emerge Australia 2018

Social Media Engagement officer - ME Australia 2018 - onwards

Millions Missing - Guest speaker 2019

ME action network promo - 2018

Call for Change UK - Voice Over/ Narrator

Call for Change Australia - Organiser

Victorian greens people with disabilities working group Co- Convenor 2018 - Current

88 days and counting - Organiser 2016 - present

Tom and Mia’s Legacy - Organiser and Spokesperson 2016 - present

Call for Change Australia - Organiser - 2021

Migrant workers centre - Volunteer

== '''Media Coverage:''' ==

*[https://www.facebook.com/EmergeAustraliaInc/videos/311107219797157 Andrew speech for Missing Millions at Melbourne Rally]

*[https://www.sbs.com.au/ondemand/watch/1334946883764 SBS - Insight - Chronic Fatigue Syndrome (2018)]

*[https://meaustralia.net/2018/10/15/insight-on-chronic-fatigue-syndrome-andrews-experience/ ME News Australia - ‘Insight’ on chronic fatigue syndrome: Andrew’s experience (2018)]

*[https://www.abc.net.au/triplej/programs/hack/what-its-like-living-with-chronic-fatigue/9046886 'A slow death': what it’s like living with Chronic Fatigue Syndrome]

*[https://abcmedia.akamaized.net/radio/local_sydney/audio/201909/nlf-2019-09-02-living-with-chronic-fatigue-syndrome.mp3 Nightlife - ABC Radio] (at 37:20)

*ME action network promo

== '''Other Advocacy work:''' ==

*[https://www.facebook.com/samira.karimi569/videos/503867967667605 Andrew’s speech on Slavery outside Parliament House Melbourne]. February 2021

==References==

[[Category:People with ME, CFS, and/or FMS]]
[[Category:Advocates or allies]]
[[Category:Australian advocates or allies]]

Andrew Bretherton

2021-10-07T19:43:03Z

Kmdenmark:reformatted ref

User talk:Kmdenmark

2021-10-07T19:32:06Z

Kmdenmark:/* Spam, Spam, not lovely .. */

[[/Old messages]]

[[/todolist]]

[[/templates]]

[[/Separate Site Notices]]

[[/Diagnostic biomarkers for ME/CFS]]

[[/EBV-dUTPase]]

[[/EET]]

[[/bulkimport]]

==Leave me a message ==

== Spelling of Indoleamine-2,3-dioxygenase vs indolamine-2,3-dioxygenase -- [[User:Loopy|Loopy]] ([[User talk:Loopy|talk]]) 20:03, April 28, 2021 (UTC) ==

Not certain which spelling is correct.

https://www.mdpi.com/2075-4418/9/3/82

The above link spells IDO as indolamine-2,3-dioxygenase. But the page at MEpedia is [[Indoleamine-2,3-dioxygenase]]. (Note the "e" missing after "indol" on the link above.

Perhaps we need to correct the MEpedia page? For IDO, IDO1, and IDO2?

--[[User:Loopy|Loopy]] ([[User talk:Loopy|talk]]) 20:04, April 28, 2021 (UTC)

== Spam, Spam, not lovely .. ==

Hi. There is much more Spam. Look to my edits. Even [[Deep_Joshi|re-filled Pages]]. Let me tell you my experience: If you do not delete the SPAM immediately, it goes epidemic. <br>
If you decide to give me sysop-Flag, you may have less work to do yourself. Regards. --[[User:Metoo|Metoo]] ([[User talk:Metoo|talk]]) 06:54, August 15, 2021 (UTC)

===Re: Spam, Spam, not lovely .. -- [[User:Kmdenmark|Kmdenmark]] ([[User talk:Kmdenmark|talk]]) 19:32, October 7, 2021 (UTC)===

: Thank you for flagging the spam pages! They are deleted now. Hope they don't grow back. [[User:Kmdenmark|Kmdenmark]] ([[User talk:Kmdenmark|talk]]) 19:32, October 7, 2021 (UTC)

MEpedia talk:Page protection

2021-10-07T18:57:02Z

Kmdenmark:/* Please edit */

==Please edit==
[[User:Kmdenmark]] Can you please change the link for top ten pages to link to [[Special:PopularPages]] instead - this will give a red link but will work once the MW 1.35 upgrade goes live. It's simply a documentation page so making the change early won't matter. ~[[User:Notjusttired|Njt]] ([[User talk:Notjusttired|talk]]) 17:46, July 20, 2021 (UTC)

===Re: Please edit -- [[User:Kmdenmark|Kmdenmark]] ([[User talk:Kmdenmark|talk]]) 18:57, October 7, 2021 (UTC)===

: [[User:Notjusttired|Njt]] I think this task has been done during my absence. If not let me know. [[User:Kmdenmark|Kmdenmark]] ([[User talk:Kmdenmark|talk]]) 18:57, October 7, 2021 (UTC)

== needs reviewing -- [[User:Notjusttired|Njt]] ([[User talk:Notjusttired|talk]]) 19:53, September 27, 2019 (EDT) ==

Please review / edit. The [[MEpedia:Admin guide]] explains how to add/remove protection. [[User:JaimeS]] [[User:JenB]] [[User:Kmdenmark]] [[User:Pyrrhus]]. [[User:Notjusttired|Njt]] ([[User talk:Notjusttired|talk]]) 19:53, September 27, 2019 (EDT)
:Looks great! Thanks for creating this!
:[[User:Pyrrhus|Pyrrhus]] ([[User talk:Pyrrhus|talk]]) 22:53, September 27, 2019 (EDT)
:: Agree! Looks great! [[User:Kmdenmark|Kmdenmark]] ([[User talk:Kmdenmark|talk]]) 17:56, October 7, 2019 (EDT)

Two-day cardiopulmonary exercise test

2021-06-11T23:33:46Z

Kmdenmark:Author links; removed issn number

'''Two-day cardiopulmonary exercise test or 2-day CPET''' is a procedure which assesses exercise capacity and recovery by performing two exercise tests 24 hours apart.<ref name=":2">{{Cite journal|last=Stevens|first=Staci|last2=Snell|first2=Chris|last3=Stevens|first3=Jared|last4=Keller|first4=Betsy|last5=VanNess|first5=J. Mark|date=2018|title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/30234078|journal=Frontiers in Pediatrics|volume=6|pages=242|doi=10.3389/fped.2018.00242|issn=2296-2360|pmc=6131594|pmid=30234078}}</ref> The hypothesis is that ME/CFS patients display a characteristic deterioration in exercise capacity on the second test, a finding that has been reported by multiple research groups.<ref name=":1" /><ref name=":3" /><ref name=":0" />[[File:CPET.jpg|alt=Photo of a woman walking on a treadmill while wearing a clear mask over her nose and mouth, and attached to a cart holding medical equipment.|thumb|350x350px|Cardiopulmonary Exercise Test]]The maximal, symptom-limited cardiopulmonary exercise test (CPET) is considered the gold standard for measuring physical capacity.<ref>{{Cite journal|last=Chandra|first=Divay|author-link=|last2=Wise|first2=Robert A.|author-link2=|last3=Kulkarni|first3=Hrishikesh S.|author-link3=|last4=Benzo|first4=Roberto P.|author-link4=|last5=Criner|first5=Gerard|author-link5=|last6=Make|first6=Barry|author-link6=|last7=Slivka|first7=William A.|last8=Ries|first8=Andrew L.|last9=Reilly|first9=John J.|date=Dec 2012|title=Optimizing the 6-Min Walk Test as a Measure of Exercise Capacity in COPD|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515028/|journal=Chest|volume=142|issue=6|pages=1545–1552|doi=10.1378/chest.11-2702|issn=0012-3692|pmc=3515028|pmid=23364913|quote=|via=}}</ref><ref>{{Cite journal|last=Demir|first=Rengin|author-link=|last2=Küçükoğlu|first2=Mehmet Serdar|author-link2=|author-link3=|author-link4=|author-link5=|author-link6=|date=Dec 2010|title=Evaluation of exercise capacity in pulmonary arterial hypertension|url=https://www.ncbi.nlm.nih.gov/m/pubmed/21248462/|journal=Turk Kardiyoloji Dernegi Arsivi: Turk Kardiyoloji Derneginin Yayin Organidir|volume=38|issue=8|pages=580–588|issn=1016-5169|pmid=21248462|quote=|via=}}</ref> This test measures gas exchange parameters using a mouthpiece or mask, while participants exercise on a treadmill or stationary bicycle with a controlled increase in resistance or power output. It is commonly used to measure the fitness level of athletes, as well as patients with cardiopulmonary disease.<ref>{{Cite journal|last=Albouaini|first=Khaled|last2=Egred|first2=Mohaned|last3=Alahmar|first3=Albert|last4=Wright|first4=David Justin|date=Nov 2007|title=Cardiopulmonary exercise testing and its application|url=https://www.ncbi.nlm.nih.gov/pubmed/17989266|journal=Postgraduate Medical Journal|volume=83|issue=985|pages=675–682|doi=10.1136/hrt.2007.121558|issn=1469-0756|pmc=2734442|pmid=17989266}}</ref> In these populations, CPET measures are highly reliable and reproducible.<ref name=":2" /> Exercise physiologists however have noted that ME/CFS patients are unable to reproduce these measurements on consecutive days, despite meeting criteria for maximal effort.<ref name=":4" /> According to a 2015 report by The National Academy of Medicine, “ME/CFS patients have significantly lower results on CPET 2 than on CPET 1 on one or more of the following parameters: VO2max, VO2 at ventilatory threshold and maximal workload or workload at ventilatory threshold.”<ref name=":5">{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK274235/|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|last=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations|last3=Institute of Medicine|date=2015|publisher=National Academies Press (US)|isbn=9780309316897|series=The National Academies Collection: Reports funded by National Institutes of Health|location=Washington (DC)|pmid=25695122}}</ref>

Specifically, VO2Max is the true maximal oxygen consumption of a participant, VO2Peak is the recorded maximal oxygen consumption of a participant and VO2 at ventilatory threshold is the oxygen consumption at the first key threshold (VT or VT1), otherwise known as the gas exchange threshold (GET). This threshold is the point at which carbon dioxide output (VCO2) and oxygen consumption no longer increase linearly, which occurs at 40-75% of VO2Max, depending on the fitness and health of the participants. The VT1 is commonly determined using the V-slope method, which notes the point of non linearity when VO2 is plotted against VCO2. The VT1 can also be indicated using the ventilatory equivalent method, plotting VE/VO2 and VE/VCO2 on the same graph and noting the point where VE/VO2 increases significantly, while VE/VCO2 remains flat (where VE is minute ventilation, which is the total amount of gas inhaled or exhaled from the lungs per minute). While the VT1 is primarily determined by peripheral metabolic factors, it is not synonymous with the lactate threshold which is the point at which lactate starts to accumulate significantly in the blood. The lactate threshold is not only dependent on lactate/pyruvate equilibrium inside the muscle cells, but the kinetics of lactate transport into and out of cells. Nor is VT1 synonymous with the onset of acidosis which is additionally affected by pH buffering within the cell and the circulatory system. It is also important to point out that this gas exchange threshold is not caused by shortness of breath, nor hyperventilation, since neither hypocapnia nor hypercapnia occur at this threshold. There is however, a second ventilatory threshold (VT2) otherwise known as the respiratory compensation point (RCP), and typically occurs at 85-90% of VO2Max. This respiratory compensation occurs when a significant reduction in blood or cerebrospinal fluid pH activates chemoreceptors, which stimulate the respiratory centre of the brain, leading to compensatory hyperventilation to help restore the pH balance.

According to researchers in the field, the abnormal results of ME/CFS patients on the 2-day CPET reflect post-exertional malaise (PEM), a marked symptom exacerbation after exercise thought to be characteristic of this condition.<ref name=":1" /> The 2015 report by National Academy of medicine indicated that the 2-day CPET protocol can be used as an objective indicator that physical exertion decreases subsequent function in patients with ME/CFS, for example in obtaining social security disability.<ref name=":5" /> The 2-day CPET protocol however is not required in making the diagnosis of ME/CFS. Some have expressed concern that exercise tests may significantly worsen the condition of ME/CFS patients.<ref name=":5" /><ref>{{Cite journal|last=Nijs|first=J.|last2=Van Oosterwijck|first2=J.|last3=Meeus|first3=M.|last4=Lambrecht|first4=L.|last5=Metzger|first5=K.|last6=Frémont|first6=M.|last7=Paul|first7=L.|date=Apr 2010|title=Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta|url=https://www.ncbi.nlm.nih.gov/pubmed/20433584|journal=Journal of Internal Medicine|volume=267|issue=4|pages=418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=1365-2796|pmid=20433584}}</ref><ref>{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref name=":0" />

==Evidence==
[[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] of the University of the Pacific, Stockton, CA, were the first to study the two-day CPET procedure in patients with ME/CFS. In a 2007 study published in the [[Journal of Chronic Fatigue Syndrome]], they compared six ME/CFS patients with six controls. At the first CPET there were no major differences between the two groups. At the second CPET however, ME/CFS patients reached significantly lower peak [[oxygen]] consumption (VO2Peak) and oxygen consumption at aerobic threshold.<ref name=":4">{{Cite journal|last=Vanness|first=J. Mark|last2=Snell|first2=Christopher R.|last3=Stevens|first3=Staci R.|date=Jan 2007|title=Diminished Cardiopulmonary Capacity During Post-Exertional Malaise|url=https://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=14|issue=2|pages=77–85|doi=10.1300/j092v14n02_07|issn=1057-3321}}</ref>

In 2010, a Dutch research group including Ruud Vermeulen and [[Frans Visser]] used the 2-day CPET in a study with 15 female ME/CFS and 15 healthy controls. Patients reached the aerobic threshold and the maximal exercise at much lower oxygen consumption than controls, an effect that was magnified during the second-day exercise test. Since levels of creatine kinase in the blood and oxidative phosphorylation in mononuclear cells were normal in patients before and after exercise, Vermeulen et al. speculated that the lowered anaerobic threshold was not so much a result of [[mitochondrion|mitochondrial]] insufficiency, but of impaired oxygen transport to the [[Muscle|muscles]].<ref>{{Cite journal|last=Vermeulen|first=Ruud C. W.|last2=Kurk|first2=Ruud M.|last3=Visser|first3=Frans C.|last4=Sluiter|first4=Wim|last5=Scholte|first5=Hans R.|date=2010-10-11|title=Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity|url=https://www.ncbi.nlm.nih.gov/pubmed/20937116|journal=Journal of Translational Medicine|volume=8|pages=93|doi=10.1186/1479-5876-8-93|issn=1479-5876|pmc=2964609|pmid=20937116}}</ref>

In 2013, [[Christopher Snell|Snell]], [[Staci Stevens|Stevens]] and [[Mark VanNess|VanNess]] tested the 2-day CPET procedure in a larger sample of 51 ME/CFS patients and 10 healthy controls. Once again, there were no sufficient differences between the groups at the first CPET. During the exercise test on the second day however, ME/CFS patients showed much lower oxygen consumption and workload at peak exercise and at aerobic threshold. Group differences were not due to lack of effort since most participants attained the ventilatory threshold and achieved a respiratory exchange ratio of greater than or equal to 1.1.<ref name=":0">{{Cite journal|last=Snell|first=C. R.|last2=Stevens|first2=S. R.|last3=Davenport|first3=T. E.|last4=Van Ness|first4=J. M.|date=2013-06-27|title=Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome|url=https://academic.oup.com/ptj/article/93/11/1484/2735315|journal=Physical Therapy|language=en|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=0031-9023}}</ref>

In 2014, the research group of [[Betsy Keller]] used the 2-day CPET protocol in a study involving 22 ME/CVS patient. A decline on several physiological measures was found (see table), while the respiratory exchange ratio indicated maximum efforts by participants during both exercise tests.<ref name=":1">{{Cite journal|last=Keller|first=Betsy A.|last2=Pryor|first2=John Luke|last3=Giloteaux|first3=Ludovic|date=2014-04-23|title=Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref>

This group followed this research up with a study of a single pair of monozygotic twins in 2016.<ref>{{Cite journal|title=A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition|url=http://www.amjcaserep.com/abstract/index/idArt/900314|journal=American Journal of Case Reports|date=2016-10-10|issn=1941-5923|pmc = 5058431|pmid=27721367|pages=720–729|volume=17|doi=10.12659/AJCR.900314|language=en|first=Ludovic|last=Giloteaux|first2=Maureen R.|last2=Hanson|first3=Betsy A.|last3=Keller}}</ref>
{| class="wikitable"
! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS (bold indicates statistical significance)
|-
|
|Number of ME/CFS patients
|VO2 peak
|VO2 at VT
|Workload peak
|Workload at VT
|HR peak
|O2pulse at VT
|-
|VanNess et al. 2007.
|6
|'''-22%'''
|'''-26%'''
|?
|?
|?
|?
|-
|Vermeulen et al. 2010.
|15
|'''-6.3%'''
|'''-7.0%'''
|'''-5.3%'''
|'''-7.0%'''
|<nowiki>-1.9%</nowiki>
|'''-8.8%'''
|-
|Snell et al. 2013.
|51
| -5%
|'''-10.8%'''
|'''-7.2%'''
|'''-55.2%'''
|?
|?
|-
|Keller et al. 2014.
|22
|'''-13.8%'''
|'''-15.8%'''
|'''-12.5%'''
|'''-21.3%'''
|'''-5.9%'''
|'''-12.6%'''
|-
|Giloteaux et al. 2016.
|1 (monozygotic twin)
|0%
| -13.4%
|0%
| -25%
| +7.4%
| -19% (calculated)
|-
|Hodges et al. 2017.
|10
|<nowiki>+5.3%</nowiki>
|<nowiki>+6.1%</nowiki>
|<nowiki>-6.7%</nowiki>
|'''-11.4%'''
|<nowiki>-0.6%</nowiki>
| +7% (calculated)
|-
|Nelson et al. 2019.
|16
| +0.4%
| -3.1%
| -1.2%
|'''-17.4%'''
| -0.5%
| +2% (calculated)
|-
|Lien et al. 2019. (numerical estimates)

|18
| -5%
| -6%
| -2%
|'''-7%'''
| +1.5%
|?
|-
|van Campen 2020.A (males)
|25
|'''-10%'''
|'''-22%'''
|'''-10%'''
|'''-30%'''
|'''-5%'''
| -16% (calculated)
|-
|van Campen 2020.B (females)
|31 ("mild" cases)
|'''-6%'''
|'''-21%'''
|'''-10%'''
|'''-26%'''
| -3%
|?
|-
|van Campen 2020.B (females)
|31 ("moderate" cases)
|'''-11%'''
|'''-21%'''
|'''-16%'''
|'''-31%'''
| -6%
|?
|-
|van Campen 2020.B (females)
|20 ("severe" cases)
|'''-12%'''
|'''-19%'''
|'''-19%'''
|'''-33%'''
| -7%
|?
|-
|Davenport 2020.
|51
| -5%
| -10%
| -9%
|'''-11%'''
| -3%
| -7% (calculated)
|-
|van Campen 2021. (males)
|25
|'''-12%'''
|'''-27%'''
|'''-10%'''
|'''-27%'''
| -7%
| -17% (calculated)
|-
|van Campen 2021. (females)
|50
|'''-10%'''
|'''-23%'''
|'''-11%'''
|'''-30%'''
| -4%
| -15% (calculated)
|}
In 2017, a research team form [[New Zealand]] compared the physiological responses during a 2-day CPET, in ten patients with ME/CFS, seven patients with [[Multiple sclerosis|Multiple Sclerosis]] (MS) and seventeen healthy controls. Curiously peak oxygen increased at the second exercise test in ME/CFS patients, but there was a significant reduction noticeable in workload at aerobic threshold, a decline that was not seen in MS-patients or healthy controls. According to the authors: <blockquote>“differences between MS and CFS/ME responses only became evident after a second maximal exercise test, thus suggesting that a repeated protocol is required to not only distinguish CFS/ME from HC, but also from other fatigue-related conditions, who may not suffer from post-exertional malaise and have a differing delayed fatigue profile.”<ref name=":3">{{Cite journal|last=Hodges|first=L. D.|last2=Nielsen|first2=T.|last3=Baken|first3=D.|date=Jul 2018|title=Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4|pages=639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref></blockquote>In 2019 the 2-day CPET procedure was tested by an Australian research team of Nelson and colleagues. They found a significant larger reduction in workload at the ventilatory threshold in patients with ME/CFS compared to healthy controls. A percentage change of −6.3% to −9.8% provided good sensitivity and specificity, indicating this test has the potential to become a biomarker for ME/CFS. However, the sample size of this study was small (16 ME/CFS patients), the control group consisted only of healthy persons (instead of patients with other chronic illnesses) and no significant difference was found in VO2 at the ventilatory threshold.<ref>{{Cite journal|last=Nelson|first=Maximillian J.|last2=Buckley|first2=Jonathan D.|last3=Thomson|first3=Rebecca L.|last4=Clark|first4=Daniel|last5=Kwiatek|first5=Richard|last6=Davison|first6=Kade|date=2019-03-14|title=Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://doi.org/10.1186/s12967-019-1836-0|journal=Journal of Translational Medicine|volume=17|issue=1|pages=80|doi=10.1186/s12967-019-1836-0|issn=1479-5876|pmc = 6417168|pmid=30871578}}</ref>

A Norwegian study published in 2019 also reported a significant larger reduction in workload at the ventilatory threshold in 18 patients with ME/CFS compared to healthy controls, although this was not the case for peak values or VO2 measurement at the ventilatory threshold. The authors also measured arterial lactate concentrations, every 30 seconds during the exercise tests. Lactate was higher per power output per kg in patients than controls and the differences increased significantly at the second exercise test. In the healthy controls lactate concentration at the ventilatory threshold decreased while this was not the case in ME/CFS patients, suggesting a problem in lactate clearance ability.<ref>{{Cite journal|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|date=2019|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://physoc.onlinelibrary.wiley.com/doi/abs/10.14814/phy2.14138|journal=Physiological Reports|language=en|volume=7|issue=11|pages=e14138|doi=10.14814/phy2.14138|issn=2051-817X}}</ref>

Researchers from the Workwell Foundation published in 2019, a case series of six women, who underwent the 2-day CPET. This study compared two healthy participants, one active, the other sedentary, two ME/CFS patients, one high functioning with high VO2peak, another with low VO2Peak, with a patient suffering from [[HIV/AIDS|human immunodeficiency virus]] (HIV) and another suffering from [[Multiple sclerosis|MS]].<ref>{{Cite journal|last=Larson|first=Benjamin|last2=Davenport|first2=Todd E.|last3=Stevens|first3=Staci R.|last4=Stevens|first4=Jared|last5=Van Ness|first5=J. Mark|last6=Snell|first6=Christopher R.|date=Oct 2019|title=Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With Fatiguing Health Conditions: A Case Series|url=http://insights.ovid.com/crossref?an=01823246-201910000-00004|journal=Cardiopulmonary Physical Therapy Journal|language=en|volume=30|issue=4|pages=145–152|doi=10.1097/CPT.0000000000000100|issn=1541-7891|pmc=|pmid=|quote=|last7=|first7=|last8=|first8=|author-link=|author-link2=Todd Davenport|access-date=|author-link3=Staci Stevens|author-link4=|author-link5=Mark VanNess|author-link6=Christopher Snell|via=}}</ref> The healthy participants and the MS patient reproduced or improved their exercise parameters, namely VO2, workload, heart-rate and minute ventilation at both the ventilatory threshold and peak exercise. The HIV patient reproduced all of these findings except peak workload and peak minute ventilation. The ME/CFS patients were unable to reproduce VO2, workload, heart rate or minute ventilation at the ventilatory threshold. These results continue to suggest that the inability to reproduce workload at the ventilatory threshold is specific to ME/CFS patients, but patients with other fatiguing conditions will need to be tested to confirm this. This study was followed up in 2020 with 51 patients and 10 controls, focusing on additional statistical analysis and discussing the meaning of test-retest reliability in the context of ME/CFS. The main positive finding was a significant group*test (difference) in work rate at the ventilatory threshold. <ref>{{Cite journal|last=Davenport|first=Todd E.|last2=Stevens|first2=Staci R.|last3=Stevens|first3=M. A. Jared|last4=Snell|first4=Christopher R.|last5=Van Ness|first5=J. Mark|date=2020-06-16|title=Properties of measurements obtained during cardiopulmonary exercise testing in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-203170|journal=Work|pages=1–10|doi=10.3233/WOR-203170}}</ref>

In 2020, researchers from Stichting Cardio Zorg, a cardiology clinic in the Netherlands published two studies of clinical 2-day CPET results for ME/CFS patients with exercise intolerance. The first study consisted of male patients, to see whether the results from previous studies which had predominantly female patients would be replicated.<ref>{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Rowe|first2=Peter C.|last3=Visser|first3=Frans C.|date=2020|title=Validity of 2-Day Cardiopulmonary Exercise Testing in Male Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.scirp.org/journal/doi.aspx?doi=10.4236/ape.2020.101007|journal=Advances in Physical Education|volume=10|issue=01|pages=68–80|doi=10.4236/ape.2020.101007|issn=2164-0386}}</ref> A second study focused on female patients with differing severity, which were subgrouped according to: “Symptom severity impact must result in a 50% or greater reduction in a patient’s premorbid activity level for a diagnosis of ME. Mild: approximately 50% reduction in activity, moderate: mostly housebound, severe: mostly bedbound and very severe: bedbound and dependent on help for physical functions”.<ref>{{Cite journal|last=van Campen|first=C (Linda) MC|last2=Rowe|first2=Peter C.|last3=Visser|first3=Frans C.|date=2020-06-30|title=Two-Day Cardiopulmonary Exercise Testing in Females with a Severe Grade of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison with Patients with Mild and Moderate Disease|url=https://www.mdpi.com/2227-9032/8/3/192|journal=Healthcare|language=en|volume=8|issue=3|pages=192|doi=10.3390/healthcare8030192|issn=2227-9032}}</ref> This research was followed up in 2021 with a retrospective clinical comparison between 26 male idiopathic chronic fatigue (ICF) cases who did not suffer from PEM and 25 male ME/CFS patients who satisfied the 2011 ME International Consensus Criteria and the 1994 Center for Disease Control criteria for CFS. <ref name=":6">{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Visser|first2=Frans C.|date=Jun 2021|title=Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol|url=https://www.mdpi.com/2227-9032/9/6/683|journal=Healthcare|language=en|volume=9|issue=6|pages=683|doi=10.3390/healthcare9060683|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Linda van Campen|author-link2=Frans Visser|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> Notably, most ME/CFS patients had a decline in VO2 and workload performance at peak and the ventilatory threshold on the second day, compared to all idiopathic chronic fatigue cases who were able to match or exceed their first day performance. The authors concluded that this decline in performance on the second day was disease-specific.<ref name=":6" /> A related comparison was performed for female patients with similar results.<ref>{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Visser|first2=Frans C.|date=Jun 2021|title=Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol|url=https://www.mdpi.com/2227-9032/9/6/682|journal=Healthcare|language=en|volume=9|issue=6|pages=682|doi=10.3390/healthcare9060682|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Linda van Campen|author-link2=Frans Visser|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> However there were several ICF patients that also had a reduction in peak workload and workload at the ventilatory threshold, despite the overall trend for an increase for ICF patients and a decrease for ME/CFS patients.

Unpublished studies have reported negative results for the repeated CPET procedure. In her thesis, Tessa-Maree Nielsen<ref>Nielsen TM. [https://mro.massey.ac.nz/bitstream/handle/10179/14653/02_whole.pdf?sequence=2&isAllowed=y The Timeline of Post Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. 2018.]</ref> at the Massey University, [[New Zealand]], performed the second exercise test 48 hours and 72 hours later, instead of the usual 24 hours. The study did not find significant reductions of workload at the ventilatory threshold in ME/CFS patients compared to controls. The eight ME/CFS patients in the 72 hours group had a workload at ventilatory threshold that was slightly higher instead of lower than during the first test. In a 2018 presentation,<ref>[https://www.youtube.com/watch?v=xpyz9K62Izg Presentation Ruud Vermeulen (03-06-2018). Minute 34.00.]</ref> Ruud Vermeulen reported to have data on approximately 500 ME/CFS patients who performed the repeated CPET procedure. He stated the test on the second day did not show any difference in VO2max compared to the first day, as shown in the graphs he presented.

Two-Day CPET studies have also considered other clinical groups, including [[Gulf War Illness|Gulf-War-Syndrome]]<ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Alexander|first2=Thomas|last3=Qian|first3=Wei|last4=Klein‐Adams|first4=Jacquelyn C.|last5=Lange|first5=Gudrun|last6=H. Natelson|first6=Benjamin|last7=Cook|first7=Dane B.|last8=Hill|first8=Helene Z.|last9=Falvo|first9=Michael J.|date=Sep 2020|title=An analysis of 2‐day cardiopulmonary exercise testing to assess unexplained fatigue|url=https://onlinelibrary.wiley.com/doi/abs/10.14814/phy2.14564|journal=Physiological Reports|language=en|volume=8|issue=17|doi=10.14814/phy2.14564|pmid=32889791|pages=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=Gudrun Lange|author-link6=Benjamin Natelson|via=|pmc=|author-link7=Dane Cook}}</ref> and Sarcoidosis.<ref>{{Cite journal|last=Braam|first=A.W.E.|last2=de Haan|first2=S.N.|last3=Vorselaars|first3=A.D.M.|last4=Rijkers|first4=G.T.|last5=Grutters|first5=J.C.|last6=van den Elshout|first6=F.J.J.|last7=Korenromp|first7=I.H.E.|date=Oct 2013|title=Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis|url=https://linkinghub.elsevier.com/retrieve/pii/S0889159113001967|journal=Brain, Behavior, and Immunity|language=en|volume=33|pages=57–64|doi=10.1016/j.bbi.2013.05.006|issue=|pmc=|pmid=|quote=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> The study of Gulf-War-Syndrome patients did not reveal any significant group by time effects and in particular, no time effects at VT1. The study of Sarcoidosis patients did not find any group by time effects, however they focused on peak performance and ignored differences in performance at sub-maximal thresholds such as VT1. In addition, the study of Sarcoidosis patients did find an exercise effect on several biomarkers, however changes in these markers were not related to self-reported fatigue.

== Use as a Biomarker ==
[[Christopher Snell|Snell]] et al. suggested 2-day CPET could be used "diagnostically as an objective indicator of an abnormal postexertion response and possibly even a [[Diagnostic biomarker|biomarker]] for the condition."<ref name=":0" /> Using the data from the two exercise tests, their research team was able to correctly classify 95% of the total sample, as a patient or healthy control.

== Criticism ==
While a unique reduction in physiological capacity was observed in ME/CFS by several studies and different research groups, sample sizes were rather small and disagreement exists on which physiological measure accurately displayed ME/CFS patients’ [[Post-exertional malaise|abnormal exertional response]].<ref name=":1" />

Another objection to the 2-day CPET as a biomarker for ME/CFS was raised by Snell et al themselves. They suggested it might be unethical<ref name=":0" /> to use this method to detect ME/CFS patients since many of these patients might suffer relapse as a result of exercise testing. In their 2010 study, 60% of ME/CFS patients reported that it took them more than 5 days to recover from a single (maximal) CPET. It is therefore possible that in some ME/CFS patients a 2-day CPET might cause a long-lasting relapse. Science-reporter and ME/CFS patient [[Simon McGrath]] for example wrote: “You couldn’t pay me enough money to take even one max test. My last relapse, which took me nearly 2 years to get over, happened after way less than maximal [[exertion]] – a 2-day test is not for everyone."<ref>{{Cite news|url=https://www.healthrising.org/blog/2014/05/20/declining-production-exercise-study-reveal-broad-decline-energy-output-chronic-fatigue-syndrome/|title=Declining Production: Exercise Study Reveals Broad Declines in Energy Output in Chronic Fatigue Syndrome - Health Rising|date=2014-05-20|work=Health Rising|access-date=2018-08-17|language=en-US}}</ref>

Others have noted that the CPET-procedure is not very practical. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, it may not be available to most clinicians.<ref>https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf</ref> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref>{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref> For these reasons PEM is commonly assessed using self-reporting questionnaires.

[[Brian Vastag]] was able to prove his PEM was a severe symptom causing disability with CPET, winning his long term disability (LTD) claim.<ref name=":02">{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|url-status=|access-date=2019-02-02}}</ref>

==Cost and availability==
*[[Workwell Foundation]] (United States, CA)
*[[Betsy Keller]] at Ithaca College (United States, NY) Cost is $2200. Because they are based in a college setting (not healthcare setting), they cannot process insurance (including Medicare or Medicaid), so the patient would need to work directly with their insurer about reimbursement. (private email)
*[[Laura Black]] at Hunter-Hopkins Center, Charlotte, NC
*[[Open Medicine Institute]] Clinic
*[http://physiologic.com.au/ Physiologic 334 Scottsdale Drive, Robina, Gold Coast, Australia]
*[https://www.s4me.info/threads/uk-locations-that-offer-cpet-vo2max-testing.4999/ Many UK universities] offer standard CPETs which can be adapted for patients with ME.

==Talks and interviews==
*2013, [https://www.youtube.com/watch?v=fHulHdMPAd4 CPET Presentation by Dr. Christopher Snell, Part I][https://www.youtube.com/watch?v=piUDax7I-Ek CPET Presentation by Dr. Christopher Snell, Part II]
*2014, [https://www.youtube.com/watch?v=q_cnva7zyKM&feature=youtu.be Mark VanNess 'Exercise and ME/CFS' at Bristol Watershed. Part One]

==See also==

*[[Betsy Keller]]
*[[Christopher Snell]]
*[[Exercise]]
*[[Mark VanNess]]
*[[Post-exertional malaise]]
*[[Staci Stevens]]
==Learn more==

*[http://www.workwellfoundation.org/testing-for-disability/ The Workwell Foundation: Testing for Disability]
*2007, [http://www.name-us.org/MECFSExplainPages/2007CiccolellaLegalStressTest.pdf Legal and Scientific Considerations of the Exercise Stress Test]
*2013, [http://www.cortjohnson.org/blog/2013/07/30/busted-exercise-study-finds-energy-production-system-is-broken-in-chronic-fatigue-syndrome/ Busted! Exercise Study Finds Energy Production System is Broken in Chronic Fatigue Syndrome]
*2013, [http://phoenixrising.me/archives/17902/ Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity]
*2018, [https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/ Victory For ME Disability Claim – U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability]<ref name=":02" />
*2019, [https://www.healthrising.org/blog/2019/01/17/decoding-2-day-cpet-chronic-fatigue-syndrome/ Decoding the 2-day Cardiopulmonary Exercise Test (CPET) in Chronic Fatigue Syndrome (ME/CFS)] by C. Christian

==References==
{{reflist}}
[[Category:Medical tests]]
[[Category:Cardiology]]

Two-day cardiopulmonary exercise test

2021-06-11T23:28:39Z

Kmdenmark:CS1error - date

'''Two-day cardiopulmonary exercise test or 2-day CPET''' is a procedure which assesses exercise capacity and recovery by performing two exercise tests 24 hours apart.<ref name=":2">{{Cite journal|last=Stevens|first=Staci|last2=Snell|first2=Chris|last3=Stevens|first3=Jared|last4=Keller|first4=Betsy|last5=VanNess|first5=J. Mark|date=2018|title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/30234078|journal=Frontiers in Pediatrics|volume=6|pages=242|doi=10.3389/fped.2018.00242|issn=2296-2360|pmc=6131594|pmid=30234078}}</ref> The hypothesis is that ME/CFS patients display a characteristic deterioration in exercise capacity on the second test, a finding that has been reported by multiple research groups.<ref name=":1" /><ref name=":3" /><ref name=":0" />[[File:CPET.jpg|alt=Photo of a woman walking on a treadmill while wearing a clear mask over her nose and mouth, and attached to a cart holding medical equipment.|thumb|350x350px|Cardiopulmonary Exercise Test]]The maximal, symptom-limited cardiopulmonary exercise test (CPET) is considered the gold standard for measuring physical capacity.<ref>{{Cite journal|last=Chandra|first=Divay|author-link=|last2=Wise|first2=Robert A.|author-link2=|last3=Kulkarni|first3=Hrishikesh S.|author-link3=|last4=Benzo|first4=Roberto P.|author-link4=|last5=Criner|first5=Gerard|author-link5=|last6=Make|first6=Barry|author-link6=|last7=Slivka|first7=William A.|last8=Ries|first8=Andrew L.|last9=Reilly|first9=John J.|date=Dec 2012|title=Optimizing the 6-Min Walk Test as a Measure of Exercise Capacity in COPD|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515028/|journal=Chest|volume=142|issue=6|pages=1545–1552|doi=10.1378/chest.11-2702|issn=0012-3692|pmc=3515028|pmid=23364913|quote=|via=}}</ref><ref>{{Cite journal|last=Demir|first=Rengin|author-link=|last2=Küçükoğlu|first2=Mehmet Serdar|author-link2=|author-link3=|author-link4=|author-link5=|author-link6=|date=Dec 2010|title=Evaluation of exercise capacity in pulmonary arterial hypertension|url=https://www.ncbi.nlm.nih.gov/m/pubmed/21248462/|journal=Turk Kardiyoloji Dernegi Arsivi: Turk Kardiyoloji Derneginin Yayin Organidir|volume=38|issue=8|pages=580–588|issn=1016-5169|pmid=21248462|quote=|via=}}</ref> This test measures gas exchange parameters using a mouthpiece or mask, while participants exercise on a treadmill or stationary bicycle with a controlled increase in resistance or power output. It is commonly used to measure the fitness level of athletes, as well as patients with cardiopulmonary disease.<ref>{{Cite journal|last=Albouaini|first=Khaled|last2=Egred|first2=Mohaned|last3=Alahmar|first3=Albert|last4=Wright|first4=David Justin|date=Nov 2007|title=Cardiopulmonary exercise testing and its application|url=https://www.ncbi.nlm.nih.gov/pubmed/17989266|journal=Postgraduate Medical Journal|volume=83|issue=985|pages=675–682|doi=10.1136/hrt.2007.121558|issn=1469-0756|pmc=2734442|pmid=17989266}}</ref> In these populations, CPET measures are highly reliable and reproducible.<ref name=":2" /> Exercise physiologists however have noted that ME/CFS patients are unable to reproduce these measurements on consecutive days, despite meeting criteria for maximal effort.<ref name=":4" /> According to a 2015 report by The National Academy of Medicine, “ME/CFS patients have significantly lower results on CPET 2 than on CPET 1 on one or more of the following parameters: VO2max, VO2 at ventilatory threshold and maximal workload or workload at ventilatory threshold.”<ref name=":5">{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK274235/|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|last=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations|last3=Institute of Medicine|date=2015|publisher=National Academies Press (US)|isbn=9780309316897|series=The National Academies Collection: Reports funded by National Institutes of Health|location=Washington (DC)|pmid=25695122}}</ref>

Specifically, VO2Max is the true maximal oxygen consumption of a participant, VO2Peak is the recorded maximal oxygen consumption of a participant and VO2 at ventilatory threshold is the oxygen consumption at the first key threshold (VT or VT1), otherwise known as the gas exchange threshold (GET). This threshold is the point at which carbon dioxide output (VCO2) and oxygen consumption no longer increase linearly, which occurs at 40-75% of VO2Max, depending on the fitness and health of the participants. The VT1 is commonly determined using the V-slope method, which notes the point of non linearity when VO2 is plotted against VCO2. The VT1 can also be indicated using the ventilatory equivalent method, plotting VE/VO2 and VE/VCO2 on the same graph and noting the point where VE/VO2 increases significantly, while VE/VCO2 remains flat (where VE is minute ventilation, which is the total amount of gas inhaled or exhaled from the lungs per minute). While the VT1 is primarily determined by peripheral metabolic factors, it is not synonymous with the lactate threshold which is the point at which lactate starts to accumulate significantly in the blood. The lactate threshold is not only dependent on lactate/pyruvate equilibrium inside the muscle cells, but the kinetics of lactate transport into and out of cells. Nor is VT1 synonymous with the onset of acidosis which is additionally affected by pH buffering within the cell and the circulatory system. It is also important to point out that this gas exchange threshold is not caused by shortness of breath, nor hyperventilation, since neither hypocapnia nor hypercapnia occur at this threshold. There is however, a second ventilatory threshold (VT2) otherwise known as the respiratory compensation point (RCP), and typically occurs at 85-90% of VO2Max. This respiratory compensation occurs when a significant reduction in blood or cerebrospinal fluid pH activates chemoreceptors, which stimulate the respiratory centre of the brain, leading to compensatory hyperventilation to help restore the pH balance.

According to researchers in the field, the abnormal results of ME/CFS patients on the 2-day CPET reflect post-exertional malaise (PEM), a marked symptom exacerbation after exercise thought to be characteristic of this condition.<ref name=":1" /> The 2015 report by National Academy of medicine indicated that the 2-day CPET protocol can be used as an objective indicator that physical exertion decreases subsequent function in patients with ME/CFS, for example in obtaining social security disability.<ref name=":5" /> The 2-day CPET protocol however is not required in making the diagnosis of ME/CFS. Some have expressed concern that exercise tests may significantly worsen the condition of ME/CFS patients.<ref name=":5" /><ref>{{Cite journal|last=Nijs|first=J.|last2=Van Oosterwijck|first2=J.|last3=Meeus|first3=M.|last4=Lambrecht|first4=L.|last5=Metzger|first5=K.|last6=Frémont|first6=M.|last7=Paul|first7=L.|date=Apr 2010|title=Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta|url=https://www.ncbi.nlm.nih.gov/pubmed/20433584|journal=Journal of Internal Medicine|volume=267|issue=4|pages=418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=1365-2796|pmid=20433584}}</ref><ref>{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref name=":0" />

==Evidence==
[[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] of the University of the Pacific, Stockton, CA, were the first to study the two-day CPET procedure in patients with ME/CFS. In a 2007 study published in the [[Journal of Chronic Fatigue Syndrome]], they compared six ME/CFS patients with six controls. At the first CPET there were no major differences between the two groups. At the second CPET however, ME/CFS patients reached significantly lower peak [[oxygen]] consumption (VO2Peak) and oxygen consumption at aerobic threshold.<ref name=":4">{{Cite journal|last=Vanness|first=J. Mark|last2=Snell|first2=Christopher R.|last3=Stevens|first3=Staci R.|date=Jan 2007|title=Diminished Cardiopulmonary Capacity During Post-Exertional Malaise|url=https://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=14|issue=2|pages=77–85|doi=10.1300/j092v14n02_07|issn=1057-3321}}</ref>

In 2010, a Dutch research group including Ruud Vermeulen and [[Frans Visser]] used the 2-day CPET in a study with 15 female ME/CFS and 15 healthy controls. Patients reached the aerobic threshold and the maximal exercise at much lower oxygen consumption than controls, an effect that was magnified during the second-day exercise test. Since levels of creatine kinase in the blood and oxidative phosphorylation in mononuclear cells were normal in patients before and after exercise, Vermeulen et al. speculated that the lowered anaerobic threshold was not so much a result of [[mitochondrion|mitochondrial]] insufficiency, but of impaired oxygen transport to the [[Muscle|muscles]].<ref>{{Cite journal|last=Vermeulen|first=Ruud C. W.|last2=Kurk|first2=Ruud M.|last3=Visser|first3=Frans C.|last4=Sluiter|first4=Wim|last5=Scholte|first5=Hans R.|date=2010-10-11|title=Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity|url=https://www.ncbi.nlm.nih.gov/pubmed/20937116|journal=Journal of Translational Medicine|volume=8|pages=93|doi=10.1186/1479-5876-8-93|issn=1479-5876|pmc=2964609|pmid=20937116}}</ref>

In 2013, [[Christopher Snell|Snell]], [[Staci Stevens|Stevens]] and [[Mark VanNess|VanNess]] tested the 2-day CPET procedure in a larger sample of 51 ME/CFS patients and 10 healthy controls. Once again, there were no sufficient differences between the groups at the first CPET. During the exercise test on the second day however, ME/CFS patients showed much lower oxygen consumption and workload at peak exercise and at aerobic threshold. Group differences were not due to lack of effort since most participants attained the ventilatory threshold and achieved a respiratory exchange ratio of greater than or equal to 1.1.<ref name=":0">{{Cite journal|last=Snell|first=C. R.|last2=Stevens|first2=S. R.|last3=Davenport|first3=T. E.|last4=Van Ness|first4=J. M.|date=2013-06-27|title=Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome|url=https://academic.oup.com/ptj/article/93/11/1484/2735315|journal=Physical Therapy|language=en|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=0031-9023}}</ref>

In 2014, the research group of [[Betsy Keller]] used the 2-day CPET protocol in a study involving 22 ME/CVS patient. A decline on several physiological measures was found (see table), while the respiratory exchange ratio indicated maximum efforts by participants during both exercise tests.<ref name=":1">{{Cite journal|last=Keller|first=Betsy A.|last2=Pryor|first2=John Luke|last3=Giloteaux|first3=Ludovic|date=2014-04-23|title=Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref>

This group followed this research up with a study of a single pair of monozygotic twins in 2016.<ref>{{Cite journal|title=A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition|url=http://www.amjcaserep.com/abstract/index/idArt/900314|journal=American Journal of Case Reports|date=2016-10-10|issn=1941-5923|pmc = 5058431|pmid=27721367|pages=720–729|volume=17|doi=10.12659/AJCR.900314|language=en|first=Ludovic|last=Giloteaux|first2=Maureen R.|last2=Hanson|first3=Betsy A.|last3=Keller}}</ref>
{| class="wikitable"
! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS (bold indicates statistical significance)
|-
|
|Number of ME/CFS patients
|VO2 peak
|VO2 at VT
|Workload peak
|Workload at VT
|HR peak
|O2pulse at VT
|-
|VanNess et al. 2007.
|6
|'''-22%'''
|'''-26%'''
|?
|?
|?
|?
|-
|Vermeulen et al. 2010.
|15
|'''-6.3%'''
|'''-7.0%'''
|'''-5.3%'''
|'''-7.0%'''
|<nowiki>-1.9%</nowiki>
|'''-8.8%'''
|-
|Snell et al. 2013.
|51
| -5%
|'''-10.8%'''
|'''-7.2%'''
|'''-55.2%'''
|?
|?
|-
|Keller et al. 2014.
|22
|'''-13.8%'''
|'''-15.8%'''
|'''-12.5%'''
|'''-21.3%'''
|'''-5.9%'''
|'''-12.6%'''
|-
|Giloteaux et al. 2016.
|1 (monozygotic twin)
|0%
| -13.4%
|0%
| -25%
| +7.4%
| -19% (calculated)
|-
|Hodges et al. 2017.
|10
|<nowiki>+5.3%</nowiki>
|<nowiki>+6.1%</nowiki>
|<nowiki>-6.7%</nowiki>
|'''-11.4%'''
|<nowiki>-0.6%</nowiki>
| +7% (calculated)
|-
|Nelson et al. 2019.
|16
| +0.4%
| -3.1%
| -1.2%
|'''-17.4%'''
| -0.5%
| +2% (calculated)
|-
|Lien et al. 2019. (numerical estimates)

|18
| -5%
| -6%
| -2%
|'''-7%'''
| +1.5%
|?
|-
|van Campen 2020.A (males)
|25
|'''-10%'''
|'''-22%'''
|'''-10%'''
|'''-30%'''
|'''-5%'''
| -16% (calculated)
|-
|van Campen 2020.B (females)
|31 ("mild" cases)
|'''-6%'''
|'''-21%'''
|'''-10%'''
|'''-26%'''
| -3%
|?
|-
|van Campen 2020.B (females)
|31 ("moderate" cases)
|'''-11%'''
|'''-21%'''
|'''-16%'''
|'''-31%'''
| -6%
|?
|-
|van Campen 2020.B (females)
|20 ("severe" cases)
|'''-12%'''
|'''-19%'''
|'''-19%'''
|'''-33%'''
| -7%
|?
|-
|Davenport 2020.
|51
| -5%
| -10%
| -9%
|'''-11%'''
| -3%
| -7% (calculated)
|-
|van Campen 2021. (males)
|25
|'''-12%'''
|'''-27%'''
|'''-10%'''
|'''-27%'''
| -7%
| -17% (calculated)
|-
|van Campen 2021. (females)
|50
|'''-10%'''
|'''-23%'''
|'''-11%'''
|'''-30%'''
| -4%
| -15% (calculated)
|}
In 2017, a research team form [[New Zealand]] compared the physiological responses during a 2-day CPET, in ten patients with ME/CFS, seven patients with [[Multiple sclerosis|Multiple Sclerosis]] (MS) and seventeen healthy controls. Curiously peak oxygen increased at the second exercise test in ME/CFS patients, but there was a significant reduction noticeable in workload at aerobic threshold, a decline that was not seen in MS-patients or healthy controls. According to the authors: <blockquote>“differences between MS and CFS/ME responses only became evident after a second maximal exercise test, thus suggesting that a repeated protocol is required to not only distinguish CFS/ME from HC, but also from other fatigue-related conditions, who may not suffer from post-exertional malaise and have a differing delayed fatigue profile.”<ref name=":3">{{Cite journal|last=Hodges|first=L. D.|last2=Nielsen|first2=T.|last3=Baken|first3=D.|date=Jul 2018|title=Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4|pages=639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref></blockquote>In 2019 the 2-day CPET procedure was tested by an Australian research team of Nelson and colleagues. They found a significant larger reduction in workload at the ventilatory threshold in patients with ME/CFS compared to healthy controls. A percentage change of −6.3% to −9.8% provided good sensitivity and specificity, indicating this test has the potential to become a biomarker for ME/CFS. However, the sample size of this study was small (16 ME/CFS patients), the control group consisted only of healthy persons (instead of patients with other chronic illnesses) and no significant difference was found in VO2 at the ventilatory threshold.<ref>{{Cite journal|last=Nelson|first=Maximillian J.|last2=Buckley|first2=Jonathan D.|last3=Thomson|first3=Rebecca L.|last4=Clark|first4=Daniel|last5=Kwiatek|first5=Richard|last6=Davison|first6=Kade|date=2019-03-14|title=Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://doi.org/10.1186/s12967-019-1836-0|journal=Journal of Translational Medicine|volume=17|issue=1|pages=80|doi=10.1186/s12967-019-1836-0|issn=1479-5876|pmc = 6417168|pmid=30871578}}</ref>

A Norwegian study published in 2019 also reported a significant larger reduction in workload at the ventilatory threshold in 18 patients with ME/CFS compared to healthy controls, although this was not the case for peak values or VO2 measurement at the ventilatory threshold. The authors also measured arterial lactate concentrations, every 30 seconds during the exercise tests. Lactate was higher per power output per kg in patients than controls and the differences increased significantly at the second exercise test. In the healthy controls lactate concentration at the ventilatory threshold decreased while this was not the case in ME/CFS patients, suggesting a problem in lactate clearance ability.<ref>{{Cite journal|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|date=2019|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://physoc.onlinelibrary.wiley.com/doi/abs/10.14814/phy2.14138|journal=Physiological Reports|language=en|volume=7|issue=11|pages=e14138|doi=10.14814/phy2.14138|issn=2051-817X}}</ref>

Researchers from the Workwell Foundation published in 2019, a case series of six women, who underwent the 2-day CPET. This study compared two healthy participants, one active, the other sedentary, two ME/CFS patients, one high functioning with high VO2peak, another with low VO2Peak, with a patient suffering from [[HIV/AIDS|human immunodeficiency virus]] (HIV) and another suffering from [[Multiple sclerosis|MS]].<ref>{{Cite journal|last=Larson|first=Benjamin|last2=Davenport|first2=Todd E.|last3=Stevens|first3=Staci R.|last4=Stevens|first4=Jared|last5=Van Ness|first5=J. Mark|last6=Snell|first6=Christopher R.|date=Oct 2019|title=Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With Fatiguing Health Conditions: A Case Series|url=http://insights.ovid.com/crossref?an=01823246-201910000-00004|journal=Cardiopulmonary Physical Therapy Journal|language=en|volume=30|issue=4|pages=145–152|doi=10.1097/CPT.0000000000000100|issn=1541-7891|pmc=|pmid=|quote=|last7=|first7=|last8=|first8=|author-link=|author-link2=Todd Davenport|access-date=|author-link3=Staci Stevens|author-link4=|author-link5=Mark VanNess|author-link6=Christopher Snell|via=}}</ref> The healthy participants and the MS patient reproduced or improved their exercise parameters, namely VO2, workload, heart-rate and minute ventilation at both the ventilatory threshold and peak exercise. The HIV patient reproduced all of these findings except peak workload and peak minute ventilation. The ME/CFS patients were unable to reproduce VO2, workload, heart rate or minute ventilation at the ventilatory threshold. These results continue to suggest that the inability to reproduce workload at the ventilatory threshold is specific to ME/CFS patients, but patients with other fatiguing conditions will need to be tested to confirm this. This study was followed up in 2020 with 51 patients and 10 controls, focusing on additional statistical analysis and discussing the meaning of test-retest reliability in the context of ME/CFS. The main positive finding was a significant group*test (difference) in work rate at the ventilatory threshold. <ref>{{Cite journal|last=Davenport|first=Todd E.|last2=Stevens|first2=Staci R.|last3=Stevens|first3=M. A. Jared|last4=Snell|first4=Christopher R.|last5=Van Ness|first5=J. Mark|date=2020-06-16|title=Properties of measurements obtained during cardiopulmonary exercise testing in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-203170|journal=Work|pages=1–10|doi=10.3233/WOR-203170}}</ref>

In 2020, researchers from Stichting Cardio Zorg, a cardiology clinic in the Netherlands published two studies of clinical 2-day CPET results for ME/CFS patients with exercise intolerance. The first study consisted of male patients, to see whether the results from previous studies which had predominantly female patients would be replicated.<ref>{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Rowe|first2=Peter C.|last3=Visser|first3=Frans C.|date=2020|title=Validity of 2-Day Cardiopulmonary Exercise Testing in Male Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.scirp.org/journal/doi.aspx?doi=10.4236/ape.2020.101007|journal=Advances in Physical Education|volume=10|issue=01|pages=68–80|doi=10.4236/ape.2020.101007|issn=2164-0386}}</ref> A second study focused on female patients with differing severity, which were subgrouped according to: “Symptom severity impact must result in a 50% or greater reduction in a patient’s premorbid activity level for a diagnosis of ME. Mild: approximately 50% reduction in activity, moderate: mostly housebound, severe: mostly bedbound and very severe: bedbound and dependent on help for physical functions”.<ref>{{Cite journal|last=van Campen|first=C (Linda) MC|last2=Rowe|first2=Peter C.|last3=Visser|first3=Frans C.|date=2020-06-30|title=Two-Day Cardiopulmonary Exercise Testing in Females with a Severe Grade of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison with Patients with Mild and Moderate Disease|url=https://www.mdpi.com/2227-9032/8/3/192|journal=Healthcare|language=en|volume=8|issue=3|pages=192|doi=10.3390/healthcare8030192|issn=2227-9032}}</ref> This research was followed up in 2021 with a retrospective clinical comparison between 26 male idiopathic chronic fatigue (ICF) cases who did not suffer from PEM and 25 male ME/CFS patients who satisfied the 2011 ME International Consensus Criteria and the 1994 Center for Disease Control criteria for CFS. <ref name=":6">{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Visser|first2=Frans C.|date=Jun 2021|title=Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol|url=https://www.mdpi.com/2227-9032/9/6/683|journal=Healthcare|language=en|volume=9|issue=6|pages=683|doi=10.3390/healthcare9060683|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Linda van Campen|author-link2=Frans Visser|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> Notably, most ME/CFS patients had a decline in VO2 and workload performance at peak and the ventilatory threshold on the second day, compared to all idiopathic chronic fatigue cases who were able to match or exceed their first day performance. The authors concluded that this decline in performance on the second day was disease-specific.<ref name=":6" /> A related comparison was performed for female patients with similar results.<ref>{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Visser|first2=Frans C.|date=Jun 2021|title=Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol|url=https://www.mdpi.com/2227-9032/9/6/682|journal=Healthcare|language=en|volume=9|issue=6|pages=682|doi=10.3390/healthcare9060682|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Linda van Campen|author-link2=Frans Visser|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> However there were several ICF patients that also had a reduction in peak workload and workload at the ventilatory threshold, despite the overall trend for an increase for ICF patients and a decrease for ME/CFS patients.

Unpublished studies have reported negative results for the repeated CPET procedure. In her thesis, Tessa-Maree Nielsen<ref>Nielsen TM. [https://mro.massey.ac.nz/bitstream/handle/10179/14653/02_whole.pdf?sequence=2&isAllowed=y The Timeline of Post Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. 2018.]</ref> at the Massey University, [[New Zealand]], performed the second exercise test 48 hours and 72 hours later, instead of the usual 24 hours. The study did not find significant reductions of workload at the ventilatory threshold in ME/CFS patients compared to controls. The eight ME/CFS patients in the 72 hours group had a workload at ventilatory threshold that was slightly higher instead of lower than during the first test. In a 2018 presentation,<ref>[https://www.youtube.com/watch?v=xpyz9K62Izg Presentation Ruud Vermeulen (03-06-2018). Minute 34.00.]</ref> Ruud Vermeulen reported to have data on approximately 500 ME/CFS patients who performed the repeated CPET procedure. He stated the test on the second day did not show any difference in VO2max compared to the first day, as shown in the graphs he presented.

Two-Day CPET studies have also considered other clinical groups, including [[Gulf War Illness|Gulf-War-Syndrome]]<ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Alexander|first2=Thomas|last3=Qian|first3=Wei|last4=Klein‐Adams|first4=Jacquelyn C.|last5=Lange|first5=Gudrun|last6=H. Natelson|first6=Benjamin|last7=Cook|first7=Dane B.|last8=Hill|first8=Helene Z.|last9=Falvo|first9=Michael J.|date=Sep 2020|title=An analysis of 2‐day cardiopulmonary exercise testing to assess unexplained fatigue|url=https://onlinelibrary.wiley.com/doi/abs/10.14814/phy2.14564|journal=Physiological Reports|language=en|volume=8|issue=17|doi=10.14814/phy2.14564|issn=2051-817Xpmc = 7507580|pmid=32889791|pages=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> and Sarcoidosis.<ref>{{Cite journal|last=Braam|first=A.W.E.|last2=de Haan|first2=S.N.|last3=Vorselaars|first3=A.D.M.|last4=Rijkers|first4=G.T.|last5=Grutters|first5=J.C.|last6=van den Elshout|first6=F.J.J.|last7=Korenromp|first7=I.H.E.|date=Oct 2013|title=Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis|url=https://linkinghub.elsevier.com/retrieve/pii/S0889159113001967|journal=Brain, Behavior, and Immunity|language=en|volume=33|pages=57–64|doi=10.1016/j.bbi.2013.05.006|issue=|pmc=|pmid=|quote=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> The study of Gulf-War-Syndrome patients did not reveal any significant group by time effects and in particular, no time effects at VT1. The study of Sarcoidosis patients did not find any group by time effects, however they focused on peak performance and ignored differences in performance at sub-maximal thresholds such as VT1. In addition, the study of Sarcoidosis patients did find an exercise effect on several biomarkers, however changes in these markers were not related to self-reported fatigue.

== Use as a Biomarker ==
[[Christopher Snell|Snell]] et al. suggested 2-day CPET could be used "diagnostically as an objective indicator of an abnormal postexertion response and possibly even a [[Diagnostic biomarker|biomarker]] for the condition."<ref name=":0" /> Using the data from the two exercise tests, their research team was able to correctly classify 95% of the total sample, as a patient or healthy control.

== Criticism ==
While a unique reduction in physiological capacity was observed in ME/CFS by several studies and different research groups, sample sizes were rather small and disagreement exists on which physiological measure accurately displayed ME/CFS patients’ [[Post-exertional malaise|abnormal exertional response]].<ref name=":1" />

Another objection to the 2-day CPET as a biomarker for ME/CFS was raised by Snell et al themselves. They suggested it might be unethical<ref name=":0" /> to use this method to detect ME/CFS patients since many of these patients might suffer relapse as a result of exercise testing. In their 2010 study, 60% of ME/CFS patients reported that it took them more than 5 days to recover from a single (maximal) CPET. It is therefore possible that in some ME/CFS patients a 2-day CPET might cause a long-lasting relapse. Science-reporter and ME/CFS patient [[Simon McGrath]] for example wrote: “You couldn’t pay me enough money to take even one max test. My last relapse, which took me nearly 2 years to get over, happened after way less than maximal [[exertion]] – a 2-day test is not for everyone."<ref>{{Cite news|url=https://www.healthrising.org/blog/2014/05/20/declining-production-exercise-study-reveal-broad-decline-energy-output-chronic-fatigue-syndrome/|title=Declining Production: Exercise Study Reveals Broad Declines in Energy Output in Chronic Fatigue Syndrome - Health Rising|date=2014-05-20|work=Health Rising|access-date=2018-08-17|language=en-US}}</ref>

Others have noted that the CPET-procedure is not very practical. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, it may not be available to most clinicians.<ref>https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf</ref> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref>{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref> For these reasons PEM is commonly assessed using self-reporting questionnaires.

[[Brian Vastag]] was able to prove his PEM was a severe symptom causing disability with CPET, winning his long term disability (LTD) claim.<ref name=":02">{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|url-status=|access-date=2019-02-02}}</ref>

==Cost and availability==
*[[Workwell Foundation]] (United States, CA)
*[[Betsy Keller]] at Ithaca College (United States, NY) Cost is $2200. Because they are based in a college setting (not healthcare setting), they cannot process insurance (including Medicare or Medicaid), so the patient would need to work directly with their insurer about reimbursement. (private email)
*[[Laura Black]] at Hunter-Hopkins Center, Charlotte, NC
*[[Open Medicine Institute]] Clinic
*[http://physiologic.com.au/ Physiologic 334 Scottsdale Drive, Robina, Gold Coast, Australia]
*[https://www.s4me.info/threads/uk-locations-that-offer-cpet-vo2max-testing.4999/ Many UK universities] offer standard CPETs which can be adapted for patients with ME.

==Talks and interviews==
*2013, [https://www.youtube.com/watch?v=fHulHdMPAd4 CPET Presentation by Dr. Christopher Snell, Part I][https://www.youtube.com/watch?v=piUDax7I-Ek CPET Presentation by Dr. Christopher Snell, Part II]
*2014, [https://www.youtube.com/watch?v=q_cnva7zyKM&feature=youtu.be Mark VanNess 'Exercise and ME/CFS' at Bristol Watershed. Part One]

==See also==

*[[Betsy Keller]]
*[[Christopher Snell]]
*[[Exercise]]
*[[Mark VanNess]]
*[[Post-exertional malaise]]
*[[Staci Stevens]]
==Learn more==

*[http://www.workwellfoundation.org/testing-for-disability/ The Workwell Foundation: Testing for Disability]
*2007, [http://www.name-us.org/MECFSExplainPages/2007CiccolellaLegalStressTest.pdf Legal and Scientific Considerations of the Exercise Stress Test]
*2013, [http://www.cortjohnson.org/blog/2013/07/30/busted-exercise-study-finds-energy-production-system-is-broken-in-chronic-fatigue-syndrome/ Busted! Exercise Study Finds Energy Production System is Broken in Chronic Fatigue Syndrome]
*2013, [http://phoenixrising.me/archives/17902/ Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity]
*2018, [https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/ Victory For ME Disability Claim – U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability]<ref name=":02" />
*2019, [https://www.healthrising.org/blog/2019/01/17/decoding-2-day-cpet-chronic-fatigue-syndrome/ Decoding the 2-day Cardiopulmonary Exercise Test (CPET) in Chronic Fatigue Syndrome (ME/CFS)] by C. Christian

==References==
{{reflist}}
[[Category:Medical tests]]
[[Category:Cardiology]]

Two-day cardiopulmonary exercise test

2021-06-11T23:26:45Z

Kmdenmark:CS1 error-date

'''Two-day cardiopulmonary exercise test or 2-day CPET''' is a procedure which assesses exercise capacity and recovery by performing two exercise tests 24 hours apart.<ref name=":2">{{Cite journal|last=Stevens|first=Staci|last2=Snell|first2=Chris|last3=Stevens|first3=Jared|last4=Keller|first4=Betsy|last5=VanNess|first5=J. Mark|date=2018|title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/30234078|journal=Frontiers in Pediatrics|volume=6|pages=242|doi=10.3389/fped.2018.00242|issn=2296-2360|pmc=6131594|pmid=30234078}}</ref> The hypothesis is that ME/CFS patients display a characteristic deterioration in exercise capacity on the second test, a finding that has been reported by multiple research groups.<ref name=":1" /><ref name=":3" /><ref name=":0" />[[File:CPET.jpg|alt=Photo of a woman walking on a treadmill while wearing a clear mask over her nose and mouth, and attached to a cart holding medical equipment.|thumb|350x350px|Cardiopulmonary Exercise Test]]The maximal, symptom-limited cardiopulmonary exercise test (CPET) is considered the gold standard for measuring physical capacity.<ref>{{Cite journal|last=Chandra|first=Divay|author-link=|last2=Wise|first2=Robert A.|author-link2=|last3=Kulkarni|first3=Hrishikesh S.|author-link3=|last4=Benzo|first4=Roberto P.|author-link4=|last5=Criner|first5=Gerard|author-link5=|last6=Make|first6=Barry|author-link6=|last7=Slivka|first7=William A.|last8=Ries|first8=Andrew L.|last9=Reilly|first9=John J.|date=Dec 2012|title=Optimizing the 6-Min Walk Test as a Measure of Exercise Capacity in COPD|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515028/|journal=Chest|volume=142|issue=6|pages=1545–1552|doi=10.1378/chest.11-2702|issn=0012-3692|pmc=3515028|pmid=23364913|quote=|via=}}</ref><ref>{{Cite journal|last=Demir|first=Rengin|author-link=|last2=Küçükoğlu|first2=Mehmet Serdar|author-link2=|author-link3=|author-link4=|author-link5=|author-link6=|date=Dec 2010|title=Evaluation of exercise capacity in pulmonary arterial hypertension|url=https://www.ncbi.nlm.nih.gov/m/pubmed/21248462/|journal=Turk Kardiyoloji Dernegi Arsivi: Turk Kardiyoloji Derneginin Yayin Organidir|volume=38|issue=8|pages=580–588|issn=1016-5169|pmid=21248462|quote=|via=}}</ref> This test measures gas exchange parameters using a mouthpiece or mask, while participants exercise on a treadmill or stationary bicycle with a controlled increase in resistance or power output. It is commonly used to measure the fitness level of athletes, as well as patients with cardiopulmonary disease.<ref>{{Cite journal|last=Albouaini|first=Khaled|last2=Egred|first2=Mohaned|last3=Alahmar|first3=Albert|last4=Wright|first4=David Justin|date=Nov 2007|title=Cardiopulmonary exercise testing and its application|url=https://www.ncbi.nlm.nih.gov/pubmed/17989266|journal=Postgraduate Medical Journal|volume=83|issue=985|pages=675–682|doi=10.1136/hrt.2007.121558|issn=1469-0756|pmc=2734442|pmid=17989266}}</ref> In these populations, CPET measures are highly reliable and reproducible.<ref name=":2" /> Exercise physiologists however have noted that ME/CFS patients are unable to reproduce these measurements on consecutive days, despite meeting criteria for maximal effort.<ref name=":4" /> According to a 2015 report by The National Academy of Medicine, “ME/CFS patients have significantly lower results on CPET 2 than on CPET 1 on one or more of the following parameters: VO2max, VO2 at ventilatory threshold and maximal workload or workload at ventilatory threshold.”<ref name=":5">{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK274235/|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|last=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations|last3=Institute of Medicine|date=2015|publisher=National Academies Press (US)|isbn=9780309316897|series=The National Academies Collection: Reports funded by National Institutes of Health|location=Washington (DC)|pmid=25695122}}</ref>

Specifically, VO2Max is the true maximal oxygen consumption of a participant, VO2Peak is the recorded maximal oxygen consumption of a participant and VO2 at ventilatory threshold is the oxygen consumption at the first key threshold (VT or VT1), otherwise known as the gas exchange threshold (GET). This threshold is the point at which carbon dioxide output (VCO2) and oxygen consumption no longer increase linearly, which occurs at 40-75% of VO2Max, depending on the fitness and health of the participants. The VT1 is commonly determined using the V-slope method, which notes the point of non linearity when VO2 is plotted against VCO2. The VT1 can also be indicated using the ventilatory equivalent method, plotting VE/VO2 and VE/VCO2 on the same graph and noting the point where VE/VO2 increases significantly, while VE/VCO2 remains flat (where VE is minute ventilation, which is the total amount of gas inhaled or exhaled from the lungs per minute). While the VT1 is primarily determined by peripheral metabolic factors, it is not synonymous with the lactate threshold which is the point at which lactate starts to accumulate significantly in the blood. The lactate threshold is not only dependent on lactate/pyruvate equilibrium inside the muscle cells, but the kinetics of lactate transport into and out of cells. Nor is VT1 synonymous with the onset of acidosis which is additionally affected by pH buffering within the cell and the circulatory system. It is also important to point out that this gas exchange threshold is not caused by shortness of breath, nor hyperventilation, since neither hypocapnia nor hypercapnia occur at this threshold. There is however, a second ventilatory threshold (VT2) otherwise known as the respiratory compensation point (RCP), and typically occurs at 85-90% of VO2Max. This respiratory compensation occurs when a significant reduction in blood or cerebrospinal fluid pH activates chemoreceptors, which stimulate the respiratory centre of the brain, leading to compensatory hyperventilation to help restore the pH balance.

According to researchers in the field, the abnormal results of ME/CFS patients on the 2-day CPET reflect post-exertional malaise (PEM), a marked symptom exacerbation after exercise thought to be characteristic of this condition.<ref name=":1" /> The 2015 report by National Academy of medicine indicated that the 2-day CPET protocol can be used as an objective indicator that physical exertion decreases subsequent function in patients with ME/CFS, for example in obtaining social security disability.<ref name=":5" /> The 2-day CPET protocol however is not required in making the diagnosis of ME/CFS. Some have expressed concern that exercise tests may significantly worsen the condition of ME/CFS patients.<ref name=":5" /><ref>{{Cite journal|last=Nijs|first=J.|last2=Van Oosterwijck|first2=J.|last3=Meeus|first3=M.|last4=Lambrecht|first4=L.|last5=Metzger|first5=K.|last6=Frémont|first6=M.|last7=Paul|first7=L.|date=Apr 2010|title=Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta|url=https://www.ncbi.nlm.nih.gov/pubmed/20433584|journal=Journal of Internal Medicine|volume=267|issue=4|pages=418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=1365-2796|pmid=20433584}}</ref><ref>{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref name=":0" />

==Evidence==
[[Mark VanNess]], [[Christopher Snell]] and [[Staci Stevens]] of the University of the Pacific, Stockton, CA, were the first to study the two-day CPET procedure in patients with ME/CFS. In a 2007 study published in the [[Journal of Chronic Fatigue Syndrome]], they compared six ME/CFS patients with six controls. At the first CPET there were no major differences between the two groups. At the second CPET however, ME/CFS patients reached significantly lower peak [[oxygen]] consumption (VO2Peak) and oxygen consumption at aerobic threshold.<ref name=":4">{{Cite journal|last=Vanness|first=J. Mark|last2=Snell|first2=Christopher R.|last3=Stevens|first3=Staci R.|date=Jan 2007|title=Diminished Cardiopulmonary Capacity During Post-Exertional Malaise|url=https://www.tandfonline.com/doi/abs/10.1300/J092v14n02_07|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=14|issue=2|pages=77–85|doi=10.1300/j092v14n02_07|issn=1057-3321}}</ref>

In 2010, a Dutch research group including Ruud Vermeulen and [[Frans Visser]] used the 2-day CPET in a study with 15 female ME/CFS and 15 healthy controls. Patients reached the aerobic threshold and the maximal exercise at much lower oxygen consumption than controls, an effect that was magnified during the second-day exercise test. Since levels of creatine kinase in the blood and oxidative phosphorylation in mononuclear cells were normal in patients before and after exercise, Vermeulen et al. speculated that the lowered anaerobic threshold was not so much a result of [[mitochondrion|mitochondrial]] insufficiency, but of impaired oxygen transport to the [[Muscle|muscles]].<ref>{{Cite journal|last=Vermeulen|first=Ruud C. W.|last2=Kurk|first2=Ruud M.|last3=Visser|first3=Frans C.|last4=Sluiter|first4=Wim|last5=Scholte|first5=Hans R.|date=2010-10-11|title=Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity|url=https://www.ncbi.nlm.nih.gov/pubmed/20937116|journal=Journal of Translational Medicine|volume=8|pages=93|doi=10.1186/1479-5876-8-93|issn=1479-5876|pmc=2964609|pmid=20937116}}</ref>

In 2013, [[Christopher Snell|Snell]], [[Staci Stevens|Stevens]] and [[Mark VanNess|VanNess]] tested the 2-day CPET procedure in a larger sample of 51 ME/CFS patients and 10 healthy controls. Once again, there were no sufficient differences between the groups at the first CPET. During the exercise test on the second day however, ME/CFS patients showed much lower oxygen consumption and workload at peak exercise and at aerobic threshold. Group differences were not due to lack of effort since most participants attained the ventilatory threshold and achieved a respiratory exchange ratio of greater than or equal to 1.1.<ref name=":0">{{Cite journal|last=Snell|first=C. R.|last2=Stevens|first2=S. R.|last3=Davenport|first3=T. E.|last4=Van Ness|first4=J. M.|date=2013-06-27|title=Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome|url=https://academic.oup.com/ptj/article/93/11/1484/2735315|journal=Physical Therapy|language=en|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=0031-9023}}</ref>

In 2014, the research group of [[Betsy Keller]] used the 2-day CPET protocol in a study involving 22 ME/CVS patient. A decline on several physiological measures was found (see table), while the respiratory exchange ratio indicated maximum efforts by participants during both exercise tests.<ref name=":1">{{Cite journal|last=Keller|first=Betsy A.|last2=Pryor|first2=John Luke|last3=Giloteaux|first3=Ludovic|date=2014-04-23|title=Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref>

This group followed this research up with a study of a single pair of monozygotic twins in 2016.<ref>{{Cite journal|title=A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition|url=http://www.amjcaserep.com/abstract/index/idArt/900314|journal=American Journal of Case Reports|date=2016-10-10|issn=1941-5923|pmc = 5058431|pmid=27721367|pages=720–729|volume=17|doi=10.12659/AJCR.900314|language=en|first=Ludovic|last=Giloteaux|first2=Maureen R.|last2=Hanson|first3=Betsy A.|last3=Keller}}</ref>
{| class="wikitable"
! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS (bold indicates statistical significance)
|-
|
|Number of ME/CFS patients
|VO2 peak
|VO2 at VT
|Workload peak
|Workload at VT
|HR peak
|O2pulse at VT
|-
|VanNess et al. 2007.
|6
|'''-22%'''
|'''-26%'''
|?
|?
|?
|?
|-
|Vermeulen et al. 2010.
|15
|'''-6.3%'''
|'''-7.0%'''
|'''-5.3%'''
|'''-7.0%'''
|<nowiki>-1.9%</nowiki>
|'''-8.8%'''
|-
|Snell et al. 2013.
|51
| -5%
|'''-10.8%'''
|'''-7.2%'''
|'''-55.2%'''
|?
|?
|-
|Keller et al. 2014.
|22
|'''-13.8%'''
|'''-15.8%'''
|'''-12.5%'''
|'''-21.3%'''
|'''-5.9%'''
|'''-12.6%'''
|-
|Giloteaux et al. 2016.
|1 (monozygotic twin)
|0%
| -13.4%
|0%
| -25%
| +7.4%
| -19% (calculated)
|-
|Hodges et al. 2017.
|10
|<nowiki>+5.3%</nowiki>
|<nowiki>+6.1%</nowiki>
|<nowiki>-6.7%</nowiki>
|'''-11.4%'''
|<nowiki>-0.6%</nowiki>
| +7% (calculated)
|-
|Nelson et al. 2019.
|16
| +0.4%
| -3.1%
| -1.2%
|'''-17.4%'''
| -0.5%
| +2% (calculated)
|-
|Lien et al. 2019. (numerical estimates)

|18
| -5%
| -6%
| -2%
|'''-7%'''
| +1.5%
|?
|-
|van Campen 2020.A (males)
|25
|'''-10%'''
|'''-22%'''
|'''-10%'''
|'''-30%'''
|'''-5%'''
| -16% (calculated)
|-
|van Campen 2020.B (females)
|31 ("mild" cases)
|'''-6%'''
|'''-21%'''
|'''-10%'''
|'''-26%'''
| -3%
|?
|-
|van Campen 2020.B (females)
|31 ("moderate" cases)
|'''-11%'''
|'''-21%'''
|'''-16%'''
|'''-31%'''
| -6%
|?
|-
|van Campen 2020.B (females)
|20 ("severe" cases)
|'''-12%'''
|'''-19%'''
|'''-19%'''
|'''-33%'''
| -7%
|?
|-
|Davenport 2020.
|51
| -5%
| -10%
| -9%
|'''-11%'''
| -3%
| -7% (calculated)
|-
|van Campen 2021. (males)
|25
|'''-12%'''
|'''-27%'''
|'''-10%'''
|'''-27%'''
| -7%
| -17% (calculated)
|-
|van Campen 2021. (females)
|50
|'''-10%'''
|'''-23%'''
|'''-11%'''
|'''-30%'''
| -4%
| -15% (calculated)
|}
In 2017, a research team form [[New Zealand]] compared the physiological responses during a 2-day CPET, in ten patients with ME/CFS, seven patients with [[Multiple sclerosis|Multiple Sclerosis]] (MS) and seventeen healthy controls. Curiously peak oxygen increased at the second exercise test in ME/CFS patients, but there was a significant reduction noticeable in workload at aerobic threshold, a decline that was not seen in MS-patients or healthy controls. According to the authors: <blockquote>“differences between MS and CFS/ME responses only became evident after a second maximal exercise test, thus suggesting that a repeated protocol is required to not only distinguish CFS/ME from HC, but also from other fatigue-related conditions, who may not suffer from post-exertional malaise and have a differing delayed fatigue profile.”<ref name=":3">{{Cite journal|last=Hodges|first=L. D.|last2=Nielsen|first2=T.|last3=Baken|first3=D.|date=Jul 2018|title=Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4|pages=639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref></blockquote>In 2019 the 2-day CPET procedure was tested by an Australian research team of Nelson and colleagues. They found a significant larger reduction in workload at the ventilatory threshold in patients with ME/CFS compared to healthy controls. A percentage change of −6.3% to −9.8% provided good sensitivity and specificity, indicating this test has the potential to become a biomarker for ME/CFS. However, the sample size of this study was small (16 ME/CFS patients), the control group consisted only of healthy persons (instead of patients with other chronic illnesses) and no significant difference was found in VO2 at the ventilatory threshold.<ref>{{Cite journal|last=Nelson|first=Maximillian J.|last2=Buckley|first2=Jonathan D.|last3=Thomson|first3=Rebecca L.|last4=Clark|first4=Daniel|last5=Kwiatek|first5=Richard|last6=Davison|first6=Kade|date=2019-03-14|title=Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://doi.org/10.1186/s12967-019-1836-0|journal=Journal of Translational Medicine|volume=17|issue=1|pages=80|doi=10.1186/s12967-019-1836-0|issn=1479-5876|pmc = 6417168|pmid=30871578}}</ref>

A Norwegian study published in 2019 also reported a significant larger reduction in workload at the ventilatory threshold in 18 patients with ME/CFS compared to healthy controls, although this was not the case for peak values or VO2 measurement at the ventilatory threshold. The authors also measured arterial lactate concentrations, every 30 seconds during the exercise tests. Lactate was higher per power output per kg in patients than controls and the differences increased significantly at the second exercise test. In the healthy controls lactate concentration at the ventilatory threshold decreased while this was not the case in ME/CFS patients, suggesting a problem in lactate clearance ability.<ref>{{Cite journal|last=Lien|first=Katarina|last2=Johansen|first2=Bjørn|last3=Veierød|first3=Marit B.|last4=Haslestad|first4=Annicke S.|last5=Bøhn|first5=Siv K.|last6=Melsom|first6=Morten N.|last7=Kardel|first7=Kristin R.|last8=Iversen|first8=Per O.|date=2019|title=Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://physoc.onlinelibrary.wiley.com/doi/abs/10.14814/phy2.14138|journal=Physiological Reports|language=en|volume=7|issue=11|pages=e14138|doi=10.14814/phy2.14138|issn=2051-817X}}</ref>

Researchers from the Workwell Foundation published in 2019, a case series of six women, who underwent the 2-day CPET. This study compared two healthy participants, one active, the other sedentary, two ME/CFS patients, one high functioning with high VO2peak, another with low VO2Peak, with a patient suffering from [[HIV/AIDS|human immunodeficiency virus]] (HIV) and another suffering from [[Multiple sclerosis|MS]].<ref>{{Cite journal|last=Larson|first=Benjamin|last2=Davenport|first2=Todd E.|last3=Stevens|first3=Staci R.|last4=Stevens|first4=Jared|last5=Van Ness|first5=J. Mark|last6=Snell|first6=Christopher R.|date=Oct 2019|title=Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With Fatiguing Health Conditions: A Case Series|url=http://insights.ovid.com/crossref?an=01823246-201910000-00004|journal=Cardiopulmonary Physical Therapy Journal|language=en|volume=30|issue=4|pages=145–152|doi=10.1097/CPT.0000000000000100|issn=1541-7891|pmc=|pmid=|quote=|last7=|first7=|last8=|first8=|author-link=|author-link2=Todd Davenport|access-date=|author-link3=Staci Stevens|author-link4=|author-link5=Mark VanNess|author-link6=Christopher Snell|via=}}</ref> The healthy participants and the MS patient reproduced or improved their exercise parameters, namely VO2, workload, heart-rate and minute ventilation at both the ventilatory threshold and peak exercise. The HIV patient reproduced all of these findings except peak workload and peak minute ventilation. The ME/CFS patients were unable to reproduce VO2, workload, heart rate or minute ventilation at the ventilatory threshold. These results continue to suggest that the inability to reproduce workload at the ventilatory threshold is specific to ME/CFS patients, but patients with other fatiguing conditions will need to be tested to confirm this. This study was followed up in 2020 with 51 patients and 10 controls, focusing on additional statistical analysis and discussing the meaning of test-retest reliability in the context of ME/CFS. The main positive finding was a significant group*test (difference) in work rate at the ventilatory threshold. <ref>{{Cite journal|last=Davenport|first=Todd E.|last2=Stevens|first2=Staci R.|last3=Stevens|first3=M. A. Jared|last4=Snell|first4=Christopher R.|last5=Van Ness|first5=J. Mark|date=2020-06-16|title=Properties of measurements obtained during cardiopulmonary exercise testing in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-203170|journal=Work|pages=1–10|doi=10.3233/WOR-203170}}</ref>

In 2020, researchers from Stichting Cardio Zorg, a cardiology clinic in the Netherlands published two studies of clinical 2-day CPET results for ME/CFS patients with exercise intolerance. The first study consisted of male patients, to see whether the results from previous studies which had predominantly female patients would be replicated.<ref>{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Rowe|first2=Peter C.|last3=Visser|first3=Frans C.|date=2020|title=Validity of 2-Day Cardiopulmonary Exercise Testing in Male Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.scirp.org/journal/doi.aspx?doi=10.4236/ape.2020.101007|journal=Advances in Physical Education|volume=10|issue=01|pages=68–80|doi=10.4236/ape.2020.101007|issn=2164-0386}}</ref> A second study focused on female patients with differing severity, which were subgrouped according to: “Symptom severity impact must result in a 50% or greater reduction in a patient’s premorbid activity level for a diagnosis of ME. Mild: approximately 50% reduction in activity, moderate: mostly housebound, severe: mostly bedbound and very severe: bedbound and dependent on help for physical functions”.<ref>{{Cite journal|last=van Campen|first=C (Linda) MC|last2=Rowe|first2=Peter C.|last3=Visser|first3=Frans C.|date=2020-06-30|title=Two-Day Cardiopulmonary Exercise Testing in Females with a Severe Grade of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison with Patients with Mild and Moderate Disease|url=https://www.mdpi.com/2227-9032/8/3/192|journal=Healthcare|language=en|volume=8|issue=3|pages=192|doi=10.3390/healthcare8030192|issn=2227-9032}}</ref> This research was followed up in 2021 with a retrospective clinical comparison between 26 male idiopathic chronic fatigue (ICF) cases who did not suffer from PEM and 25 male ME/CFS patients who satisfied the 2011 ME International Consensus Criteria and the 1994 Center for Disease Control criteria for CFS. <ref name=":6">{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Visser|first2=Frans C.|date=Jun 2021|title=Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol|url=https://www.mdpi.com/2227-9032/9/6/683|journal=Healthcare|language=en|volume=9|issue=6|pages=683|doi=10.3390/healthcare9060683|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Linda van Campen|author-link2=Frans Visser|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> Notably, most ME/CFS patients had a decline in VO2 and workload performance at peak and the ventilatory threshold on the second day, compared to all idiopathic chronic fatigue cases who were able to match or exceed their first day performance. The authors concluded that this decline in performance on the second day was disease-specific.<ref name=":6" /> A related comparison was performed for female patients with similar results.<ref>{{Cite journal|last=van Campen|first=C. (Linda) M. C.|last2=Visser|first2=Frans C.|date=2021/6|title=Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol|url=https://www.mdpi.com/2227-9032/9/6/682|journal=Healthcare|language=en|volume=9|issue=6|pages=682|doi=10.3390/healthcare9060682}}</ref> However there were several ICF patients that also had a reduction in peak workload and workload at the ventilatory threshold, despite the overall trend for an increase for ICF patients and a decrease for ME/CFS patients.

Unpublished studies have reported negative results for the repeated CPET procedure. In her thesis, Tessa-Maree Nielsen<ref>Nielsen TM. [https://mro.massey.ac.nz/bitstream/handle/10179/14653/02_whole.pdf?sequence=2&isAllowed=y The Timeline of Post Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. 2018.]</ref> at the Massey University, [[New Zealand]], performed the second exercise test 48 hours and 72 hours later, instead of the usual 24 hours. The study did not find significant reductions of workload at the ventilatory threshold in ME/CFS patients compared to controls. The eight ME/CFS patients in the 72 hours group had a workload at ventilatory threshold that was slightly higher instead of lower than during the first test. In a 2018 presentation,<ref>[https://www.youtube.com/watch?v=xpyz9K62Izg Presentation Ruud Vermeulen (03-06-2018). Minute 34.00.]</ref> Ruud Vermeulen reported to have data on approximately 500 ME/CFS patients who performed the repeated CPET procedure. He stated the test on the second day did not show any difference in VO2max compared to the first day, as shown in the graphs he presented.

Two-Day CPET studies have also considered other clinical groups, including [[Gulf War Illness|Gulf-War-Syndrome]]<ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Alexander|first2=Thomas|last3=Qian|first3=Wei|last4=Klein‐Adams|first4=Jacquelyn C.|last5=Lange|first5=Gudrun|last6=H. Natelson|first6=Benjamin|last7=Cook|first7=Dane B.|last8=Hill|first8=Helene Z.|last9=Falvo|first9=Michael J.|date=Sep 2020|title=An analysis of 2‐day cardiopulmonary exercise testing to assess unexplained fatigue|url=https://onlinelibrary.wiley.com/doi/abs/10.14814/phy2.14564|journal=Physiological Reports|language=en|volume=8|issue=17|doi=10.14814/phy2.14564|issn=2051-817Xpmc = 7507580|pmid=32889791|pages=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> and Sarcoidosis.<ref>{{Cite journal|last=Braam|first=A.W.E.|last2=de Haan|first2=S.N.|last3=Vorselaars|first3=A.D.M.|last4=Rijkers|first4=G.T.|last5=Grutters|first5=J.C.|last6=van den Elshout|first6=F.J.J.|last7=Korenromp|first7=I.H.E.|date=Oct 2013|title=Influence of repeated maximal exercise testing on biomarkers and fatigue in sarcoidosis|url=https://linkinghub.elsevier.com/retrieve/pii/S0889159113001967|journal=Brain, Behavior, and Immunity|language=en|volume=33|pages=57–64|doi=10.1016/j.bbi.2013.05.006|issue=|pmc=|pmid=|quote=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref> The study of Gulf-War-Syndrome patients did not reveal any significant group by time effects and in particular, no time effects at VT1. The study of Sarcoidosis patients did not find any group by time effects, however they focused on peak performance and ignored differences in performance at sub-maximal thresholds such as VT1. In addition, the study of Sarcoidosis patients did find an exercise effect on several biomarkers, however changes in these markers were not related to self-reported fatigue.

== Use as a Biomarker ==
[[Christopher Snell|Snell]] et al. suggested 2-day CPET could be used "diagnostically as an objective indicator of an abnormal postexertion response and possibly even a [[Diagnostic biomarker|biomarker]] for the condition."<ref name=":0" /> Using the data from the two exercise tests, their research team was able to correctly classify 95% of the total sample, as a patient or healthy control.

== Criticism ==
While a unique reduction in physiological capacity was observed in ME/CFS by several studies and different research groups, sample sizes were rather small and disagreement exists on which physiological measure accurately displayed ME/CFS patients’ [[Post-exertional malaise|abnormal exertional response]].<ref name=":1" />

Another objection to the 2-day CPET as a biomarker for ME/CFS was raised by Snell et al themselves. They suggested it might be unethical<ref name=":0" /> to use this method to detect ME/CFS patients since many of these patients might suffer relapse as a result of exercise testing. In their 2010 study, 60% of ME/CFS patients reported that it took them more than 5 days to recover from a single (maximal) CPET. It is therefore possible that in some ME/CFS patients a 2-day CPET might cause a long-lasting relapse. Science-reporter and ME/CFS patient [[Simon McGrath]] for example wrote: “You couldn’t pay me enough money to take even one max test. My last relapse, which took me nearly 2 years to get over, happened after way less than maximal [[exertion]] – a 2-day test is not for everyone."<ref>{{Cite news|url=https://www.healthrising.org/blog/2014/05/20/declining-production-exercise-study-reveal-broad-decline-energy-output-chronic-fatigue-syndrome/|title=Declining Production: Exercise Study Reveals Broad Declines in Energy Output in Chronic Fatigue Syndrome - Health Rising|date=2014-05-20|work=Health Rising|access-date=2018-08-17|language=en-US}}</ref>

Others have noted that the CPET-procedure is not very practical. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, it may not be available to most clinicians.<ref>https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf</ref> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref>{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref> For these reasons PEM is commonly assessed using self-reporting questionnaires.

[[Brian Vastag]] was able to prove his PEM was a severe symptom causing disability with CPET, winning his long term disability (LTD) claim.<ref name=":02">{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|url-status=|access-date=2019-02-02}}</ref>

==Cost and availability==
*[[Workwell Foundation]] (United States, CA)
*[[Betsy Keller]] at Ithaca College (United States, NY) Cost is $2200. Because they are based in a college setting (not healthcare setting), they cannot process insurance (including Medicare or Medicaid), so the patient would need to work directly with their insurer about reimbursement. (private email)
*[[Laura Black]] at Hunter-Hopkins Center, Charlotte, NC
*[[Open Medicine Institute]] Clinic
*[http://physiologic.com.au/ Physiologic 334 Scottsdale Drive, Robina, Gold Coast, Australia]
*[https://www.s4me.info/threads/uk-locations-that-offer-cpet-vo2max-testing.4999/ Many UK universities] offer standard CPETs which can be adapted for patients with ME.

==Talks and interviews==
*2013, [https://www.youtube.com/watch?v=fHulHdMPAd4 CPET Presentation by Dr. Christopher Snell, Part I][https://www.youtube.com/watch?v=piUDax7I-Ek CPET Presentation by Dr. Christopher Snell, Part II]
*2014, [https://www.youtube.com/watch?v=q_cnva7zyKM&feature=youtu.be Mark VanNess 'Exercise and ME/CFS' at Bristol Watershed. Part One]

==See also==

*[[Betsy Keller]]
*[[Christopher Snell]]
*[[Exercise]]
*[[Mark VanNess]]
*[[Post-exertional malaise]]
*[[Staci Stevens]]
==Learn more==

*[http://www.workwellfoundation.org/testing-for-disability/ The Workwell Foundation: Testing for Disability]
*2007, [http://www.name-us.org/MECFSExplainPages/2007CiccolellaLegalStressTest.pdf Legal and Scientific Considerations of the Exercise Stress Test]
*2013, [http://www.cortjohnson.org/blog/2013/07/30/busted-exercise-study-finds-energy-production-system-is-broken-in-chronic-fatigue-syndrome/ Busted! Exercise Study Finds Energy Production System is Broken in Chronic Fatigue Syndrome]
*2013, [http://phoenixrising.me/archives/17902/ Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity]
*2018, [https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/ Victory For ME Disability Claim – U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability]<ref name=":02" />
*2019, [https://www.healthrising.org/blog/2019/01/17/decoding-2-day-cpet-chronic-fatigue-syndrome/ Decoding the 2-day Cardiopulmonary Exercise Test (CPET) in Chronic Fatigue Syndrome (ME/CFS)] by C. Christian

==References==
{{reflist}}
[[Category:Medical tests]]
[[Category:Cardiology]]

Mental health

2021-06-11T17:09:21Z

Kmdenmark:CS1 error- dates; punctuation

'''Mental health''' is a broad term that can refer to cognitive, behavioral, emotional, psychological, and/or social well-being.<ref>{{Cite web|url=http://www.mentalhealth.gov/basics/what-is-mental-health|title=What Is Mental Health?|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=August 29, 2017|website=www.mentalhealth.gov|publisher=U.S. Department of Health & Human Services|archive-url=|archive-date=|url-status=|access-date=2019-02-18}}</ref><ref>{{Cite web|url=https://www.psychiatry.org/patients-families/what-is-mental-illness|title=What Is Mental Illness?|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=August 2018|website=www.psychiatry.org|publisher=American Psychiatric Association|archive-url=|archive-date=|url-status=|access-date=2019-02-18}}</ref><ref>{{Cite web|url=https://www.who.int/features/factfiles/mental_health/en/|title=Mental health: a state of well-being|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=WHO|archive-url=|archive-date=|url-status=|access-date=2019-02-18}}</ref> Mental illness refers to a psychiatric illness, for example [[depression]], [[anxiety]] or [[Anorexia and eating disorders|anorexia nervosa]].

== ME/CFS ==
Brown et al (2010) found that patients with [[chronic fatigue syndrome]] who had both a mental illness before CFS and a current mental illness had greater [[pain]], great [[sleep dysfunction]], and more physical symptoms compared to patients with CFS who did not have a mental illness, or patients whose mental illness only began after they became ill with chronic fatigue syndrome.<ref name=":1">{{Cite journal|last=Brown|first=Molly M.|author-link=Molly Brown|last2=Kaplan|first2=Carly|author-link2=Carly Kaplan|last3=Jason|first3=Leonard A.|author-link3=Leonard Jason|last4=Keys|first4=Christopher B.|author-link4=Christopher Keys|author-link5=|author-link6=|date=2010|title=Subgroups of chronic fatigue syndrome based on psychiatric disorder onset and current psychiatric status|url=http://www.scirp.org/journal/doi.aspx?DOI=10.4236/health.2010.22015|journal=Health|volume=02|issue=02|pages=90–96|doi=10.4236/health.2010.22015|issn=1949-4998|quote=|via=}}</ref> Level of fatigue was not significantly associated with past or current psychiatric illness, and even chronic fatigue syndrome patients with no psychiatric history had severe disability.<ref name=":1" />

McManimen et al (2018) found that CFS patients who were both depressed and suicidal experienced significantly more stigma and dismissal from doctors and family members regarding their symptoms compared to patients who were neither depressed nor suicidal. Depression and suicidal ideation were also associated with more severe CFS symptoms and a lower quality of life.<ref name=":2" />

In a study comparing functional status and well-being of CFS patients, multiple sclerosis patients, and healthy, controls, Kingdon et al (2018) found that CFS patients scored significantly lower than both MS patients and healthy controls in nearly every category that was studied, including mental health.<ref name=":3" /> Additionally, Eaton-Fitch et al (2020) found that health-related quality of life (HRQoL) in a cohort of Australian CFS patients was significantly lower than the HRQoL of healthy controls.<ref name=":5" />

Loades et al (2017) found that adolescents with CFS and depression experienced significantly more interference with school and social adjustment than adolescent CFS patients who were not depressed; anxiety was not found to have a significant effect on any of the categories studied.<ref name=":4" />

Boulazreg and Rokach (2020) discuss the implications of loneliness and isolation caused by CFS on CFS patients and their caregivers and families. Coping mechanisms for patients, families, and caregivers to deal with loneliness and isolation are also discussed.<ref name=":6" />

==Studies==
*2006, Differential diagnosis of [[chronic fatigue syndrome]] and [[major depressive disorder]]<ref name="Hawk, 2006">{{Citation
| last1 = Hawk | first1 = C | authorlink1 =
| last2 = Jason | first2 = L | authorlink2 = Leonard Jason
| last3 = Torres-Harding | first3 = S | authorlink3 = Susan Torres-Harding
| title = Differential diagnosis of chronic fatigue syndrome and major depressive disorder
| journal = International Journal of Behavioral Medicine | volume = 13 | issue = 3 | page = 244-51
| date = 2006
| pmid = 17078775
| doi = 10.1207/s15327558ijbm1303_8
| url = http://www.healthrising.org/wp-content/uploads/2014/04/Hawk.-Jason.-Differential-Diagnosis-of-Chronic-Fatigue-Syndrome-and-Major-Depressive-Disorder.pdf
}}
</ref> - [http://www.healthrising.org/wp-content/uploads/2014/04/Hawk.-Jason.-Differential-Diagnosis-of-Chronic-Fatigue-Syndrome-and-Major-Depressive-Disorder.pdf (Full Text)]
*2008, A Systematic Review of Chronic Fatigue Syndrome: Don't Assume It's [[Depression]]<ref name="Griffith, 2008">{{Citation
| last1 = Griffith | first1 = J. P. | authorlink1 =
| last2 = Zarrouf | first2 = F. A. | authorlink2 =
| title = A Systematic Review of Chronic Fatigue Syndrome: Don’t Assume It’s Depression
| journal = Primary Care Companion to The Journal of Clinical Psychiatry | volume = 10 | issue = 2 | page = 120–128
| date = 2008
| pmid = 18458765
}}
</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292451/ (Full Text)]
*2009, A review on [[cognitive behavioral therapy]] (CBT) and [[graded exercise therapy]] (GET) in [[myalgic encephalomyelitis]] (ME) / [[chronic fatigue syndrome]] (CFS): [[Cognitive behavioral therapy|CBT]]/[[Graded exercise therapy|GET]] is not only ineffective and not evidence-based, but also potentially harmful for many patients with [[ME/CFS]]<ref name=":0">{{Cite journal|last=Twisk|first=Frank N. M.|last2=Maes|first2=Michael|date=2009|title=A review on cognitive behavioral therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS|url=https://www.ncbi.nlm.nih.gov/m/pubmed/19855350/|journal=Neuro Endocrinology Letters|volume=30|issue=3|pages=284–299|issn=0172-780X|pmid=19855350|quote=|author-link=Frank Twisk|author-link2=Michael Maes|author-link3=|author-link4=|author-link5=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/m/pubmed/19855350/ Abstract])
*2010, Subgroups of chronic fatigue syndrome based on psychiatric disorder onset and current psychiatric status<ref name=":1" /> - [https://www.scirp.org/fileOperation/downLoad.aspx?path=Health20100200003_77432052.pdf&type=journal (Full text)]
*2011, [[Anxiety]] and depression in [[CFS/ME|chronic fatigue syndrome/myalgic encephalomyelitis]] (CFS/ME): Examining the incidence of health anxiety in [[CFS/ME]]<ref name="Daniels, 2017">{{Citation
| last1 = Daniels | first1 = J | authorlink1 =
| last2 = Brigden | first2 = A | authorlink2 =
| last3 = Kacorova | first3 = A | authorlink3 =
| title = Anxiety and depression in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): Examining the incidence of health anxiety in CFS/ME
| journal = Psychol Psychother | volume = 90 | issue = 3 | page = 502-509
| date = 2017
| pmid =
| doi = 10.1111/papt.12118
}}
</ref> - [https://www.ncbi.nlm.nih.gov/pubmed/28244209 (Abstract)]
*2011, [https://pdfs.semanticscholar.org/e464/4b1ccceb7e10b0f1 Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]
*2011, Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up<ref>{{Cite journal|last=Núñez|first=Montserrat|author-link=Montqserrat Núñez|last2=Fernández-Solà|first2=Joaquim|author-link2=Joaquim Fernández-Solà|last3=Nuñez|first3=Esther|author-link3=Esther Nuñez|last4=Fernández-Huerta|first4=José-Manuel|author-link4=José-Manuel Fernández-Huerta|last5=Godás-Sieso|first5=Teresa|author-link5=Teresa Godás-Sieso|last6=Gomez-Gil|first6=Esther|author-link6=Esther Gomez-Gil|date=Mar 2011|title=Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up|url=http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.467.4965&rep=rep1&type=pdf|journal=Clinical Rheumatology|volume=30|issue=3|pages=381–389|doi=10.1007/s10067-010-1677-y|issn=1434-9949|pmid=21234629|quote=|via=}}</ref> - [http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.467.4965&rep=rep1&type=pdf (Full)]
*2016, Cognitive behavioural therapy in the treatment of chronic fatigue syndrome: A narrative review on efficacy and informed consent<ref name="keith">{{Cite journal|last=Geraghty|first=Keith J|author-link=Keith Geraghty|last2=Blease|first2=Charlotte|author-link2=Charlotte Blease|date=2016-09-15|title=Cognitive behavioural therapy in the treatment of chronic fatigue syndrome: A narrative review on efficacy and informed consent|url=https://www.researchgate.net/profile/Keith_Geraghty/publication/308181085_Cognitive_behavioural_therapy_in_the_treatment_of_chronic_fatigue_syndrome_A_narrative_review_on_efficacy_and_informed_consent/links/5a15a37e4585153b546ca7c7/Cognitive-behavioural-therapy-in-the-treatment-of-chronic-fatigue-syndrome-A-narrative-review-on-efficacy-and-informed-consent.pdf|journal=Journal of Health Psychology|volume=23|issue=1|pages=127–138|doi=10.1177/1359105316667798|issn=1359-1053|via=}}</ref> - [https://www.researchgate.net/profile/Keith_Geraghty/publication/308181085_Cognitive_behavioural_therapy_in_the_treatment_of_chronic_fatigue_syndrome_A_narrative_review_on_efficacy_and_informed_consent/links/5a15a37e4585153b546ca7c7/Cognitive-behavioural-therapy-in-the-treatment-of-chronic-fatigue-syndrome-A-narrative-review-on-efficacy-and-informed-consent.pdf (Full)]
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27513528?dopt=Abstract Group Cognitive Behaviour Therapy for Chronic Fatigue Syndrome]<ref>{{Cite journal|last=Illegems|first=Jela|last2=Moorkens|first2=Greta|last3=Van Den Eede|first3=Filip|date=2016|title=Group Cognitive Behaviour Therapy for Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/27513528?dopt=Abstract|journal=Psychotherapy and Psychosomatics|volume=85|issue=5|pages=308|doi=10.1159/000445166|issn=1423-0348|pmid=27513528}}</ref>
* 2017, [[ME/CFS|Myalgic encephalomyelitis/chronic fatigue syndrome]] patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys<ref name="GeraghtyHannKurtev2017">{{Cite journal|last1= Geraghty|first1 = Keith|authorlink1 = Keith Geraghty|last2 = Hann |first2 = Mark|authorlink2 = Mark Hann |last3 = Kurtev |first3 = Stoyan|authorlink3 = Stoyan Kurtev| title = Myalgic encephalomyelitis/chronic fatigue syndrome patients’ reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys|journal = Journal of Health Psychology |volume = |issue = |page = | date = Aug 29, 2017|pmid= |doi= 10.1177/1359105317726152|url= https://doi.org/10.1177/1359105317726152}}</ref> - [https://doi.org/10.1177/1359105317726152 (Full text)]
*2017, [https://journals.sagepub.com/doi/pdf/10.1177/1359105317707215 Cognitive Behavioural Therapy and Objective Assessments in Chronic Fatigue Syndrome]<ref>{{Cite journal|last=McPhee|first=Graham|author-link=Graham McPhee|date=2017|title=Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome|url=https://journals.sagepub.com/doi/pdf/10.1177/1359105317707215|journal=Journal of Health Psychology|volume=22|issue=9|pages=1181–1186|doi=10.1177/1359105317707215|issn=1461-7277|pmid=28805529|via=}}</ref>
*2017, The presence of co-morbid mental health problems in a cohort of adolescents with chronic fatigue syndrome<ref name=":4">{{Cite journal|last=Loades|first=Maria Elizabeth|last2=Rimes|first2=Katharine A|last3=Ali|first3=Sheila|last4=Lievesley|first4=Kate|last5=Chalder|first5=Trudie|date=Jul 2018|title=The presence of co-morbid mental health problems in a cohort of adolescents with chronic fatigue syndrome|url=http://journals.sagepub.com/doi/10.1177/1359104517736357|journal=Clinical Child Psychology and Psychiatry|language=en|volume=23|issue=3|pages=398–408|doi=10.1177/1359104517736357|issn=1359-1045|pmc=PMC6150417|pmid=29096528|quote=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
*2018, Rethinking the treatment of Chronic Fatigue Syndrome<ref>{{Cite journal|last=Wilshire|first=Carolyn E.|author-link=Carolyn Wilshire|last2=Kindlon|first2=Tom|author-link2=Tom Kindlon|last3=Courtney|first3=Robert|author-link3=Robert Courtney|last4=Matthees|first4=Alem|author-link4=Alem Matthees|last5=Tuller|first5=David|author-link5=David Tuller|last6=Geraghty|first6=Keith|author-link6=Keith Geraghty|last7=Levin|first7=Bruce|author-link7=Bruce Levin|date=2018-03-22|title=Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT|url=https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-018-0218-3|journal=BMC Psychology|language=en|volume=6|issue=1|pages=|doi=10.1186/s40359-018-0218-3|issn=2050-7283|pmc=5863477|pmid=29562932|quote=|via=}}</ref>
*2018, [https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/cognitivebehavioural-therapy-for-chronic-fatigue-syndrome-neither-efficacious-nor-safe/C8B85E1E18395A44E4535281167FD413 Cognitive–behavioural therapy for chronic fatigue syndrome: neither efficacious nor safe]<ref>{{Cite journal|last=Twisk|first=Frank|author-link=Frank Twisk|last2=Corsius|first2=Lou|date=Aug 2018|title=Cognitive–behavioural therapy for chronic fatigue syndrome: neither efficacious nor safe|url=https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/cognitivebehavioural-therapy-for-chronic-fatigue-syndrome-neither-efficacious-nor-safe/C8B85E1E18395A44E4535281167FD413|journal=The British Journal of Psychiatry|language=en|volume=213|issue=2|pages=500–501|doi=10.1192/bjp.2018.136|issn=0007-1250|via=}}</ref>
*2018, Functional status and well-being in people with myalgic encephalomyelitis/chronic fatigue syndrome compared with people with multiple sclerosis and healthy controls<ref name=":3">{{Cite journal|last=Kingdon|first=Caroline C.|last2=Bowman|first2=Erinna W.|last3=Curran|first3=Hayley|last4=Nacul|first4=Luis|last5=Lacerda|first5=Eliana M.|date=2018-12-01|title=Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=2|issue=4|pages=381–392|doi=10.1007/s41669-018-0071-6|issn=2509-4254|pmc=PMC6249197|pmid=29536371}}</ref>
*2018, Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome<ref name=":2">{{Cite journal|last=McManimen|first=Stephanie L.|last2=McClellan|first2=Damani|last3=Stoothoff|first3=Jamie|last4=Jason|first4=Leonard A.|date=2018|title=Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/jcop.21984|journal=Journal of Community Psychology|language=en|volume=46|issue=8|pages=959–971|doi=10.1002/jcop.21984|issn=1520-6629|pmc=PMC7944645|pmid=30311972}}</ref>
*2020, The lonely, isolating, and alienating impacts of myalgic encephalomyelitis/chronic fatigue syndrome<ref name=":6">{{Cite journal|last=Boulazreg|first=Samir|last2=Rokach|first2=Ami|date=2020-10-20|title=The Lonely, Isolating, and Alienating Implications of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.mdpi.com/2227-9032/8/4/413|journal=Healthcare|language=en|volume=8|issue=4|pages=413|doi=10.3390/healthcare8040413|issn=2227-9032|pmc=PMC7711762|pmid=33092097}}</ref>
*2020, Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome<ref name=":5">{{Cite journal|last=Eaton-Fitch|first=N.|last2=Johnston|first2=S. C.|last3=Zalewski|first3=P.|last4=Staines|first4=D.|last5=Marshall-Gradisnik|first5=S.|date=2020-06-01|title=Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study|url=https://doi.org/10.1007/s11136-019-02411-6|journal=Quality of Life Research|language=en|volume=29|issue=6|pages=1521–1531|doi=10.1007/s11136-019-02411-6|issn=1573-2649|pmc=PMC7253372|pmid=31970624}}</ref>

== See also ==
* [[Anxiety]]
* [[Cognitive behavioral therapy]]
* [[Depression]]
* [[:Category:Mental disorders|Mental disorders]] (category)
* [[Patient mental health]]
* [[:Category:Psychological signs and symptoms|Psychological signs and symptoms]] (category)

==References==
{{reflist}}

{{stub}}

[[Category:Mental disorders]]

List of chronic diseases linked to infectious pathogens

2021-06-11T17:03:43Z

Kmdenmark:fixed CS1 error - dates

Many chronic diseases are linked to infectious [[pathogen]]s (meaning the pathogens are found in patients with the disease much more frequently than in healthy controls).<ref>{{Cite book|title=Preface|language=en|url=https://www.ncbi.nlm.nih.gov/books/NBK83716/|date=2004|publisher=National Academies Press (US)|last=Institute of Medicine (US) Forum on Microbial Threats|last2=Knobler|first2=Stacey L.|last3=O'Connor|first3=Siobhán|last4=Lemon|first4=Stanley M.|last5=Najafi|first5=Marjan}}</ref><ref>{{Cite journal|last=O'Connor|first=Siobhán M.|last2=Taylor|first2=Christopher E.|last3=Hughes|first3=James M.|date=Jul 2006|title=Emerging infectious determinants of chronic diseases|url=https://pubmed.ncbi.nlm.nih.gov/16836820/|journal=Emerging Infectious Diseases|volume=12|issue=7|pages=1051–1057|doi=10.3201/eid1207.060037|issn=1080-6040|pmc=3291059|pmid=16836820}}</ref> When a pathogen such as a [[virus]], [[bacteria|bacterium]], [[fungus]] or protozoan is linked to a disease, researchers will start to investigate whether the pathogen might be the cause the disease, or might be playing a causal role.
==Links to chronic disease==
There are several explanations for why a pathogen is found associated with a disease:
* The pathogen is an "innocent bystander" that plays no causal role in the disease, but is more prevalent in patients with the disease (for example because the disease compromises the immune response).
* The pathogen increases the risk of getting the disease, but does not actually cause the disease. For example, genital herpes increases the risk of catching HIV, but does not cause AIDS.<ref>{{Cite journal|last=Freeman|first=Esther E.|last2=Weiss|first2=Helen A.|last3=Glynn|first3=Judith R.|last4=Cross|first4=Pamela L.|last5=Whitworth|first5=James A.|last6=Hayes|first6=Richard J.|date=2006-01-02|title=Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies|url=https://pubmed.ncbi.nlm.nih.gov/16327322/|journal=AIDS (London, England)|volume=20|issue=1|pages=73–83|doi=10.1097/01.aids.0000198081.09337.a7|issn=0269-9370|pmid=16327322}}</ref>
* The pathogen causes the disease, but only combined with other causal factors (such as host genetic factors, or toxic exposure).
* The pathogen is a singular cause of the disease.

==Diseases associated with infectious pathogens==
In the following list of diseases linked to infectious pathogens, there is a good possibility that the pathogens might cause the disease, but further research is need to work out whether these pathogens do play a causal role.

This list covers some of the most common human diseases linked to infectious pathogens, but it is not intended to be a comprehensive list of pathogen-associated diseases.
{| class="wikitable alternance" cellpadding="0"
| style="text-align: center;" width="24%" | '''Disease'''
| style="text-align: center;" | '''Pathogens Linked to the Disease'''
|-
|'''[[acute flaccid myelitis|Acute flaccid myelitis]]'''
| Acute flaccid myelitis, a serious but rare neurological disease, is believed to be associated with the [[enterovirus#EV-D68|EV-D68 enterovirus]]<ref name="ev68-CDC2020">{{Cite web|url=https://www.cdc.gov/non-polio-enterovirus/about/ev-d68.html|title=Non-Polio Enterovirus {{!}} About EV-D68 {{!}} Enterovirus D68|last=Centers for Disease Control|first=|authorlink=Centers for Disease Control|last2=|first2=|authorlink2=|date=2020-08-12|website=[[Centers for Disease Control]]|language=en-us|archive-url=|archive-date=|url-status=|access-date=2020-08-18}}</ref> EV-D68 is a non-polio [[enterovirus]].<ref name="ev68-CDC2020" />
|-
| '''Alzheimer's disease'''
| Alzheimer's disease is associated with the bacteria porphyromonas gingivalis,<ref name="Benedyk2019">{{cite journal | last=Dominy | first=Stephen S. | last2=Lynch | first2=Casey | last3=Ermini | first3=Florian | last4=Benedyk | first4=Malgorzata | last5=Marczyk | first5=Agata | last6=Konradi | first6=Andrei | last7=Nguyen | first7=Mai | last8=Haditsch | first8=Ursula | last9=Raha | first9=Debasish | last10=Griffin | first10=Christina | last11=Holsinger | first11=Leslie J. | title=Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors | journal=Science Advances | volume=5 | issue=1 | date=2019-01-01 | issn=2375-2548 | doi=10.1126/sciadv.aau3333 | url=http://advances.sciencemag.org/content/5/1/eaau3333 | access-date=2020-08-18 | page=}}</ref> [[chlamydia pneumoniae]]<ref name="Shima">{{Cite journal|last=Shima|first=Kensuke|author-link=|last2=Kuhlenbäumer|first2=Gregor|author-link2=|last3=Rupp|first3=Jan|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=2010|title=Chlamydia pneumoniae infection and Alzheimer's disease: a connection to remember?|url=https://pubmed.ncbi.nlm.nih.gov/20445987/|journal=Medical Microbiology and Immunology|volume=199|issue=4|pages=283–289|doi=10.1007/s00430-010-0162-1|issn=1432-1831|pmc=|pmid=20445987|access-date=|quote=|via=}}</ref> and [[helicobacter pylori]],<ref name="Kountouras">{{Cite journal|last=Kountouras|first=Jannis|author-link=|last2=Boziki|first2=Marina|author-link2=|last3=Gavalas|first3=Emmanuel|author-link3=|last4=Zavos|first4=Christos|author-link4=|last5=Grigoriadis|first5=Nikolaos|author-link5=|last6=Deretzi|first6=Georgia|author-link6=|last7=Tzilves|first7=Dimitrios|last8=Katsinelos|first8=Panagiotis|last9=Tsolaki|first9=Magda|date=May 2009|title=Eradication of Helicobacter pylori may be beneficial in the management of Alzheimer’s disease|url=http://link.springer.com/10.1007/s00415-009-5011-z|journal=Journal of Neurology|language=en|volume=256|issue=5|pages=758–767|doi=10.1007/s00415-009-5011-z|issn=0340-5354|pmc=|pmid=|access-date=|quote=|via=}}</ref> and with the protozoan parasite [[toxoplasma gondii]].<ref name="Kusbeci">{{Cite journal|last=Kusbeci|first=Ozge Yilmaz|last2=Miman|first2=Ozlem|last3=Yaman|first3=Mehmet|last4=Aktepe|first4=Orhan Cem|last5=Yazar|first5=Suleyman|date=Jan 2011|title=Could Toxoplasma gondii have any role in Alzheimer disease?|url=https://pubmed.ncbi.nlm.nih.gov/20921875/|journal=Alzheimer Disease and Associated Disorders|volume=25|issue=1|pages=1–3|doi=10.1097/WAD.0b013e3181f73bc2|issn=1546-4156|pmid=20921875}}</ref><br />
[[Herpes simplex virus]] 1 is associated with Alzheimer's disease in individuals who possess the APOE-4 form of the APOE gene (APOE-4 enables the herpes virus to enter the brain).<ref name="Itzhaki">{{Cite journal|last=Itzhaki|first=Ruth F.|last2=Wozniak|first2=Matthew A.|date=2008-04-28|editor-last=Miklossy|editor-first=Judith|editor2-last=Martins|editor2-first=Ralph N.|title=Herpes Simplex Virus Type 1 in Alzheimer's Disease: The Enemy Within|url=https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JAD-2008-13405|journal=Journal of Alzheimer's Disease|volume=13|issue=4|pages=393–405|doi=10.3233/JAD-2008-13405}}</ref><br /><br />Fungal infections have been found in the brains of Alzheimer patients.<ref name="Pisa">{{Cite journal|last=Pisa|first=Diana|author-link=|last2=Alonso|first2=Ruth|author-link2=|last3=Rábano|first3=Alberto|author-link3=|last4=Rodal|first4=Izaskun|author-link4=|last5=Carrasco|first5=Luis|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Dec 2015|title=Different Brain Regions are Infected with Fungi in Alzheimer’s Disease|url=http://www.nature.com/articles/srep15015|journal=Scientific Reports|language=en|volume=5|issue=1|pages=15015|doi=10.1038/srep15015|issn=2045-2322|pmc=4606562|pmid=26468932|access-date=|quote=|via=}}</ref>[[Human_herpesvirus_6|HHV-6A]] and [[Human_herpesvirus_7|HHV-7]] have been found more frequently in the brains of Alzheimer's patients than those of healthy controls.<ref name="Readhead">{{Cite journal|last=Readhead|first=Ben|author-link=|last2=Haure-Mirande|first2=Jean-Vianney|author-link2=|last3=Funk|first3=Cory C.|author-link3=|last4=Richards|first4=Matthew A.|author-link4=|last5=Shannon|first5=Paul|author-link5=|last6=Haroutunian|first6=Vahram|author-link6=|last7=Sano|first7=Mary|last8=Liang|first8=Winnie S.|last9=Beckmann|first9=Noam D.|date=Jul 2018|title=Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus|url=https://doi.org/10.1016/j.neuron.2018.05.023|journal=Neuron|volume=99|issue=1|pages=64–82.e7|doi=10.1016/j.neuron.2018.05.023|issn=0896-6273|pmc=6551233|pmid=29937276|access-date=|quote=|via=}}</ref>
|-
| '''[[Amyotrophic lateral sclerosis]]'''
| Amyotrophic lateral sclerosis, the most common of five forms of motor neuron disease, is associated with [[echovirus]], an [[enterovirus]] infection of the central nervous system,<ref name="pmid12618659">{{Cite journal|last=Corcia|first=P.|last2=Giraud|first2=P.|last3=Guennoc|first3=A.-M.|last4=de Toffol|first4=B.|last5=Autret|first5=A.|date=Jan 2003|title=[Acute motor axonal neuropathy, enterovirus and Amyotrophic lateral sclerosis: can there be a link?]|url=https://pubmed.ncbi.nlm.nih.gov/12618659/|journal=Revue Neurologique|volume=159|issue=1|pages=80–82|issn=0035-3787|pmid=12618659}}</ref> and with [[retrovirus]]<ref name="pmid18209202">{{Cite journal|last=McCormick|first=A. L.|last2=Brown|first2=R. H.|last3=Cudkowicz|first3=M. E.|last4=Al-Chalabi|first4=A.|last5=Garson|first5=J. A.|date=2008-01-22|title=Quantification of reverse transcriptase in ALS and elimination of a novel retroviral candidate|url=https://pubmed.ncbi.nlm.nih.gov/18209202/|journal=Neurology|volume=70|issue=4|pages=278–283|doi=10.1212/01.wnl.0000297552.13219.b4|issn=1526-632X|pmid=18209202}}</ref> activity (it is not known whether this retrovirus activity arises from a human endogenous retrovirus, or from an exogenous retrovirus).
|-
| '''[[Anorexia_and_eating_disorders#Anorexia|Anorexia nervosa]]'''
| Infection with borrelia<ref name="pmid7943444" /> species bacteria is associated with anorexia nervosa. In rare cases, anorexia nervosa may arise after infection with [[streptococcus]]<ref name="pmid10933123">{{Cite journal|last=Sokol|first=M. S.|date=2000|title=Infection-triggered anorexia nervosa in children: clinical description of four cases|url=https://pubmed.ncbi.nlm.nih.gov/10933123/|journal=Journal of Child and Adolescent Psychopharmacology|volume=10|issue=2|pages=133–145|doi=10.1089/cap.2000.10.133|issn=1044-5463|pmid=10933123}}</ref> species bacteria. [[Anorexia (appetite loss)|Anorexia]] (the symptom of appetite loss, which is distinct from anorexia nervosa) is associated with the protozoan parasite dientamoeba fragilis.<ref name="pmid15258093" />
|-
| '''[[Anxiety|Anxiety disorder]]'''
| Anxiety is associated with [[cytomegalovirus]],<ref name="pmid17703915">{{Cite journal|last=Phillips|first=Anna C.|author-link=|last2=Carroll|first2=Douglas|author-link2=|last3=Khan|first3=Naeem|author-link3=|last4=Moss|first4=Paul|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jan 2008|title=Cytomegalovirus is associated with depression and anxiety in older adults|url=https://pubmed.ncbi.nlm.nih.gov/17703915/|journal=Brain, Behavior, and Immunity|volume=22|issue=1|pages=52–55|doi=10.1016/j.bbi.2007.06.012|issn=1090-2139|pmc=|pmid=17703915|access-date=|quote=|via=}}</ref><ref name="pmid24472683">{{Cite journal|last=Rector|first=Jerrald L.|last2=Dowd|first2=Jennifer B.|last3=Loerbroks|first3=Adrian|last4=Burns|first4=Victoria E.|last5=Moss|first5=Paul A.|last6=Jarczok|first6=Marc N.|last7=Stalder|first7=Tobias|last8=Hoffman|first8=Kristina|last9=Fischer|first9=Joachim E.|date=May 2014|title=Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample|url=https://pubmed.ncbi.nlm.nih.gov/24472683/|journal=Brain, Behavior, and Immunity|volume=38|pages=133–141|doi=10.1016/j.bbi.2014.01.012|issn=1090-2139|pmid=24472683}}</ref> and the bacterium [[helicobacter pylori]].<ref name="pmid18422970">{{Cite journal|last=Addolorato|first=G.|last2=Mirijello|first2=A.|last3=D'Angelo|first3=C.|last4=Leggio|first4=L.|last5=Ferrulli|first5=A.|last6=Abenavoli|first6=L.|last7=Vonghia|first7=L.|last8=Cardone|first8=S.|last9=Leso|first9=V.|date=Jul 2008|title=State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting|url=https://pubmed.ncbi.nlm.nih.gov/18422970/|journal=International Journal of Clinical Practice|volume=62|issue=7|pages=1063–1069|doi=10.1111/j.1742-1241.2008.01763.x|issn=1742-1241|pmid=18422970}}</ref> Anxiety is associated with [[toxoplasma gondii]],<ref name="pmid25124709">{{Cite journal|last=Markovitz|first=Adam A.|last2=Simanek|first2=Amanda M.|last3=Yolken|first3=Robert H.|last4=Galea|first4=Sandro|last5=Koenen|first5=Karestan C.|last6=Chen|first6=Shu|last7=Aiello|first7=Allison E.|date=Jan 2015|title=Toxoplasma gondii and anxiety disorders in a community-based sample|url=https://pubmed.ncbi.nlm.nih.gov/25124709/|journal=Brain, Behavior, and Immunity|volume=43|pages=192–197|doi=10.1016/j.bbi.2014.08.001|issn=1090-2139|pmid=25124709}}</ref> or at least associated with higher levels of IgG antibodies to this parasite.<ref name="pmid25185399">{{Cite journal|last=Gale|first=Shawn D.|last2=Brown|first2=Bruce L.|last3=Berrett|first3=Andrew|last4=Erickson|first4=Lance D.|last5=Hedges|first5=Dawson W.|date=Aug 2014|title=Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults|url=https://pubmed.ncbi.nlm.nih.gov/25185399/|journal=Folia Parasitologica|volume=61|issue=4|pages=285–292|issn=0015-5683|pmid=25185399}}</ref> Anxiety as a personality trait is associated with higher antibody titers to [[Epstein-Barr virus]].<ref name="pmid8500440">{{Cite journal|last=Esterling|first=B. A.|last2=Antoni|first2=M. H.|last3=Kumar|first3=M.|last4=Schneiderman|first4=N.|date=Mar 1993|title=Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students|url=https://pubmed.ncbi.nlm.nih.gov/8500440/|journal=Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association|volume=12|issue=2|pages=132–139|doi=10.1037//0278-6133.12.2.132|issn=0278-6133|pmid=8500440}}</ref>
|-
| '''[[Asthma]]'''
| Asthma is associated with [[rhinovirus]], human respiratory syncytial virus,<ref name="pmid19532096">{{cite journal | last=Gern | first=James E | title=Rhinovirus and the initiation of asthma | journal=Current opinion in allergy and clinical immunology | volume=9 | issue=1 | date=2009 | issn=1528-4050 | pmid=19532096 | pmc=2760477 | doi=10.1097/aci.0b013e32831f8f1b | pages=73–78}}</ref> and the bacterium chlamydia pneumoniae.<ref name="pmid10541419">{{cite journal | last=Hahn | first=David L. | title=Chlamydia pneumoniae, asthma, and COPD: what is the evidence? | journal=Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology | volume=83 | issue=4 | date=1999 | issn=1081-1206 | pmid=10541419 | doi=10.1016/s1081-1206(10)62666-x | pages=271–292}}</ref> Chlamydia pneumoniae is particularly associated with adult-onset asthma.<ref name="pmid2056624">{{cite journal | last=Hahn | first=DL | last2=Dodge | first2=RW | last3=Golubjatnikov | first3=R | title=Association of Chlamydia pneumoniae (strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma. | journal=JAMA | volume=266 | issue=2 | date=Jul 10, 1991 | issn=0098-7484 | pmid=2056624 | pages=225–30}}</ref>
|-
| '''Atherosclerosis'''
| Atherosclerosis is associated with cytomegalovirus,<ref name="pmid25834719">{{Cite journal|last=Heybar|first=Habib|last2=Alavi|first2=Seyed Mohammad|last3=Farashahi Nejad|first3=Mehdi|last4=Latifi|first4=Mahmood|date=Mar 2015|title=Cytomegalovirus infection and atherosclerosis in candidate of coronary artery bypass graft|url=https://pubmed.ncbi.nlm.nih.gov/25834719/|journal=Jundishapur Journal of Microbiology|volume=8|issue=3|pages=e15476|doi=10.5812/jjm.15476|issn=2008-3645|pmc=4377172|pmid=25834719}}</ref> and the bacteria helicobacter pylori<ref name="pmid25725176">{{Cite journal|last=Karbasi-Afshar|first=Reza|last2=Khedmat|first2=Hossein|last3=Izadi|first3=Morteza|date=2015|title=Helicobacter pylori Infection and atherosclerosis: a systematic review|url=https://pubmed.ncbi.nlm.nih.gov/25725176/|journal=Acta Medica Iranica|volume=53|issue=2|pages=78–88|issn=1735-9694|pmid=25725176}}</ref> and [[chlamydia pneumoniae]].<ref name="pmid12468766">{{Cite journal|last=Prager|first=Manfred|last2=Türel|first2=Zeynep|last3=Speidl|first3=Walter S.|last4=Zorn|first4=Gerlinde|last5=Kaun|first5=Christoph|last6=Niessner|first6=Alexander|last7=Heinze|first7=Georg|last8=Huk|first8=Igor|last9=Maurer|first9=Gerald|date=Dec 2002|title=Chlamydia pneumoniae in carotid artery atherosclerosis: a comparison of its presence in atherosclerotic plaque, healthy vessels, and circulating leukocytes from the same individuals|url=https://pubmed.ncbi.nlm.nih.gov/12468766/|journal=Stroke|volume=33|issue=12|pages=2756–2761|doi=10.1161/01.str.0000039322.66575.77|issn=1524-4628|pmid=12468766}}</ref>
|-
| '''Attention deficit hyperactivity disorder'''
| Attention deficit hyperactivity disorder (ADHD) and learning disabilities are associated with the bacteria [[borrelia burgdorferi]] and [[streptococcus]], and with HIV and [[Enterovirus#enterovirus_71|enterovirus 71]].<br />
Febrile seizures due to [[human herpesvirus 6]] or [[influenza#influenza_A|subtype A]] are a risk factor for ADHD. Viral infections during pregnancy, at birth, and in early childhood are risk factors for ADHD.<ref name="pmid18245408">{{cite journal | last=Millichap | first=J. G. | title=Etiologic Classification of Attention-Deficit/Hyperactivity Disorder | journal=Pediatrics | publisher=American Academy of Pediatrics (AAP) | volume=121 | issue=2 | date=Jan 28, 2008 | issn=0031-4005 | pmid=18245408 | doi=10.1542/peds.2007-1332 | pages=e358–e365|url =https://pubmed.ncbi.nlm.nih.gov/18245408}}</ref>
|-
| '''Autism'''
| Autism is linked to congenital infection with [[rubella virus]] or [[cytomegalovirus]].<ref name="pmid5172438">{{Cite journal|last=Chess|first=S.|date=Jan 1971|title=Autism in children with congenital rubella|url=https://pubmed.ncbi.nlm.nih.gov/5172438/|journal=Journal of Autism and Childhood Schizophrenia|volume=1|issue=1|pages=33–47|doi=10.1007/BF01537741|issn=0021-9185|pmid=5172438}}</ref><ref name="pmid12959425">{{cite journal | last=Yamashita | first=Yushiro | last2=Fujimoto | first2=Chizu | last3=Nakajima | first3=Eisuke | last4=Isagai | first4=Takeo | last5=Matsuishi | first5=Toyojiro | title= Possible association between congenital cytomegalovirus infection and autistic disorder |journal=Journal of autism and developmental disorders | volume=33 | issue=4 | date=2003 | issn=0162-3257 | pmid=12959425 | doi=10.1023/a:1025023131029 | pages=455–459}}</ref> [[Clostridia]] bacterial species are associated with autism (these bacteria are present in greater numbers in the guts of autistic children).<ref name="pmid12173102">{{cite journal | last=Finegold | first=Sydney M. | last2=Molitoris | first2=Denise | last3=Song | first3=Yuli | last4=Liu | first4=Chengxu | last5=Vaisanen | first5=Marja‐Liisa | last6=Bolte | first6=Ellen | last7=McTeague | first7=Maureen | last8=Sandler | first8=Richard | last9=Wexler | first9=Hannah | last10=Marlowe | first10=Elizabeth M. | last11=Collins | first11=Matthew D. | last12=Lawson | first12=Paul A. | last13=Summanen | first13=Paula | last14=Baysallar | first14=Mehmet | last15=Tomzynski | first15=Thomas J. | last16=Read | first16=Erik | last17=Johnson | first17=Eric | last18=Rolfe | first18=Rial | last19=Nasir | first19=Palwasha | last20=Shah | first20=Haroun | last21=Haake | first21=David A. | last22=Manning | first22=Patricia | last23=Kaul | first23=Ajay | title=Gastrointestinal Microflora Studies in Late‐Onset Autism | journal=Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | volume=35 | issue=s1 | date=Sep 1, 2002 | issn=1058-4838 | pmid=12173102 | doi=10.1086/341914 | pages=S6–S16}}</ref>
|-
| '''[[Autoimmune disease]]s'''
| Autoimmune diseases are strongly associated with [[enterovirus]]es such as [[Coxsackie B]] virus.<ref name="pmid18357776">{{cite book | last=Rose | first=N. R. | title=Current Topics in Microbiology and Immunology | chapter=Autoimmunity in Coxsackievirus Infection | journal=Current topics in microbiology and immunology | publisher=Springer Berlin Heidelberg | location=Berlin, Heidelberg | volume=323 | date=2008 | isbn=978-3-540-75545-6 | pmid=18357776 | doi=10.1007/978-3-540-75546-3_14 | pages=293–314}}</ref> [[Autoimmune disease]]s are also associated with Epstein-Barr virus,<ref name="pmid19028369">{{Cite journal|last=Toussirot|first=Eric|last2=Roudier|first2=Jean|date=Oct 2008|title=Epstein-Barr virus in autoimmune diseases|url=https://pubmed.ncbi.nlm.nih.gov/19028369/|journal=Best Practice & Research. Clinical Rheumatology|volume=22|issue=5|pages=883–896|doi=10.1016/j.berh.2008.09.007|issn=1532-1770|pmid=19028369}}</ref> cytomegalovirus,<ref name="pmid17894021">{{Cite journal|last=Barzilai|first=O.|last2=Sherer|first2=Y.|last3=Ram|first3=M.|last4=Izhaky|first4=D.|last5=Anaya|first5=J. M.|last6=Shoenfeld|first6=Y.|date=Jun 2007|title=Epstein-Barr virus and cytomegalovirus in autoimmune diseases: are they truly notorious? A preliminary report|url=https://pubmed.ncbi.nlm.nih.gov/17894021/|journal=Annals of the New York Academy of Sciences|volume=1108|pages=567–577|doi=10.1196/annals.1422.059|issn=0077-8923|pmid=17894021}}</ref> [[parvovirus B19]],<ref name="pmid12848949">{{Cite journal|last=Lehmann|first=Hartwig W.|last2=von Landenberg|first2=Philipp|last3=Modrow|first3=Susanne|date=Jun 2003|title=Parvovirus B19 infection and autoimmune disease|url=https://pubmed.ncbi.nlm.nih.gov/12848949/|journal=Autoimmunity Reviews|volume=2|issue=4|pages=218–223|doi=10.1016/s1568-9972(03)00014-4|issn=1568-9972|pmid=12848949}}</ref> and HIV,<ref name="pmid19532080">{{Cite journal|last=Stratton|first=Richard|last2=Slapak|first2=Gabrielle|last3=Mahungu|first3=Tabitha|last4=Kinloch-de Loes|first4=Sabine|date=Feb 2009|title=Autoimmunity and HIV|url=https://pubmed.ncbi.nlm.nih.gov/19532080/|journal=Current Opinion in Infectious Diseases|volume=22|issue=1|pages=49–56|doi=10.1097/QCO.0b013e3283210006|issn=1473-6527|pmid=19532080}}</ref> and the bacterium mycobacterium tuberculosis.<ref name="pmid19543859">{{Cite journal|last=Shapira|first=Yinon|last2=Agmon-Levin|first2=Nancy|last3=Shoenfeld|first3=Yehuda|date=Apr 2010|title=Mycobacterium tuberculosis, autoimmunity, and vitamin D|url=https://pubmed.ncbi.nlm.nih.gov/19543859/|journal=Clinical Reviews in Allergy & Immunology|volume=38|issue=2-3|pages=169–177|doi=10.1007/s12016-009-8150-1|issn=1559-0267|pmid=19543859}}</ref> Autoimmune thyroid disease is associated with [[Epstein-Barr virus]],<ref name="pmid18473192">{{Cite journal|last=Thomas|first=Dimitrios|last2=Karachaliou|first2=Feneli|last3=Kallergi|first3=Konstantina|last4=Vlachopapadopoulou|first4=Elpis|last5=Antonaki|first5=Georgia|last6=Chatzimarkou|first6=Fotini|last7=Fotinou|first7=Aspasia|last8=Kaldrymides|first8=Philippos|last9=Michalacos|first9=Stefanos|date=Apr 2008|title=Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease|url=https://pubmed.ncbi.nlm.nih.gov/18473192/|journal=Endocrine|volume=33|issue=2|pages=171–175|doi=10.1007/s12020-008-9068-8|issn=1355-008X|pmid=18473192}}</ref> and [[helicobacter pylori]].<ref name="pmid16263823">{{Cite journal|last=Larizza|first=Daniela|last2=Calcaterra|first2=Valeria|last3=Martinetti|first3=Miryam|last4=Negrini|first4=Riccardo|last5=De Silvestri|first5=Annalisa|last6=Cisternino|first6=Mariangela|last7=Iannone|first7=A. M.|last8=Solcia|first8=Enrico|date=Jan 2006|title=Helicobacter pylori infection and autoimmune thyroid disease in young patients: the disadvantage of carrying the human leukocyte antigen-DRB1*0301 allele|url=https://pubmed.ncbi.nlm.nih.gov/16263823/|journal=The Journal of Clinical Endocrinology and Metabolism|volume=91|issue=1|pages=176–179|doi=10.1210/jc.2005-1272|issn=0021-972X|pmid=16263823}}</ref>
|-
| '''Bipolar disorder'''
| Bipolar disorder is associated with [[Borna disease virus]],<ref name="pmid12857781">{{Cite journal|last=Bode|first=Liv|last2=Ludwig|first2=Hans|date=Jul 2003|title=Borna disease virus infection, a human mental-health risk|url=https://pubmed.ncbi.nlm.nih.gov/12857781/|journal=Clinical Microbiology Reviews|volume=16|issue=3|pages=534–545|doi=10.1128/cmr.16.3.534-545.2003|issn=0893-8512|pmid=12857781}}</ref> and with Borrelia species bacteria.<ref name="pmid7943444">{{Cite journal|last=Fallon|first=B. A.|author-link=|last2=Nields|first2=J. A.|author-link2=|last3=|first3=|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Nov 1994|title=Lyme disease: a neuropsychiatric illness|url=https://pubmed.ncbi.nlm.nih.gov/7943444/|journal=The American Journal of Psychiatry|volume=151|issue=11|pages=1571–1583|doi=10.1176/ajp.151.11.1571|issn=0002-953X|pmc=|pmid=7943444|access-date=|quote=|via=}}</ref> The level of cognitive impairment in bipolar disorder is associated with [[herpes simplex virus]] 1.<ref name="pmid15013827">{{Cite journal|last=Dickerson|first=Faith B.|last2=Boronow|first2=John J.|last3=Stallings|first3=Cassie|last4=Origoni|first4=Andrea E.|last5=Cole|first5=Sara|last6=Krivogorsky|first6=Bogdana|last7=Yolken|first7=Robert H.|date=2004-03-15|title=Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder|url=https://pubmed.ncbi.nlm.nih.gov/15013827/|journal=Biological Psychiatry|volume=55|issue=6|pages=588–593|doi=10.1016/j.biopsych.2003.10.008|issn=0006-3223|pmid=15013827}}</ref>
|-
| '''Cancer'''
|
Some estimates currently attribute 15% to 20% of all cancers to infectious pathogen causes.<ref name="pmid9184771">{{Cite journal|last=Pisani|first=P.|last2=Parkin|first2=D. M.|last3=Muñoz|first3=N.|last4=Ferlay|first4=J.|date=Jun 1997|title=Cancer and infection: estimates of the attributable fraction in 1990|url=https://pubmed.ncbi.nlm.nih.gov/9184771/|journal=Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology|volume=6|issue=6|pages=387–400|issn=1055-9965|pmid=9184771}}</ref><ref name="pmid18805702">{{Cite journal|last=de Martel|first=Catherine|last2=Franceschi|first2=Silvia|date=Jun 2009|title=Infections and cancer: established associations and new hypotheses|url=https://pubmed.ncbi.nlm.nih.gov/18805702/|journal=Critical Reviews in Oncology/Hematology|volume=70|issue=3|pages=183–194|doi=10.1016/j.critrevonc.2008.07.021|issn=1879-0461|pmid=18805702}}</ref> In future, this percentage may be revised upwards if the pathogens currently associated with cancers (such as those listed below) are proven to actually cause those cancers. (For the sake of completeness, some pathogens proven to cause cancers are included in the list, in addition to pathogens that have been linked to cancers, but are not yet proven to cause the cancer.)

'''Adrenal tumor''' is associated with BK virus and simian virus 40.<ref name="pmid17684484">{{Cite journal|last=Barzon|first=L.|last2=Trevisan|first2=M.|last3=Masi|first3=G.|last4=Pacenti|first4=M.|last5=Sinigaglia|first5=A.|last6=Macchi|first6=V.|last7=Porzionato|first7=A.|last8=De Caro|first8=R.|last9=Favia|first9=G.|date=2008-01-31|title=Detection of polyomaviruses and herpesviruses in human adrenal tumors|url=https://pubmed.ncbi.nlm.nih.gov/17684484/|journal=Oncogene|volume=27|issue=6|pages=857–864|doi=10.1038/sj.onc.1210699|issn=1476-5594|pmid=17684484}}</ref><br />'''Anal cancer''' is associated with human papillomaviruses (HPV).<ref name="pmid20839262">{{Cite journal|last=Abramowitz|first=Laurent|last2=Jacquard|first2=Anne-Carole|last3=Jaroud|first3=Fatiha|last4=Haesebaert|first4=Julie|last5=Siproudhis|first5=Laurent|last6=Pradat|first6=Pierre|last7=Aynaud|first7=Olivier|last8=Leocmach|first8=Yann|last9=Soubeyrand|first9=Benoît|date=2011-07-15|title=Human papillomavirus genotype distribution in anal cancer in France: the EDiTH V study|url=https://pubmed.ncbi.nlm.nih.gov/20839262/|journal=International Journal of Cancer|volume=129|issue=2|pages=433–439|doi=10.1002/ijc.25671|issn=1097-0215|pmid=20839262}}</ref>
<br />'''Bladder cancer''' can be caused by schistosoma helminths.<ref name="pmid21178421">{{Cite journal|last=Botelho|first=Monica Catarina|last2=Machado|first2=Jose Carlos|last3=da Costa|first3=Jose Manuel Correia|date=Mar 2010|title=Schistosoma haematobium and bladder cancer: what lies beneath?|url=https://pubmed.ncbi.nlm.nih.gov/21178421/|journal=Virulence|volume=1|issue=2|pages=84–87|doi=10.4161/viru.1.2.10487|issn=2150-5608|pmid=21178421}}</ref><br />'''Brain tumor'''. Glioblastoma multiforme is associated with [[cytomegalovirus]],<ref name="pmid21490182">{{Cite journal|last=Dziurzynski|first=Kristine|last2=Wei|first2=Jun|last3=Qiao|first3=Wei|last4=Hatiboglu|first4=Mustafa Aziz|last5=Kong|first5=Ling-Yuan|last6=Wu|first6=Adam|last7=Wang|first7=Yongtao|last8=Cahill|first8=Daniel|last9=Levine|first9=Nicholas|date=2011-07-15|title=Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype|url=https://pubmed.ncbi.nlm.nih.gov/21490182/|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research|volume=17|issue=14|pages=4642–4649|doi=10.1158/1078-0432.CCR-11-0414|issn=1557-3265|pmc=3139801|pmid=21490182}}</ref> [[BK virus]], [[JC virus]], and [[simian virus 40]].<ref name="pmid16626046">{{Cite journal|last=Barbanti-Brodano|first=Giuseppe|last2=Sabbioni|first2=Silvia|last3=Martini|first3=Fernanda|last4=Negrini|first4=Massimo|last5=Corallini|first5=Alfredo|last6=Tognon|first6=Mauro|date=2006|title=BK virus, JC virus and Simian Virus 40 infection in humans, and association with human tumors|url=https://pubmed.ncbi.nlm.nih.gov/16626046/|journal=Advances in Experimental Medicine and Biology|volume=577|pages=319–341|doi=10.1007/0-387-32957-9_23|issn=0065-2598|pmid=16626046}}</ref><br />'''Breast cancer''' is associated with bovine leukemia virus,<ref name="pmid28640828">{{Cite journal|last=Buehring|first=Gertrude C.|last2=Shen|first2=HuaMin|last3=Schwartz|first3=Daniel A.|last4=Lawson|first4=James S.|date=2017|title=Bovine leukemia virus linked to breast cancer in Australian women and identified before breast cancer development|url=https://pubmed.ncbi.nlm.nih.gov/28640828/|journal=PloS One|volume=12|issue=6|pages=e0179367|doi=10.1371/journal.pone.0179367|issn=1932-6203|pmc=5480893|pmid=28640828}}</ref> mouse mammary tumor virus, [[Epstein-Barr virus]], and human papillomaviruses (HPV).<ref name="pmid17661684">{{Cite journal|last=Lawson|first=James S.|last2=Günzburg|first2=Walter H.|last3=Whitaker|first3=Noel J.|date=Jun 2006|title=Viruses and human breast cancer|url=https://pubmed.ncbi.nlm.nih.gov/17661684/|journal=Future Microbiology|volume=1|issue=1|pages=33–51|doi=10.2217/17460913.1.1.33|issn=1746-0921|pmid=17661684}}</ref><br />'''Carcinoid tumors''' are associated with [[enterovirus]] infections.<ref name="pmid21278394">{{Cite journal|last=Chia|first=John|author-link=John Chia|last2=Chia|first2=Andrew|author-link2=Andrew Chia|last3=El-Habbal|first3=Rabiha|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Aug 2011|title=Carcinoid tumour associated with enterovirus infection|url=https://pubmed.ncbi.nlm.nih.gov/21278394/|journal=Journal of Clinical Pathology|volume=64|issue=8|pages=722–724|doi=10.1136/jcp.2010.082271|issn=1472-4146|pmc=|pmid=21278394|access-date=|quote=|via=}}</ref><br />'''Cervical cancer''' can be caused by HPV.<ref name="pmid11919208">{{Cite journal|last=Bosch|first=F. X.|last2=Lorincz|first2=A.|last3=Muñoz|first3=N.|last4=Meijer|first4=C. J. L. M.|last5=Shah|first5=K. V.|date=Apr 2002|title=The causal relation between human papillomavirus and cervical cancer|url=https://pubmed.ncbi.nlm.nih.gov/11919208/|journal=Journal of Clinical Pathology|volume=55|issue=4|pages=244–265|doi=10.1136/jcp.55.4.244|issn=0021-9746|pmc=1769629|pmid=11919208}}</ref><br />'''Colorectal cancer''' is associated with the bacteria [[helicobacter pylori]], [[streptococcus bovis]] and [[fusobacterium nucleatum]],<ref name="pmid22009989">{{Cite journal|last=Castellarin|first=Mauro|last2=Warren|first2=René L.|last3=Freeman|first3=J. Douglas|last4=Dreolini|first4=Lisa|last5=Krzywinski|first5=Martin|last6=Strauss|first6=Jaclyn|last7=Barnes|first7=Rebecca|last8=Watson|first8=Peter|last9=Allen-Vercoe|first9=Emma|date=Feb 2012|title=Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/22009989/|journal=Genome Research|volume=22|issue=2|pages=299–306|doi=10.1101/gr.126516.111|issn=1549-5469|pmc=3266037|pmid=22009989}}</ref> with HPV,<ref name="pmid18990738">{{Cite journal|last=Burnett-Hartman|first=Andrea N.|last2=Newcomb|first2=Polly A.|last3=Potter|first3=John D.|date=Nov 2008|title=Infectious agents and colorectal cancer: a review of Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus|url=https://pubmed.ncbi.nlm.nih.gov/18990738/|journal=Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology|volume=17|issue=11|pages=2970–2979|doi=10.1158/1055-9965.EPI-08-0571|issn=1055-9965|pmc=2676114|pmid=18990738}}</ref> and with the helminth [[schistosoma japonicum]].<ref name="pmid20704754">{{Cite journal|last=H Salim|first=Omer E.|last2=Hamid|first2=Hytham K. S.|last3=Mekki|first3=Salwa O.|last4=Suleiman|first4=Suleiman H.|last5=Ibrahim|first5=Shakir Z.|date=2010-08-13|title=Colorectal carcinoma associated with schistosomiasis: a possible causal relationship|url=https://pubmed.ncbi.nlm.nih.gov/20704754/|journal=World Journal of Surgical Oncology|volume=8|pages=68|doi=10.1186/1477-7819-8-68|issn=1477-7819|pmc=2928231|pmid=20704754}}</ref> JC virus may be a risk factor for colorectal cancer.<ref name="pmid20167111">{{Cite journal|last=Coelho|first=Tatiana R.|last2=Almeida|first2=Luis|last3=Lazo|first3=Pedro A.|date=2010-02-18|title=JC virus in the pathogenesis of colorectal cancer, an etiological agent or another component in a multistep process?|url=https://pubmed.ncbi.nlm.nih.gov/20167111/|journal=Virology Journal|volume=7|pages=42|doi=10.1186/1743-422X-7-42|issn=1743-422X|pmc=2830963|pmid=20167111}}</ref><br />'''Gallbladder cancer''' is associated with the bacterium salmonella typhi.<ref name="pmid20539059">{{Cite journal|last=Samaras|first=Vassilis|last2=Rafailidis|first2=Petros I.|last3=Mourtzoukou|first3=Eleni G.|last4=Peppas|first4=George|last5=Falagas|first5=Matthew E.|date=2010-06-03|title=Chronic bacterial and parasitic infections and cancer: a review|url=https://pubmed.ncbi.nlm.nih.gov/20539059/|journal=Journal of Infection in Developing Countries|volume=4|issue=5|pages=267–281|doi=10.3855/jidc.819|issn=1972-2680|pmid=20539059}}</ref><br />'''Hodgkin's lymphoma''' is associated with Epstein-Barr virus,<ref name="pmid19017178">{{Cite journal|last=Hjalgrim|first=H.|last2=Engels|first2=E. A.|date=Dec 2008|title=Infectious aetiology of Hodgkin and non-Hodgkin lymphomas: a review of the epidemiological evidence|url=https://pubmed.ncbi.nlm.nih.gov/19017178/|journal=Journal of Internal Medicine|volume=264|issue=6|pages=537–548|doi=10.1111/j.1365-2796.2008.02031.x|issn=1365-2796|pmid=19017178}}</ref> [[hepatitis C virus]],<ref name="pmid15788203">{{Cite journal|last=Mazzaro|first=C.|last2=Tirelli|first2=U.|last3=Pozzato|first3=G.|date=Apr 2005|title=Hepatitis C virus and non-Hodgkin's lymphoma 10 years later|url=https://pubmed.ncbi.nlm.nih.gov/15788203/|journal=Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver|volume=37|issue=4|pages=219–226|doi=10.1016/j.dld.2005.01.003|issn=1590-8658|pmid=15788203}}</ref> and HIV.<ref name="pmid19339934">{{Cite journal|last=Carbone|first=Antonino|last2=Gloghini|first2=Annunziata|last3=Serraino|first3=Diego|last4=Spina|first4=Michele|date=Jan 2009|title=HIV-associated Hodgkin lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/19339934/|journal=Current opinion in HIV and AIDS|volume=4|issue=1|pages=3–10|doi=10.1097/COH.0b013e32831a722b|issn=1746-6318|pmid=19339934}}</ref><br />'''Kaposi's Sarcoma''' can be caused by Kaposi's sarcoma herpesvirus and HIV.<br />'''Liver cancer'''. Hepatocellular carcinoma can be caused by [[hepatitis B virus]], [[hepatitis C virus]],<ref name="pmid15907199">{{Cite journal|last=Michielsen|first=Peter P.|last2=Francque|first2=Sven M.|last3=van Dongen|first3=Jurgen L.|date=2005-05-20|title=Viral hepatitis and hepatocellular carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/15907199/|journal=World Journal of Surgical Oncology|volume=3|pages=27|doi=10.1186/1477-7819-3-27|issn=1477-7819|pmc=1166580|pmid=15907199}}</ref> and by the helminth schistosoma japonicum.<ref name="pmid7510038">{{Cite journal|last=Ishii|first=A.|last2=Matsuoka|first2=H.|last3=Aji|first3=T.|last4=Ohta|first4=N.|last5=Arimoto|first5=S.|last6=Wataya|first6=Y.|last7=Hayatsu|first7=H.|date=1994-03-01|title=Parasite infection and cancer: with special emphasis on Schistosoma japonicum infections (Trematoda). A review|url=https://pubmed.ncbi.nlm.nih.gov/7510038/|journal=Mutation Research|volume=305|issue=2|pages=273–281|doi=10.1016/0027-5107(94)90247-x|issn=0027-5107|pmid=7510038}}</ref><br />'''Lung cancer''' is associated with the bacterium clamydia pneumoniae,<ref name="pmid20501758">{{cite journal | last=Chaturvedi | first=Anil K. | last2=Gaydos | first2=Charlotte A. | last3=Agreda | first3=Patricia | last4=Holden | first4=Jeffrey P. | last5=Chatterjee | first5=Nilanjan | last6=Goedert | first6=James J. | last7=Caporaso | first7=Neil E. | last8=Engels | first8=Eric A. | title=Chlamydia pneumoniae Infection and Risk for Lung Cancer | journal=Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | volume=19 | issue=6 | date=May 25, 2010 | issn=1055-9965 | pmid=20501758 | doi=10.1158/1055-9965.epi-09-1261 | pages=1498–1505}}</ref> with HPV, and with Merkel cell [[polyomavirus]].<ref name="pmid20699096">{{cite journal | last=Joh | first=Joongho | last2=Jenson | first2=A. Bennett | last3=Moore | first3=Grace D. | last4=Rezazedeh | first4=Arash | last5=Slone | first5=Stephen P. | last6=Ghim | first6=Shin-je | last7=Kloecker | first7=Goetz H. | title=Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV) in non small cell lung cancer | journal=Experimental and molecular pathology | volume=89 | issue=3 | date=2010 | issn=0014-4800 | pmid=20699096 | doi=10.1016/j.yexmp.2010.08.001 | pages=222–226}}</ref><br />'''Leukemia'''. Adult T-cell leukemia can be caused by human T-cell leukemia virus-1.<br />'''Mesothelioma''' is associated with simian virus 40,<ref name="pmid18520265">{{Cite journal|last=Rivera|first=Zeyana|last2=Strianese|first2=Oriana|last3=Bertino|first3=Pietro|last4=Yang|first4=Haining|last5=Pass|first5=Harvey|last6=Carbone|first6=Michele|date=Jul 2008|title=The relationship between simian virus 40 and mesothelioma|url=https://pubmed.ncbi.nlm.nih.gov/18520265/|journal=Current Opinion in Pulmonary Medicine|volume=14|issue=4|pages=316–321|doi=10.1097/MCP.0b013e3283018220|issn=1531-6971|pmid=18520265}}</ref> especially in conjunction with asbestos exposure.<br />'''Nasopharyngeal carcinoma''' can be caused by Epstein-Barr virus.<br />'''Non-Hodgkin lymphoma''' is associated with HIV and simian virus 40.<ref name="pmid15202523">{{Cite journal|last=Butel|first=Janet S.|last2=Vilchez|first2=Regis A.|last3=Jorgensen|first3=Jeffrey L.|last4=Kozinetz|first4=Claudia A.|date=2003|title=Association between SV40 and non-Hodgkin's lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/15202523/|journal=Leukemia & Lymphoma|volume=44|issue=Suppl 3|pages=S33–39|doi=10.1080/10428190310001623784|issn=1042-8194|pmid=15202523}}</ref><br />'''Oropharyngeal cancer''' can be caused by HPV.<br />'''Ovarian cancer''' is associated with [[mumps virus]].<ref name="pmid445337">{{Cite journal|last=Menczer|first=J.|last2=Modan|first2=M.|last3=Ranon|first3=L.|last4=Golan|first4=A.|date=Apr 1979|title=Possible role of mumps virus in the etiology of ovarian cancer|url=https://pubmed.ncbi.nlm.nih.gov/445337/|journal=Cancer|volume=43|issue=4|pages=1375–1379|doi=10.1002/1097-0142(197904)43:43.0.co;2-d|issn=0008-543X|pmid=445337}}</ref><br />'''Pancreatic cancer''' is associated with hepatitis B virus,<ref name="pmid19840258">{{cite journal | last=Iloeje | first=Uchenna H. | last2=Yang | first2=Hwai-I | last3=Jen | first3=Chin-Lan | last4=Su | first4=Jun | last5=Wang | first5=Li-Yu | last6=You | first6=San-Lin | last7=Lu | first7=Sheng-Nan | last8=Chen | first8=Chien-Jen | title=Risk of pancreatic cancer in chronic hepatitis B virus infection: data from the REVEAL-HBV cohort study | journal=Liver international : official journal of the International Association for the Study of the Liver | volume=30 | issue=3 | date=2010 | issn=1478-3223 | pmid=19840258 | doi=10.1111/j.1478-3231.2009.02147.x | pages=423–429}}</ref> and the bacterium helicobacter pylori.<ref name="pmid21206097">{{cite journal | last=Trikudanathan | first=G | last2=Philip | first2=A | last3=Dasanu | first3=CA | last4=Baker | first4=WL | title=Association between Helicobacter pylori infection and pancreatic cancer. A cumulative meta-analysis. | journal=JOP : Journal of the pancreas | volume=12 | issue=1 | date=Jan 5, 2011 | issn=1590-8577 | pmid=21206097 | pages=26–31}}</ref><br />'''Prostate cancer''' is associated with BK virus,<ref name="pmid26699530">{{Cite journal|last=Tognon|first=Mauro|last2=Provenzano|first2=Maurizio|date=2015-12-23|title=New insights on the association between the prostate cancer and the small DNA tumour virus, BK polyomavirus|url=https://pubmed.ncbi.nlm.nih.gov/26699530/|journal=Journal of Translational Medicine|volume=13|pages=387|doi=10.1186/s12967-015-0754-z|issn=1479-5876|pmc=4690311|pmid=26699530}}</ref> and HPV.<ref name="pmid30508006">{{Cite journal|last=Medel-Flores|first=Olivia|last2=Valenzuela-Rodríguez|first2=Vania Alejandra|last3=Ocadiz-Delgado|first3=Rodolfo|last4=Castro-Muñoz|first4=Leonardo Josué|last5=Hernández-Leyva|first5=Sandra|last6=Lara-Hernández|first6=Gabriel|last7=Silva-Escobedo|first7=Jesús-Gabriel|last8=Vidal|first8=Patricio Gariglio|last9=Sánchez-Monroy|first9=Virginia|date=Oct 2018|title=Association between HPV infection and prostate cancer in a Mexican population|url=https://pubmed.ncbi.nlm.nih.gov/30508006/|journal=Genetics and Molecular Biology|volume=41|issue=4|pages=781–789|doi=10.1590/1678-4685-GMB-2017-0331|issn=1415-4757|pmc=6415601|pmid=30508006}}</ref><br />'''Skin neoplasm''' is associated with HPV.<ref name="pmid12873884">{{cite journal | last=Masini | first=Cinzia | last2=Fuchs | first2=Pawel G. | last3=Gabrielli | first3=Fabrizio | last4=Stark | first4=Sabine | last5=Sera | first5=Francesco | last6=Ploner | first6=Miriam | last7=Melchi | first7=Carmelo Franco | last8=Primavera | first8=Grazia | last9=Pirchio | first9=Giulio | last10=Picconi | first10=Orietta | last11=Petasecca | first11=Pierpaolo | last12=Cattaruzza | first12=Maria Sofia | last13=Pfister | first13=Herbert J. | last14=Abeni | first14=Damiano | title=Evidence for the Association of Human Papillomavirus Infection and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals | journal=Archives of dermatology| volume=139 | issue=7 | date=Jul 1, 2003 | issn=0003-987X | pmid=12873884 | doi=10.1001/archderm.139.7.890 | page=}}</ref><br />'''Squamous cell carcinoma''' is associated with HPV.<ref name="pmid24629358">{{Cite journal|last=Wang|first=Jennifer|last2=Aldabagh|first2=Bishr|last3=Yu|first3=Justin|last4=Arron|first4=Sarah Tuttleton|date=Apr 2014|title=Role of human papillomavirus in cutaneous squamous cell carcinoma: a meta-analysis|url=https://pubmed.ncbi.nlm.nih.gov/24629358/|journal=Journal of the American Academy of Dermatology|volume=70|issue=4|pages=621–629|doi=10.1016/j.jaad.2014.01.857|issn=1097-6787|pmc=3959664|pmid=24629358}}</ref><br />'''Stomach cancer''' is associated with the bacterium helicobacter pylori.<ref name="pmid26171139">{{Cite journal|last=Ishaq|first=Sauid|last2=Nunn|first2=Lois|date=2015|title=Helicobacter pylori and gastric cancer: a state of the art review|url=https://pubmed.ncbi.nlm.nih.gov/26171139/|journal=Gastroenterology and Hepatology from Bed to Bench|volume=8|issue=Suppl 1|pages=S6–S14|issn=2008-2258|pmc=4495426|pmid=26171139}}</ref><br />'''Thyroid cancer''' is associated with simian virus 40.<ref name="pmid12574230">{{Cite journal|last=Vivaldi|first=Agnese|last2=Pacini|first2=Furio|last3=Martini|first3=Fernanda|last4=Iaccheri|first4=Laura|last5=Pezzetti|first5=Furio|last6=Elisei|first6=Rossella|last7=Pinchera|first7=Aldo|last8=Faviana|first8=Pinuccia|last9=Basolo|first9=Fulvio|date=Feb 2003|title=Simian virus 40-like sequences from early and late regions in human thyroid tumors of different histotypes|url=https://pubmed.ncbi.nlm.nih.gov/12574230/|journal=The Journal of Clinical Endocrinology and Metabolism|volume=88|issue=2|pages=892–899|doi=10.1210/jc.2002-020436|issn=0021-972X|pmid=12574230}}</ref>
|-
| '''Chronic fatigue syndrome'''
| [[ME/CFS]] is associated with [[enterovirus]]es (such as [[coxsackie B]] virus),<ref name="pmid17872383">{{cite journal | last=Chia | first=J K S | last2=Chia | first2=A Y | title=Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach | journal=Journal of clinical pathology | volume=61 | issue=1 | date=Sep 14, 2007 | issn=0021-9746 | pmid=17872383 | doi=10.1136/jcp.2007.050054 | pages=43–48}}</ref><ref name="pmid19828908">{{cite journal | last=Chia | first=J. | last2=Chia | first2=A. | last3=Voeller | first3=M. | last4=Lee | first4=T. | last5=Chang | first5=R. | title=Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence | journal=Journal of clinical pathology | volume=63 | issue=2 | date=2010 | issn=0021-9746 | pmid=19828908 | doi=10.1136/jcp.2009.070466 | pages=165–168}}</ref> partial reactivation of [[Epstein-Barr virus]],<ref name="pmid23155374">{{cite journal | last=Lerner | first=A. Martin | last2=Ariza | first2=Maria E. | last3=Williams | first3=Marshall | last4=Jason | first4=Leonard | last5=Beqaj | first5=Safedin | last6=Fitzgerald | first6=James T. | last7=Lemeshow | first7=Stanley | last8=Glaser | first8=Ronald | editor-last=Moormann | editor-first=Ann M. | title=Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset | journal=PloS one | volume=7 | issue=11 | date=Nov 14, 2012 | issn=1932-6203 | pmid=23155374 | pmc=3498272 | doi=10.1371/journal.pone.0047891 | page=e47891}}</ref> [[human herpesvirus 6#HHPV-6A|human herpesvirus 6A]],<ref name="pmid7650209">{{Cite journal|last=Di Luca|first=D.|last2=Zorzenon|first2=M.|last3=Mirandola|first3=P.|last4=Colle|first4=R.|last5=Botta|first5=G. A.|last6=Cassai|first6=E.|date=Jun 1995
|title=Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/7650209/|journal=Journal of Clinical Microbiology|volume=33|issue=6|pages=1660–1661|doi=10.1128/JCM.33.6.1660-1661.1995|issn=0095-1137|pmid=7650209}}</ref> [[human herpesvirus 7]],<ref name="pmid17276369">{{cite journal| vauthors=Chapenko S, Krumina A, Kozireva S, Nora Z, Sultanova A, Viksna L | display-authors=etal| title=Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome. | journal=J Clin Virol | date= 2006 | volume= 37 | issue= Suppl 1| pages= S47-51 | pmid=17276369 | doi=10.1016/S1386-6532(06)70011-7 | pmc= | url=https://pubmed.ncbi.nlm.nih.gov/17276369 }} </ref> and [[parvovirus B19]].<ref name="pmid18277075">{{cite journal | last=Seishima | first=Mariko | last2=Mizutani | first2=Yoko | last3=Shibuya | first3=Yoshinao | last4=Arakawa | first4=Chikako | title=Chronic Fatigue Syndrome after Human Parvovirus B19 Infection without Persistent Viremia | journal=Dermatology (Basel, Switzerland) | volume=216 | issue=4 | date=2008 | issn=1018-8665 | pmid=18277075 | doi=10.1159/000116723 | pages=341–346}}</ref><ref name="pmid11911112">{{cite journal | last=Kerr | first=JR | last2=Bracewell | first2=J | last3=Laing | first3=I | last4=Mattey | first4=DL | last5=Bernstein | first5=RM | last6=Bruce | first6=IN | last7=Tyrrell | first7=DA | title=Chronic fatigue syndrome and arthralgia following parvovirus B19 infection. | journal=The Journal of rheumatology | volume=29 | issue=3 | date=2002 | issn=0315-162X | pmid=11911112 | pages=595–602}}</ref> The intracellular bacterium [[chlamydia pneumoniae]]<ref name="pmid10476765">{{cite journal | last=Chia | first=John K. S. | last2=Chia | first2=Laura Y. | title=Chronic Chlamydia pneumoniae Infection: A Treatable Cause of Chronic Fatigue Syndrome | journal=Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | volume=29 | issue=2 | date=1999 | issn=1058-4838 | pmid=10476765 | doi=10.1086/520239 | pages=452–453}}</ref> is also linked chronic fatigue syndrome.
|-
| '''Chronic myocarditis'''
| Chronic myocarditis is associated with the [[enterovirus]] [[coxsackie B]] virus.<ref name="pmid18357775">{{cite book | last=Chapman | first=N. M. | last2=Kim | first2=K. -S. | title=Current Topics in Microbiology and Immunology | chapter=Persistent Coxsackievirus Infection: Enterovirus Persistence in Chronic Myocarditis and Dilated Cardiomyopathy | journal=Current topics in microbiology and immunology | publisher=Springer | location=Berlin, Heidelberg | volume=323 | date=2008 | isbn=978-3-540-75545-6 | pmid=18357775 | doi=10.1007/978-3-540-75546-3_13 | pages=275–292}}</ref>
|-
| '''Chronic obstructive pulmonary disease'''
| Chronic obstructive pulmonary disease (COPD), which includes both chronic bronchitis and emphysema, is associated with chlamydia pneumoniae<ref name="pmid9129592">{{Cite journal|last=Von Hertzen|first=L.|last2=Alakärppä|first2=H.|last3=Koskinen|first3=R.|last4=Liippo|first4=K.|last5=Surcel|first5=H. M.|last6=Leinonen|first6=M.|last7=Saikku|first7=P.|date=Apr 1997|title=Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease|url=https://pubmed.ncbi.nlm.nih.gov/9129592/|journal=Epidemiology and Infection|volume=118|issue=2|pages=155–164|doi=10.1017/s095026889600725x|issn=0950-2688|pmc=2808789|pmid=9129592}}</ref> and Epstein-Barr virus.<ref name="pmid18287127">{{cite journal | last=McManus | first=T. E. | last2=Marley | first2=A-M. | last3=Baxter | first3=N. | last4=Christie | first4=S. N. | last5=Elborn | first5=J. S. | last6=O'Neill | first6=H. J. | last7=Coyle | first7=P. V. | last8=Kidney | first8=J. C. | title=High levels of Epstein-Barr virus in COPD | journal=The European respiratory journal | volume=31 | issue=6 | date=Mar 5, 2008 | issn=0903-1936 | pmid=18287127 | doi=10.1183/09031936.00107507 | pages=1221–1226}}</ref>
|-
| '''Crohn's disease'''
| Crohn's disease is linked to a thin layer of infection on the intestinal lining with the fungus [[candida tropicalis]], in tandem with the bacteria [[escherichia coli]] (e-coli) and serratia marcescens.<ref name="pmid27651359">{{Cite journal|last=Hoarau|first=G.|last2=Mukherjee|first2=P. K.|last3=Gower-Rousseau|first3=C.|last4=Hager|first4=C.|last5=Chandra|first5=J.|last6=Retuerto|first6=M. A.|last7=Neut|first7=C.|last8=Vermeire|first8=S.|last9=Clemente|first9=J.|date=2016-09-20|title=Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn's Disease|url=https://pubmed.ncbi.nlm.nih.gov/27651359/|journal=mBio|volume=7|issue=5|doi=10.1128/mBio.01250-16|issn=2150-7511|pmc=5030358|pmid=27651359}}</ref><br /><br />One study found ileocecal Crohn's disease is associated with viral species from the [[enterovirus]] genus (but note that all the study cohort with ileocecal Crohn's disease had disease-associated mutations in either their NOD2 or ATG16L1 genes).<ref name="pmid23804031">{{Cite journal|last=Nyström|first=Niklas|last2=Berg|first2=Tove|last3=Lundin|first3=Elin|last4=Skog|first4=Oskar|last5=Hansson|first5=Inga|last6=Frisk|first6=Gun|last7=Juko-Pecirep|first7=Ivana|last8=Nilsson|first8=Mats|last9=Gyllensten|first9=Ulf|date=2013-06-27|title=Human enterovirus species B in ileocecal Crohn's disease|url=https://pubmed.ncbi.nlm.nih.gov/23804031/|journal=Clinical and Translational Gastroenterology|volume=4|pages=e38|doi=10.1038/ctg.2013.7|issn=2155-384X|pmc=3696939|pmid=23804031}}</ref><br /><br />Crohn's disease is associated with mycobacterium avium subspecies paratuberculosis.<ref name="pmid20857526">{{cite journal | last=Mendoza | first=Juan L | title=High prevalence of viableMycobacterium aviumsubspeciesparatuberculosisin Crohn’s disease | journal=World journal of gastroenterology | volume=16 | issue=36 | date=Sep 28, 2010 | issn=1007-9327 | pmid=20857526 | pmc=2945487 | doi=10.3748/wjg.v16.i36.4558 | page=4558}}</ref><br /><br />In a mouse model, Crohn's disease is precipitated by the [[norovirus]] CR6 strain,<ref name=":0" /> but only in combination with a variant of the Crohn's susceptibility gene ATG16L1, and chemical toxic damage to the gut. In other words, in this mouse model, Crohn's is precipitated only when these three causal factors (virus, gene, and toxin) act in combination.
|-
| '''Coronary heart disease'''
| Coronary heart disease is associated with herpes simplex virus 1 and the bacterium chlamydia pneumoniae.<ref name="pmid10645920">{{cite journal | last=Roivainen | first=Merja | last2=Viik-Kajander | first2=Maarit | last3=Palosuo | first3=Timo | last4=Toivanen | first4=Petri | last5=Leinonen | first5=Maija | last6=Saikku | first6=Pekka | last7=Tenkanen | first7=Leena | last8=Manninen | first8=Vesa | last9=Hovi | first9=Tapani | last10=Mänttäri | first10=Matti | title=Infections, Inflammation, and the Risk of Coronary Heart Disease | journal=Circulation | volume=101 | issue=3 | date=Jan 25, 2000 | issn=0009-7322 | pmid=10645920 | doi=10.1161/01.cir.101.3.252 | pages=252–257}}</ref> Coronary heart disease is linked to cytomegalovirus.<ref>{{Cite journal|last=Du|first=Yu|last2=Zhang|first2=Guangxue|last3=Liu|first3=Zhijun|date=2018-02-06|title=Human cytomegalovirus infection and coronary heart disease: a systematic review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801777/|journal=Virology Journal|volume=15|doi=10.1186/s12985-018-0937-3|issn=1743-422X|pmc=5801777|pmid=29409508}}</ref>
|-
| '''Dementia'''
| Dementia is associated with herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, [[West Nile virus]], [[Borna disease virus]], and HIV. Dementia is also associated with the helminth taenia solium (pork tapeworm), and with borrelia<ref name="pmid7943444" /> species bacteria.
|-
| '''[[Depression]]'''
|
Depression is associated with [[cytomegalovirus]]<ref name="pmid17703915" /> and [[West Nile virus]],<ref name="pmid17552106">{{cite journal | last=Murray | first=Kristy O. | last2=Resnick | first2=Melissa | last3=Miller | first3=Vicki | title=Depression after Infection with West Nile Virus1 | journal=Emerging infectious diseases | volume=13 | issue=3 | date=2007 | issn=1080-6040 | pmid=17552106 | pmc=2725905 | doi=10.3201/eid1303.060602 | pages=479–481}}</ref> and the protozoan parasite [[toxoplasma gondii]].<ref name="pmid15018628">{{cite journal | last=Kar | first=Nilamadhab | last2=Misra | first2=Baikunthanath | title=Toxoplasma seropositivity and depression: a case report | journal=BMC psychiatry | volume=4 | issue=1 | date=Feb 5, 2004 | issn=1471-244X | pmid=15018628 | pmc=356918 | doi=10.1186/1471-244x-4-1 | page=}}</ref> It is thought that depression may be precipitated by the effect of immune signals (such as pro-inflammatory cytokines) reaching the brain from infections located in the peripheries of the body.<ref name="pmid18073775">{{cite journal | last=Dantzer | first=Robert | last2=O'Connor | first2=Jason C. | last3=Freund | first3=Gregory G. | last4=Johnson | first4=Rodney W. | last5=Kelley | first5=Keith W. | title=From inflammation to sickness and depression: when the immune system subjugates the brain | journal=Nature reviews. Neuroscience | volume=9 | issue=1 | date=2008 | issn=1471-003X | pmid=18073775 | pmc=2919277 | doi=10.1038/nrn2297 | pages=46–56}}</ref><ref name="pmid19389580">{{cite journal | last=Dantzer | first=Robert | title=Cytokine, Sickness Behavior, and Depression | journal=Immunology and allergy clinics of North America | volume=29 | issue=2 | date=2009 | issn=0889-8561 | pmid=19389580 | pmc=2740752 | doi=10.1016/j.iac.2009.02.002 | pages=247–264}}</ref>

'''[[depression|Major depressive disorder]]''' is associated with [[Borna disease virus]],<ref name="pmid12857781" /> as well as [[bartonella]]<ref name="pmid18092060">{{Cite journal|last=Schaller|first=James L.|last2=Burkland|first2=Glenn A.|last3=Langhoff|first3=P. J.|date=2007-09-13|title=Do bartonella infections cause agitation, panic disorder, and treatment-resistant depression?|url=https://pubmed.ncbi.nlm.nih.gov/18092060/|journal=MedGenMed: Medscape General Medicine|volume=9|issue=3|pages=54|issn=1531-0132|pmc=2100128|pmid=18092060}}</ref> and [[borrelia]]<ref name="pmid7943444" /> species bacteria.<br />'''Seasonal affective disorder''' is associated with Epstein-Barr virus.<ref name="Natelson1994a">{{Cite journal|last=Natelson|first=Benjamin H.|author-link=Benjamin Natelson|last2=Ye|first2=Ning|author-link2=|last3=Moul|first3=Douglas E.|author-link3=|last4=Jenkins|first4=Frank J.|author-link4=|last5=Oren|first5=Dan A.|author-link5=|last6=Tapp|first6=Walter N.|author-link6=|last7=Cheng|first7=Yung-Chi|last8=|first8=|date=Jan 1994|title=High titers of anti-epstein-barr virus DNA polymerase are found in patients with severe fatiguing illness|url=http://doi.wiley.com/10.1002/jmv.1890420109|journal=Journal of Medical Virology|language=en|volume=42|issue=1|pages=42–46|doi=10.1002/jmv.1890420109|pmc=|pmid=|access-date=|quote=|via=}}</ref>
|-
| '''[[Diabetes#type_1|Diabetes mellitus type 1]]'''
| Type 1 diabetes is associated with viral species from the enterovirus genus,<ref name="pmid21292721">{{cite journal | last=Yeung | first=W.-C. G. | last2=Rawlinson | first2=W. D. | last3=Craig | first3=M. E. | title=Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies | journal=BMJ (Clinical research ed.) | volume=342 | issue=feb03 1 | date=Feb 3, 2011 | issn=0959-8138 | pmid=21292721 | pmc=3033438 | doi=10.1136/bmj.d35 | pages=d35–d35}}</ref><ref name="pmid19266182">{{cite journal | last=Richardson | first=S. J. | last2=Willcox | first2=A. | last3=Bone | first3=A. J. | last4=Foulis | first4=A. K. | last5=Morgan | first5=N. G. | title=The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes | journal=Diabetologia | volume=52 | issue=6 | date=Mar 6, 2009 | issn=0012-186X | pmid=19266182 | doi=10.1007/s00125-009-1276-0 | pages=1143–1151}}</ref> such as [[echovirus]] 4,<ref name="pmid11905853">{{cite journal | last=García | first=Igrid | last2=Abalos | first2=Ivonne | last3=Jofrat | first3=Raisa | last4=Molina | first4=Gisela | last5=Díaz-díaz | first5=Oscar | last6=Dimario | first6=Umberto | title=Echovirus 4 and type 1 Diabetes Mellitus | journal=Autoimmunity | volume=34 | issue=4 | date=2001 | issn=0891-6934 | pmid=11905853 | doi=10.3109/08916930109014696 | pages=275–281}}</ref> echovirus 16,<ref name="pmid12898016">{{cite journal | last=Cabrera-Rode | first=E. | last2=Sarmiento | first2=L. | last3=Tiberti | first3=C. | last4=Molina | first4=G. | last5=Barrios | first5=J. | last6=Hernández | first6=D. | last7=Díaz-Horta | first7=O. | last8=Di Mario | first8=U. | title=Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16 | journal=Diabetologia | volume=46 | issue=10 | date=Jul 29, 2003 | issn=0012-186X | pmid=12898016 | doi=10.1007/s00125-003-1179-4 | pages=1348–1353}}</ref> and [[coxsackie B4 virus]].<ref name="pmid18951821">{{cite journal | last=Jaïdane | first=H. | last2=Hober | first2=D. | title=Role of coxsackievirus B4 in the pathogenesis of type 1 diabetes | journal=Diabetes & metabolism | volume=34 | issue=6 | date=2008 | issn=1262-3636 | pmid=18951821 | doi=10.1016/j.diabet.2008.05.008 | pages=537–548}}</ref><ref name="pmid17360338">{{cite journal | last=Dotta | first=F. | last2=Censini | first2=S. | last3=van Halteren | first3=A. G. S. | last4=Marselli | first4=L. | last5=Masini | first5=M. | last6=Dionisi | first6=S. | last7=Mosca | first7=F. | last8=Boggi | first8=U. | last9=Muda | first9=A. O. | last10=Prato | first10=S. D. | last11=Elliott | first11=J. F. | last12=Covacci | first12=A. | last13=Rappuoli | first13=R. | last14=Roep | first14=B. O. | last15=Marchetti | first15=P. | title=Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients | journal=Proceedings of the National Academy of Sciences of the United States of America | volume=104 | issue=12 | date=Mar 14, 2007 | issn=0027-8424 | pmid=17360338 | pmc=1829272 | doi=10.1073/pnas.0700442104 | pages=5115–5120}}</ref> [[coxsackie B]] virus can infect and destroy the insulin-producing beta cells in the pancreas, and also damage these cells via indirect autoimmune mechanisms).<ref name="pmid15236922">{{cite journal | last=KAWASHIMA | first=H | last2=IHARA | first2=T | last3=IOI | first3=H | last4=OANA | first4=S | last5=SATO | first5=S | last6=KATO | first6=N | last7=TAKAMI | first7=T | last8=KASHIWAGI | first8=Y | last9=TAKEKUMA | first9=K | last10=HOSHIKA | first10=A | title=Enterovirus-related type 1 diabetes mellitus and antibodies to glutamic acid decarboxylase in Japan | journal=The Journal of infection | volume=49 | issue=2 | date=2004 | issn=0163-4453 | pmid=15236922 | doi=10.1016/j.jinf.2004.01.012 | pages=147–151}}</ref><br />
Coxsackie B1 virus is associated with a higher risk of the beta cell autoimmunity that portends type 1 diabetes, whereas Coxsackie B3 and B6 viruses is associated with a ''reduced'' risk of such autoimmunity (possibly due to immune cross-protection against Coxsackie B1 virus).<ref name="pmid23974921">{{Cite journal|last=Laitinen|first=Olli H.|last2=Honkanen|first2=Hanna|last3=Pakkanen|first3=Outi|last4=Oikarinen|first4=Sami|last5=Hankaniemi|first5=Minna M.|last6=Huhtala|first6=Heini|last7=Ruokoranta|first7=Tanja|last8=Lecouturier|first8=Valérie|last9=André|first9=Philippe|date=Feb 2014|title=Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes|url=https://pubmed.ncbi.nlm.nih.gov/23974921/|journal=Diabetes|volume=63|issue=2|pages=446–455|doi=10.2337/db13-0619|issn=1939-327X|pmid=23974921}}</ref><br /><br />In boys, human [[parechovirus]] infection has been linked to a subsequent appearance of diabetes-associated autoantibodies.<ref name="pmid23852688">{{Cite journal|last=Kolehmainen|first=P.|last2=Koskiniemi|first2=M.|last3=Oikarinen|first3=S.|last4=Veijola|first4=R.|last5=Simell|first5=O.|last6=Ilonen|first6=J.|last7=Knip|first7=M.|last8=Hyöty|first8=H.|last9=Tauriainen|first9=S.|date=Sep 2013|title=Human parechovirus and the risk of type 1 diabetes|url=https://pubmed.ncbi.nlm.nih.gov/23852688/|journal=Journal of Medical Virology|volume=85|issue=9|pages=1619–1623|doi=10.1002/jmv.23659|issn=1096-9071|pmid=23852688}}</ref> Like enterovirus, parechovirus is a genus in the [[picornavirus]] family.
|-
| '''[[Diabetes#type_2|Diabetes mellitus type 2]]'''
| Type 2 diabetes is associated with cytomegalovirus,<ref name="pmid16108236">{{cite journal| vauthors=Roberts BW, Cech I| title=Association of type 2 diabetes mellitus and seroprevalence for cytomegalovirus. | journal=South Med J | date=2005 | volume= 98 | issue= 7 | pages= 686-92 | pmid=16108236 | doi=10.1097/01.SMJ.0000163310.12516.2D | pmc= | url=https://pubmed.ncbi.nlm.nih.gov/16108236 }} </ref> [[hepatitis C virus]],<ref name="pmid19340895">{{cite journal | last=Negro | first=Francesco | last2=Alaei | first2=Mahnaz | title=Hepatitis C virus and type 2 diabetes | journal=World journal of gastroenterology | volume=15 | issue=13 | date=Apr 7, 2009 | issn=1007-9327 | pmid=19340895 | pmc=2669937 | doi=10.3748/wjg.15.1537 | page=1537}}</ref> [[enteroviruses]]<ref name="pmid19266182" /> and ljungan virus,<ref name="pmid19780970">{{cite journal | last=Holmberg | first=Rebecka | last2=Klitz | first2=William | last3=Blixt | first3=Martin | last4=Berggren | first4=Per-Olof | last5=Juntti-Berggren | first5=Lisa | last6=Niklasson | first6=Bo | title=Antiviral treatments reduce severity of diabetes in Ljungan virus-infected CD-1 mice and delay onset in diabetes-prone BB rats | journal=Microbiology and immunology | volume=53 | issue=10 | date=2009 | issn=0385-5600 | pmid=19780970 | doi=10.1111/j.1348-0421.2009.00160.x | pages=567–572}}</ref> In rabbits, exposure to toxic shock syndrome toxin-1 from a staphylococcus aureus infection leads to impaired glucose tolerance, the hallmark of type 2 diabetes in humans.<ref name="pmid25714716">{{Cite journal|last=Vu|first=Bao G.|last2=Stach|first2=Christopher S.|last3=Kulhankova|first3=Katarina|last4=Salgado-Pabón|first4=Wilmara|last5=Klingelhutz|first5=Aloysius J.|last6=Schlievert|first6=Patrick M.|date=2015-02-24|title=Chronic superantigen exposure induces systemic inflammation, elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes|url=https://pubmed.ncbi.nlm.nih.gov/25714716/|journal=mBio|volume=6|issue=2|pages=e02554|doi=10.1128/mBio.02554-14|issn=2150-7511|pmc=4358007|pmid=25714716}}</ref>
|-
| '''Dilated cardiomyopathy'''
| Dilated cardiomyopathy is associated with [[enterovirus]]es such as [[coxsackie B]] virus.<ref name="pmid12015932">{{cite journal | last=San Martín | first=Miguel A. | last2=García | first2=Ángel | last3=Rodríguez | first3=Francisco J. | last4=Terol | first4=Ignacio | title=Autoinmunidad y miocardiopatía dilatada: situación actual y perspectivas | journal=Revista espanola de cardiologia | volume=55 | issue=5 | date=2002 | issn=0300-8932 | pmid=12015932 | doi=10.1016/s0300-8932(02)76644-x | pages=514–524 | language=es}}</ref>
|-
| '''Epilepsy'''
| Mesial temporal lobe epilepsy is associated with infection by [[human herpesvirus 6#HPV6B|human herpesvirus 6 virus variant B]] (HHV-6B) of the astrocyte cells of the brain.<ref name="pmid17535102">{{cite journal | last=Fotheringham | first=Julie | last2=Donati | first2=Donatella | last3=Akhyani | first3=Nahid | last4=Fogdell-Hahn | first4=Anna | last5=Vortmeyer | first5=Alexander | last6=Heiss | first6=John D | last7=Williams | first7=Elizabeth | last8=Weinstein | first8=Steven | last9=Bruce | first9=Derek A | last10=Gaillard | first10=William D | last11=Sato | first11=Susumu | last12=Theodore | first12=William H | last13=Jacobson | first13=Steven | editor-last=Graeber | editor-first=Manuel | title=Association of Human Herpesvirus-6B with Mesial Temporal Lobe Epilepsy | journal=PLoS medicine | volume=4 | issue=5 | date=May 29, 2007 | issn=1549-1676 | pmid=17535102 | pmc=1880851 | doi=10.1371/journal.pmed.0040180 | page=e180}}</ref><ref name="pmid25840441">{{Cite journal|last=Kawamura|first=Yoshiki|last2=Nakayama|first2=Ai|last3=Kato|first3=Taichi|last4=Miura|first4=Hiroki|last5=Ishihara|first5=Naoko|last6=Ihira|first6=Masaru|last7=Takahashi|first7=Yukitoshi|last8=Matsuda|first8=Kazumi|last9=Yoshikawa|first9=Tetsushi|date=2015-10-01|title=Pathogenic Role of Human Herpesvirus 6B Infection in Mesial Temporal Lobe Epilepsy|url=https://pubmed.ncbi.nlm.nih.gov/25840441/|journal=The Journal of Infectious Diseases|volume=212|issue=7|pages=1014–1021|doi=10.1093/infdis/jiv160|issn=1537-6613|pmid=25840441}}</ref> Epilepsy is associated with HPV infection of the brain.<ref name="pmid23280839">{{Cite journal|last=Chen|first=Julie|last2=Tsai|first2=Victoria|last3=Parker|first3=Whitney E.|last4=Aronica|first4=Eleonora|last5=Baybis|first5=Marianna|last6=Crino|first6=Peter B.|date=Dec 2012|title=Detection of human papillomavirus in human focal cortical dysplasia type IIB|url=https://pubmed.ncbi.nlm.nih.gov/23280839/|journal=Annals of Neurology|volume=72|issue=6|pages=881–892|doi=10.1002/ana.23795|issn=1531-8249|pmid=23280839}}</ref>
|-
| '''[[Guillain-Barré syndrome]]'''
| Guillain-Barré syndrome is associated with the bacterium [[campylobacter jejuni]],<ref name="pmid24000328">{{Cite journal|last=Nyati|first=Kishan Kumar|last2=Nyati|first2=Roopanshi|date=2013|title=Role of Campylobacter jejuni infection in the pathogenesis of Guillain-Barré syndrome: an update|url=https://pubmed.ncbi.nlm.nih.gov/24000328/|journal=BioMed Research International|volume=2013|pages=852195|doi=10.1155/2013/852195|issn=2314-6141|pmc=3755430|pmid=24000328}}</ref> and with the viruses cytomegalovirus<ref name="pmid8797462">{{Cite journal|last=Visser|first=L. H.|last2=van der Meché|first2=F. G.|last3=Meulstee|first3=J.|last4=Rothbarth|first4=P. P.|last5=Jacobs|first5=B. C.|last6=Schmitz|first6=P. I.|last7=van Doorn|first7=P. A.|date=Sep 1996|title=Cytomegalovirus infection and Guillain-Barré syndrome: the clinical, electrophysiologic, and prognostic features. Dutch Guillain-Barré Study Group|url=https://pubmed.ncbi.nlm.nih.gov/8797462/|journal=Neurology|volume=47|issue=3|pages=668–673|doi=10.1212/wnl.47.3.668|issn=0028-3878|pmid=8797462}}</ref> and enterovirus.<ref name="pmid10815319">{{cite journal| vauthors=Clement O, Vázquez M, Pérez EE, Magaña A, Santillán MA, Briseño B| title=[Enterovirus determination in cases with a diagnosis of the Guillain-Barré syndrome by using the acid-concentration technic]. | journal=Gac Med Mex | date= 2000 | volume= 136 | issue= 2 | pages= 93-7 | pmid=10815319 | doi= | pmc= | url=https://europepmc.article/med/10815319 }} </ref>
|-
| '''[[Hypertension]]'''
| Hypertension (high blood pressure) is associated with enteroviruses such as [[Coxsackie_B#B5|coxsackievirus B5]] and [[echovirus]].<ref name="pmid24940338">{{Cite journal|last=Okonko|first=I. O.|last2=Adebiyi|first2=A. A.|last3=Ogah|first3=O. S.|last4=Adu|first4=F. D.|date=Dec 2013|title=Enteroviruses as a possible cause of hypertension, dilated cardiomyopathy (DCM) and hypertensive heart failure (HHF) in South western Nigeria|url=https://pubmed.ncbi.nlm.nih.gov/24940338/|journal=African Health Sciences|volume=13|issue=4|pages=1098–1106|doi=10.4314/ahs.v13i4.34|issn=1729-0503|pmc=4056497|pmid=24940338}}</ref>
|-
| '''Infertility'''
| Infertility is associated with an infection of the endometrium with the A variant of [[human herpesvirus 6]] virus (HHV-6A ).<ref name="pmid27367597">{{Cite journal|last=Marci|first=Roberto|last2=Gentili|first2=Valentina|last3=Bortolotti|first3=Daria|last4=Lo Monte|first4=Giuseppe|last5=Caselli|first5=Elisabetta|last6=Bolzani|first6=Silvia|last7=Rotola|first7=Antonella|last8=Di Luca|first8=Dario|last9=Rizzo|first9=Roberta|date=2016|title=Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility|url=https://pubmed.ncbi.nlm.nih.gov/27367597/|journal=PloS One|volume=11|issue=7|pages=e0158304|doi=10.1371/journal.pone.0158304|issn=1932-6203|pmc=4930213|pmid=27367597}}</ref>
|-
| '''[[Interstitial cystitis]]'''
| The ulcerative form of interstitial cystitis is associated with an infection of the bladder tissues with polyomavirus, and in particular BK virus.<ref name="pmid26325074">{{Cite journal|last=Winter|first=Benjamin J.|last2=O'Connell|first2=Helen E.|last3=Bowden|first3=Scott|last4=Carey|first4=Marcus|last5=Eisen|first5=Damon P.|date=2015|title=A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration|url=https://pubmed.ncbi.nlm.nih.gov/26325074/|journal=PloS One|volume=10|issue=9|pages=e0137310|doi=10.1371/journal.pone.0137310|issn=1932-6203|pmc=4556646|pmid=26325074}}</ref> Interstitial cystitis is associated with an infection of the bladder tissues with [[Epstein-Barr virus]].<ref name="pmid29653163">{{Cite journal|last=Jhang|first=Jia-Fong|last2=Hsu|first2=Yung-Hsiang|last3=Peng|first3=Chih-Wen|last4=Jiang|first4=Yuan-Hong|last5=Ho|first5=Han-Chen|last6=Kuo|first6=Hann-Chorng|date=Sep 2018|title=Epstein-Barr Virus as a Potential Etiology of Persistent Bladder Inflammation in Human Interstitial Cystitis/Bladder Pain Syndrome|url=https://pubmed.ncbi.nlm.nih.gov/29653163/|journal=The Journal of Urology|volume=200|issue=3|pages=590–596|doi=10.1016/j.juro.2018.03.133|issn=1527-3792|pmid=29653163}}</ref>
|-
| '''[[Irritable bowel syndrome]]'''
| Irritable bowel syndrome (IBS) is associated with the bacteria [[Escherichia coli]]<ref name="pmid17359324">{{cite journal | last=Sobieszczańska | first=B.M. | last2=Osek | first2=J. | last3=Waśko-Czopnik | first3=D. | last4=Dworniczek | first4=E. | last5=Jermakow | first5=K. | title=Association of enteroaggregative Escherichia coli with irritable bowel syndrome | journal=Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | volume=13 | issue=4 | date=2007 | issn=1198-743X | pmid=17359324 | doi=10.1111/j.1469-0691.2006.01669.x | pages=404–407}}</ref> and Mycobacterium avium subspecies paratuberculosis,<ref name="pmid17913930">{{cite journal | last=Scanu | first=A. M. | last2=Bull | first2=T. J. | last3=Cannas | first3=S. | last4=Sanderson | first4=J. D. | last5=Sechi | first5=L. A. | last6=Dettori | first6=G. | last7=Zanetti | first7=S. | last8=Hermon-Taylor | first8=J. | title=Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities | journal=Journal of clinical microbiology | volume=45 | issue=12 | date=Oct 3, 2007 | issn=0095-1137 | pmid=17913930 | pmc=2168579 | doi=10.1128/jcm.01371-07 | pages=3883–3890}}</ref> the protozoan parasite [[Giardia lamblia]],<ref name="pmid19821794">{{cite journal | last=Morken | first=Mette Helvik | last2=Valeur | first2=Jørgen | last3=Norin | first3=Elisabeth | last4=Midtvedt | first4=Tore | last5=Nysæter | first5=Gunnar | last6=Berstad | first6=Arnold | title=Antibiotic or bacterial therapy in post-giardiasis irritable bowel syndrome | journal=Scandinavian journal of gastroenterology | volume=44 | issue=11 | date=Oct 13, 2009 | issn=0036-5521 | pmid=19821794 | doi=10.3109/00365520903274401 | pages=1296–1303}}</ref> and pathogenic strains of the protozoan parasite [[blastocystis hominis]].<ref name="pmid19393117">{{cite journal | last=STENSVOLD | first=C. R. | last2=LEWIS | first2=H. C. | last3=HAMMERUM | first3=A. M. | last4=PORSBO | first4=L. J. | last5=NIELSEN | first5=S. S. | last6=OLSEN | first6=K. E. P. | last7=ARENDRUP | first7=M. C. | last8=NIELSEN | first8=H. V. | last9=MØLBAK | first9=K. | title=Blastocystis: unravelling potential risk factors and clinical significance of a common but neglected parasite | journal=Epidemiology and infection | volume=137 | issue=11 | date=Apr 27, 2009 | issn=0950-2688 | pmid=19393117 | doi=10.1017/s0950268809002672 | pages=1655–1663}}</ref> Irritable bowel syndrome in those with HIV is associated with the protozoan Dientamoeba fragilis.<ref name="pmid15258093">{{Cite journal|last=Johnson|first=Eugene H.|author-link=|last2=Windsor|first2=Jeffrey J.|author-link2=|last3=Clark|first3=C. Graham|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jul 2004|title=Emerging from obscurity: biological, clinical, and diagnostic aspects of Dientamoeba fragilis|url=https://pubmed.ncbi.nlm.nih.gov/15258093/|journal=Clinical Microbiology Reviews|volume=17|issue=3|pages=553–570, table of contents|doi=10.1128/CMR.17.3.553-570.2004|issn=0893-8512|pmc=|pmid=15258093|access-date=|quote=|via=}}</ref>
|-
| '''Lower back pain'''
| Lower back pain is associated with a spinal disc infection with anaerobic bacteria, especially the bacterium Propionibacterium acnes.<ref name="pmid23404353">{{Cite journal|last=Albert|first=Hanne B.|last2=Sorensen|first2=Joan S.|last3=Christensen|first3=Berit Schiott|last4=Manniche|first4=Claus|date=Apr 2013|title=Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy|url=https://pubmed.ncbi.nlm.nih.gov/23404353/|journal=European Spine Journal: Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society|volume=22|issue=4|pages=697–707|doi=10.1007/s00586-013-2675-y|issn=1432-0932|pmc=3631045|pmid=23404353}}</ref><ref name="pmid23397187">{{Cite journal|last=Albert|first=Hanne B.|last2=Lambert|first2=Peter|last3=Rollason|first3=Jess|last4=Sorensen|first4=Joan Solgaard|last5=Worthington|first5=Tony|last6=Pedersen|first6=Mogens Bach|last7=Nørgaard|first7=Hanne Schack|last8=Vernallis|first8=Ann|last9=Busch|first9=Frederik|date=Apr 2013|title=Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae?|url=https://pubmed.ncbi.nlm.nih.gov/23397187/|journal=European Spine Journal: Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society|volume=22|issue=4|pages=690–696|doi=10.1007/s00586-013-2674-z|issn=1432-0932|pmc=3631023|pmid=23397187}}</ref>
|-
| '''[[Systemic lupus erythematosus|Lupus]]'''
| Lupus is associated with the viruses [[parvovirus B19]],<ref name="pmid18549931">{{Cite journal|last=Aslanidis|first=Spyros|last2=Pyrpasopoulou|first2=Athina|last3=Kontotasios|first3=Kostas|last4=Doumas|first4=Stella|last5=Zamboulis|first5=Chryssanthos|date=Jul 2008|title=Parvovirus B19 infection and systemic lupus erythematosus: Activation of an aberrant pathway?|url=https://pubmed.ncbi.nlm.nih.gov/18549931/|journal=European Journal of Internal Medicine|volume=19|issue=5|pages=314–318|doi=10.1016/j.ejim.2007.09.013|issn=1879-0828|pmid=18549931}}</ref> Epstein-Barr virus,<ref name="pmid16896283">{{Cite journal|last=James|first=Judith A.|last2=Harley|first2=John B.|last3=Scofield|first3=R. Hal|date=Sep 2006|title=Epstein-Barr virus and systemic lupus erythematosus|url=https://pubmed.ncbi.nlm.nih.gov/16896283/|journal=Current Opinion in Rheumatology|volume=18|issue=5|pages=462–467|doi=10.1097/01.bor.0000240355.37927.94|issn=1040-8711|pmid=16896283}}</ref> and cytomegalovirus.<ref name="pmid9272302">{{Cite journal|last=Rider|first=J. R.|last2=Ollier|first2=W. E.|last3=Lock|first3=R. J.|last4=Brookes|first4=S. T.|last5=Pamphilon|first5=D. H.|date=Jul 1997|title=Human cytomegalovirus infection and systemic lupus erythematosus|url=https://pubmed.ncbi.nlm.nih.gov/9272302/|journal=Clinical and Experimental Rheumatology|volume=15|issue=4|pages=405–409|issn=0392-856X|pmid=9272302}}</ref>
|-
| '''Macular degeneration'''
| Neovascular (wet) macular degeneration is associated with high titers of cytomegalovirus.<ref name="pmid15364212">{{Cite journal|last=Miller|first=Daniel M.|last2=Espinosa-Heidmann|first2=Diego G.|last3=Legra|first3=Jessica|last4=Dubovy|first4=Sander R.|last5=Sũner|first5=Ivan J.|last6=Sedmak|first6=Daniel D.|last7=Dix|first7=Richard D.|last8=Cousins|first8=Scott W.|date=Sep 2004|title=The association of prior cytomegalovirus infection with neovascular age-related macular degeneration|url=https://pubmed.ncbi.nlm.nih.gov/15364212/|journal=American Journal of Ophthalmology|volume=138|issue=3|pages=323–328|doi=10.1016/j.ajo.2004.03.018|issn=0002-9394|pmid=15364212}}</ref><ref name="pmid22570607">{{Cite journal|last=Cousins|first=Scott W.|last2=Espinosa-Heidmann|first2=Diego G.|last3=Miller|first3=Daniel M.|last4=Pereira-Simon|first4=Simone|last5=Hernandez|first5=Eleut P.|last6=Chien|first6=Hsin|last7=Meier-Jewett|first7=Courtney|last8=Dix|first8=Richard D.|date=2012|title=Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization|url=https://pubmed.ncbi.nlm.nih.gov/22570607/|journal=PLoS pathogens|volume=8|issue=4|pages=e1002671|doi=10.1371/journal.ppat.1002671|issn=1553-7374|pmc=3343109|pmid=22570607}}</ref>
|-
| '''Metabolic syndrome'''
| Metabolic syndrome is associated with the bacteria Chlamydia pneumoniae<ref name="pmid20016424">{{Cite journal|last=Lin|first=Ching-Yih|last2=Su|first2=Shih-Bin|last3=Chang|first3=Chih-Ching|last4=Lee|first4=Tsung-Ming|last5=Shieh|first5=Jiunn-Min|last6=Guo|first6=How-Ran|date=Dec 2009|title=The association between Chlamydia pneumoniae and metabolic syndrome in Taiwanese adults|url=https://pubmed.ncbi.nlm.nih.gov/20016424/|journal=Southern Medical Journal|volume=102|issue=12|pages=1203–1208|doi=10.1097/SMJ.0b013e3181c043d9|issn=1541-8243|pmid=20016424}}</ref> and helicobacter pylori, as well as the viruses cytomegalovirus] and herpes simplex virus 1.<ref name="pmid17140429">{{Cite journal|last=Nabipour|first=Iraj|last2=Vahdat|first2=Katayon|last3=Jafari|first3=Seyed Mojtaba|last4=Pazoki|first4=Raha|last5=Sanjdideh|first5=Zahra|date=2006-12-01|title=The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: the Persian Gulf Healthy Heart Study|url=https://pubmed.ncbi.nlm.nih.gov/17140429/|journal=Cardiovascular Diabetology|volume=5|pages=25|doi=10.1186/1475-2840-5-25|issn=1475-2840|pmc=1697801|pmid=17140429}}</ref>
|-
| '''[[Multiple sclerosis]]'''
| Multiple sclerosis, a demyelinating disease, is associated with Epstein-Barr virus<ref name="pmid16927411">{{Cite journal|last=Haahr|first=Sven|last2=Höllsberg|first2=Per|date=Sep 2006|title=Multiple sclerosis is linked to Epstein-Barr virus infection|url=https://pubmed.ncbi.nlm.nih.gov/16927411/|journal=Reviews in Medical Virology|volume=16|issue=5|pages=297–310|doi=10.1002/rmv.503|issn=1052-9276|pmid=16927411}}</ref> (and strongly associated with certain genetic variants of this virus<ref name="pmid25740864">{{Cite journal|last=Mechelli|first=Rosella|last2=Manzari|first2=Caterina|last3=Policano|first3=Claudia|last4=Annese|first4=Anita|last5=Picardi|first5=Ernesto|last6=Umeton|first6=Renato|last7=Fornasiero|first7=Arianna|last8=D'Erchia|first8=Anna Maria|last9=Buscarinu|first9=Maria Chiara|date=2015-03-31|title=Epstein-Barr virus genetic variants are associated with multiple sclerosis|url=https://pubmed.ncbi.nlm.nih.gov/25740864/|journal=Neurology|volume=84|issue=13|pages=1362–1368|doi=10.1212/WNL.0000000000001420|issn=1526-632X|pmc=4388746|pmid=25740864}}</ref> which is found in the brain tissues of most ME patients,<ref name="pmid29394264">{{Cite journal|last=Hassani|first=Asma|last2=Corboy|first2=John R.|last3=Al-Salam|first3=Suhail|last4=Khan|first4=Gulfaraz|date=2018|title=Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells|url=https://pubmed.ncbi.nlm.nih.gov/29394264/|journal=PloS One|volume=13|issue=2|pages=e0192109|doi=10.1371/journal.pone.0192109|issn=1932-6203|pmc=5796799|pmid=29394264}}</ref> [[human herpesvirus 6]],<ref name="pmid20926836">{{Cite journal|last=Voumvourakis|first=Konstantine I.|last2=Kitsos|first2=Dimitrios K.|last3=Tsiodras|first3=Sotirios|last4=Petrikkos|first4=George|last5=Stamboulis|first5=Eleftherios|date=Nov 2010|title=Human herpesvirus 6 infection as a trigger of multiple sclerosis|url=https://pubmed.ncbi.nlm.nih.gov/20926836/|journal=Mayo Clinic Proceedings|volume=85|issue=11|pages=1023–1030|doi=10.4065/mcp.2010.0350|issn=1942-5546|pmc=2966366|pmid=20926836}}</ref> human herpesvirus 6 variant A,<ref name="pmid32038605">{{Cite journal|last=Engdahl|first=Elin|last2=Gustafsson|first2=Rasmus|last3=Huang|first3=Jesse|last4=Biström|first4=Martin|last5=Lima Bomfim|first5=Izaura|last6=Stridh|first6=Pernilla|last7=Khademi|first7=Mohsen|last8=Brenner|first8=Nicole|last9=Butt|first9=Julia|date=2019|title=Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis|url=https://pubmed.ncbi.nlm.nih.gov/32038605/|journal=Frontiers in Immunology|volume=10|pages=2715|doi=10.3389/fimmu.2019.02715|issn=1664-3224|pmc=6988796|pmid=32038605}}</ref> [[varicella zoster virus]],<ref name="pmid18306233">{{Cite journal|last=Sotelo|first=Julio|last2=Martínez-Palomo|first2=Adolfo|last3=Ordoñez|first3=Graciela|last4=Pineda|first4=Benjamin|date=Mar 2008|title=Varicella-zoster virus in cerebrospinal fluid at relapses of multiple sclerosis|url=https://pubmed.ncbi.nlm.nih.gov/18306233/|journal=Annals of Neurology|volume=63|issue=3|pages=303–311|doi=10.1002/ana.21316|issn=1531-8249|pmid=18306233}}</ref> and the bacterium chlamydia pneumoniae.<ref name="pmid12606878">{{Cite journal|last=Munger|first=Kassandra L.|last2=Peeling|first2=Rosanna W.|last3=Hernán|first3=Miguel A.|last4=Chasan-Taber|first4=Lisa|last5=Olek|first5=Michael J.|last6=Hankinson|first6=Susan E.|last7=Hunter|first7=David|last8=Ascherio|first8=Alberto|date=Mar 2003|title=Infection with Chlamydia pneumoniae and risk of multiple sclerosis|url=https://pubmed.ncbi.nlm.nih.gov/12606878/|journal=Epidemiology (Cambridge, Mass.)|volume=14|issue=2|pages=141–147|doi=10.1097/01.EDE.0000050699.23957.8E|issn=1044-3983|pmid=12606878}}</ref>
|-
| '''Myocardial infarction'''
| Myocardial infarction (heart attack) is associated with chlamydia pneumoniae,<ref name="pmid15791511">{{Cite journal|last=Arcari|first=Christine M.|last2=Gaydos|first2=Charlotte A.|last3=Nieto|first3=F. Javier|last4=Krauss|first4=Margot|last5=Nelson|first5=Kenrad E.|date=2005-04-15|title=Association between Chlamydia pneumoniae and acute myocardial infarction in young men in the United States military: the importance of timing of exposure measurement|url=https://pubmed.ncbi.nlm.nih.gov/15791511/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=40|issue=8|pages=1123–1130|doi=10.1086/428730|issn=1537-6591|pmid=15791511}}</ref> [[cytomegalovirus]]<ref name="pmid14618212">{{Cite journal|last=Gabrylewicz|first=Bogna|last2=Mazurek|first2=Urszula|last3=Ochała|first3=Andrzej|last4=Sliupkas-Dyrda|first4=Elektra|last5=Garbocz|first5=Piotr|last6=Pyrlik|first6=Andrzej|last7=Mróz|first7=Iwona|last8=Wilczok|first8=Tadeusz|last9=Tendera|first9=Michał|date=Oct 2003|title=Cytomegalovirus infection in acute myocardial infarction. Is there a causative relationship?|url=https://pubmed.ncbi.nlm.nih.gov/14618212/|journal=Kardiologia Polska|volume=59|issue=10|pages=283–292|issn=0022-9032|pmid=14618212}}</ref> and [[Coxsackie B virus]] (an enterovirus).<ref name="pmid18061067" /><br />
Coxsackie B virus and enterovirus are also associated with sudden unexpected death due to myocarditis.<ref name="pmid22966951">{{Cite journal|last=Gaaloul|first=Imed|last2=Riabi|first2=Samira|last3=Harrath|first3=Rafik|last4=Evans|first4=Mark|last5=Salem|first5=Nidhal H.|last6=Mlayeh|first6=Souheil|last7=Huber|first7=Sally|last8=Aouni|first8=Mahjoub|date=2012-09-11|title=Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem|url=https://pubmed.ncbi.nlm.nih.gov/22966951/|journal=BMC infectious diseases|volume=12|pages=212|doi=10.1186/1471-2334-12-212|issn=1471-2334|pmc=3462138|pmid=22966951}}</ref> An autopsy study found 40% of those who died of sudden heart attack had enterovirus markers in their endomyocardial tissues, compared to 8% in controls.<ref name="pmid18061067">{{Cite journal|last=Andréoletti|first=Laurent|last2=Ventéo|first2=Lydie|last3=Douche-Aourik|first3=Fatima|last4=Canas|first4=Frédéric|last5=Lorin de la Grandmaison|first5=Geoffroy|last6=Jacques|first6=Jérôme|last7=Moret|first7=Hélène|last8=Jovenin|first8=Nicolas|last9=Mosnier|first9=Jean-François|date=2007-12-04|title=Active Coxsackieviral B infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction|url=https://pubmed.ncbi.nlm.nih.gov/18061067/|journal=Journal of the American College of Cardiology|volume=50|issue=23|pages=2207–2214|doi=10.1016/j.jacc.2007.07.080|issn=1558-3597|pmid=18061067}}</ref>
|-
| '''Myopia'''
| Myopia (short-sightedness) is associated with childhood febrile illnesses of [[measles]], rubella, pertussis and mumps.<ref name="pmid26846593">{{Cite journal|last=Guggenheim|first=J. A.|last2=Williams|first2=C.|last3=UK Biobank Eye and Vision Consortium|date=Apr 2016|title=Childhood febrile illness and the risk of myopia in UK Biobank participants|url=https://pubmed.ncbi.nlm.nih.gov/26846593/|journal=Eye (London, England)|volume=30|issue=4|pages=608–614|doi=10.1038/eye.2016.7|issn=1476-5454|pmc=4834038|pmid=26846593}}</ref>
|-
| '''Obesity'''
|
Obesity is associated with [[adenovirus 36]], which is found in 30% of obese people, but only in 11% of non-obese people.<ref name="pmid15611785">{{Cite journal|last=Atkinson|first=R. L.|last2=Dhurandhar|first2=N. V.|last3=Allison|first3=D. B.|last4=Bowen|first4=R. L.|last5=Israel|first5=B. A.|last6=Albu|first6=J. B.|last7=Augustus|first7=A. S.|date=Mar 2005|title=Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids|url=https://pubmed.ncbi.nlm.nih.gov/15611785/|journal=International Journal of Obesity (2005)|volume=29|issue=3|pages=281–286|doi=10.1038/sj.ijo.0802830|issn=0307-0565|pmid=15611785}}</ref><ref name="pmid19593728">{{Cite journal|last=Atkinson|first=Richard L.|last2=Lee|first2=Insil|last3=Shin|first3=Hye-Jung|last4=He|first4=Jia|date=Apr 2010|title=Human adenovirus-36 antibody status is associated with obesity in children|url=https://pubmed.ncbi.nlm.nih.gov/19593728/|journal=International journal of pediatric obesity: IJPO: an official journal of the International Association for the Study of Obesity|volume=5|issue=2|pages=157–160|doi=10.3109/17477160903111789|issn=1747-7174|pmid=19593728}}</ref> It has further been demonstrated that animals experimentally infected with adenovirus 36 (and likewise adenovirus 5 or adenovirus 37) will develop increased obesity.<ref name="pmid19960394">{{Cite journal|last=McAllister|first=Emily J.|last2=Dhurandhar|first2=Nikhil V.|last3=Keith|first3=Scott W.|last4=Aronne|first4=Louis J.|last5=Barger|first5=Jamie|last6=Baskin|first6=Monica|last7=Benca|first7=Ruth M.|last8=Biggio|first8=Joseph|last9=Boggiano|first9=Mary M.|date=Nov 2009|title=Ten putative contributors to the obesity epidemic|url=https://pubmed.ncbi.nlm.nih.gov/19960394/|journal=Critical Reviews in Food Science and Nutrition|volume=49|issue=10|pages=868–913|doi=10.1080/10408390903372599|issn=1549-7852|pmc=2932668|pmid=19960394}}</ref> And it is known adenovirus 36 causes a proliferation of fat cells (adipocytes).<ref name="pmid26184280">{{Cite journal|last=Ponterio|first=Eleonora|last2=Gnessi|first2=Lucio|date=2015-07-08|title=Adenovirus 36 and Obesity: An Overview|url=https://pubmed.ncbi.nlm.nih.gov/26184280/|journal=Viruses|volume=7|issue=7|pages=3719–3740|doi=10.3390/v7072787|issn=1999-4915|pmc=4517116|pmid=26184280}}</ref><br /><br />Evidence suggests that obesity may be a viral disease, and that the worldwide obesity epidemic that began in the 1980s may be in part due to viral infection.<ref name="pmid17420782">{{Cite journal|last=Vasilakopoulou|first=A.|last2=le Roux|first2=C. W.|date=Sep 2007|title=Could a virus contribute to weight gain?|url=https://pubmed.ncbi.nlm.nih.gov/17420782/|journal=International Journal of Obesity (2005)|volume=31|issue=9|pages=1350–1356|doi=10.1038/sj.ijo.0803623|issn=0307-0565|pmid=17420782}}</ref><ref name="pmid17908526">{{Cite journal|last=Atkinson|first=Richard L.|date=Oct 2007|title=Viruses as an etiology of obesity|url=https://pubmed.ncbi.nlm.nih.gov/17908526/|journal=Mayo Clinic Proceedings|volume=82|issue=10|pages=1192–1198|doi=10.4065/82.10.1192|issn=0025-6196|pmid=17908526}}</ref>
Obesity is also associated with higher gut levels of certain Firmicutes bacteria in relation to bacteroidetes bacteria. Overweight individuals tend have more Firmicutes bacteria (such as clostridium, [[staphylococcus]], [[streptococcus]], and helicobacter pylori) in their gut, whereas normal weight individuals tend have more bacteroidetes bacteria.<ref name="pmid17183309">{{Cite journal|last=Ley|first=Ruth E.|last2=Turnbaugh|first2=Peter J.|last3=Klein|first3=Samuel|last4=Gordon|first4=Jeffrey I.|date=2006-12-21|title=Microbial ecology: human gut microbes associated with obesity|url=https://pubmed.ncbi.nlm.nih.gov/17183309/|journal=Nature|volume=444|issue=7122|pages=1022–1023|doi=10.1038/4441022a|issn=1476-4687|pmid=17183309}}</ref>
|-
| '''Obsessive-compulsive disorder'''
| Obsessive-compulsive disorder is associated with streptococcus<ref name="pmid17703915" /> and borrelia<ref name="pmid7943444" /> species bacteria.
|-
| '''Panic disorder'''
| Panic disorder is associated with borrelia<ref name="pmid7943444" /> and bartonella species bacteria.<ref name="pmid18092060" />
|-
| '''Parkinson's disease'''
| Parkinson's disease is associated with [[enterovirus]],<ref name="pmid29899977">{{Cite journal|last=Dourmashkin|first=Robert R.|last2=McCall|first2=Sherman A.|last3=Dourmashkin|first3=Neil|last4=Hannah|first4=Matthew J.|date=2018|title=Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson's disease|url=https://pubmed.ncbi.nlm.nih.gov/29899977/|journal=F1000Research|volume=7|pages=302|doi=10.12688/f1000research.13626.2|issn=2046-1402|pmc=5968367|pmid=29899977}}</ref> [[influenza#influenza_A|influenza A]] virus,<ref name="pmid10507986">{{Cite journal|last=Takahashi|first=M.|last2=Yamada|first2=T.|date=Jun 1999|title=Viral etiology for Parkinson's disease--a possible role of influenza A virus infection|url=https://pubmed.ncbi.nlm.nih.gov/10507986/|journal=Japanese Journal of Infectious Diseases|volume=52|issue=3|pages=89–98|issn=1344-6304|pmid=10507986}}</ref> as well as the protozoan parasite toxoplasma gondii.<ref name="pmid20350582">{{Cite journal|last=Miman|first=Ozlem|last2=Kusbeci|first2=Ozge Yilmaz|last3=Aktepe|first3=Orhan Cem|last4=Cetinkaya|first4=Zafer|date=2010-05-21|title=The probable relation between Toxoplasma gondii and Parkinson's disease|url=https://pubmed.ncbi.nlm.nih.gov/20350582/|journal=Neuroscience Letters|volume=475|issue=3|pages=129–131|doi=10.1016/j.neulet.2010.03.057|issn=1872-7972|pmid=20350582}}</ref>
|-
| '''Psoriasis'''
| Psoriasis is associated with a helicobacter pylori trigger.<ref name="pmid17642857">{{Cite journal|last=Qayoom|first=S.|last2=Ahmad|first2=Q. M.|date=Mar 2003|title=Psoriasis and Helicobacter pylori|url=https://pubmed.ncbi.nlm.nih.gov/17642857/|journal=Indian Journal of Dermatology, Venereology and Leprology|volume=69|issue=2|pages=133–134|issn=0973-3922|pmid=17642857}}</ref>
|-
| '''[[Rheumatoid arthritis]]'''
| Rheumatoid arthritis is linked to the bacterium porphyromonas gingivalis,<ref name="pmid27605245">{{Cite journal|last=Johansson|first=Linda|last2=Sherina|first2=Natalia|last3=Kharlamova|first3=Nastya|last4=Potempa|first4=Barbara|last5=Larsson|first5=Barbro|last6=Israelsson|first6=Lena|last7=Potempa|first7=Jan|last8=Rantapää-Dahlqvist|first8=Solbritt|last9=Lundberg|first9=Karin|date=2016-09-07|title=Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis|url=https://pubmed.ncbi.nlm.nih.gov/27605245/|journal=Arthritis Research & Therapy|volume=18|pages=201|doi=10.1186/s13075-016-1100-4|issn=1478-6362|pmc=5015325|pmid=27605245}}</ref> and the bacterium proteus mirabilis.<ref name="pmid17206398">{{Cite journal|last=Rashid|first=Taha|last2=Ebringer|first2=Alan|date=Jul 2007|title=Rheumatoid arthritis is linked to Proteus--the evidence|url=https://pubmed.ncbi.nlm.nih.gov/17206398/|journal=Clinical Rheumatology|volume=26|issue=7|pages=1036–1043|doi=10.1007/s10067-006-0491-z|issn=0770-3198|pmid=17206398}}</ref> Rheumatoid arthritis is associated with [[parvovirus B19]].<ref name="pmid18549931" /> Antibodies to [[borrelia]] outer surface protein A are associated with rheumatoid arthritis.<ref name="pmid17881508">{{Cite journal|last=Hsieh|first=Yu-Fan|last2=Liu|first2=Han-Wen|last3=Hsu|first3=Tsai-Ching|last4=Wei|first4=James C.-C.|last5=Shih|first5=Chien-Ming|last6=Krause|first6=Peter J.|last7=Tsay|first7=Gregory J.|date=Nov 2007|title=Serum reactivity against Borrelia burgdorferi OspA in patients with rheumatoid arthritis|url=https://pubmed.ncbi.nlm.nih.gov/17881508/|journal=Clinical and vaccine immunology: CVI|volume=14|issue=11|pages=1437–1441|doi=10.1128/CVI.00151-07|issn=1556-6811|pmc=2168181|pmid=17881508}}</ref>
|-
| '''Sarcoidosis'''
| Sarcoidosis is associated with mycobacteria<ref name="pmid16926652">{{Cite journal|last=Drake|first=Wonder Puryear|last2=Newman|first2=Lee S.|date=Sep 2006|title=Mycobacterial antigens may be important in sarcoidosis pathogenesis|url=https://pubmed.ncbi.nlm.nih.gov/16926652/|journal=Current Opinion in Pulmonary Medicine|volume=12|issue=5|pages=359–363|doi=10.1097/01.mcp.0000239554.01068.94|issn=1070-5287|pmid=16926652}}</ref> species and the bacterium [[helicobacter pylori]].<ref name="pmid15068230">{{Cite journal|last=Herndon|first=Betty L.|last2=Vlach|first2=Victoria|last3=Dew|first3=Michelle|last4=Willsie|first4=Sandra K.|date=Mar 2004|title=Helicobacter pylori-related immunoglobulins in sarcoidosis|url=https://pubmed.ncbi.nlm.nih.gov/15068230/|journal=Journal of Investigative Medicine: The Official Publication of the American Federation for Clinical Research|volume=52|issue=2|pages=137–143|doi=10.1136/jim-52-02-23|issn=1081-5589|pmid=15068230}}</ref>
|-
| '''Schizophrenia'''
| Schizophrenia is associated with [[Borna disease virus]],<ref name="pmid12857781" /> the bacterium chlamydia trachomatis,<ref name="pmid20602604">{{Cite journal|last=Krause|first=Daniela|last2=Matz|first2=Judith|last3=Weidinger|first3=Elif|last4=Wagner|first4=Jenny|last5=Wildenauer|first5=Agnes|last6=Obermeier|first6=Michael|last7=Riedel|first7=Michael|last8=Müller|first8=Norbert|date=Aug 2010|title=The association of infectious agents and schizophrenia|url=https://pubmed.ncbi.nlm.nih.gov/20602604/|journal=The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry|volume=11|issue=5|pages=739–743|doi=10.3109/15622971003653246|issn=1814-1412|pmid=20602604}}</ref> borrelia species bacteria (Lyme disease),<ref name="pmid7943444" /> and Bartonella henselae bacteria (cat scratch disease).<ref>{{Cite journal|last=Lashnits|first=Erin|last2=Maggi|first2=Ricardo|last3=Jarskog|first3=Fredrik|last4=Bradley|first4=Julie|last5=Breitschwerdt|first5=Edward|last6=Frohlich|first6=Flavio|date=2021-03-15|title=Schizophrenia and Bartonella spp. Infection: A Pilot Case-Control Study|url=https://pubmed.ncbi.nlm.nih.gov/33728987/|journal=Vector Borne and Zoonotic Diseases (Larchmont, N.Y.)|doi=10.1089/vbz.2020.2729|issn=1557-7759|pmid=33728987}}</ref> One study found a central nervous system infection as a child (particularly with coxsackievirus B5) increases the risk of developing schizophrenia as an adult by nearly 5-fold.<ref name="pmid9279617">{{Cite journal|last=Rantakallio|first=P.|last2=Jones|first2=P.|last3=Moring|first3=J.|last4=Von Wendt|first4=L.|date=Aug 1997|title=Association between central nervous system infections during childhood and adult onset schizophrenia and other psychoses: a 28-year follow-up|url=https://pubmed.ncbi.nlm.nih.gov/9279617/|journal=International Journal of Epidemiology|volume=26|issue=4|pages=837–843|doi=10.1093/ije/26.4.837|issn=0300-5771|pmid=9279617}}</ref> A large study found [[influenza]] virus infection during the first trimester of pregnancy increases the risk the baby will get schizophrenia later in life by 7-fold; there was no increased risk if the mother caught influenza during the second or third trimesters.<ref name="pmid15289276">{{Cite journal|last=Brown|first=Alan S.|last2=Begg|first2=Melissa D.|last3=Gravenstein|first3=Stefan|last4=Schaefer|first4=Catherine A.|last5=Wyatt|first5=Richard J.|last6=Bresnahan|first6=Michaeline|last7=Babulas|first7=Vicki P.|last8=Susser|first8=Ezra S.|date=Aug 2004|title=Serologic evidence of prenatal influenza in the etiology of schizophrenia|url=https://pubmed.ncbi.nlm.nih.gov/15289276/|journal=Archives of General Psychiatry|volume=61|issue=8|pages=774–780|doi=10.1001/archpsyc.61.8.774|issn=0003-990X|pmid=15289276}}</ref> Schizophrenia is linked to an aberrant immune response to [[Epstein-Barr virus]].<ref name="pmid30462333">{{Cite journal|last=Dickerson|first=Faith|last2=Jones-Brando|first2=Lorraine|last3=Ford|first3=Glen|last4=Genovese|first4=Giulio|last5=Stallings|first5=Cassie|last6=Origoni|first6=Andrea|last7=O'Dushlaine|first7=Colm|last8=Katsafanas|first8=Emily|last9=Sweeney|first9=Kevin|date=2019-09-11|title=Schizophrenia is Associated With an Aberrant Immune Response to Epstein-Barr Virus|url=https://pubmed.ncbi.nlm.nih.gov/30462333/|journal=Schizophrenia Bulletin|volume=45|issue=5|pages=1112–1119|doi=10.1093/schbul/sby164|issn=1745-1701|pmc=6737467|pmid=30462333}}</ref>
|-
| '''[[Sjögren's syndrome]]'''
| Primary Sjögren's syndrome is associated with the [[enterovirus]] [[coxsackie B]] virus.<ref name="pmid15457458">{{Cite journal|last=Triantafyllopoulou|first=Antigoni|last2=Tapinos|first2=Nikos|last3=Moutsopoulos|first3=Haralampos M.|date=Sep 2004|title=Evidence for coxsackievirus infection in primary Sjögren's syndrome|url=https://pubmed.ncbi.nlm.nih.gov/15457458/|journal=Arthritis and Rheumatism|volume=50|issue=9|pages=2897–2902|doi=10.1002/art.20463|issn=0004-3591|pmid=15457458}}</ref>
|-
| '''Stroke'''
| Persistent [[enterovirus]] infection ([[Coxsackie B virus]] or [[echovirus]]) is linked to the development of acute stroke.<ref name="pmid28511156">{{Cite journal|last=Andriushkova|first=Natalia G.|last2=Turchyna|first2=Nataliia S.|last3=Poniatowski|first3=Vadym A.|last4=Dolinchuk|first4=Ludmyla V.|last5=Melnyk|first5=Valentyna V.|last6=Shyrobokov|first6=Volodymyr P.|last7=Zakharchenko|first7=Nataliia V.|date=2017|title=The role of the persistent enterovirus infection in development of acute stroke|url=https://pubmed.ncbi.nlm.nih.gov/28511156/|journal=Wiadomosci Lekarskie (Warsaw, Poland: 1960)|volume=70|issue=2|pages=187–191|issn=0043-5147|pmid=28511156}}</ref> Stroke is associated with the bacteria chlamydia pneumoniae,<ref name="pmid9472881">{{Cite journal|last=Cook|first=P. J.|last2=Honeybourne|first2=D.|last3=Lip|first3=G. Y.|last4=Beevers|first4=D. G.|last5=Wise|first5=R.|last6=Davies|first6=P.|date=Feb 1998|title=Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project|url=https://pubmed.ncbi.nlm.nih.gov/9472881/|journal=Stroke|volume=29|issue=2|pages=404–410|doi=10.1161/01.str.29.2.404|issn=0039-2499|pmid=9472881}}</ref> [[helicobacter pylori]],<ref name="pmid12063957">{{Cite journal|last=Ponzetto|first=Antonio|last2=Marchet|first2=Alberto|last3=Pellicano|first3=Rinaldo|last4=Lovera|first4=Nicoletta|last5=Chianale|first5=Gigliola|last6=Nobili|first6=Marcello|last7=Rizzetto|first7=Mario|last8=Cerrato|first8=Paolo|date=May 2002|title=Association of Helicobacter pylori infection with ischemic stroke of non-cardiac origin: the BAT.MA.N. project study|url=https://pubmed.ncbi.nlm.nih.gov/12063957/|journal=Hepato-Gastroenterology|volume=49|issue=45|pages=631–634|issn=0172-6390|pmid=12063957}}</ref> mycobacterium tuberculosis,<ref name="pmid20035070">{{Cite journal|last=Sheu|first=Jau-Jiuan|last2=Chiou|first2=Hung-Yi|last3=Kang|first3=Jiunn-Horng|last4=Chen|first4=Yi-Hua|last5=Lin|first5=Herng-Ching|date=Feb 2010|title=Tuberculosis and the risk of ischemic stroke: a 3-year follow-up study|url=https://pubmed.ncbi.nlm.nih.gov/20035070/|journal=Stroke|volume=41|issue=2|pages=244–249|doi=10.1161/STROKEAHA.109.567735|issn=1524-4628|pmid=20035070}}</ref> and mycoplasma_pneumoniae,<ref name="pmid16148858">{{Cite journal|last=Leonardi|first=Salvatore|last2=Pavone|first2=Piero|last3=Rotolo|first3=Novella|last4=La Rosa|first4=Mario|date=Sep 2005|title=Stroke in two children with Mycoplasma pneumoniae infection. A causal or casual relationship?|url=https://pubmed.ncbi.nlm.nih.gov/16148858/|journal=The Pediatric Infectious Disease Journal|volume=24|issue=9|pages=843–845|doi=10.1097/01.inf.0000177284.88356.56|issn=0891-3668|pmid=16148858}}</ref> as well as the virus [[varicella zoster virus]]<ref name="pmid19815828">{{Cite journal|last=Kang|first=Jiunn-Horng|author-link=|last2=Ho|first2=Jau-Der|author-link2=|last3=Chen|first3=Yi-Hua|author-link3=|last4=Lin|first4=Herng-Ching|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Nov 2009|title=Increased risk of stroke after a herpes zoster attack: a population-based follow-up study|url=https://pubmed.ncbi.nlm.nih.gov/19815828/|journal=Stroke|volume=40|issue=11|pages=3443–3448|doi=10.1161/STROKEAHA.109.562017|issn=1524-4628|pmc=|pmid=19815828|access-date=|quote=|via=}}</ref> and the fungus histoplasma.<ref name="pmid18755412">{{Cite journal|last=Cleary|first=John D.|last2=Pearson|first2=Margaret|last3=Oliver|first3=Jake|last4=Chapman|first4=Stanley W.|date=Sep 2008|title=Association between Histoplasma exposure and stroke|url=https://pubmed.ncbi.nlm.nih.gov/18755412/|journal=Journal of Stroke and Cerebrovascular Diseases: The Official Journal of National Stroke Association|volume=17|issue=5|pages=312–319|doi=10.1016/j.jstrokecerebrovasdis.2008.01.015|issn=1532-8511|pmid=18755412}}</ref>
|-
| '''Tourette syndrome'''
| Tourette's is associated with the bacterium [[streptococcus]].<ref name="pmid15995031">{{Cite journal|last=Mell|first=Loren K.|author-link=|last2=Davis|first2=Robert L.|author-link2=|last3=Owens|first3=David|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jul 2005|title=Association between streptococcal infection and obsessive-compulsive disorder, Tourette's syndrome, and tic disorder|url=https://pubmed.ncbi.nlm.nih.gov/15995031/|journal=Pediatrics|volume=116|issue=1|pages=56–60|doi=10.1542/peds.2004-2058|issn=1098-4275|pmc=|pmid=15995031|access-date=|quote=|via=}}</ref> Aggravating or contributory microbes in Tourette's may include the bacteria mycoplasma pneumoniae,<ref name="pmid15590039">{{Cite journal|last=Müller|first=Norbert|last2=Riedel|first2=Michael|last3=Blendinger|first3=Christa|last4=Oberle|first4=Karin|last5=Jacobs|first5=Enno|last6=Abele-Horn|first6=Marianne|date=2004-12-15|title=Mycoplasma pneumoniae infection and Tourette's syndrome|url=https://pubmed.ncbi.nlm.nih.gov/15590039/|journal=Psychiatry Research|volume=129|issue=2|pages=119–125|doi=10.1016/j.psychres.2004.04.009|issn=0165-1781|pmid=15590039}}</ref> chlamydia pneumoniae, chlamydia trachomatis, and the protozoan parasite toxoplasma gondii.<ref name="pmid19890596">{{Cite journal|last=Krause|first=Daniela|last2=Matz|first2=Judith|last3=Weidinger|first3=Elif|last4=Wagner|first4=Jenny|last5=Wildenauer|first5=Agnes|last6=Obermeier|first6=Michael|last7=Riedel|first7=Michael|last8=Müller|first8=Norbert|date=Jun 2010|title=Association between intracellular infectious agents and Tourette's syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19890596/|journal=European Archives of Psychiatry and Clinical Neuroscience|volume=260|issue=4|pages=359–363|doi=10.1007/s00406-009-0084-3|issn=1433-8491|pmid=19890596}}</ref>
|-
|'''Valvular heart disease'''
|Heart valve disease is linked to enterovirus<ref>{{Cite journal|last=Li|first=Y.|last2=Pan|first2=Z.|last3=Ji|first3=Y.|last4=Peng|first4=T.|last5=Archard|first5=L. C.|last6=Zhang|first6=H.|date=Apr 2002|title=Enterovirus replication in valvular tissue from patients with chronic rheumatic heart disease|url=https://pubmed.ncbi.nlm.nih.gov/11922647/|journal=European Heart Journal|volume=23|issue=7|pages=567–573|doi=10.1053/euhj.2001.2837|issn=0195-668X|pmid=11922647}}</ref> and coxsackievirus B<ref>{{Cite journal|last=Burch|first=G. E.|last2=Sun|first2=S. C.|last3=Colcolough|first3=H. L.|last4=Sohal|first4=R. S.|last5=DePasquale|first5=N. P.|date=Jul 1967|title=Coxsackie B viral myocarditis and valvulitis identified in routine autopsy specimens by immunofluorescent techniques|url=https://pubmed.ncbi.nlm.nih.gov/5338726/|journal=American Heart Journal|volume=74|issue=1|pages=13–23|doi=10.1016/0002-8703(67)90035-x|issn=0002-8703|pmid=5338726}}</ref> infection of the heart valve tissue.
|-
| '''Vasculitis'''
| Vasculitis is associated with HIV, parvovirus B19,<ref name="pmid18549931" /> and [[hepatitis B virus]]. The [[hepatitis C virus]] is an established and proven cause of vasculitis.
|}

==Pathogens as a cause of chronic diseases==
One champion of the theory that pathogens are the likely cause of many chronic diseases is evolutionary biologist [[wikipedia:Paul_W._Ewald|Professor Paul W. Ewald]], who is one of an increasing number of researchers who believe that many chronic diseases of presently unknown etiology will probably turn out to be caused by persistent low-level microbial infections.<ref name="PlagueTime">{{Cite book|title=Plague Time: The New Germ Theory of Disease|isbn=978-0-385-72184-4|language=en|url=https://books.google.co.uk/books?id=nUApzQwoZ44C&q=%22Bad+genes+and+bad+environments+have+often+been+falsely+accused,+or,+at+least+they+have+taken+more+than+their+share+of+the+blame&redir_esc=y|date=2002|publisher=Anchor Books|last=Ewald|first=Paul W.}}</ref><ref name="InfectiousCausation">{{Cite journal|last=Cochran|first=G. M.|last2=Ewald|first2=P. W.|last3=Cochran|first3=K. D.|date=2000|title=Infectious causation of disease: an evolutionary perspective|url=https://pubmed.ncbi.nlm.nih.gov/10893730/|journal=Perspectives in Biology and Medicine|volume=43|issue=3|pages=406–448|doi=10.1353/pbm.2000.0016|issn=0031-5982|pmid=10893730}}</ref>

Professor Ewald supports his thesis with an argument from evolutionary biology, explaining that "''chronic diseases, if they are common and damaging, must be powerful eliminators of any genetic instruction that may cause them''".<ref name="PlagueTime" /> In other words, a disease-causing gene which reduces an animal's survival and its creation of offspring will tend to eliminate itself over a number of generations. Therefore such genetic diseases are self-extinguishing.

Professor Ewald explains that the only genetic diseases which are likely to persist are those which provide a compensating benefit. For example, genes that encode for sickle cell anemia disease are maintained and persist down the generations, as these genes also protect against malaria.

One large meta-analysis found the vast majority of diseases have a very small genetic contribution of only 5% to 10% at most. Though notable exceptions include Crohn's disease, celiac disease and macular degeneration, which have a genetic contribution of about 40% to 50%.<ref name="Pafron2019">{{Cite journal|last=Patron|first=Jonas|last2=Serra-Cayuela|first2=Arnau|last3=Han|first3=Beomsoo|last4=Li|first4=Carin|last5=Wishart|first5=David Scott|date=2019|title=Assessing the performance of genome-wide association studies for predicting disease risk|url=https://pubmed.ncbi.nlm.nih.gov/31805043/|journal=PloS One|volume=14|issue=12|pages=e0220215|doi=10.1371/journal.pone.0220215|issn=1932-6203|pmc=6894795|pmid=31805043}}</ref>

Infectious pathogens are one of several potential causes of disease; other causal factors include environmental toxins (naturally-occurring and man-made), radiation, genetics, epigenetics, events during pregnancy, stress, diet and lifestyle factors.

More than one causal factor may be involved in the development of a disease, and an illness may only manifest when several causal factors are present at the same time. For example, in a mouse model, Crohn's disease can be precipitated by a norovirus, but only when both a specific gene variant is present and a certain toxin has damaged the gut.<ref name=":0">{{Cite journal|last=Cadwell|first=Ken|last2=Patel|first2=Khushbu K.|last3=Maloney|first3=Nicole S.|last4=Liu|first4=Ta-Chiang|last5=Ng|first5=Aylwin C. Y.|last6=Storer|first6=Chad E.|last7=Head|first7=Richard D.|last8=Xavier|first8=Ramnik|last9=Stappenbeck|first9=Thaddeus S.|date=2010-06-25|title=Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine|url=https://pubmed.ncbi.nlm.nih.gov/20602997/|journal=Cell|volume=141|issue=7|pages=1135–1145|doi=10.1016/j.cell.2010.05.009|issn=1097-4172|pmc=2908380|pmid=20602997}}</ref> Thus a pathogen's ability to cause a disease may be contingent upon several other causal factors.

Pathogen-associated diseases include many of the most common and costly chronic illnesses.<ref>{{Cite journal|last=Kockaya|first=Guvenc|last2=Wertheimer|first2=Albert|date=2010-10-26|title=What are the top most costly diseases for USA? The alignment of burden of illness with prevention and screening expenditures|url=http://www.scirp.org/Journal/Paperabs.aspx?paperid=2817|journal=Health|language=en|volume=2|issue=10|pages=1174–1178|doi=10.4236/health.2010.210172}}</ref> About 70% of all deaths in the United States result from chronic diseases, with the treatment of chronic diseases accounting for 75% of all US healthcare costs.<ref>{{Cite web|date=2009|title=Almanac of Chronic Disease|url=http://www.fightchronicdisease.org/sites/default/files/docs/2009AlmanacofChronicDisease_updated81009.pdf|last=Carmona|first=Richard H.|authorlink=|website=|archive-url=|archive-date=|url-status=|access-date=|at=Forward|publisher=Partnership to Fight Chronic Disease}}</ref>

==Difficulties in determining if a pathogen causes the disease==
Determining whether a pathogen plays a causal role in a given chronic disease is difficult for the following reasons:
* The time between contracting the infectious pathogen and the appearance of the first chronic disease symptoms can be lengthy, sometimes decades.
* An infection may be asymptomatic when first contracted and go unnoticed.
* An infectious pathogen may not cause its associated disease in every person.
* Only specific strains of a pathogen may be linked to a disease; other strains may not be so harmful (for example, multiple sclerosis is strongly associated with certain genetic variants of Epstein-Barr virus).<ref>{{Cite journal|last=Mechelli|first=Rosella|last2=Manzari|first2=Caterina|last3=Policano|first3=Claudia|last4=Annese|first4=Anita|last5=Picardi|first5=Ernesto|last6=Umeton|first6=Renato|last7=Fornasiero|first7=Arianna|last8=D'Erchia|first8=Anna Maria|last9=Buscarinu|first9=Maria Chiara|date=2015-03-31|title=Epstein-Barr virus genetic variants are associated with multiple sclerosis|url=https://pubmed.ncbi.nlm.nih.gov/25740864/|journal=Neurology|volume=84|issue=13|pages=1362–1368|doi=10.1212/WNL.0000000000001420|issn=1526-632X|pmc=4388746|pmid=25740864}}</ref>
* A given disease may be precipitated by more than one pathogen.
* A pathogen may precipitate the disease only in combination with one or more other causal factors.
* A pathogenic microbe may only precipitate the disease when it breaches into and infects specific organs. When it infects different organs, a different disease (or no disease) may be precipitated.
* Some pathogens are not easily detectable, and it is difficult to link hard-to-detect pathogens to a disease.
* For obvious ethical reasons, you cannot inoculate pathogenic microbes into humans to see if they do cause the disease.
* A pathogen may cause a disease indirectly, such as via autoimmune processes induced by the pathogen.
In spite of the difficulties in obtaining proof of causality, investigation into the link between pathogenic microbes and chronic disease is ongoing, and there is a large volume of published studies which demonstrate these associations.

==Notable studies==
* 2004, [https://www.ncbi.nlm.nih.gov/books/NBK83689/ The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary] - Forum on Microbial Threats
* 2004, [http://web.archive.org/web/20170810011700/ftp://ftp.cdc.gov/pub/eid/vol4no3/adobe/cassell.pdf Infectious Causes of Chronic Inflammatory Diseases and Cancer] - Lilly Research Laboratories
* 2006, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291059/ Emerging Infectious Determinants of Chronic Diseases]
* 2006, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1479565 The infection connection: Helicobacter pylori is more than just the cause of gastric ulcers: it offers an unprecedented opportunity to study changes in human micro ecology and the nature of chronic disease]
* 2008, [http://www.bjmp.org/content/role-chronic-bacterial-and-viral-infections-neurodegenerative-neurobehavioral-psychiatric-au Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1]
* 2010, [http://www.bjmp.org/content/role-chronic-bacterial-and-viral-infections-neurodegenerative-neurobehavioural-psychiatric-a Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioural, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 2]
* 2012, [http://mpkb.org/home/pathogenesis/evidence_bacteria Evidence That Chronic Disease is Caused by Pathogens] - Autoimmunity Research Foundation
* 2013, [https://pubmed.ncbi.nlm.nih.gov/23935899 Causal Inference Regarding Infectious Aetiology of Chronic Conditions: A Systematic Review]
* 2016, [https://www.youtube.com/watch?v=5q9zAG92V9M Toward a Unified, Evolutionary Theory of Cancer] - Paul Ewald (video presentation focusing on the infectious causes of cancer)

==Articles and blogs==
* [http://www.health.harvard.edu/blog/can-an-infection-suddenly-cause-ocd-201202274417 Can an Infection Suddenly Cause OCD?] - Harvard Health Blog, 2012
* [http://www.atsu.edu/faculty/chamberlain/Website/Lects/Mechanis.htm Mechanisms of Viral Pathogenicity] - Gerald Tritz (Lecture Notes)
* [https://www.nih.gov/news-events/nih-research-matters/crohns-disease-triggers-may-include-viruses-other-factors Crohn’s Disease Triggers May Include Viruses and Other Factors] - National Institutes of Health, 2010
* [http://www.alzforum.org/res/for/journal/detail.asp?liveID=36 Challenging the Primacy of Genetics in Late-Onset Alzheimer Disease] - Alzheimer Research Forum, 2005
*[http://web.archive.org/web/20141005051114/http://www.amednews.com/article/20040719/health/307199977/2/ Infection Eyed as Culprit In Chronic Disease] - American Medical News, 2004

== Learn more==
* [[wikipedia:Paul_W._Ewald|Professor Paul W. Ewald - Wikipedia]]
* [http://www.amazon.com/Plague-Time-Germ-Theory-Disease/dp/0385721846 Plague Time: The New Germ Theory of Disease] - Paul W. Ewald, ''Anchor'', 2002
* [http://microbeminded.com/2017/11/11/interview-with-evolutionary-biologist-paul-ewald-infection-and-chronic-disease/ Interview With Evolutionary Biologist Paul Ewald] - Amy Proal, 2008
* [https://books.google.com/books/about/Stealth_Germs_in_Your_Body.html?id=QcYTiaI0Pe0C Stealth Germs in Your Body] - Erno Daniel, Sterling Publishing Company, 2008
* [http://www.sciencedaily.com/releases/2015/05/150521095016.htm Infections can affect your IQ] - Science Daily, 2015
* [https://www.theatlantic.com/magazine/archive/1999/02/a-new-germ-theory/377430/ A New Germ Theory] - The Atlantic Monthly Magazine, 1999
* [https://www.discovermagazine.com/health/the-big-idea-that-might-beat-cancer-and-cut-health-care-costs-by-80-percent The Big Idea That Might Beat Cancer and Cut Health-Care Costs by 80 Percent] - Discover Magazine, 2009
* [http://www.psychologytoday.com/articles/199907/the-infection-connection The Infection Connection] - Psychology Today, 1999
* [http://www.psychologytoday.com/blog/the-perfectionists-handbook/201202/can-infections-result-in-mental-illness Can Infections Result in Mental Illness?] - Psychology Today, 2012
* [http://www.forbes.com/global/1999/1115/0223102a.html Do Germs Cause Cancer?] - Forbes, 1999
* [http://www.sciencedaily.com/releases/2008/05/080522155752.htm The Emerging Role Of Infection In Alzheimer's Disease] - Science Daily, 2008
* [http://www.medicaldaily.com/people-hospitalized-infections-are-62-more-likely-develop-mood-disorder-246876 People Hospitalized For Infections Are 62% More Likely To Develop A Mood Disorder] - Medical Daily, 2013
* [http://www.livescience.com/43356-chronic-infections-cognitive-decline.html Chronic Infections Linked with Memory Problems Later in Life] - Live Science, 2014

==See also==
*[[Virus]]
*[[Pathogen]]s
*[[:Category:Triggers and risk factors|Triggers and risk factors (category)]]

== References ==
{{Reflist}}

[[Category:Infectious agents]]
[[Category:Lists]]

Nuno Sepúlveda

2021-06-01T19:28:30Z

Kmdenmark:added study and ref

[[File:Nuno Sepulveda.png|200px|thumb|right]]
'''Nuno Sepúlveda''' , BSs, MSc, PhD, is an Assistant Professor of Biostatistics and Statistical Genetics at London School of Hygiene and Tropical Medicine.<ref>{{Cite web|url=https://www.lshtm.ac.uk/aboutus/people/sepulveda.nuno|title=Nuno Sepulveda|website=LSHTM|language=en|access-date=2019-01-23}}</ref> He is a team member of the UK research group, [[CureME]].<ref>{{Cite web|url=https://cureme.lshtm.ac.uk/about-us/cureme-team/|title=People|website=CureMe|language=en|access-date=2019-01-23}}</ref>

== EUROMENE ==
Dr. Sepúlveda is a member of the Working Group on Epidemiology of ME/CFS across Europe on behalf of the [[EUROMENE]], a European Union not-for-profit research organization committed to tackling the cause and treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.<ref>{{Cite web|url=https://www.cost.eu/actions/CA15111/|title=Action CA15111|website=COST|language=en-GB|access-date=2020-03-04}}</ref>

== Research studies ==
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepúlveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]

* 2019, Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref>{{Cite journal|last=Cliff|first=Jacqueline M.|author-link=Jacqueline Cliff|last2=King|first2=Elizabeth C.|author-link2=|last3=Lee|first3=Ji-Sook|author-link3=|last4=Sepúlveda|first4=Nuno|author-link4=Nuno Sepúlveda|last5=Wolf|first5=Asia-Sophia|author-link5=|last6=Kingdon|first6=Caroline|author-link6=Caroline Kingdon|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Dockrell|first8=Hazel M.|author-link8=Hazel Dockrell|last9=Nacul|first9=Luis|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana|author-link10=Eliana Lacerda|last11=Riley|first11=Eleanor|author-link11=Eleanor Riley|date=2019-04-16|title=Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.frontiersin.org/article/10.3389/fimmu.2019.00796/full|journal=Frontiers in Immunology|volume=10|issue=|pages=|doi=10.3389/fimmu.2019.00796|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.00796/full (Full text)]
* 2019, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory [[T cell|T cells]] and chronic human [[Herpesviruses|herpesvirus]] infections<ref>{{Cite journal|last=Sepúlveda|first=Nuno|author-link=Nuno Sepulveda|last2=Carneiro|first2=Jorge|author-link2=|last3=Eliana M. Lacerda|first3=Eliana M.|author-link3=Eliana Lacerda|last4=Nacul|first4=Luis C.|author-link4=Luis Nacul|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Oct 2019|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections|url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract|journal=Frontiers in Immunology|volume=|issue=|pages=|doi=10.3389/fimmu.2019.02684|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract (Abstract)]
* 2020, A potential antigenic mimicry between viral and human proteins linking Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with [[Autoimmune disease|autoimmunity]]: The case of HPV immunization<ref>{{Cite journal|last=Phelan|first=J|author-link=|last2=Grabowska|first2=AD|author-link2=|last3=Sepúlveda|first3=N|author-link3=Nuno Sepúlveda|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=13 Feb 2020|title=A potential antigenic mimicry between viral and human proteins linking Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with autoimmunity: The case of HPV immunization|url=|journal=Autoimmunity Review|volume=102487|issue=|pages=|doi=10.1016/j.autrev.2020.102487|pmc=|pmid=|access-date=|quote=|via=}}</ref>
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology <ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

== Online presence ==
*[https://www.lshtm.ac.uk/aboutus/people/sepulveda.nuno Faculty page for LSHTM]
*[https://www.researchgate.net/profile/Nuno_Sepulveda/2 ResearchGate]

== See also ==
* [[EUROMENE]]
* "[http://simmaronresearch.com/2020/05/immune-battle-chronic-fatigue-syndrome-herpesviruses-regulatory-t-cell/ A Never-Ending Immune War Being Waged in ME/CFS? The Regulatory T-cell / Herpesvirus Hypothesis]" explores Sepulveda's Treg hypothesis and determines how he got interested in ME/CFS.

== Learn more ==
{{reflist}}
[[Category:Researchers]]
[[Category:UK researchers]]
[[Category:Portugal researchers]]

Carmen Scheibenbogen

2021-06-01T19:27:56Z

Kmdenmark:added study and ref

[[File:Carmen Scheibenbogen.png|200px|thumb|right|Source:Invest in ME]]
Professor Doctor '''Carmen Scheibenbogen''' is an Internal Medicine physician, [[ME/CFS]] doctor and the Professor for Immunology and Deputy Chair, Institute of Medical Immunology, at the University Hospital [[Charité Berlin|Charité]] in Berlin, Germany. Her research focuses on the role of [[Epstein-Barr virus]] ([[EBV]]), particularly the characterization of [[EBV]] specific [[B cell]] and [[T cell]] response and the enhanced antibody response against [[EBV]] peptides in [[myalgic encephalomyelitis]] (ME) versus healthy controls.<ref>{{Cite web|url=http://investinme.org/cindex.shtml|title=Invest in ME Research - International ME Conferences and Colloquiums Home Page|website=investinme.org|access-date=2019-11-14}}</ref>

==EUROMENE==
Professor Scheibenbogen is the Leader of the [[Biomarkers]] Working Group of [[EUROMENE]], a European Union, COST Action CA15111, not-for-profit research organization committed to tackling the cause and treatment for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]].<ref>{{Cite web|url=https://www.cost.eu/actions/CA15111/|title=Action CA15111|website=COST|language=en-GB|access-date=2019-11-14}}</ref>

==Diagnostic test==
Professor Scheibenbogen helped create the [[CellTrend Diagnostic Test]] which may help identify a subset of 20-30% of all patients with [[ME/CFS]]. These patients have elevated levels of three auto-antibodies, i.e., against the b2-adrenergic receptor, against the muscarinic cholinergic receptor 3 (M3) and against the muscarinic cholinergic receptor 4 (M4).<ref>{{Cite web|url=https://www.celltrend.de/en/pots-cfs-me-crps.html|title=POTS - CFS/ME - CRPS|website=CellTrend Luckenwalde|language=en-US|access-date=2020-02-18}}</ref>

==Awards==

*2016 [[Ramsay Award]] Program grant recipient, sponsored by the [[Solve ME/CFS Initiative]] for [[Autoimmunity |Autoimmune]] Signature in [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]. This grant was shared with [[Madlen Löbel]], Charité Universitätsmedizin Berlin.<ref>{{Cite web|url=https://solvecfs.org/2016-ramsay-award-program-results/|title=2016 Ramsay Award Program Results|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-11-14}}</ref>
*2017 [[Ramsay Award]] Program grant was awarded to a team comprised of Dr. Carmen Scheibenbogen and Dr. [[Franziska Sotzny]] of Charité Universitätsmedizin Berlin, sponsored by the [[Solve ME/CFS Initiative]] for researching immunometabolism of [[T cell]]s and monocytes in [[ME/CFS]].<ref>{{Cite web|url=https://solvecfs.org/2017-ramsay-award-program-results/|title=2017 Ramsay Award Program Results|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-11-14}}</ref>

==Notable studies==

*2014, Deficient [[EBV]]-Specific [[B cell|B-]] and [[T cell|T-Cell]] Response in Patients with [[Chronic Fatigue Syndrome]]<ref name="Loebel, 2014" /> - [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085387 (Full Text)]
*2015, Frequent IgG subclass and mannose binding lectin deficiency in patients with [[chronic fatigue syndrome]]<ref name="Guenther, 2015" /> - [https://www.sciencedirect.com/science/article/abs/pii/S0198885915004656 (Full Text)]
*2015, Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome<ref name="Loebel, 2015" /> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-015-0628-4 (Full Text)]
*2016, Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with [[Chronic Fatigue Syndrome]]<ref name="Loebel, 2016" /> - [https://www.sciencedirect.com/science/article/pii/S0889159115300209?via%3Dihub (Full Text)]
*2017, Serological profiling of the [[EBV]] immune response in [[Chronic Fatigue Syndrome]] using a peptide microarray<ref name="Loebel, 2017" /> -[http://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0179124 (Full Text)]
*2017, The European ME/CFS [[Biomarker]] Landscape project: an initiative of the European network EUROMENE<ref>{{Cite journal|last=Scheibenbogen|first=Carmen|author-link=Carmen Scheibenbogen|last2=Freitag|first2=Helma|author-link2=Helma Freitag|last3=Blanco|first3=Julià|author-link3=Julià Blanco|last4=Capelli|first4=Enrica|author-link4=Enrica Capelli|last5=Lacerda|first5=Eliana|author-link5=Eliana Lacerda|last6=Authier|first6=Jerome|author-link6=François Jérôme Authier|last7=Meeus|first7=Mira|author-link7=Mira Meeus|last8=Castro Marrero|first8=Jesus|author-link8=Jesús Castro-Marrero|last9=Nora-Krukle|first9=Zaiga|author-link9=Zaiga Nora-Krukle|last10=Oltra|first10=Elisa|author-link10=Elisa Oltra|last11= Strand|first11=Elin Bolle|author-link11=Elin Bolle Strand|last12= Shikova|first12= Evelina|author-link12= Evelina Shikova|last13= Sekulic|first13=Slobodan|author-link13=Slobodan Sekulic|last14=Murovska|first14=Modra|author-link14=Modra Murovska|date=2017-07-26|title=The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1263-z|journal=Journal of Translational Medicine|language=en|volume=15|issue=1|pages=|doi=10.1186/s12967-017-1263-z|issn=1479-5876|pmc=5530475|pmid=28747192|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530475/ (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an [[autoimmune disease]]<ref name="Sotzny, 2018" /> - [https://www.sciencedirect.com/science/article/pii/S1568997218300880 (Full Text)]
*2018, [[Immunoadsorption]] to remove ß2 adrenergic receptor antibodies in [[Chronic Fatigue Syndrome]] [[ME/CFS|CFS/ME]]<ref>{{Cite journal|last=Scheibenbogen|first=Carmen|author-link=Carmen Scheibenbogen|last2=Loebel|first2=Madlen|author-link2=Madlen Löbel|last3=Freitag|first3=Helma|author-link3=Helma Freitag|last4=Krueger|first4=Anne|last5=Bauer|first5=Sandra|last6=Antelmann|first6=Michaela|last7=Doehner|first7=Wolfram|last8=Scherbakov|first8=Nadja|last9=Heidecke|first9=Harald|last10=Reinke|first10=Petra|last11=Volk|first11=Hans-Dieter|last12=Grabowski|first12=Patricia|author-link12=Patricia Grabowski|date=2018|title=Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME|url=http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193672|journal=PLoS ONE|volume=13|issue=3|pages=e0193672|doi=10.1371/journal.pone.0193672|via=}}</ref> - [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193672 (Full Text)]
*2018, The expression signature of very long non-coding [[RNA]] in [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref>{{Cite journal|last=Yang|first=Chin-An|last2=Bauer|first2=Sandra|author-link2=Sandra Bauer|last3=Ho|first3=Yu-Chen|last4=Sotzny|first4=Franziska|author-link4=Franziska Sotzny|last5=Chang|first5=Jan-Gowth|last6=Scheibenbogen|first6=Carmen|author-link6=Carmen Scheibenbogen|date=2018-08-17|title=The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x|journal=Journal of Translational Medicine|language=en|volume=16|issue=1|pages=|doi=10.1186/s12967-018-1600-x|issn=1479-5876|via=}}</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
*2018, Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)<ref>{{Cite journal|last=Rasa|first=Santa|author-link=Santa Rasa|last2=Nora-Krukle|first2=Zaiga|author-link2=Zaiga Nora-Krukle|last3=Henning|first3=Nina|author-link3=|last4=Eliassen|first4=Eva|author-link4=|last5=Shikova|first5=Evelina|author-link5=Evelina Shikova|last6=Harrer|first6=Thomas|author-link6=Thomas Harrer|last7=Scheibenbogen|first7=Carmen|author-link7=Carmen Scheibenbogen|last8=Murovska|first8=Modra|author-link8=Modra Murovska|last9=Prusty|first9=Bhupesh K.|author-link9=Bhupesh Prusty|last10=European Network on ME/CFS (EUROMENE)|first10=|author-link10=EUROMENE|date=2018-10-01|title=Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y|journal=Journal of Translational Medicine|language=en|volume=16|issue=1|pages=|doi=10.1186/s12967-018-1644-y|issn=1479-5876|pmc=|pmid=30285773|quote=|via=}}</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y (Full text)]
*2020, IgG stimulated β2 adrenergic receptor activation is attenuated in patients with ME/CFS<ref name="IgG2020">{{Cite journal|last=Hartwig|first=Jelka|last2=Sotzny|first2=Franziska|last3=Bauer|first3=Sandra|last4=Heidecke|first4=Harald|last5=Riemekasten|first5=Gabriela|last6=Dragun|first6=Duska|last7=Meisel|first7=Christian|last8=Dames|first8=Claudia|last9=Grabowski|first9=Patricia|date=2020-03-01|title=IgG stimulated β2 adrenergic receptor activation is attenuated in patients with ME/CFS|url=http://www.sciencedirect.com/science/article/pii/S2666354620300120|journal=Brain, Behavior, & Immunity - Health|language=en|volume=3|pages=100047|doi=10.1016/j.bbih.2020.100047|issn=2666-3546}}</ref> - [https://www.sciencedirect.com/science/article/pii/S2666354620300120 (Full text)]
*2020, Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Schreiner2020">{{Cite journal|last=Schreiner|first=Philipp|author-link=|last2=Harrer|first2=Thomas|author-link2=Thomas Harrer|last3=Scheibenbogen|first3=Carmen|author-link3=Carmen Scheibenbogen|last4=Lamer|first4=Stephanie|author-link4=|last5=Schlosser|first5=Andreas|author-link5=|last6=Naviaux|first6=Robert K.|author-link6=Robert Naviaux|last7=Prusty|first7=Bhupesh K.|author-link7=Bhupesh Prusty|last8=|first8=|date=2020-04-01|title=Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.immunohorizons.org/content/4/4/201|journal=ImmunoHorizons|language=en|volume=4|issue=4|pages=201–215|doi=10.4049/immunohorizons.2000006|issn=2573-7732|pmc=|pmid=32327453|access-date=|quote=|via=}}</ref> - [https://www.immunohorizons.org/content/4/4/201 (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology <ref name="Estevez-Lopez2020">{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2020, Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome<ref name=endothelial2020>{{Cite journal|last=Scherbakov|first=Nadja|author-link=|last2=Szklarski|first2=Marvin|author-link2=|last3=Hartwig|first3=Jelka|author-link3=|last4=Sotzny|first4=Franziska|author-link4=Franziska Sotzny|last5=Lorenz|first5=Sebastian|author-link5=|last6=Meyer|first6=Antje|author-link6=Antje Meyer|last7=Grabowski|first7=Patricia|last8=Doehner|first8=Wolfram|last9=Scheibenbogen|first9=Carmen|author-link9=Carmen Scheibenbogen|date=2020|title=Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ehf2.12633|journal=ESC Heart Failure|language=en|volume=7|issue=3|pages=1064–1071|doi=10.1002/ehf2.12633|issn=2055-5822|pmc = 7261521|pmid=32154656|access-date=|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/abs/10.1002/ehf2.12633 (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Clinic location==

*[[Charité Berlin|Charité]] University Medicine, Berlin, Germany

==Talks and interviews==

*2018, [https://cfc.charite.de/#c30485288 Talk "Chronic Fatigue Syndrome" for General Practitioners]
*2014, Speaker at the 9th [[Invest in ME International ME Conference]] [http://www.investinme.org/IIMEC9.shtml#dvd DVD available]

==Online presence==

*[http://www.ncbi.nlm.nih.gov/pubmed/?term=Scheibenbogen%20C%5BAuthor%5D&cauthor=true&cauthor_uid=26429318 PubMed]
*[http://immunologie.charite.de/ Institute for Medical Immunology]
*[https://cfc.charite.de/ Charité Fatigue Centrum]

==See also==

*[[Invest in ME International ME Conference]]
*[[EUROMENE]]
*[[Charité Berlin]]

==Learn more==

*[http://www.euromene.eu/workinggroups/Biosketch2016Scheibenbogen.pdf Curriculum Vitae for EUROMENE]

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[[Category:Researchers]]
[[Category:Germany researchers]]
[[Category:Clinicians]]
[[Category:German clinicians]]

Jesús Castro-Marrero

2021-06-01T19:27:13Z

Kmdenmark:added study and ref

[[File:Jesús Castro-Marrero.png|200px|thumb|right|Source:Vall d'Hebron Research Institute (VHIR)]]
'''Jesús Castro-Marrero''', PhD, (also known as '''Jesus Castro''') works at [[Cornell ME/CFS Collaborative Research Center]], New York, US. His research focuses on Extracellular Vesicles/Exosomes biology and decoding differences in the mRNA and miRNA expression cargo from Extracellular Vesicles (EVs) and blood immune cells (peripheral blood mononuclear cells) before and after a 24 hour [[CPET]] challenge in a gender-specific manner in individuals with [[ME/CFS]].

Previously, he was a Senior Research Associate in Biochemistry and Molecular Biology at the Vall d’Hebron University Hospital Research Institute (VHIR), Barcelona, Spain.<ref>{{Cite web|url=http://en.vhir.org/portal1/fitxa-personal.asp?id=51698|title=Vall d'Hebron Research Institute (VHIR)|website=en.vhir.org|language=en|access-date=2019-07-15}}</ref>

==EUROMENE==
Dr. Castro-Marrero is a Working Group Leader on Epidemiology of [[ME/CFS]] across Europe on behalf of the [[EUROMENE]], a European Union not-for-profit research organization committed to tackling the cause and treatment for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]].<ref>{{Cite web|url=https://www.cost.eu/actions/CA15111/|title=Action CA15111|website=COST|language=en-GB|access-date=2020-04-24}}</ref>

==Education==
*1987 - B.S. in Biochemistry, School of Biological Sciences, University of Havana, Cuba
*1999 - Ph.D. in Biochemistry and Molecular Biology, Valladolid University School of Medicine, Spain

==Notable studies==
*2013, Screening [[Natural killer cell|NK-]], [[B cell|B-]] and [[T cell|T-Cell]] phenotype and function in patients suffering from [[Chronic Fatigue Syndrome]]<ref name="Curriu, 2013" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614537/ (Full Text)]
*2013, Could [[mitochondrion|mitochondrial]] dysfunction be a differentiating marker between [[chronic fatigue syndrome]] and [[fibromyalgia]]?<ref name="Castro-Marrero, 2013">{{Citation|last1=Castro-Marrero|first1=J.|authorlink1=Jesús Castro-Marrero|last2=Cordero|first2=M.D.|authorlink2= |last3=Sáez-Francas|first3=N.|authorlink3= |last4=Jimenez-Gutierrez|first4=C.|authorlink4=|last5=Aguilar-Montilla|first5=F.J.|authorlink5= |last6=Aliste|first6=L.|authorlink6= |last7=Alegre-Martin|first7=J.|authorlink7=José Alegre |title=Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia?|journal=Antioxidants & Redox Signaling|volume=19|issue=15|page=1855-1860|date=2013|pmid=23600892|doi=10.1089/ars.2013.5346|url=https://doi.org/10.1089/ars.2013.5346|pages=|chapter=|edition=|isbn=}}</ref> - [https://www.liebertpub.com/doi/abs/10.1089/ars.2013.5346 (Abstract)]
*2014, Impact of the [[fibromyalgia]] in the [[chronic fatigue syndrome]]<ref name="Faro, 2014" /> - [http://europepmc.org/abstract/med/24387955 (Abstract)]
*2015, Does Oral [[Coenzyme Q10]] Plus [[NADH]] Supplementation Improve Fatigue and Biochemical Parameters in [[Chronic Fatigue Syndrome]]?<ref name="Castro-Marrero, 2015">{{Citation|last1=Castro-Marrero|first1=J.|authorlink1=Jesús Castro-Marrero|last2= Cordero|first2=M.D.|authorlink2=|last3=Segundo|first3=M.J.|authorlink3=|last4=Sáez-Francàs|first4=N.|authorlink4=|last5=Calvo|first5=N.|authorlink5 = |last6=Román-Malo|first6=L.|authorlink6=|last7=Aliste|first7=L.|authorlink7 = |last8=Fernández de Sevilla|first8=T.|authorlink8=|last9=Alegre|first9=J.|authorlink9=José Alegre |title=Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome?|journal=Antioxidants & Redox Signaling|volume=22|issue=8 |date=2015|pmid=25386668|doi=10.1089/ars.2014.6181|url=https://doi.org/10.1089/ars.2014.6181|pages=679–685|chapter=|edition=|isbn=}}
</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346380/ (Full Text)]
*2015, Diagnostic concordance between categorical and dimensional instrument to assess personality in [[chronic fatigue syndrome]]: PDQ-4+ and TCI-R<ref name="Calvo, 2015">{{Citation
| last1 = Calvo | first1 = N. | authorlink1 =
| last2 = Sáez-Francas | first2 = N. | authorlink2 =
| last3 = Valero | first3 = S. | authorlink3 =
| last4 = Castro-Marrero | first4 = J. | authorlink4 = Jesús Castro-Marrero
| last5 = Alegre | first5 = J. | authorlink5 = José Alegre
| last6 = Casas | first6 = M. | authorlink6 =
| title = Diagnostic concordance between categorical and dimensional instrument to assess personality in chronic fatigue syndrome: PDQ-4+ and TCI-R
| journal = European Journal of Psychological Assessment | volume = 33 | issue = | page = 158-165
| date = 2015
| pmid =
| doi = 10.1027/1015-5759/a000281
}}
</ref> - [https://econtent.hogrefe.com/doi/abs/10.1027/1015-5759/a000281 (Abstract)]
*2015, Childhood trauma in [[Chronic Fatigue Syndrome]]: focus on personality disorders and psychopathology<ref name="Sáez-Francàs, 2015" /> - [https://www.ncbi.nlm.nih.gov/pubmed/26343462 (Abstract)]
*2016, [[Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome|Gender Differences]] in [[Chronic Fatigue Syndrome]]<ref name="Faro, 2015" /> - [http://www.euromene.eu/workinggroups/pubblications/Gender%20in%20CFS-2.pdf (Full Text)]
*2017, The European ME/CFS [[Biomarker]] Landscape project: an initiative of the European network EUROMENE<ref>{{Cite journal|last=Scheibenbogen|first=Carmen|author-link=Carmen Scheibenbogen|last2=Freitag|first2=Helma|author-link2=Helma Freitag|last3=Blanco|first3=Julià|author-link3=Julià Blanco|last4=Capelli|first4=Enrica|author-link4=Enrica Capelli|last5=Lacerda|first5=Eliana|author-link5=Eliana Lacerda|last6=Authier|first6=Jerome|author-link6=François Jérôme Authier|last7=Meeus|first7=Mira|author-link7=Mira Meeus|last8=Castro Marrero|first8=Jesus|author-link8=Jesús Castro-Marrero|last9=Nora-Krukle|first9=Zaiga|author-link9=Zaiga Nora-Krukle|last10=Oltra|first10=Elisa|author-link10=Elisa Oltra|last11= Strand|first11=Elin Bolle|author-link11=Elin Bolle Strand|last12= Shikova|first12= Evelina|author-link12= Evelina Shikova|last13= Sekulic|first13=Slobodan|author-link13=Slobodan Sekulic|last14=Murovska|first14=Modra|author-link14=Modra Murovska|date=2017-07-26|title=The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1263-z|journal=Journal of Translational Medicine|language=en|volume=15|issue=1|pages=|doi=10.1186/s12967-017-1263-z|issn=1479-5876|pmc=5530475|pmid=28747192|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530475/ (Full Text)]
*2017, Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome<ref name="Castro-Marrero, 2017" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301046/ (Full Text)]
*2017, Comorbidity in [[ME/CFS|Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]: A Nationwide Population-Based Cohort Study<ref name="Faro, 2017" /> - [https://www.ncbi.nlm.nih.gov/pubmed/28596045 (Abstract)]
*2018, Circadian rhythm abnormalities and [[autonomic dysfunction]] in patients with [[ME/CFS|Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]<ref name="Cambras, 2018">{{Citation
| last1 = Cambras | first1 = T. | authorlink1 =
| last2 = Castro-Marrero | first2 = J. | authorlink2 = Jesús Castro-Marrero
| last3 = Zaragoza | first3 = MC. | authorlink3 =
| last4 = Díez-Noguera | first4 = A. | authorlink4 =
| last5 = Alegre | first5 = J. | authorlink5 = José Alegre
| title = Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
| journal = PLoS ONE | volume = 13 | issue = 6 | page = e0198106
| date = 2018
| pmid =
| doi = 10.1371/journal.pone.0198106
}}
</ref> - [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198106 (Full Text)]
*2018, Poor self‐reported sleep quality and health‐related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis<ref name="Castro-Marrero, 2018 May 16" /> - [https://www.ncbi.nlm.nih.gov/pubmed/29770505 (Abstract)]
*2018, [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] – Evidence for an [[autoimmune disease]]<ref name="Sotzny, 2018" /> - [https://www.sciencedirect.com/science/article/pii/S1568997218300880 (Full Text)]
*2018, Circulating extracellular vesicles as potential [[biomarker]]s in [[ME/CFS|chronic fatigue syndrome/myalgic encephalomyelitis]]: an exploratory pilot study<ref name="Castro-Marrero, 2018" /> - [https://www.tandfonline.com/doi/full/10.1080/20013078.2018.1453730 (Full Text)]
*2018, Dimensional Personality Assessment among a Chronic Fatigue Syndrome (CFS) sample with Personality Inventory for DSM-5 (PID-5)<ref>{{Cite journal|last=Calvo|first=Natalia|last2=Pueyo|first2=Natalia|last3=Gutiérrez|first3=Fernando|last4=Ferrer|first4=Marc|last5=Castro-Marrero|first5=Jesús|author-link5=Jesús Castro-Marrero|last6=Alegre|first6=José|author-link6=José Alegre|last7=Casas|first7=Miquel|last8=Ramos Quiroga|first8=Josep-Antoni|last9=Sáez-Francàs|first9=Naia|date=Jul 2018|title=Dimensional Personality Assessment among a Chronic Fatigue Syndrome (CFS) sample with Personality Inventory for DSM-5 (PID-5)|url=https://www.ncbi.nlm.nih.gov/pubmed/30079926|journal=Actas Espanolas De Psiquiatria|volume=46|issue=4|pages=125–132|issn=1578-2735|pmid=30079926|via=}}</ref> - [[pubmed:30079926|(Abstract)]]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2018, Low omega-3 index and polyunsaturated fatty acid status in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis<ref>{{Cite journal|last=Castro-Marrero|first=Jesús|author-link=Jesús Castro-Marrero|last2=Zaragozá|first2=Maria Cleofé|author-link2=|last3=Domingo|first3=Joan Carles|author-link3=|last4=Martinez-Martinez|first4=Alba|author-link4=|last5=Alegre|first5=José|author-link5=José Alegre|last6=von Schacky|first6=Clemens|date=Dec 2018|title=Low omega-3 index and polyunsaturated fatty acid status in patients with chronic fatigue syndrome/myalgic encephalomyelitis|url=https://linkinghub.elsevier.com/retrieve/pii/S095232781830053X|journal=Prostaglandins, Leukotrienes and Essential Fatty Acids|volume=139|issue=|pages=20–24|doi=10.1016/j.plefa.2018.11.006|issn=0952-3278|quote=|via=}}</ref> - [https://www.plefa.com/article/S0952-3278(18)30053-X/fulltext (Abstract)]
* 2019, Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain<ref>{{Cite journal|last=Castro-Marrero|first=Jesús|last2=Faro|first2=Mónica|last3=Zaragozá|first3=María Cleofé|last4=Aliste|first4=Luisa|last5=de Sevilla|first5=Tomás Fernández|last6=Alegre|first6=José|date=Dec 2019|title=Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain|url=https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7225-z|journal=BMC Public Health|language=en|volume=19|issue=1|doi=10.1186/s12889-019-7225-z|issn=1471-2458|pmc=6599355|pmid=31253111|pages=|quote=|author-link=Jesús Castro-Marrero|author-link2=|author-link3=|author-link4=|author-link5=|author-link6=José Alegre|via=}}</ref> - [https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7225-z (Full text)]
* 2020, Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis<ref>{{Cite journal|last=Escorihuela|first=Rosa María|author-link=|last2=Capdevila|first2=Lluís|author-link2=|last3=Castro|first3=Juan Ramos|author-link3=|last4=Zaragozà|first4=María Cleofé|author-link4=|last5=Maurel|first5=Sara|author-link5=|last6=Alegre|first6=José|author-link6=José Alegre|last7=Castro-Marrero|first7=Jesús|author-link7=Jesús Castro-Marrero|last8=|first8=|date=Dec 2020|title=Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-02184-z|journal=Journal of Translational Medicine|language=en|volume=18|issue=1|pages=4|doi=10.1186/s12967-019-02184-z|issn=1479-5876|pmc = 6943898|pmid=31906988|access-date=|quote=|via=}}</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-02184-z (Full text)]
*2020, Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender‐specific changes in the microRNA expression profiling in ME/CFS<ref name="Cheema2020">{{Cite journal|last=Cheema|first=Amanpreet K.|author-link=|last2=Sarria|first2=Leonor|author-link2=|last3=Bekheit|first3=Mina|author-link3=|last4=Collado|first4=Fanny|author-link4=Fanny Collado|last5=Almenar‐Pérez|first5=Eloy|author-link5=|last6=Martín‐Martínez|first6=Eva|author-link6=|last7=Alegre|first7=Jose|author-link7=José Alegre|last8=Castro‐Marrero|first8=Jesus|author-link8=Jesús Castro-Marrero|last9=Fletcher|first9=Mary A.|author-link9=Mary Ann Fletcher|date=Apr 14, 2020|title=Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/jcmm.15260|journal=Journal of Cellular and Molecular Medicine|language=en|volume=00|issue=|pages=1-13|doi=10.1111/jcmm.15260|issn=1582-4934|pmc=|pmid=32291908|access-date=|quote=|via=|last10=Klimas|first10=Nancy|author-link10=Nancy Klimas|last11=Oltra|first11=Elisa|author-link11=Elisa Oltra|last12=Nathanson|first12=Lubov|author-link12=Lubov Nathanson}}</ref> - [https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15260 (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology <ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
*2020, Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=O’Neal|first2=Adam|author-link2=|last3=Castro-Marrero|first3=Jesús|author-link3=Jesús Castro-Marrero|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Hanson|first5=Maureen R.|author-link5=Maureen Hanson|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Dec 2020|title=Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02560-0|journal=Journal of Translational Medicine|language=en|volume=18|issue=1|pages=387|doi=10.1186/s12967-020-02560-0|issn=1479-5876|pmc = 7552484|pmid=|access-date=|quote=|via=}}</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02560-0 (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Talks and interviews==

==Online presence==
*[https://www.ncbi.nlm.nih.gov/pubmed/?term=Castro-Marrero%20J%5BAuthor%5D&cauthor=true&cauthor_uid=25386668 PubMed]
*[https://www.researchgate.net/profile/Jesus_Castro-Marrero ResearchGate]
*[http://www.euromene.eu/workinggroups/CV%20Dr%20Jesus%20Castro%20-%20Ingles.pdf Curriculum Vitae]

==See also==
*[[Cornell ME/CFS Collaborative Research Center]]
*[[EUROMENE]]

==Learn more==

==References==
<references>

<ref name="Castro-Marrero, 2017">{{Citation
| last1 = Castro-Marrero | first1 = J. | authorlink1 = Jesús Castro-Marrero
| last4 = Sáez-Francàs | first4 = N. | authorlink4 =
| last5 = Santillo | first5 = D. | authorlink5 =
| last9 = Alegre | first9 = J. | authorlink9 = José Alegre
| title = Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome
| journal = British Journal of Pharmacology | volume = 174 | issue = 5 | page = 345–369
| date = 2017
| pmid = 28052319
| doi = 10.1111/bph.13702
|url=https://doi.org/10.1111/bph.13702|last2=|first2=|pages=|chapter=|edition=|isbn=}}
</ref>
<ref name="Castro-Marrero, 2018">{{Citation
| last1 = Castro-Marrero | first1 = Jesús | authorlink1 = Jesús Castro-Marrero
| last2 = Serrano-Pertierra | first2 = Esther | authorlink2 =
| last3 = Oliveira-Rodríguez | first3 = Myriam | authorlink3 =
| last4 = Zaragozá | first4 = Maria Cleofé | authorlink4 =
| last5 = Martínez-Martínez | first5 = Alba | authorlink5 =
| last6 = Blanco-López | first6 = María del Carmen | authorlink6 =
| last7 = Alegre | first7 = José | authorlink7 = José Alegre
| title = Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study
| journal = Journal of Extracellular Vesicles | volume = 7 | issue = 1 | page =
| date = 2018
| pmid =
| doi = 10.1080/20013078.2018.1453730
}}
</ref>
<ref name="Castro-Marrero, 2018 May 16">{{Citation
| last1 = Castro-Marrero | first1 = Jesús | authorlink1 = Jesús Castro-Marrero
| last2 = Zaragozá | first2 = Maria Cleofé | authorlink2 =
| last3 = González-Garcia | first3 = Sergio | authorlink3 =
| last4 = Aliste | first4 = Luisa | authorlink4 =
| last5 = Sáez-Francàs | first5 = Naia | authorlink5 =
| last6 = Romero | first6 = Odile | authorlink6 =
| last7 = Ferré | first7 = Alex | authorlink7 =
| last8 = Fernández de Sevilla | first8 = Tomás | authorlink8 =
| last9 = Alegre | first9 = José | authorlink9 = José Alegre
| title = Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis
| journal = J Sleep Res | volume = | issue = | page = e12703
| date = 2018
| pmid = 29770505
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}}
</ref>
<ref name="Curriu, 2013">{{Citation
| last1 = Curriu | first1 = Marta | authorlink1 =
| last2 = Carrillo | first2 = Jorge | authorlink2 =
| last3 = Massanella | first3 = Marta | authorlink3 =
| last4 = Rigau | first4 = Josepa | authorlink4 =
| last5 = Alegre | first5 = José | authorlink5 = José Alegre
| last6 = Puig | first6 = Jordi | authorlink6 =
| last7 = Garcia-Quintana | first7 = Ana M | authorlink7 =
| last8 = Castro-Marrero | first8 = Jesús | authorlink8 = Jesús Castro-Marrero
| last9 = Negredo | first9 = Eugènia | authorlink9 =
| last10 = Clotet | first10 = Bonaventura | authorlink10 =
| last11 = Cabrera | first11 = Cecilia | authorlink11 =
| last12 = Blanco | first12 = Julià | authorlink12 = Julià Blanco
| title = Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome
| journal = Journal of Translational Medicine | volume = 11 | issue = 68 | page =
| date = 2013
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|url=https://doi.org/10.1186/1479-5876-11-68|pages=|chapter=|edition=|isbn=}}
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<ref name="Faro, 2014">{{Citation
| last1 = Faro | first1 = M. | authorlink1 =
| last2 = Sáez-Francàs | first2 = N. | authorlink2 =
| last3 = Castro-Marrero | first3 = J. | authorlink3 = Jesús Castro-Marrero
| last4 = Aliste | first4 = L. | authorlink4 =
| last5 = Collado | first5 = A. | authorlink5 =
| last6 = Alegre | first6 = J. | authorlink6 = José Alegre
| title = Impact of the fibromyalgia in the chronic fatigue syndrome
| journal = Medicina Clinica (Barc) | volume = 142 | issue = 12 | page = 519-525
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}}
</ref>
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| last2 = Sáez-Francàs | first2 = Naia | authorlink2 =
| last3 = Castro-Marrero | first3 = Jesús | authorlink3 = Jesús Castro-Marrero
| last4 = Aliste | first4 = Luisa | authorlink4 =
| last5 = Fernández de Sevilla | first5 = Tomás | authorlink5 =
| last6 = Alegre | first6 = Jose | authorlink6 = José Alegre
| title = Gender Differences in Chronic Fatigue Syndrome
| journal = Reumatologia clinica | volume = 12 | issue = 2 | page =
| date = 2015
| pmid =
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|url=https://doi.org/10.1016/j.reuma.2015.05.007|pages=|chapter=|edition=|isbn=}}
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<ref name="Faro, 2017">{{Citation
| last1 = Castro-Marrero | first1 = J. | authorlink1 = Jesús Castro-Marrero
| last2 = Faro | first2 = M. | authorlink2 =
| last3 = Aliste | first3 = L. | authorlink3 =
| last4 = Sáez-Francàs | first4 = N. | authorlink4 =
| last5 = Calvo | first5 = N. | authorlink5 =
| last6 = Martínez-Martínez | first6 = A. | authorlink6 =
| last7 = de Sevilla | first7 = T.F. | authorlink7 =
| last8 = Alegre | first8 = J. | authorlink8 = José Alegre
| title = Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study
| journal = Psychosomatics | volume = 58 | issue = 5 | page = 533 - 543
| date = 2017
| pmid =
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}}
</ref>
<ref name="Sáez-Francàs, 2015">{{Citation
| last1 = Sáez-Francàs | first1 = Naia | authorlink1 =
| last2 = Calvo | first2 = Natalia | authorlink2 =
| last3 = Alegre | first3 = José | authorlink3 = José Alegre
| last4 = Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero
| last5 = Casas | first5 = Miguel | authorlink5 =
| title = Childhood trauma in Chronic Fatigue Syndrome: focus on personality disorders and psychopathology
| journal = Comprehensive Psychiatry | volume = 62 | issue = | page = 13-19
| date = 2015
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</ref>
<ref name="Sotzny, 2018">{{Citation
| last1 = Sotzny | first1 = Franziska | authorlink1 = Franziska Sotzny
| last2 = Blanco | first2 = Julià | authorlink2 = Julià Blanco
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero
| last5 = Steiner | first5 = Sophie | authorlink5 =
| last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska
| last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
| journal = Autoimmunity Reviews | volume = | issue = | page =
| date = 2018
| pmid =
| doi = 10.1016/j.autrev.2018.01.009
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:Spain researchers]]

Eliana Lacerda

2021-06-01T19:23:43Z

Kmdenmark:added study and ref

{{NeedsImage}}
'''Eliana Mattos Lacerda''' MD, PhD, MSc, is a Clinical Assistant Professor and part of the [[CureME]] team at the [[London School of Hygiene and Tropical Medicine]], London, UK. She oversees the [[UK ME/CFS biobank]], from recruitment of participants through to release of samples.<ref name=":0">{{Cite web|url=https://www.lshtm.ac.uk/aboutus/people/lacerda.eliana|title=Eliana Lacerda|website=LSHTM|language=en|access-date=2019-04-25}}</ref>

She has a medical background, with training in public health and occupational health.<ref name=":0" />

==EUROMENE==
Dr. Lacerda is the Vice Chair of [[EUROMENE]], a European Union not-for-profit research organization committed to tackling the cause and treatment for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]], and was a founder member of the network.<ref>{{Cite web|url=https://www.cost.eu/actions/CA15111/|title=Action CA15111|website=COST|language=en-GB|access-date=2019-04-25}}</ref>

==ME/CFS Common Data Element (CDE) Project==
Member of the Baseline/Covariate Working Group and Neurologic/Cognitive/CNS Imaging Working group of the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Common Data Element (CDE) Project sponsored by the [[National Institute of Neurological Disorders and Stroke]] and the [[Centers for Disease Control & Prevention]].<ref>{{Cite web|url=https://www.commondataelements.ninds.nih.gov/Myalgic%20Encephalomyelitis/Chronic%20Fatigue%20Syndrome#pane-138|title=Complete Myalgic Encephalomyelitis/Chronic Fatigue Syndrome CDE Roster|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NIH|archive-url=|archive-date=|url-status=|access-date=2019-10-11}}</ref>

==Notable studies==
*2010, Exploring the feasibility of establishing a disease-specific post-mortem tissue bank in the UK: a case study in ME/CFS<ref>{{Cite journal|last=Lacerda|first=E. M.|author-link=Eliana Lacerda|last2=Nacul|first2=L.|author-link2=Luis Nacul|last3=Pheby|first3=D.|author-link3=Derek Pheby|last4=Shepherd|first4=C.|author-link4=Charles Shepherd|last5=Spencer|first5=P.|author-link5=Peter Spencer|author-link6=|date=2010-11-01|title=Exploring the feasibility of establishing a disease-specific post-mortem tissue bank in the UK: a case study in ME/CFS|url=http://jcp.bmj.com/cgi/doi/10.1136/jcp.2010.082032|journal=Journal of Clinical Pathology|language=en|volume=63|issue=11|pages=1032–1034|doi=10.1136/jcp.2010.082032|issn=0021-9746|quote=|via=}}</ref> - [http://jcp.bmj.com/content/63/11/1032 (Abstract)]
*2011, A Disease Register for ME/CFS: Report of a Pilot Study<ref>{{Cite journal|last=Pheby|first=Derek|author-link=Derek Pheby|last2=Lacerda|first2=Eliana|author-link2=Eliana Lacerda|last3=Nacul|first3=Luis|author-link3=Luis Nacul|last4=Drachler|first4=Maria de Lourdes|author-link4=|last5=Campion|first5=Peter|author-link5=|last6=Howe|first6=Amanda|last7=Poland|first7=Fiona|last8=Curran|first8=Monica|last9=Featherstone|first9=Valerie|date=Dec 2011|title=A Disease Register for ME/CFS: Report of a Pilot Study|url=https://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-4-139|journal=BMC Research Notes|language=en|volume=4|issue=1|pages=|doi=10.1186/1756-0500-4-139|issn=1756-0500|pmc=3118997|pmid=21554673|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118997/ (Full Text)]
*2011, Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis<ref name="de Carvalho Leite, 2011" /> - [https://equityhealthj.biomedcentral.com/articles/10.1186/1475-9276-10-46 (Full Text)]
*2011, Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care<ref>{{Cite journal|last=Nacul|first=Luis C|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Pheby|first3=Derek|author-link3=Derek Pheby|last4=Campion|first4=Peter|author-link4=|last5=Molokhia|first5=Mariam|author-link5=|last6=Fayyaz|first6=Shagufta|author-link6=|last7=Leite|first7=Jose CDC|last8=Poland|first8=Fiona|last9=Howe|first9=Amanda|date=Dec 2011|title=Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care|url=http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91|journal=BMC Medicine|language=en|volume=9|issue=1|pages=|doi=10.1186/1741-7015-9-91|issn=1741-7015|pmc=3170215|pmid=21794183|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170215/ (Full Text)]
*2011, The functional status and well being of people with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] and their carers<ref name="Nacul, 2011" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full Text)]
*2014, Considerations in establishing a post-mortem brain and tissue bank for the study of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]: A proposed protocol<ref name="Nacul, 2014" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076507/ (Full Text)]
*2017, [[How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?]]<ref>{{Cite journal|last=Nacul|first=Luis|last2=Lacerda|first2=Eliana M.|last3=Kingdon|first3=Caroline C.|last4=Curran|first4=Hayley|last5=Bowman|first5=Erinna W.|date=2017-03-01|title=How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?|url=https://www.ncbi.nlm.nih.gov/pubmed/28810428|journal=Journal of Health Psychology|pages=1359105317695803|doi=10.1177/1359105317695803|issn=1461-7277|pmc=5581258|pmid=28810428|issue=|quote=|author-link=Luis Nacul|author-link2=Eliana Lacerda|author-link3=Caroline Kingdon|author-link4=Hayley Curran|author-link5=Erinna Bowman|via=|volume=}}</ref> - [http://journals.sagepub.com/doi/pdf/10.1177/1359105317695803 (Full Text)]
* 2017, The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and [[Multiple sclerosis|Multiple Sclerosis]]<ref>{{Cite journal|last=Lacerda|first=Eliana M|author-link=Eliana Lacerda|last2=Bowman|first2=Erinna W|author-link2=Erinna Bowman|last3=Cliff|first3=Jacqueline M|author-link3=Jacqueline Cliff|last4=Kingdon|first4=Caroline C|author-link4=Caroline Kingdon|last5=King|first5=Elizabeth C|author-link5=Elizabeth King|last6=Lee|first6=Ji-Sook|author-link6=Ji-Sook Lee|last7=Clark|first7=Taane G|author-link7=Taane Clark|last8=Dockrell|first8=Hazel M|author-link8=Hazel Dockrell|last9=Riley|first9=Eleanor M|author-link9=Eleanor Riley|last10=Curran|first10=Hayley|author-link10=Hayley Curran|last11= Nacul|first11=Luis|author-link11=Luis Nacul|date=2017-02-20|title=The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis|url=http://openbioresources.metajnl.com/articles/10.5334/ojb.28/|journal=Open Journal of Bioresources|language=en|volume=4|issue=|pages=|doi=10.5334/ojb.28|issn=2056-5542|pmc=5482226|pmid=28649428|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482226/ (Full text)]
*2017, The European ME/CFS [[Biomarker]] Landscape project: an initiative of the European network [[EUROMENE]]<ref>{{Cite journal|last=Scheibenbogen|first=Carmen|author-link=Carmen Scheibenbogen|last2=Freitag|first2=Helma|author-link2=Helma Freitag|last3=Blanco|first3=Julià|author-link3=Julià Blanco|last4=Capelli|first4=Enrica|author-link4=Enrica Capelli|last5=Lacerda|first5=Eliana|author-link5=Eliana Lacerda|last6=Authier|first6=Jerome|author-link6=François Jérôme Authier|last7=Meeus|first7=Mira|author-link7=Mira Meeus|last8=Castro Marrero|first8=Jesus|author-link8=Jesús Castro-Marrero|last9=Nora-Krukle|first9=Zaiga|author-link9=Zaiga Nora-Krukle|last10=Oltra|first10=Elisa|author-link10=Elisa Oltra|last11= Strand|first11=Elin Bolle|author-link11=Elin Bolle Strand|last12= Shikova|first12= Evelina|author-link12= Evelina Shikova|last13= Sekulic|first13=Slobodan|author-link13=Slobodan Sekulic|last14=Murovska|first14=Modra|author-link14=Modra Murovska|date=2017-07-26|title=The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1263-z|journal=Journal of Translational Medicine|language=en|volume=15|issue=1|pages=|doi=10.1186/s12967-017-1263-z|issn=1479-5876|pmc=5530475|pmid=28747192|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530475/ (Full Text)]
*2017, Editorial - ''Using a participatory approach to develop and implement the UK ME/CFS Biobank''<ref>{{Cite journal|last1=Lacerda|first1=Eliana M.|authorlink1=Eliana Lacerda|last2=Kingdon|first2=Caroline C.|authorlink2=Caroline Kingdon|last3=Bowman|first3=Erinna W.|authorlink3=Erinna Bowman|last4=Nacul|first4=Luis|authorlink4=Luis Nacul|title=Using a participatory approach to develop and implement the UK ME/CFS Biobank|journal=Fatigue: Biomedicine, Health & Behavior|volume= |issue= |page=|date=2017|pmid=|doi=10.1080/21641846.2018.1396021}}</ref>
*2018, Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls<ref>{{Cite journal|last=Kingdon|first=Caroline C.|last2=Bowman|first2=Erinna W.|last3=Curran|first3=Hayley|last4=Nacul|first4=Luis|last5=Lacerda|first5=Eliana M.|date=2018-12-01|title=Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=2|issue=4|pages=381–392|doi=10.1007/s41669-018-0071-6|issn=2509-4254|pmc=|pmid=29536371|quote=|author-link=Caroline Kingdon|author-link2=Erinna Bowman|author-link3=Hayley Curran|author-link4=Luis Nacul|author-link5=Eliana Lacerda|via=}}</ref> - [https://link.springer.com/article/10.1007%2Fs41669-018-0071-6 (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2018, The [[CureME|UK ME/CFS Biobank]]: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Lacerda|first=Eliana|author-link=Eliana Lacerda|last2=Mudie|first2=Kathleen|author-link2=|last3=Butterworth|first3=Jack D.|author-link3=|last4=Kingdon|first4=Caroline C.|author-link4=Caroline Kingdon|last5=O'Boyle|first5=Shennae|author-link5=|last6=Nacul|first6=Luis|author-link6=Luis Nacul|date=2018-12-04|title=The UK ME/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.01026|issn=1664-2295|pmc=|pmid=30564186|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full (Full text)]
* 2019, Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study.<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=McDermott|first2=Clare|author-link2=Clare McDermott|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Butterworth|first4=Jack|author-link4=Jack Butterworth|last5=Cliff|first5=Jacqueline M.|author-link5=Jacqueline Cliff|last6=Nacul|first6=Luis|author-link6=Luis Nacul|date=2019-01-10|title=Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study|url=https://www.ncbi.nlm.nih.gov/pubmed/30632248|journal=Health Expectations: An International Journal of Public Participation in Health Care and Health Policy|volume=|issue=|pages=|doi=10.1111/hex.12857|issn=1369-7625|pmid=30632248|quote=|via=}}</ref>
* 2019, Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=de Barros|first2=Barbara|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Cliff|first4=Jacqueline M.|author-link4=Jacqueline Cliff|last5=Clark|first5=Taane G.|author-link5=|last6=Mudie|first6=Kathleen|last7=Dockrell|first7=Hazel M.|author-link7=Hazel Dockrell|last8=Lacerda|first8=Eliana M.|author-link8=Eliana Lacerda|date=2019-04-10|title=Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study|url=https://www.mdpi.com/2075-4418/9/2/41|journal=Diagnostics|language=en|volume=9|issue=2|pages=41|doi=10.3390/diagnostics9020041|issn=2075-4418|quote=|via=}}</ref> - [https://www.mdpi.com/2075-4418/9/2/41 (Abstract)]
* 2019, Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref>{{Cite journal|last=Cliff|first=Jacqueline M.|author-link=Jacqueline Cliff|last2=King|first2=Elizabeth C.|author-link2=|last3=Lee|first3=Ji-Sook|author-link3=|last4=Sepúlveda|first4=Nuno|author-link4=Nuno Sepúlveda|last5=Wolf|first5=Asia-Sophia|author-link5=|last6=Kingdon|first6=Caroline|author-link6=Caroline Kingdon|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Dockrell|first8=Hazel M.|author-link8=Hazel Dockrell|last9=Nacul|first9=Luis|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana|author-link10=Eliana Lacerda|last11=Riley|first11=Eleanor|author-link11=Eleanor Riley|date=2019-04-16|title=Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.frontiersin.org/article/10.3389/fimmu.2019.00796/full|journal=Frontiers in Immunology|volume=10|issue=|pages=|doi=10.3389/fimmu.2019.00796|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.00796/full (Full text)]
* 2019, HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome<ref>{{Cite journal|last=Rodrigues|first=Lucas S|author-link=|last2=Nali|first2=Luiz H da Silva|author-link2=|last3=Leal|first3=Cibele O D|author-link3=|last4=Sabino|first4=Ester C|author-link4=|last5=Lacerda|first5=Eliana M|author-link5=Eliana Lacerda|last6=Kingdon|first6=Caroline C|author-link6=Caroline Kingdon|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Romano|first8=Camila M|date=2019-07-05|title=HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome|url=http://biorxiv.org/lookup/doi/10.1101/693465|journal=bioRxiv|volume=|issue=|pages=|doi=10.1101/693465|quote=|via=}}</ref> - [https://www.biorxiv.org/content/10.1101/693465v1.full (Full text)]
* 2019, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory [[T cell|T cells]] and chronic human [[Herpesviruses|herpesvirus]] infections<ref>{{Cite journal|last=Sepúlveda|first=Nuno|author-link=Nuno Sepúlveda|last2=Carneiro|first2=Jorge|author-link2=|last3=Eliana M. Lacerda|first3=Eliana M.|author-link3=Eliana Lacerda|last4=Nacul|first4=Luis C.|author-link4=Luis Nacul|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Oct 2019|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections|url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract|journal=Frontiers in Immunology|volume=|issue=|pages=|doi=10.3389/fimmu.2019.02684|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract (Abstract)]
* 2019, A logistic regression analysis of risk factors in ME/CFS pathogenesis<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=Geraghty|first2=Keith|author-link2=Keith Geraghty|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Palla|first4=Luigi|author-link4=|last5=Nacul|first5=Luis|author-link5=Luis Nacul|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Dec 2019|title=A logistic regression analysis of risk factors in ME/CFS pathogenesis|url=https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-019-1468-2|journal=BMC Neurology|language=en|volume=19|issue=1|pages=275|doi=10.1186/s12883-019-1468-2|issn=1471-2377|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1186/s12883-019-1468-2 (Full text)]
*2019, How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS<ref name="Stages2019">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O'Boyle|first2=Shennae|author-link2=|last3=Nacul|first3=Flavio E.|author-link3=|last4=Mudie|first4=Kathleen|author-link4=|last5=Kingdon|first5=Caroline C.|author-link5=Caroline Kingdon|last6=Cliff|first6=Jacqueline M.|author-link6=Jacqueline Cliff|last7=Clark|first7=Taane G.|last8=Dockrell|first8=Hazel M.|last9=Lacerda|first9=Eliana M.|author-link9=Eliana Lacerda|date=2019-09-17|title=How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS|url=https://www.preprints.org/manuscript/201909.0188/v1|journal=Preprints|language=en|volume=|issue=|pages=|doi=10.20944/preprints201909.0188.v1|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.preprints.org/manuscript/201909.0188/download/final_file (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology <ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

== Talks and interviews ==
* 2018, [[CFS/ME Research Collaborative Conference|UK CFS/ME Research Collaborative Conference]] - [https://www.youtube.com/watch?v=0aTQD-eMfQo&index=6&list=PLJV2oZMsotONY3AEkA-c3kVFjtVokLBD7 ''European collaboration in ME/CFS: The EUROMENE network'']
* 14 Mar 2019, [https://mecfsconference.org.au/videos/eliana-lacerda/ The European Network on ME/CFS – How Best to Connect Research & Healthcare Across Europe], given at the [[International Research Symposium - Emerge Australia|International Research Symposium]], Geelong, Australia, sponsored by [[Emerge Australia]]

==See also==
*[[CureME]]
*[[EUROMENE]]
==Learn more==
*[https://www.lshtm.ac.uk/aboutus/people/lacerda.eliana LSHTM bio]

==References==
<references>
<ref name="de Carvalho Leite, 2011">{{Citation
| last1 = de Carvalho Leite | first1 = JC | authorlink1 =
| last2 = de L Drachler | first2 = M | authorlink2 =
| last3 = Killett | first3 = A | authorlink3 =
| last4 = Kale | first4 = S | authorlink4 =
| last5 = Nacul | first5 = L | authorlink5 = Luis Nacul
| last6 = McArthur | first6 = M | authorlink6 =
| last7 = Hong | first7 = CS | authorlink7 =
| last8 = O'Driscoll | first8 = L | authorlink8 =
| last9 = Pheby | first9 = D | authorlink9 = Derek Pheby
| last10 = Campion | first10 = P | authorlink10 =
| last11 = Lacerda | first11 = E | authorlink11 = Eliana Lacerda
| last12 = Poland | first12 = F | authorlink12 =
| title = Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis
| journal = International Journal for Equity in Health | volume = 2 | issue = 10 | page = 46
| date = 2011
| pmid =
| doi = 10.1186/1475-9276-10-46
}}
</ref>
<ref name="Nacul, 2011">{{Citation
| last1 = Nacul | first1 = LC | authorlink1 = Luis Nacul
| last2 = Lacerda | first2 = EM | authorlink2 = Eliana Lacerda
| last3 = Campion | first3 = P | authorlink3 =
| last4 = Pheby | first4 = D | authorlink4 = Derek Pheby
| last5 = Drachler | first5 = M de L | authorlink5 =
| last6 = Leite | first6 = JC | authorlink6 =
| last7 = Poland | first7 = F | authorlink7 =
| last8 = Howe | first8 = A | authorlink8 =
| last9 = Fayyaz | first9 = S | authorlink9 =
| last10 = Molokhia | first10 = M | authorlink10 =
| title = The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers
| journal = BMC Public Health | volume = 11 | issue = 402 | page =
| date = 2011
| pmid =
| doi = 10.1186/1471-2458-11-402
}}</ref>
<ref name="Nacul, 2014">{{Citation
| last1 = Nacul | first1 = L | authorlink1 = Luis Nacul
| last2 = O'Donovan | first2 = DG | authorlink2 =
| last3 = Lacerda | first3 = EM | authorlink3 = Eliana Lacerda
| last4 = Gveric | first4 = D | authorlink4 =
| last5 = Goldring | first5 = K | authorlink5 =
| last6 = Hall | first6 = A | authorlink6 =
| last7 = Bowman | first7 = E | authorlink7 =
| last8 = Pheby | first8 = D | authorlink8 = Derek Pheby
| title = Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: A proposed protocol
| journal = BMC Research Notes | volume = 18 | issue = 10 | page = 370
| date = 2014
| pmid =
| doi = 10.1186/1756-0500-7-370
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:UK researchers]]
[[Category:PACE trial critics]]

Luis Nacul

2021-06-01T19:22:13Z

Kmdenmark:typo

Dr '''Luis Carlos Nacul''' is a Clinical Associate Professor and researcher at the [[London School of Hygiene and Tropical Medicine]] in London, [[United Kingdom]]. He leads the [[CureME]] team and the [[UK ME/CFS biobank]]. He serves as a Member Substitute for [[EUROMENE]], an international not-for-profit organization for [[ME/CFS]] research.

He is a doctor and general practitioner, with training across medicine, epidemiology and public health.<ref>{{Cite web|url=https://www.lshtm.ac.uk/aboutus/people/nacul.luis|title=Luis Nacul|last=London School of Hygiene and Tropical Medicine|first=|authorlink=London School of Hygiene and Tropical Medicine|date=|website=|archive-url=|archive-date=|url-status=|access-date=}}</ref> In 2018, Dr Nacul was appointed to the review committee for the [[NICE guidelines]] for [[ME/CFS]] used by the British [[NHS]].<ref>{{Cite web|url=https://www.nice.org.uk/guidance/gid-ng10091/documents/committee-member-list|title=Committee member list {{!}} NICE CG53 CFS/ME guidance update|last=[[NICE]]|first=|date=28 October 2018|website=nice.org.uk|archive-url=|archive-date=|url-status=|access-date=20 October 2018}}</ref>

==ME/CFS Common Data Element (CDE) Project==
Dr Nacul serves on the Fatigue Working Group of the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Common Data Element (CDE) Project sponsored by the [[National Institute of Neurological Disorders and Stroke]] and the [[Centers for Disease Control & Prevention]].<ref>{{Cite web|url=https://www.commondataelements.ninds.nih.gov/Myalgic%20Encephalomyelitis/Chronic%20Fatigue%20Syndrome#pane-138|title=Complete Myalgic Encephalomyelitis/Chronic Fatigue Syndrome CDE Roster|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NIH|archive-url=|archive-date=|url-status=|access-date=2019-10-11}}</ref>

==Notable studies and writings related to ME/CFS==
*2007, The Development of an Epidemiological Definition for [[Myalgic Encephalomyelitis]]/[[Chronic Fatigue Syndrome]]<ref name="Osoba, 2007" /> - [https://www.tandfonline.com/doi/abs/10.3109/10573320802092112 (Abstract)]
*2011, Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care<ref>{{Cite journal |last=Nacul|first=L. C.|authorlink =Luis Nacul|last2 =Lacerda|first2=E. M.|author-link2=Eliana Lacerda|last3=Pheby|first3=D.|author-link3=Derek Pheby|last4=Campion|first4=P.|last5=Molokhia|first5=M.|last6=Fayyaz|first6=S.|last7=Leite|first7=JCDC|last8=Poland|first8=F|last9=Howe|first9=A|last10=de L. Drachler|date=2011|title=Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care|journal =BMC Medicine|volume = 9|issue =91|url=http://doi.org/10.1186/1741-7015-9-91|doi=10.1186/1741-7015-9-91|pmc=3170215|pages=|quote=|author-link4=Peter Campion|author-link5=Mariam Molokhia|via=|author-link6=Shagufta Fayyaz|author-link7=José Leife|author-link8=Fiona Poland|author-link9=Amanda Howe|author-link10=Maria Drachler|first10=Maria}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170215/ (Full Text)]
*2011, Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis<ref name="de Carvalho Leite, 2011" /> - [https://equityhealthj.biomedcentral.com/articles/10.1186/1475-9276-10-46 (Full Text)]
*2011, The functional status and well being of people with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] and their carers<ref>{{Cite journal|last=Nacul|first=Luis C|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Campion|first3=Peter|author-link3=Peter Campion|last4=Pheby|first4=Derek|author-link4=Derek Pheby|last5=Drachler|first5=Maria de L|author-link5=Maria de L Drachler|last6=Leite|first6=José C|author-link6=José Leite|last7=Poland|first7=Fiona|author-link7=Fiona Poland|last8=Howe|first8=Amanda|author-link8=Amanda Howe|last9=Fayyaz|first9=Shagufta|author-link9=Shagufta Fayyaz|date=2011-05-27|title=The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers|url=https://doi.org/10.1186/1471-2458-11-402|journal=BMC Public Health|language=en|volume=11|issue=1|pages=402|doi=10.1186/1471-2458-11-402|issn=1471-2458|pmc=3123211|pmid=21619607|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full Text)]
*2014, Considerations in establishing a post-mortem [[brain]] and tissue bank for the study of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]: A proposed protocol<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O’Donovan|first2=Dominic G|author-link2=Dominic O'Donovan|last3=Lacerda|first3=Eliana M|author-link3=Eliana Lacerda|last4=Gveric|first4=Djordje|author-link4=Djordje Gveric|last5=Goldring|first5=Kirstin|author-link5=Kirstin Goldring|last6=Hall|first6=Alison|author-link6=Alison Hall|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Pheby|first8=Derek|author-link8=Derek Pheby|date=2014|title=Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol|url=https://doi.org/10.1186/1756-0500-7-370|journal=BMC Research Notes|language=en|volume=7|issue=1|pages=370|doi=10.1186/1756-0500-7-370|issn=1756-0500|pmc=4076507|pmid=24938650|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076507/ (Full Text)]
*2017, [[How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?]]<ref name="Nacul2017">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Kingdon|first3=Caroline C|author-link3=Caroline Kingdon|last4=Curran|first4=Hayley|author-link4=Hayley Curran|last5=Bowman|first5=Erinna W|author-link5=Erinna Bowman|date=Mar 1, 2017|title=How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?|url=https://doi.org/10.1177/1359105317695803|journal=[[Journal of Health Psychology]]|language=en|volume=|issue=|pages=1359105317695803|doi=10.1177/1359105317695803|issn=1359-1053|pmc=5581258|pmid=28810428|quote=|via=}}</ref> - [https://doi.org/10.1177/1359105317695803 (Full text)]
*2017, Public Review - Draft of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials<ref name="Common Data Elements, 2017">{{Citation|last1=Cella|first1=David|authorlink1=David Cella|last2=Dimmock|first2=Mary|authorlink2=Mary Dimmock|last3=Friedberg|first3=Fred|authorlink3=Fred Friedberg|last4=Lin|first4=Jin-Mann Sally|authorlink4=Jin-Mann Sally Lin|last5=Nacul|first5=Luis|authorlink5=Luis Nacul|last6=Saligan|first6=Leorey|authorlink6=Leorey Saligan|title=NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials|date=Dec 2017|url=https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf}}</ref> - [https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf (Full Text)]
*2017, Editorial - ''Using a participatory approach to develop and implement the UK ME/CFS Biobank''<ref>{{Cite journal|last1=Lacerda|first1=Eliana M.|authorlink1=Eliana Lacerda|last2=Kingdon|first2=Caroline C.|authorlink2=Caroline Kingdon|last3=Bowman|first3=Erinna W.|authorlink3=Erinna Bowman|last4=Nacul|first4=Luis|authorlink4=Luis Nacul|title=Using a participatory approach to develop and implement the UK ME/CFS Biobank|journal=Fatigue: Biomedicine, Health & Behavior|volume= |issue= |page=|date=2017|pmid=|doi=10.1080/21641846.2018.1396021}}</ref>
*2017, Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome<ref>{{Cite journal|title=Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29250461|journal=Fatigue: Biomedicine, Health & Behavior|date=2017|issn=2164-1846|pmc=5730342|pmid=29250461|pages=1–4|volume=5|issue=1|doi=10.1080/21641846.2017.1273863|first=Luis|last=Nacul|first2=Caroline C.|last2=Kingdon|first3=Erinna W.|last3=Bowman|first4=Hayley|last4=Curran|first5=Eliana M.|last5=Lacerda|quote=|author-link=Luis Nacul|author-link2=Caroline Kingdon|author-link3=Erinna Bowman|author-link4=Hayley Curran|author-link5=Eliana Lacerda|via=}}</ref>
* 2017, The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and [[Multiple sclerosis|Multiple Sclerosis]]<ref>{{Cite journal|last=Lacerda|first=Eliana M|author-link=Eliana Lacerda|last2=Bowman|first2=Erinna W|author-link2=Erinna Bowman|last3=Cliff|first3=Jacqueline M|author-link3=Jacqueline Cliff|last4=Kingdon|first4=Caroline C|author-link4=Caroline Kingdon|last5=King|first5=Elizabeth C|author-link5=Elizabeth King|last6=Lee|first6=Ji-Sook|author-link6=Ji-Sook Lee|last7=Clark|first7=Taane G|author-link7=Taane Clark|last8=Dockrell|first8=Hazel M|author-link8=Hazel Dockrell|last9=Riley|first9=Eleanor M|author-link9=Eleanor Riley|last10=Curran|first10=Hayley|author-link10=Hayley Curran|last11= Nacul|first11=Luis|author-link11=Luis Nacul|date=2017-02-20|title=The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis|url=http://openbioresources.metajnl.com/articles/10.5334/ojb.28/|journal=Open Journal of Bioresources|language=en|volume=4|issue=|pages=|doi=10.5334/ojb.28|issn=2056-5542|pmc=5482226|pmid=28649428|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482226/ (Full text)]
*2018, Functional Status and Well-Being in People with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] Compared with People with [[Multiple Sclerosis]] and Healthy Controls<ref>{{Cite journal|last=Kingdon|first=Caroline C.|author-link=Caroline Kingdon|last2=Bowman|first2=Erinna W.|author-link2=Erinna Bowman|last3=Curran|first3=Hayley|author-link3=Hayley Curran|last4=Nacul|first4=Luis|author-link4=Luis Nacul|last5=Lacerda|first5=Eliana M.|author-link5=Eliana Lacerda|date=2018-03-13|title=Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=|issue=|pages=|doi=10.1007/s41669-018-0071-6|issn=2509-4262|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007%2Fs41669-018-0071-6 (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2018, Hand grip strength as a clinical [[Diagnostic biomarker|biomarker]] for ME/CFS and Disease Severity<ref>{{Cite journal|last=Nacul|first=Luis Carlos|author-link=Luis Nacul|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Kingdon|first3=Caroline|author-link3=Caroline Kingdon|last4=Clark|first4=Taane G.|author-link4=Taane Clark|last5=Lacerda|first5=Eliana Mattos|author-link5=Eliana Lacerda|date=2018|title=Hand grip strength as a clinical biomarker for ME/CFS and disease severity|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.00992|issn=1664-2295|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract (Abstract)]
* 2018, The [[CureME|UK ME/CFS Biobank]]: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Lacerda|first=Eliana|author-link=Eliana Lacerda|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Butterworth|first3=Jack D.|author-link3=Jack Butterworth|last4=Kingdon|first4=Caroline C.|author-link4=Caroline Kingdon|last5=O'Boyle|first5=Shennae|author-link5=Shennae O'Boyle|last6=Nacul|first6=Luis|author-link6=Luis Nacul|date=2018-12-04|title=The UK ME/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.01026|issn=1664-2295|pmc=|pmid=30564186|quote=|via=|last7=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full (Full text)]
* 2019, Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=McDermott|first2=Clare|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Butterworth|first4=Jack|author-link4=|last5=Cliff|first5=Jacqueline M.|author-link5=Jacqueline Cliff|last6=Nacul|first6=Luis|date=2019-01-10|title=Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/hex.12857|journal=Health Expectations|language=en|volume=0|issue=0|pages=|doi=10.1111/hex.12857|issn=1369-7625|pmid=30632248|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/full/10.1111/hex.12857 (Full text)]
* 2019, Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=de Barros|first2=Barbara|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Cliff|first4=Jacqueline M.|author-link4=Jacqueline Cliff|last5=Clark|first5=Taane G.|author-link5=|last6=Mudie|first6=Kathleen|last7=Dockrell|first7=Hazel M.|author-link7=Hazel Dockrell|last8=Lacerda|first8=Eliana M.|author-link8=Eliana Lacerda|date=2019-04-10|title=Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study|url=https://www.mdpi.com/2075-4418/9/2/41|journal=Diagnostics|language=en|volume=9|issue=2|pages=41|doi=10.3390/diagnostics9020041|issn=2075-4418|quote=|via=}}</ref> - [https://www.mdpi.com/2075-4418/9/2/41 (Abstract)]
* 2019, Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref>{{Cite journal|last=Cliff|first=Jacqueline M.|author-link=Jacqueline Cliff|last2=King|first2=Elizabeth C.|author-link2=|last3=Lee|first3=Ji-Sook|author-link3=|last4=Sepúlveda|first4=Nuno|author-link4=Nuno Sepúlveda|last5=Wolf|first5=Asia-Sophia|author-link5=|last6=Kingdon|first6=Caroline|author-link6=Caroline Kingdon|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Dockrell|first8=Hazel M.|author-link8=Hazel Dockrell|last9=Nacul|first9=Luis|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana|author-link10=Eliana Lacerda|last11=Riley|first11=Eleanor|author-link11=Eleanor Riley|date=2019-04-16|title=Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.frontiersin.org/article/10.3389/fimmu.2019.00796/full|journal=Frontiers in Immunology|volume=10|issue=|pages=|doi=10.3389/fimmu.2019.00796|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.00796/full (Full text)]
* 2019, HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome<ref>{{Cite journal|last=Rodrigues|first=Lucas S|author-link=|last2=Nali|first2=Luiz H da Silva|author-link2=|last3=Leal|first3=Cibele O D|author-link3=|last4=Sabino|first4=Ester C|author-link4=|last5=Lacerda|first5=Eliana M|author-link5=Eliana Lacerda|last6=Kingdon|first6=Caroline C|author-link6=Caroline Kingdon|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Romano|first8=Camila M|date=2019-07-05|title=HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome|url=http://biorxiv.org/lookup/doi/10.1101/693465|journal=bioRxiv|volume=|issue=|pages=|doi=10.1101/693465|quote=|via=}}</ref> - [https://www.biorxiv.org/content/10.1101/693465v1.full (Full text)]
* 2019, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory [[T cell|T cells]] and chronic human [[Herpesviruses|herpesvirus]] infections<ref>{{Cite journal|last=Sepúlveda|first=Nuno|author-link=Nuno Sepulveda|last2=Carneiro|first2=Jorge|author-link2=|last3=Eliana M. Lacerda|first3=Eliana M.|author-link3=Eliana Lacerda|last4=Nacul|first4=Luis C.|author-link4=Luis Nacul|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Oct 2019|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections|url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract|journal=Frontiers in Immunology|volume=|issue=|pages=|doi=10.3389/fimmu.2019.02684|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract (Abstract)]
* 2019, A logistic regression analysis of risk factors in ME/CFS pathogenesis<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=Geraghty|first2=Keith|author-link2=Keith Geraghty|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Palla|first4=Luigi|author-link4=|last5=Nacul|first5=Luis|author-link5=Luis Nacul|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Dec 2019|title=A logistic regression analysis of risk factors in ME/CFS pathogenesis|url=https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-019-1468-2|journal=BMC Neurology|language=en|volume=19|issue=1|pages=275|doi=10.1186/s12883-019-1468-2|issn=1471-2377|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1186/s12883-019-1468-2 (Full text)]
*2019, Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Friedberg2019">{{Cite journal|last=Friedberg|first=Fred|author-link=Fred Friedberg|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Nacul|first3=Luis|author-link3=Luis Nacul|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=2020-03-01|title=Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://doi.org/10.1007/s11606-019-05375-y|journal=Journal of General Internal Medicine|language=en|volume=35|issue=3|pages=906–909|doi=10.1007/s11606-019-05375-y|issn=1525-1497|pmc = 7080939|pmid=31637650|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007/s11606-019-05375-y (Full text)]
*2019, How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS<ref name="Stages2019">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O'Boyle|first2=Shennae|author-link2=|last3=Nacul|first3=Flavio E.|author-link3=|last4=Mudie|first4=Kathleen|author-link4=|last5=Kingdon|first5=Caroline C.|author-link5=Caroline Kingdon|last6=Cliff|first6=Jacqueline M.|author-link6=Jacqueline Cliff|last7=Clark|first7=Taane G.|last8=Dockrell|first8=Hazel M.|last9=Lacerda|first9=Eliana M.|author-link9=Eliana Lacerda|date=2019-09-17|title=How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS|url=https://www.preprints.org/manuscript/201909.0188/v1|journal=Preprints|language=en|volume=|issue=|pages=|doi=10.20944/preprints201909.0188.v1|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.preprints.org/manuscript/201909.0188/download/final_file (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Talks and interviews==
*2015, Speaker at the 10th [[Invest in ME International ME Conference]] - [http://www.investinme.org/IIMEC10.shtml#dvd DVD available] Speech title - ''Incidence and Prevalence of ME''
*2018, [[CFS/ME Research Collaborative Conference|UK CFS/ME Research Collaborative Conference]] - ''[https://www.youtube.com/watch?v=5FonUVDyc0I&list=PLJV2oZMsotONY3AEkA-c3kVFjtVokLBD7&index=5 The UK ME/CFS Biobank: Accelerating global research in ME/CFS]''

* 13 Mar 2019, [https://mecfsconference.org.au/videos/luis-nacul/ ''Infrastructure & Translational Research in ME/CFS: the Experience of CureME & the UK ME/CFS Biobank''] given at the [[International Research Symposium - Emerge Australia|International Research Symposium]], Geelong, Australia, sponsored by [[Emerge Australia]]
* 21 Sep 2019, ME/FM Society of BC: Presentation by Dr. Luis Nacul - [https://www.youtube.com/watch?v=kupG4a5vJdM ''Has ME/CFS research helped clinicians and patients? Can we do better?'']

==Online presence==

==See also==
*[[CureME]]
*[[EUROMENE]]
*[[NICE guidelines]]
*[[NHS]]

==Learn more==
*[https://www.lshtm.ac.uk/aboutus/people/nacul.luis LSHTM bio]

==References==
<references>
<ref name="de Carvalho Leite, 2011">{{Citation
| last1 = de Carvalho Leite | first1 = JC | authorlink1 = José de Carvalho Leite
| last2 = de L Drachler | first2 = M | authorlink2 = Maria de L Drachler
| last3 = Killett | first3 = A | authorlink3 = Anne Killett
| last4 = Kale | first4 = S | authorlink4 = Swati Kale
| last5 = Nacul | first5 = L | authorlink5 = Luis Nacul
| last6 = McArthur | first6 = M | authorlink6 = Maggie McArthur
| last7 = Hong | first7 = CS | authorlink7 = Chia Hong
| last8 = O'Driscoll | first8 = L | authorlink8 = Lucy Driscoll
| last9 = Pheby | first9 = D | authorlink9 = Derek Pheby
| last10 = Campion | first10 = P | authorlink10 = Peter Campion
| last11 = Lacerda | first11 = E | authorlink11 = Eliana Lacerda
| last12 = Poland | first12 = F | authorlink12 = Fiona Poland
| title = Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis
| journal = International Journal for Equity in Health | volume = 2 | issue = 10 | page = 46
| date = 2011
| pmid =
| doi = 10.1186/1475-9276-10-46
|url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229491/
| pmc = 3229491
}}
</ref>
<ref name="Osoba, 2007">{{Citation
| last1 = Osoba | first1 = Tolu | authorlink1 = Tolu Osoba
| last2 = Pheby | first2 = Derek | authorlink2 = Derek Pheby
| last3 = Gray | first3 = Selena | authorlink3 = Selena Gray
| last4 = Nacul | first4 = Luis | authorlink4 = Luis Nacul
| title = The Development of an Epidemiological Definition for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| journal = Journal of Chronic Fatigue Syndrome | volume = 14 | issue = 4 | page = 61-84
| date = 2007
| pmid =
| doi = 10.3109/10573320802092112
| url = https://doi.org/10.3109%2F10573320802092112
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:UK researchers]]

Luis Nacul

2021-06-01T19:21:17Z

Kmdenmark:added authorlink

Dr '''Luis Carlos Nacul''' is a Clinical Associate Professor and researcher at the [[London School of Hygiene and Tropical Medicine]] in London, [[United Kingdom]]. He leads the [[CureME]] team and the [[UK ME/CFS biobank]]. He serves as a Member Substitute for [[EUROMENE]], an international not-for-profit organization for [[ME/CFS]] research.

He is a doctor and general practitioner, with training across medicine, epidemiology and public health.<ref>{{Cite web|url=https://www.lshtm.ac.uk/aboutus/people/nacul.luis|title=Luis Nacul|last=London School of Hygiene and Tropical Medicine|first=|authorlink=London School of Hygiene and Tropical Medicine|date=|website=|archive-url=|archive-date=|url-status=|access-date=}}</ref> In 2018, Dr Nacul was appointed to the review committee for the [[NICE guidelines]] for [[ME/CFS]] used by the British [[NHS]].<ref>{{Cite web|url=https://www.nice.org.uk/guidance/gid-ng10091/documents/committee-member-list|title=Committee member list {{!}} NICE CG53 CFS/ME guidance update|last=[[NICE]]|first=|date=28 October 2018|website=nice.org.uk|archive-url=|archive-date=|url-status=|access-date=20 October 2018}}</ref>

==ME/CFS Common Data Element (CDE) Project==
Dr Nacul serves on the Fatigue Working Group of the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Common Data Element (CDE) Project sponsored by the [[National Institute of Neurological Disorders and Stroke]] and the [[Centers for Disease Control & Prevention]].<ref>{{Cite web|url=https://www.commondataelements.ninds.nih.gov/Myalgic%20Encephalomyelitis/Chronic%20Fatigue%20Syndrome#pane-138|title=Complete Myalgic Encephalomyelitis/Chronic Fatigue Syndrome CDE Roster|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NIH|archive-url=|archive-date=|url-status=|access-date=2019-10-11}}</ref>

==Notable studies and writings related to ME/CFS==
*2007, The Development of an Epidemiological Definition for [[Myalgic Encephalomyelitis]]/[[Chronic Fatigue Syndrome]]<ref name="Osoba, 2007" /> - [https://www.tandfonline.com/doi/abs/10.3109/10573320802092112 (Abstract)]
*2011, Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care<ref>{{Cite journal |last=Nacul|first=L. C.|authorlink =Luis Nacul|last2 =Lacerda|first2=E. M.|author-link2=Eliana Lacerda|last3=Pheby|first3=D.|author-link3=Derek Pheby|last4=Campion|first4=P.|last5=Molokhia|first5=M.|last6=Fayyaz|first6=S.|last7=Leite|first7=JCDC|last8=Poland|first8=F|last9=Howe|first9=A|last10=de L. Drachler|date=2011|title=Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care|journal =BMC Medicine|volume = 9|issue =91|url=http://doi.org/10.1186/1741-7015-9-91|doi=10.1186/1741-7015-9-91|pmc=3170215|pages=|quote=|author-link4=Peter Campion|author-link5=Mariam Molokhia|via=|author-link6=Shagufta Fayyaz|author-link7=José Leife|author-link8=Fiona Poland|author-link9=Amanda Howe|author-link10=Maria Drachler|first10=Maria}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170215/ (Full Text)]
*2011, Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis<ref name="de Carvalho Leite, 2011" /> - [https://equityhealthj.biomedcentral.com/articles/10.1186/1475-9276-10-46 (Full Text)]
*2011, The functional status and well being of people with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] and their carers<ref>{{Cite journal|last=Nacul|first=Luis C|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Campion|first3=Peter|author-link3=Peter Campion|last4=Pheby|first4=Derek|author-link4=Derek Pheby|last5=Drachler|first5=Maria de L|author-link5=Maria de L Drachler|last6=Leite|first6=José C|author-link6=José Leite|last7=Poland|first7=Fiona|author-link7=Fiona Poland|last8=Howe|first8=Amanda|author-link8=Amanda Howe|last9=Fayyaz|first9=Shagufta|author-link9=Shagufta Fayyaz|date=2011-05-27|title=The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers|url=https://doi.org/10.1186/1471-2458-11-402|journal=BMC Public Health|language=en|volume=11|issue=1|pages=402|doi=10.1186/1471-2458-11-402|issn=1471-2458|pmc=3123211|pmid=21619607|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full Text)]
*2014, Considerations in establishing a post-mortem [[brain]] and tissue bank for the study of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]: A proposed protocol<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O’Donovan|first2=Dominic G|author-link2=Dominic O'Donovan|last3=Lacerda|first3=Eliana M|author-link3=Eliana Lacerda|last4=Gveric|first4=Djordje|author-link4=Djordje Gveric|last5=Goldring|first5=Kirstin|author-link5=Kirstin Goldring|last6=Hall|first6=Alison|author-link6=Alison Hall|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Pheby|first8=Derek|author-link8=Derek Pheby|date=2014|title=Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol|url=https://doi.org/10.1186/1756-0500-7-370|journal=BMC Research Notes|language=en|volume=7|issue=1|pages=370|doi=10.1186/1756-0500-7-370|issn=1756-0500|pmc=4076507|pmid=24938650|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076507/ (Full Text)]
*2017, [[How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?]]<ref name="Nacul2017">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Kingdon|first3=Caroline C|author-link3=Caroline Kingdon|last4=Curran|first4=Hayley|author-link4=Hayley Curran|last5=Bowman|first5=Erinna W|author-link5=Erinna Bowman|date=Mar 1, 2017|title=How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?|url=https://doi.org/10.1177/1359105317695803|journal=[[Journal of Health Psychology]]|language=en|volume=|issue=|pages=1359105317695803|doi=10.1177/1359105317695803|issn=1359-1053|pmc=5581258|pmid=28810428|quote=|via=}}</ref> - [https://doi.org/10.1177/1359105317695803 (Full text)]
*2017, Public Review - Draft of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials<ref name="Common Data Elements, 2017">{{Citation|last1=Cella|first1=David|authorlink1=David Cella|last2=Dimmock|first2=Mary|authorlink2=Mary Dimmock|last3=Friedberg|first3=Fred|authorlink3=Fred Friedberg|last4=Lin|first4=Jin-Mann Sally|authorlink4=Jin-Mann Sally Lin|last5=Nacul|first5=Luis|authorlink5=Luis Nacul|last6=Saligan|first6=Leorey|authorlink6=Leorey Saligan|title=NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials|date=Dec 2017|url=https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf}}</ref> - [https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf (Full Text)]
*2017, Editorial - ''Using a participatory approach to develop and implement the UK ME/CFS Biobank''<ref>{{Cite journal|last1=Lacerda|first1=Eliana M.|authorlink1=Eliana Lacerda|last2=Kingdon|first2=Caroline C.|authorlink2=Caroline Kingdon|last3=Bowman|first3=Erinna W.|authorlink3=Erinna Bowman|last4=Nacul|first4=Luis|authorlink4=Luis Nacul|title=Using a participatory approach to develop and implement the UK ME/CFS Biobank|journal=Fatigue: Biomedicine, Health & Behavior|volume= |issue= |page=|date=2017|pmid=|doi=10.1080/21641846.2018.1396021}}</ref>
*2017, Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome<ref>{{Cite journal|title=Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29250461|journal=Fatigue: Biomedicine, Health & Behavior|date=2017|issn=2164-1846|pmc=5730342|pmid=29250461|pages=1–4|volume=5|issue=1|doi=10.1080/21641846.2017.1273863|first=Luis|last=Nacul|first2=Caroline C.|last2=Kingdon|first3=Erinna W.|last3=Bowman|first4=Hayley|last4=Curran|first5=Eliana M.|last5=Lacerda|quote=|author-link=Luis Nacul|author-link2=Caroline Kingdon|author-link3=Erinna Bowman|author-link4=Hayley Curran|author-link5=Eliana Lacerda|via=}}</ref>
* 2017, The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and [[Multiple sclerosis|Multiple Sclerosis]]<ref>{{Cite journal|last=Lacerda|first=Eliana M|author-link=Eliana Lacerda|last2=Bowman|first2=Erinna W|author-link2=Erinna Bowman|last3=Cliff|first3=Jacqueline M|author-link3=Jacqueline Cliff|last4=Kingdon|first4=Caroline C|author-link4=Caroline Kingdon|last5=King|first5=Elizabeth C|author-link5=Elizabeth King|last6=Lee|first6=Ji-Sook|author-link6=Ji-Sook Lee|last7=Clark|first7=Taane G|author-link7=Taane Clark|last8=Dockrell|first8=Hazel M|author-link8=Hazel Dockrell|last9=Riley|first9=Eleanor M|author-link9=Eleanor Riley|last10=Curran|first10=Hayley|author-link10=Hayley Curran|last11= Nacul|first11=Luis|author-link11=Luis Nacul|date=2017-02-20|title=The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis|url=http://openbioresources.metajnl.com/articles/10.5334/ojb.28/|journal=Open Journal of Bioresources|language=en|volume=4|issue=|pages=|doi=10.5334/ojb.28|issn=2056-5542|pmc=5482226|pmid=28649428|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482226/ (Full text)]
*2018, Functional Status and Well-Being in People with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] Compared with People with [[Multiple Sclerosis]] and Healthy Controls<ref>{{Cite journal|last=Kingdon|first=Caroline C.|author-link=Caroline Kingdon|last2=Bowman|first2=Erinna W.|author-link2=Erinna Bowman|last3=Curran|first3=Hayley|author-link3=Hayley Curran|last4=Nacul|first4=Luis|author-link4=Luis Nacul|last5=Lacerda|first5=Eliana M.|author-link5=Eliana Lacerda|date=2018-03-13|title=Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=|issue=|pages=|doi=10.1007/s41669-018-0071-6|issn=2509-4262|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007%2Fs41669-018-0071-6 (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2018, Hand grip strength as a clinical [[Diagnostic biomarker|biomarker]] for ME/CFS and Disease Severity<ref>{{Cite journal|last=Nacul|first=Luis Carlos|author-link=Luis Nacul|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Kingdon|first3=Caroline|author-link3=Caroline Kingdon|last4=Clark|first4=Taane G.|author-link4=Taane Clark|last5=Lacerda|first5=Eliana Mattos|author-link5=Eliana Lacerda|date=2018|title=Hand grip strength as a clinical biomarker for ME/CFS and disease severity|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.00992|issn=1664-2295|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract (Abstract)]
* 2018, The [[CureME|UK ME/CFS Biobank]]: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Lacerda|first=Eliana|author-link=Eliana Lacerda|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Butterworth|first3=Jack D.|author-link3=Jack Butterworth|last4=Kingdon|first4=Caroline C.|author-link4=Caroline Kingdon|last5=O'Boyle|first5=Shennae|author-link5=Shennae O'Boyle|last6=Nacul|first6=Luis|author-link6=Luis Nacul|date=2018-12-04|title=The UK ME/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.01026|issn=1664-2295|pmc=|pmid=30564186|quote=|via=|last7=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full (Full text)]
* 2019, Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=McDermott|first2=Clare|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Butterworth|first4=Jack|author-link4=|last5=Cliff|first5=Jacqueline M.|author-link5=Jacqueline Cliff|last6=Nacul|first6=Luis|date=2019-01-10|title=Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/hex.12857|journal=Health Expectations|language=en|volume=0|issue=0|pages=|doi=10.1111/hex.12857|issn=1369-7625|pmid=30632248|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/full/10.1111/hex.12857 (Full text)]
* 2019, Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=de Barros|first2=Barbara|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Cliff|first4=Jacqueline M.|author-link4=Jacqueline Cliff|last5=Clark|first5=Taane G.|author-link5=|last6=Mudie|first6=Kathleen|last7=Dockrell|first7=Hazel M.|author-link7=Hazel Dockrell|last8=Lacerda|first8=Eliana M.|author-link8=Eliana Lacerda|date=2019-04-10|title=Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study|url=https://www.mdpi.com/2075-4418/9/2/41|journal=Diagnostics|language=en|volume=9|issue=2|pages=41|doi=10.3390/diagnostics9020041|issn=2075-4418|quote=|via=}}</ref> - [https://www.mdpi.com/2075-4418/9/2/41 (Abstract)]
* 2019, Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref>{{Cite journal|last=Cliff|first=Jacqueline M.|author-link=Jacqueline Cliff|last2=King|first2=Elizabeth C.|author-link2=|last3=Lee|first3=Ji-Sook|author-link3=|last4=Sepúlveda|first4=Nuno|author-link4=Nuno Sepúlveda|last5=Wolf|first5=Asia-Sophia|author-link5=|last6=Kingdon|first6=Caroline|author-link6=Caroline Kingdon|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Dockrell|first8=Hazel M.|author-link8=Hazel Dockrell|last9=Nacul|first9=Luis|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana|author-link10=Eliana Lacerda|last11=Riley|first11=Eleanor|author-link11=Eleanor Riley|date=2019-04-16|title=Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.frontiersin.org/article/10.3389/fimmu.2019.00796/full|journal=Frontiers in Immunology|volume=10|issue=|pages=|doi=10.3389/fimmu.2019.00796|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.00796/full (Full text)]
* 2019, HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome<ref>{{Cite journal|last=Rodrigues|first=Lucas S|author-link=|last2=Nali|first2=Luiz H da Silva|author-link2=|last3=Leal|first3=Cibele O D|author-link3=|last4=Sabino|first4=Ester C|author-link4=|last5=Lacerda|first5=Eliana M|author-link5=Eliana Lacerda|last6=Kingdon|first6=Caroline C|author-link6=Caroline Kingdon|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Romano|first8=Camila M|date=2019-07-05|title=HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome|url=http://biorxiv.org/lookup/doi/10.1101/693465|journal=bioRxiv|volume=|issue=|pages=|doi=10.1101/693465|quote=|via=}}</ref> - [https://www.biorxiv.org/content/10.1101/693465v1.full (Full text)]
* 2019, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory [[T cell|T cells]] and chronic human [[Herpesviruses|herpesvirus]] infections<ref>{{Cite journal|last=Sepúlveda|first=Nuno|author-link=Nuno Sepulveda|last2=Carneiro|first2=Jorge|author-link2=|last3=Eliana M. Lacerda|first3=Eliana M.|author-link3=Eliana Lacerda|last4=Nacul|first4=Luis C.|author-link4=Luis Nacul|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Oct 2019|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections|url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract|journal=Frontiers in Immunology|volume=|issue=|pages=|doi=10.3389/fimmu.2019.02684|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract (Abstract)]
* 2019, A logistic regression analysis of risk factors in ME/CFS pathogenesis<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=Geraghty|first2=Keith|author-link2=Keith Geraghty|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Palla|first4=Luigi|author-link4=|last5=Nacul|first5=Luis|author-link5=Luis Nacul|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Dec 2019|title=A logistic regression analysis of risk factors in ME/CFS pathogenesis|url=https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-019-1468-2|journal=BMC Neurology|language=en|volume=19|issue=1|pages=275|doi=10.1186/s12883-019-1468-2|issn=1471-2377|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1186/s12883-019-1468-2 (Full text)]
*2019, Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Friedberg2019">{{Cite journal|last=Friedberg|first=Fred|author-link=Fred Friedberg|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Nacul|first3=Luis|author-link3=Luis Nacul|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=2020-03-01|title=Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://doi.org/10.1007/s11606-019-05375-y|journal=Journal of General Internal Medicine|language=en|volume=35|issue=3|pages=906–909|doi=10.1007/s11606-019-05375-y|issn=1525-1497|pmc = 7080939|pmid=31637650|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007/s11606-019-05375-y (Full text)]
*2019, How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS<ref name="Stages2019">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O'Boyle|first2=Shennae|author-link2=|last3=Nacul|first3=Flavio E.|author-link3=|last4=Mudie|first4=Kathleen|author-link4=|last5=Kingdon|first5=Caroline C.|author-link5=Caroline Kingdon|last6=Cliff|first6=Jacqueline M.|author-link6=Jacqueline Cliff|last7=Clark|first7=Taane G.|last8=Dockrell|first8=Hazel M.|last9=Lacerda|first9=Eliana M.|author-link9=Eliana Lacerda|date=2019-09-17|title=How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS|url=https://www.preprints.org/manuscript/201909.0188/v1|journal=Preprints|language=en|volume=|issue=|pages=|doi=10.20944/preprints201909.0188.v1|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.preprints.org/manuscript/201909.0188/download/final_file (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|author-link9=Luís Nacul|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Talks and interviews==
*2015, Speaker at the 10th [[Invest in ME International ME Conference]] - [http://www.investinme.org/IIMEC10.shtml#dvd DVD available] Speech title - ''Incidence and Prevalence of ME''
*2018, [[CFS/ME Research Collaborative Conference|UK CFS/ME Research Collaborative Conference]] - ''[https://www.youtube.com/watch?v=5FonUVDyc0I&list=PLJV2oZMsotONY3AEkA-c3kVFjtVokLBD7&index=5 The UK ME/CFS Biobank: Accelerating global research in ME/CFS]''

* 13 Mar 2019, [https://mecfsconference.org.au/videos/luis-nacul/ ''Infrastructure & Translational Research in ME/CFS: the Experience of CureME & the UK ME/CFS Biobank''] given at the [[International Research Symposium - Emerge Australia|International Research Symposium]], Geelong, Australia, sponsored by [[Emerge Australia]]
* 21 Sep 2019, ME/FM Society of BC: Presentation by Dr. Luis Nacul - [https://www.youtube.com/watch?v=kupG4a5vJdM ''Has ME/CFS research helped clinicians and patients? Can we do better?'']

==Online presence==

==See also==
*[[CureME]]
*[[EUROMENE]]
*[[NICE guidelines]]
*[[NHS]]

==Learn more==
*[https://www.lshtm.ac.uk/aboutus/people/nacul.luis LSHTM bio]

==References==
<references>
<ref name="de Carvalho Leite, 2011">{{Citation
| last1 = de Carvalho Leite | first1 = JC | authorlink1 = José de Carvalho Leite
| last2 = de L Drachler | first2 = M | authorlink2 = Maria de L Drachler
| last3 = Killett | first3 = A | authorlink3 = Anne Killett
| last4 = Kale | first4 = S | authorlink4 = Swati Kale
| last5 = Nacul | first5 = L | authorlink5 = Luis Nacul
| last6 = McArthur | first6 = M | authorlink6 = Maggie McArthur
| last7 = Hong | first7 = CS | authorlink7 = Chia Hong
| last8 = O'Driscoll | first8 = L | authorlink8 = Lucy Driscoll
| last9 = Pheby | first9 = D | authorlink9 = Derek Pheby
| last10 = Campion | first10 = P | authorlink10 = Peter Campion
| last11 = Lacerda | first11 = E | authorlink11 = Eliana Lacerda
| last12 = Poland | first12 = F | authorlink12 = Fiona Poland
| title = Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis
| journal = International Journal for Equity in Health | volume = 2 | issue = 10 | page = 46
| date = 2011
| pmid =
| doi = 10.1186/1475-9276-10-46
|url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229491/
| pmc = 3229491
}}
</ref>
<ref name="Osoba, 2007">{{Citation
| last1 = Osoba | first1 = Tolu | authorlink1 = Tolu Osoba
| last2 = Pheby | first2 = Derek | authorlink2 = Derek Pheby
| last3 = Gray | first3 = Selena | authorlink3 = Selena Gray
| last4 = Nacul | first4 = Luis | authorlink4 = Luis Nacul
| title = The Development of an Epidemiological Definition for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| journal = Journal of Chronic Fatigue Syndrome | volume = 14 | issue = 4 | page = 61-84
| date = 2007
| pmid =
| doi = 10.3109/10573320802092112
| url = https://doi.org/10.3109%2F10573320802092112
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:UK researchers]]

Franziska Sotzny

2021-06-01T19:18:15Z

Kmdenmark:added authorlink

[[File:Franziska_Sotzny.png|200px|thumb|right]]
Dr. '''Franziska Sotzny''', is a post-doctorate researcher at the Institute of Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.

==Awards==
*2017 Ramsay Award Program grant was awarded to a team comprised of Dr. [[Carmen Scheibenbogen]] and Dr. Franziska Sotzny of Charité Universitätsmedizin Berlin, sponsored by the [[Solve ME/CFS Initiative]] for researching immunometabolism of [[T cell]]s and monocytes in [[ME/CFS]].<ref>http://solvecfs.org/2017-ramsay-award-program-results/</ref>

==EUROMENE==
Dr. Sotzny is a participant of the [[Biomarkers]] Working Group of [[EUROMENE]], a European Union, COST Action CA15111, not-for-profit research organization committed to tackling the cause and treatment for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]].<ref>http://www.cost.eu/COST_Actions/ca/CA15111?management</ref>

==Notable studies==
*2017, Serological profiling of the [[EBV]] immune response in [[Chronic Fatigue Syndrome]] using a peptide microarray<ref name="Loebel, 2017" /> [http://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0179124 (Full Text)]
*2018, [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] – Evidence for an [[autoimmune disease]]<ref name="Sotzny, 2018" /> [https://www.sciencedirect.com/science/article/pii/S1568997218300880 (Full Text)]
*2018, The expression signature of very long non-coding [[RNA]] in [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref>{{Cite journal|last=Yang|first=Chin-An|last2=Bauer|first2=Sandra|author-link2=Sandra Bauer|last3=Ho|first3=Yu-Chen|last4=Sotzny|first4=Franziska|author-link4=Franziska Sotzny|last5=Chang|first5=Jan-Gowth|last6=Scheibenbogen|first6=Carmen|author-link6=Carmen Scheibenbogen|date=2018-08-17|title=The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x|journal=Journal of Translational Medicine|language=en|volume=16|issue=1|pages=|doi=10.1186/s12967-018-1600-x|issn=1479-5876|via=}}</ref> [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x (Full Text)]
* 2020, Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome<ref name=endothelial2020>{{Cite journal|last=Scherbakov|first=Nadja|author-link=|last2=Szklarski|first2=Marvin|author-link2=|last3=Hartwig|first3=Jelka|author-link3=|last4=Sotzny|first4=Franziska|author-link4=Franziska Sotzny|last5=Lorenz|first5=Sebastian|author-link5=|last6=Meyer|first6=Antje|author-link6=Antje Meyer|last7=Grabowski|first7=Patricia|last8=Doehner|first8=Wolfram|last9=Scheibenbogen|first9=Carmen|author-link9=Carmen Scheibenbogen|date=2020|title=Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ehf2.12633|journal=ESC Heart Failure|language=en|volume=7|issue=3|pages=1064–1071|doi=10.1002/ehf2.12633|issn=2055-5822|pmc = 7261521|pmid=32154656|access-date=|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/abs/10.1002/ehf2.12633 (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|author-link9=Luís Nacul|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Talks and interviews==

==Online presence==
*[https://www.ncbi.nlm.nih.gov/pubmed/?term=Sotzny%20F%5BAuthor%5D&cauthor=true&cauthor_uid=28604802 PubMed]

==Learn more==

==See also==
*[[EUROMENE]]

==References==
<references>
<ref name="Loebel, 2017">{{Citation
| last1 = Loebel | first1 = Madlen | authorlink1 = Madlen Loebel
| last2 = Eckey | first2 = Maren | authorlink2 =
| last3 = Sotzny | first3 = Franziska | authorlink3 = Franziska Sotzny
| last4 = Hahn | first4 = Elisabeth | authorlink4 =
| last5 = Bauer | first5 = Sandra | authorlink5 = Sandra Bauer
| last6 = Grabowski | first6 = Patricia | authorlink6 =
| last7 = Zerweck | first7 = Johannes | authorlink7 =
| last8 = Holenya | first8 = Pavlo | authorlink8 =
| last9 = Hanitsch | first9 = Leif G. | authorlink9 =
| last10 = Wittke | first10 = Kirsten | authorlink10 =
| last11 = Borchmann | first11 = Peter | authorlink11 =
| last12 = Rüffer | first12 = Jens-Ulrich | authorlink12 =
| last13 = Hiepe | first13 = Falk | authorlink13 =
| last14 = Ruprecht | first14 = Klemens | authorlink14 =
| last15 = Behrends | first15 = Uta | authorlink15 =
| last16 = Meindl | first16 = Carola | authorlink16 =
| last17 = Volk | first17 = Hans-Dieter | authorlink17=
| last18 = Reimer | first18 = Ulf | authorlink18 =
| last19 = Scheibenbogen | first19 = Carmen | authorlink19 = Carmen Scheibenbogen
| title = Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray
| journal = PLOS ONE | volume = 12 | issue = 6 | page = e0179124
| date = 2017
| doi = 10.1371/journal.pone.0179124
}}
</ref>
<ref name="Sotzny, 2018">{{Citation
| last1 = Sotzny | first1 = Franziska | authorlink1 = Franziska Sotzny
| last2 = Blanco | first2 = Julià | authorlink2 = Julià Blanco
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero
| last5 = Steiner | first5 = Sophie | authorlink5 =
| last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska
| last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
| journal = Autoimmunity Reviews | volume = | issue = | page =
| date = 2018
| pmid =
| doi = 10.1016/j.autrev.2018.01.009
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:Germany researchers]]

Franziska Sotzny

2021-06-01T19:10:49Z

Kmdenmark:added study and ref

[[File:Franziska_Sotzny.png|200px|thumb|right]]
Dr. '''Franziska Sotzny''', is a post-doctorate researcher at the Institute of Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.

==Awards==
*2017 Ramsay Award Program grant was awarded to a team comprised of Dr. [[Carmen Scheibenbogen]] and Dr. Franziska Sotzny of Charité Universitätsmedizin Berlin, sponsored by the [[Solve ME/CFS Initiative]] for researching immunometabolism of [[T cell]]s and monocytes in [[ME/CFS]].<ref>http://solvecfs.org/2017-ramsay-award-program-results/</ref>

==EUROMENE==
Dr. Sotzny is a participant of the [[Biomarkers]] Working Group of [[EUROMENE]], a European Union, COST Action CA15111, not-for-profit research organization committed to tackling the cause and treatment for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]].<ref>http://www.cost.eu/COST_Actions/ca/CA15111?management</ref>

==Notable studies==
*2017, Serological profiling of the [[EBV]] immune response in [[Chronic Fatigue Syndrome]] using a peptide microarray<ref name="Loebel, 2017" /> [http://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0179124 (Full Text)]
*2018, [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] – Evidence for an [[autoimmune disease]]<ref name="Sotzny, 2018" /> [https://www.sciencedirect.com/science/article/pii/S1568997218300880 (Full Text)]
*2018, The expression signature of very long non-coding [[RNA]] in [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref>{{Cite journal|last=Yang|first=Chin-An|last2=Bauer|first2=Sandra|author-link2=Sandra Bauer|last3=Ho|first3=Yu-Chen|last4=Sotzny|first4=Franziska|author-link4=Franziska Sotzny|last5=Chang|first5=Jan-Gowth|last6=Scheibenbogen|first6=Carmen|author-link6=Carmen Scheibenbogen|date=2018-08-17|title=The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x|journal=Journal of Translational Medicine|language=en|volume=16|issue=1|pages=|doi=10.1186/s12967-018-1600-x|issn=1479-5876|via=}}</ref> [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x (Full Text)]
* 2020, Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome<ref name=endothelial2020>{{Cite journal|last=Scherbakov|first=Nadja|author-link=|last2=Szklarski|first2=Marvin|author-link2=|last3=Hartwig|first3=Jelka|author-link3=|last4=Sotzny|first4=Franziska|author-link4=Franziska Sotzny|last5=Lorenz|first5=Sebastian|author-link5=|last6=Meyer|first6=Antje|author-link6=Antje Meyer|last7=Grabowski|first7=Patricia|last8=Doehner|first8=Wolfram|last9=Scheibenbogen|first9=Carmen|author-link9=Carmen Scheibenbogen|date=2020|title=Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ehf2.12633|journal=ESC Heart Failure|language=en|volume=7|issue=3|pages=1064–1071|doi=10.1002/ehf2.12633|issn=2055-5822|pmc = 7261521|pmid=32154656|access-date=|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/abs/10.1002/ehf2.12633 (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Talks and interviews==

==Online presence==
*[https://www.ncbi.nlm.nih.gov/pubmed/?term=Sotzny%20F%5BAuthor%5D&cauthor=true&cauthor_uid=28604802 PubMed]

==Learn more==

==See also==
*[[EUROMENE]]

==References==
<references>
<ref name="Loebel, 2017">{{Citation
| last1 = Loebel | first1 = Madlen | authorlink1 = Madlen Loebel
| last2 = Eckey | first2 = Maren | authorlink2 =
| last3 = Sotzny | first3 = Franziska | authorlink3 = Franziska Sotzny
| last4 = Hahn | first4 = Elisabeth | authorlink4 =
| last5 = Bauer | first5 = Sandra | authorlink5 = Sandra Bauer
| last6 = Grabowski | first6 = Patricia | authorlink6 =
| last7 = Zerweck | first7 = Johannes | authorlink7 =
| last8 = Holenya | first8 = Pavlo | authorlink8 =
| last9 = Hanitsch | first9 = Leif G. | authorlink9 =
| last10 = Wittke | first10 = Kirsten | authorlink10 =
| last11 = Borchmann | first11 = Peter | authorlink11 =
| last12 = Rüffer | first12 = Jens-Ulrich | authorlink12 =
| last13 = Hiepe | first13 = Falk | authorlink13 =
| last14 = Ruprecht | first14 = Klemens | authorlink14 =
| last15 = Behrends | first15 = Uta | authorlink15 =
| last16 = Meindl | first16 = Carola | authorlink16 =
| last17 = Volk | first17 = Hans-Dieter | authorlink17=
| last18 = Reimer | first18 = Ulf | authorlink18 =
| last19 = Scheibenbogen | first19 = Carmen | authorlink19 = Carmen Scheibenbogen
| title = Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray
| journal = PLOS ONE | volume = 12 | issue = 6 | page = e0179124
| date = 2017
| doi = 10.1371/journal.pone.0179124
}}
</ref>
<ref name="Sotzny, 2018">{{Citation
| last1 = Sotzny | first1 = Franziska | authorlink1 = Franziska Sotzny
| last2 = Blanco | first2 = Julià | authorlink2 = Julià Blanco
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero
| last5 = Steiner | first5 = Sophie | authorlink5 =
| last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska
| last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
| journal = Autoimmunity Reviews | volume = | issue = | page =
| date = 2018
| pmid =
| doi = 10.1016/j.autrev.2018.01.009
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:Germany researchers]]

Luis Nacul

2021-06-01T19:09:53Z

Kmdenmark:added study authors

Dr '''Luis Carlos Nacul''' is a Clinical Associate Professor and researcher at the [[London School of Hygiene and Tropical Medicine]] in London, [[United Kingdom]]. He leads the [[CureME]] team and the [[UK ME/CFS biobank]]. He serves as a Member Substitute for [[EUROMENE]], an international not-for-profit organization for [[ME/CFS]] research.

He is a doctor and general practitioner, with training across medicine, epidemiology and public health.<ref>{{Cite web|url=https://www.lshtm.ac.uk/aboutus/people/nacul.luis|title=Luis Nacul|last=London School of Hygiene and Tropical Medicine|first=|authorlink=London School of Hygiene and Tropical Medicine|date=|website=|archive-url=|archive-date=|url-status=|access-date=}}</ref> In 2018, Dr Nacul was appointed to the review committee for the [[NICE guidelines]] for [[ME/CFS]] used by the British [[NHS]].<ref>{{Cite web|url=https://www.nice.org.uk/guidance/gid-ng10091/documents/committee-member-list|title=Committee member list {{!}} NICE CG53 CFS/ME guidance update|last=[[NICE]]|first=|date=28 October 2018|website=nice.org.uk|archive-url=|archive-date=|url-status=|access-date=20 October 2018}}</ref>

==ME/CFS Common Data Element (CDE) Project==
Dr Nacul serves on the Fatigue Working Group of the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Common Data Element (CDE) Project sponsored by the [[National Institute of Neurological Disorders and Stroke]] and the [[Centers for Disease Control & Prevention]].<ref>{{Cite web|url=https://www.commondataelements.ninds.nih.gov/Myalgic%20Encephalomyelitis/Chronic%20Fatigue%20Syndrome#pane-138|title=Complete Myalgic Encephalomyelitis/Chronic Fatigue Syndrome CDE Roster|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NIH|archive-url=|archive-date=|url-status=|access-date=2019-10-11}}</ref>

==Notable studies and writings related to ME/CFS==
*2007, The Development of an Epidemiological Definition for [[Myalgic Encephalomyelitis]]/[[Chronic Fatigue Syndrome]]<ref name="Osoba, 2007" /> - [https://www.tandfonline.com/doi/abs/10.3109/10573320802092112 (Abstract)]
*2011, Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care<ref>{{Cite journal |last=Nacul|first=L. C.|authorlink =Luis Nacul|last2 =Lacerda|first2=E. M.|author-link2=Eliana Lacerda|last3=Pheby|first3=D.|author-link3=Derek Pheby|last4=Campion|first4=P.|last5=Molokhia|first5=M.|last6=Fayyaz|first6=S.|last7=Leite|first7=JCDC|last8=Poland|first8=F|last9=Howe|first9=A|last10=de L. Drachler|date=2011|title=Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care|journal =BMC Medicine|volume = 9|issue =91|url=http://doi.org/10.1186/1741-7015-9-91|doi=10.1186/1741-7015-9-91|pmc=3170215|pages=|quote=|author-link4=Peter Campion|author-link5=Mariam Molokhia|via=|author-link6=Shagufta Fayyaz|author-link7=José Leife|author-link8=Fiona Poland|author-link9=Amanda Howe|author-link10=Maria Drachler|first10=Maria}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170215/ (Full Text)]
*2011, Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis<ref name="de Carvalho Leite, 2011" /> - [https://equityhealthj.biomedcentral.com/articles/10.1186/1475-9276-10-46 (Full Text)]
*2011, The functional status and well being of people with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] and their carers<ref>{{Cite journal|last=Nacul|first=Luis C|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Campion|first3=Peter|author-link3=Peter Campion|last4=Pheby|first4=Derek|author-link4=Derek Pheby|last5=Drachler|first5=Maria de L|author-link5=Maria de L Drachler|last6=Leite|first6=José C|author-link6=José Leite|last7=Poland|first7=Fiona|author-link7=Fiona Poland|last8=Howe|first8=Amanda|author-link8=Amanda Howe|last9=Fayyaz|first9=Shagufta|author-link9=Shagufta Fayyaz|date=2011-05-27|title=The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers|url=https://doi.org/10.1186/1471-2458-11-402|journal=BMC Public Health|language=en|volume=11|issue=1|pages=402|doi=10.1186/1471-2458-11-402|issn=1471-2458|pmc=3123211|pmid=21619607|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full Text)]
*2014, Considerations in establishing a post-mortem [[brain]] and tissue bank for the study of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]: A proposed protocol<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O’Donovan|first2=Dominic G|author-link2=Dominic O'Donovan|last3=Lacerda|first3=Eliana M|author-link3=Eliana Lacerda|last4=Gveric|first4=Djordje|author-link4=Djordje Gveric|last5=Goldring|first5=Kirstin|author-link5=Kirstin Goldring|last6=Hall|first6=Alison|author-link6=Alison Hall|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Pheby|first8=Derek|author-link8=Derek Pheby|date=2014|title=Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol|url=https://doi.org/10.1186/1756-0500-7-370|journal=BMC Research Notes|language=en|volume=7|issue=1|pages=370|doi=10.1186/1756-0500-7-370|issn=1756-0500|pmc=4076507|pmid=24938650|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076507/ (Full Text)]
*2017, [[How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?]]<ref name="Nacul2017">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Kingdon|first3=Caroline C|author-link3=Caroline Kingdon|last4=Curran|first4=Hayley|author-link4=Hayley Curran|last5=Bowman|first5=Erinna W|author-link5=Erinna Bowman|date=Mar 1, 2017|title=How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?|url=https://doi.org/10.1177/1359105317695803|journal=[[Journal of Health Psychology]]|language=en|volume=|issue=|pages=1359105317695803|doi=10.1177/1359105317695803|issn=1359-1053|pmc=5581258|pmid=28810428|quote=|via=}}</ref> - [https://doi.org/10.1177/1359105317695803 (Full text)]
*2017, Public Review - Draft of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials<ref name="Common Data Elements, 2017">{{Citation|last1=Cella|first1=David|authorlink1=David Cella|last2=Dimmock|first2=Mary|authorlink2=Mary Dimmock|last3=Friedberg|first3=Fred|authorlink3=Fred Friedberg|last4=Lin|first4=Jin-Mann Sally|authorlink4=Jin-Mann Sally Lin|last5=Nacul|first5=Luis|authorlink5=Luis Nacul|last6=Saligan|first6=Leorey|authorlink6=Leorey Saligan|title=NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials|date=Dec 2017|url=https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf}}</ref> - [https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf (Full Text)]
*2017, Editorial - ''Using a participatory approach to develop and implement the UK ME/CFS Biobank''<ref>{{Cite journal|last1=Lacerda|first1=Eliana M.|authorlink1=Eliana Lacerda|last2=Kingdon|first2=Caroline C.|authorlink2=Caroline Kingdon|last3=Bowman|first3=Erinna W.|authorlink3=Erinna Bowman|last4=Nacul|first4=Luis|authorlink4=Luis Nacul|title=Using a participatory approach to develop and implement the UK ME/CFS Biobank|journal=Fatigue: Biomedicine, Health & Behavior|volume= |issue= |page=|date=2017|pmid=|doi=10.1080/21641846.2018.1396021}}</ref>
*2017, Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome<ref>{{Cite journal|title=Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29250461|journal=Fatigue: Biomedicine, Health & Behavior|date=2017|issn=2164-1846|pmc=5730342|pmid=29250461|pages=1–4|volume=5|issue=1|doi=10.1080/21641846.2017.1273863|first=Luis|last=Nacul|first2=Caroline C.|last2=Kingdon|first3=Erinna W.|last3=Bowman|first4=Hayley|last4=Curran|first5=Eliana M.|last5=Lacerda|quote=|author-link=Luis Nacul|author-link2=Caroline Kingdon|author-link3=Erinna Bowman|author-link4=Hayley Curran|author-link5=Eliana Lacerda|via=}}</ref>
* 2017, The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and [[Multiple sclerosis|Multiple Sclerosis]]<ref>{{Cite journal|last=Lacerda|first=Eliana M|author-link=Eliana Lacerda|last2=Bowman|first2=Erinna W|author-link2=Erinna Bowman|last3=Cliff|first3=Jacqueline M|author-link3=Jacqueline Cliff|last4=Kingdon|first4=Caroline C|author-link4=Caroline Kingdon|last5=King|first5=Elizabeth C|author-link5=Elizabeth King|last6=Lee|first6=Ji-Sook|author-link6=Ji-Sook Lee|last7=Clark|first7=Taane G|author-link7=Taane Clark|last8=Dockrell|first8=Hazel M|author-link8=Hazel Dockrell|last9=Riley|first9=Eleanor M|author-link9=Eleanor Riley|last10=Curran|first10=Hayley|author-link10=Hayley Curran|last11= Nacul|first11=Luis|author-link11=Luis Nacul|date=2017-02-20|title=The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis|url=http://openbioresources.metajnl.com/articles/10.5334/ojb.28/|journal=Open Journal of Bioresources|language=en|volume=4|issue=|pages=|doi=10.5334/ojb.28|issn=2056-5542|pmc=5482226|pmid=28649428|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482226/ (Full text)]
*2018, Functional Status and Well-Being in People with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] Compared with People with [[Multiple Sclerosis]] and Healthy Controls<ref>{{Cite journal|last=Kingdon|first=Caroline C.|author-link=Caroline Kingdon|last2=Bowman|first2=Erinna W.|author-link2=Erinna Bowman|last3=Curran|first3=Hayley|author-link3=Hayley Curran|last4=Nacul|first4=Luis|author-link4=Luis Nacul|last5=Lacerda|first5=Eliana M.|author-link5=Eliana Lacerda|date=2018-03-13|title=Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=|issue=|pages=|doi=10.1007/s41669-018-0071-6|issn=2509-4262|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007%2Fs41669-018-0071-6 (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2018, Hand grip strength as a clinical [[Diagnostic biomarker|biomarker]] for ME/CFS and Disease Severity<ref>{{Cite journal|last=Nacul|first=Luis Carlos|author-link=Luis Nacul|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Kingdon|first3=Caroline|author-link3=Caroline Kingdon|last4=Clark|first4=Taane G.|author-link4=Taane Clark|last5=Lacerda|first5=Eliana Mattos|author-link5=Eliana Lacerda|date=2018|title=Hand grip strength as a clinical biomarker for ME/CFS and disease severity|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.00992|issn=1664-2295|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract (Abstract)]
* 2018, The [[CureME|UK ME/CFS Biobank]]: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Lacerda|first=Eliana|author-link=Eliana Lacerda|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Butterworth|first3=Jack D.|author-link3=Jack Butterworth|last4=Kingdon|first4=Caroline C.|author-link4=Caroline Kingdon|last5=O'Boyle|first5=Shennae|author-link5=Shennae O'Boyle|last6=Nacul|first6=Luis|author-link6=Luis Nacul|date=2018-12-04|title=The UK ME/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.01026|issn=1664-2295|pmc=|pmid=30564186|quote=|via=|last7=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full (Full text)]
* 2019, Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=McDermott|first2=Clare|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Butterworth|first4=Jack|author-link4=|last5=Cliff|first5=Jacqueline M.|author-link5=Jacqueline Cliff|last6=Nacul|first6=Luis|date=2019-01-10|title=Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/hex.12857|journal=Health Expectations|language=en|volume=0|issue=0|pages=|doi=10.1111/hex.12857|issn=1369-7625|pmid=30632248|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/full/10.1111/hex.12857 (Full text)]
* 2019, Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=de Barros|first2=Barbara|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Cliff|first4=Jacqueline M.|author-link4=Jacqueline Cliff|last5=Clark|first5=Taane G.|author-link5=|last6=Mudie|first6=Kathleen|last7=Dockrell|first7=Hazel M.|author-link7=Hazel Dockrell|last8=Lacerda|first8=Eliana M.|author-link8=Eliana Lacerda|date=2019-04-10|title=Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study|url=https://www.mdpi.com/2075-4418/9/2/41|journal=Diagnostics|language=en|volume=9|issue=2|pages=41|doi=10.3390/diagnostics9020041|issn=2075-4418|quote=|via=}}</ref> - [https://www.mdpi.com/2075-4418/9/2/41 (Abstract)]
* 2019, Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref>{{Cite journal|last=Cliff|first=Jacqueline M.|author-link=Jacqueline Cliff|last2=King|first2=Elizabeth C.|author-link2=|last3=Lee|first3=Ji-Sook|author-link3=|last4=Sepúlveda|first4=Nuno|author-link4=Nuno Sepúlveda|last5=Wolf|first5=Asia-Sophia|author-link5=|last6=Kingdon|first6=Caroline|author-link6=Caroline Kingdon|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Dockrell|first8=Hazel M.|author-link8=Hazel Dockrell|last9=Nacul|first9=Luis|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana|author-link10=Eliana Lacerda|last11=Riley|first11=Eleanor|author-link11=Eleanor Riley|date=2019-04-16|title=Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.frontiersin.org/article/10.3389/fimmu.2019.00796/full|journal=Frontiers in Immunology|volume=10|issue=|pages=|doi=10.3389/fimmu.2019.00796|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.00796/full (Full text)]
* 2019, HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome<ref>{{Cite journal|last=Rodrigues|first=Lucas S|author-link=|last2=Nali|first2=Luiz H da Silva|author-link2=|last3=Leal|first3=Cibele O D|author-link3=|last4=Sabino|first4=Ester C|author-link4=|last5=Lacerda|first5=Eliana M|author-link5=Eliana Lacerda|last6=Kingdon|first6=Caroline C|author-link6=Caroline Kingdon|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Romano|first8=Camila M|date=2019-07-05|title=HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome|url=http://biorxiv.org/lookup/doi/10.1101/693465|journal=bioRxiv|volume=|issue=|pages=|doi=10.1101/693465|quote=|via=}}</ref> - [https://www.biorxiv.org/content/10.1101/693465v1.full (Full text)]
* 2019, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory [[T cell|T cells]] and chronic human [[Herpesviruses|herpesvirus]] infections<ref>{{Cite journal|last=Sepúlveda|first=Nuno|author-link=Nuno Sepulveda|last2=Carneiro|first2=Jorge|author-link2=|last3=Eliana M. Lacerda|first3=Eliana M.|author-link3=Eliana Lacerda|last4=Nacul|first4=Luis C.|author-link4=Luis Nacul|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Oct 2019|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections|url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract|journal=Frontiers in Immunology|volume=|issue=|pages=|doi=10.3389/fimmu.2019.02684|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract (Abstract)]
* 2019, A logistic regression analysis of risk factors in ME/CFS pathogenesis<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=Geraghty|first2=Keith|author-link2=Keith Geraghty|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Palla|first4=Luigi|author-link4=|last5=Nacul|first5=Luis|author-link5=Luis Nacul|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Dec 2019|title=A logistic regression analysis of risk factors in ME/CFS pathogenesis|url=https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-019-1468-2|journal=BMC Neurology|language=en|volume=19|issue=1|pages=275|doi=10.1186/s12883-019-1468-2|issn=1471-2377|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1186/s12883-019-1468-2 (Full text)]
*2019, Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Friedberg2019">{{Cite journal|last=Friedberg|first=Fred|author-link=Fred Friedberg|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Nacul|first3=Luis|author-link3=Luis Nacul|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=2020-03-01|title=Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://doi.org/10.1007/s11606-019-05375-y|journal=Journal of General Internal Medicine|language=en|volume=35|issue=3|pages=906–909|doi=10.1007/s11606-019-05375-y|issn=1525-1497|pmc = 7080939|pmid=31637650|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007/s11606-019-05375-y (Full text)]
*2019, How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS<ref name="Stages2019">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O'Boyle|first2=Shennae|author-link2=|last3=Nacul|first3=Flavio E.|author-link3=|last4=Mudie|first4=Kathleen|author-link4=|last5=Kingdon|first5=Caroline C.|author-link5=Caroline Kingdon|last6=Cliff|first6=Jacqueline M.|author-link6=Jacqueline Cliff|last7=Clark|first7=Taane G.|last8=Dockrell|first8=Hazel M.|last9=Lacerda|first9=Eliana M.|author-link9=Eliana Lacerda|date=2019-09-17|title=How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS|url=https://www.preprints.org/manuscript/201909.0188/v1|journal=Preprints|language=en|volume=|issue=|pages=|doi=10.20944/preprints201909.0188.v1|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.preprints.org/manuscript/201909.0188/download/final_file (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|last10=Lacerda|first10=Eliana M|author-link10= Eliana Lacerda|last11=Castro-Marrero|first11=Jesus|author-link11=Jesus Castro-Marrero|last12=Scheibenbogen|first12=Carmen|author-link12=Carmen Scheibenbogen|last13=Westermeier|first13=Francisco|author-link13=|last14=Sepúlveda|first14=Nuno|author-link14=Nuno Sepúlveda|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Talks and interviews==
*2015, Speaker at the 10th [[Invest in ME International ME Conference]] - [http://www.investinme.org/IIMEC10.shtml#dvd DVD available] Speech title - ''Incidence and Prevalence of ME''
*2018, [[CFS/ME Research Collaborative Conference|UK CFS/ME Research Collaborative Conference]] - ''[https://www.youtube.com/watch?v=5FonUVDyc0I&list=PLJV2oZMsotONY3AEkA-c3kVFjtVokLBD7&index=5 The UK ME/CFS Biobank: Accelerating global research in ME/CFS]''

* 13 Mar 2019, [https://mecfsconference.org.au/videos/luis-nacul/ ''Infrastructure & Translational Research in ME/CFS: the Experience of CureME & the UK ME/CFS Biobank''] given at the [[International Research Symposium - Emerge Australia|International Research Symposium]], Geelong, Australia, sponsored by [[Emerge Australia]]
* 21 Sep 2019, ME/FM Society of BC: Presentation by Dr. Luis Nacul - [https://www.youtube.com/watch?v=kupG4a5vJdM ''Has ME/CFS research helped clinicians and patients? Can we do better?'']

==Online presence==

==See also==
*[[CureME]]
*[[EUROMENE]]
*[[NICE guidelines]]
*[[NHS]]

==Learn more==
*[https://www.lshtm.ac.uk/aboutus/people/nacul.luis LSHTM bio]

==References==
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<ref name="de Carvalho Leite, 2011">{{Citation
| last1 = de Carvalho Leite | first1 = JC | authorlink1 = José de Carvalho Leite
| last2 = de L Drachler | first2 = M | authorlink2 = Maria de L Drachler
| last3 = Killett | first3 = A | authorlink3 = Anne Killett
| last4 = Kale | first4 = S | authorlink4 = Swati Kale
| last5 = Nacul | first5 = L | authorlink5 = Luis Nacul
| last6 = McArthur | first6 = M | authorlink6 = Maggie McArthur
| last7 = Hong | first7 = CS | authorlink7 = Chia Hong
| last8 = O'Driscoll | first8 = L | authorlink8 = Lucy Driscoll
| last9 = Pheby | first9 = D | authorlink9 = Derek Pheby
| last10 = Campion | first10 = P | authorlink10 = Peter Campion
| last11 = Lacerda | first11 = E | authorlink11 = Eliana Lacerda
| last12 = Poland | first12 = F | authorlink12 = Fiona Poland
| title = Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis
| journal = International Journal for Equity in Health | volume = 2 | issue = 10 | page = 46
| date = 2011
| pmid =
| doi = 10.1186/1475-9276-10-46
|url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229491/
| pmc = 3229491
}}
</ref>
<ref name="Osoba, 2007">{{Citation
| last1 = Osoba | first1 = Tolu | authorlink1 = Tolu Osoba
| last2 = Pheby | first2 = Derek | authorlink2 = Derek Pheby
| last3 = Gray | first3 = Selena | authorlink3 = Selena Gray
| last4 = Nacul | first4 = Luis | authorlink4 = Luis Nacul
| title = The Development of an Epidemiological Definition for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| journal = Journal of Chronic Fatigue Syndrome | volume = 14 | issue = 4 | page = 61-84
| date = 2007
| pmid =
| doi = 10.3109/10573320802092112
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}}
</ref>
</references>

[[Category:Researchers]]
[[Category:UK researchers]]

Luis Nacul

2021-06-01T18:59:34Z

Kmdenmark:added study

Dr '''Luis Carlos Nacul''' is a Clinical Associate Professor and researcher at the [[London School of Hygiene and Tropical Medicine]] in London, [[United Kingdom]]. He leads the [[CureME]] team and the [[UK ME/CFS biobank]]. He serves as a Member Substitute for [[EUROMENE]], an international not-for-profit organization for [[ME/CFS]] research.

He is a doctor and general practitioner, with training across medicine, epidemiology and public health.<ref>{{Cite web|url=https://www.lshtm.ac.uk/aboutus/people/nacul.luis|title=Luis Nacul|last=London School of Hygiene and Tropical Medicine|first=|authorlink=London School of Hygiene and Tropical Medicine|date=|website=|archive-url=|archive-date=|url-status=|access-date=}}</ref> In 2018, Dr Nacul was appointed to the review committee for the [[NICE guidelines]] for [[ME/CFS]] used by the British [[NHS]].<ref>{{Cite web|url=https://www.nice.org.uk/guidance/gid-ng10091/documents/committee-member-list|title=Committee member list {{!}} NICE CG53 CFS/ME guidance update|last=[[NICE]]|first=|date=28 October 2018|website=nice.org.uk|archive-url=|archive-date=|url-status=|access-date=20 October 2018}}</ref>

==ME/CFS Common Data Element (CDE) Project==
Dr Nacul serves on the Fatigue Working Group of the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Common Data Element (CDE) Project sponsored by the [[National Institute of Neurological Disorders and Stroke]] and the [[Centers for Disease Control & Prevention]].<ref>{{Cite web|url=https://www.commondataelements.ninds.nih.gov/Myalgic%20Encephalomyelitis/Chronic%20Fatigue%20Syndrome#pane-138|title=Complete Myalgic Encephalomyelitis/Chronic Fatigue Syndrome CDE Roster|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=NIH|archive-url=|archive-date=|url-status=|access-date=2019-10-11}}</ref>

==Notable studies and writings related to ME/CFS==
*2007, The Development of an Epidemiological Definition for [[Myalgic Encephalomyelitis]]/[[Chronic Fatigue Syndrome]]<ref name="Osoba, 2007" /> - [https://www.tandfonline.com/doi/abs/10.3109/10573320802092112 (Abstract)]
*2011, Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care<ref>{{Cite journal |last=Nacul|first=L. C.|authorlink =Luis Nacul|last2 =Lacerda|first2=E. M.|author-link2=Eliana Lacerda|last3=Pheby|first3=D.|author-link3=Derek Pheby|last4=Campion|first4=P.|last5=Molokhia|first5=M.|last6=Fayyaz|first6=S.|last7=Leite|first7=JCDC|last8=Poland|first8=F|last9=Howe|first9=A|last10=de L. Drachler|date=2011|title=Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care|journal =BMC Medicine|volume = 9|issue =91|url=http://doi.org/10.1186/1741-7015-9-91|doi=10.1186/1741-7015-9-91|pmc=3170215|pages=|quote=|author-link4=Peter Campion|author-link5=Mariam Molokhia|via=|author-link6=Shagufta Fayyaz|author-link7=José Leife|author-link8=Fiona Poland|author-link9=Amanda Howe|author-link10=Maria Drachler|first10=Maria}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170215/ (Full Text)]
*2011, Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis<ref name="de Carvalho Leite, 2011" /> - [https://equityhealthj.biomedcentral.com/articles/10.1186/1475-9276-10-46 (Full Text)]
*2011, The functional status and well being of people with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] and their carers<ref>{{Cite journal|last=Nacul|first=Luis C|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Campion|first3=Peter|author-link3=Peter Campion|last4=Pheby|first4=Derek|author-link4=Derek Pheby|last5=Drachler|first5=Maria de L|author-link5=Maria de L Drachler|last6=Leite|first6=José C|author-link6=José Leite|last7=Poland|first7=Fiona|author-link7=Fiona Poland|last8=Howe|first8=Amanda|author-link8=Amanda Howe|last9=Fayyaz|first9=Shagufta|author-link9=Shagufta Fayyaz|date=2011-05-27|title=The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers|url=https://doi.org/10.1186/1471-2458-11-402|journal=BMC Public Health|language=en|volume=11|issue=1|pages=402|doi=10.1186/1471-2458-11-402|issn=1471-2458|pmc=3123211|pmid=21619607|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full Text)]
*2014, Considerations in establishing a post-mortem [[brain]] and tissue bank for the study of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]: A proposed protocol<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O’Donovan|first2=Dominic G|author-link2=Dominic O'Donovan|last3=Lacerda|first3=Eliana M|author-link3=Eliana Lacerda|last4=Gveric|first4=Djordje|author-link4=Djordje Gveric|last5=Goldring|first5=Kirstin|author-link5=Kirstin Goldring|last6=Hall|first6=Alison|author-link6=Alison Hall|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Pheby|first8=Derek|author-link8=Derek Pheby|date=2014|title=Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol|url=https://doi.org/10.1186/1756-0500-7-370|journal=BMC Research Notes|language=en|volume=7|issue=1|pages=370|doi=10.1186/1756-0500-7-370|issn=1756-0500|pmc=4076507|pmid=24938650|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076507/ (Full Text)]
*2017, [[How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?]]<ref name="Nacul2017">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=Lacerda|first2=Eliana M|author-link2=Eliana Lacerda|last3=Kingdon|first3=Caroline C|author-link3=Caroline Kingdon|last4=Curran|first4=Hayley|author-link4=Hayley Curran|last5=Bowman|first5=Erinna W|author-link5=Erinna Bowman|date=Mar 1, 2017|title=How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?|url=https://doi.org/10.1177/1359105317695803|journal=[[Journal of Health Psychology]]|language=en|volume=|issue=|pages=1359105317695803|doi=10.1177/1359105317695803|issn=1359-1053|pmc=5581258|pmid=28810428|quote=|via=}}</ref> - [https://doi.org/10.1177/1359105317695803 (Full text)]
*2017, Public Review - Draft of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials<ref name="Common Data Elements, 2017">{{Citation|last1=Cella|first1=David|authorlink1=David Cella|last2=Dimmock|first2=Mary|authorlink2=Mary Dimmock|last3=Friedberg|first3=Fred|authorlink3=Fred Friedberg|last4=Lin|first4=Jin-Mann Sally|authorlink4=Jin-Mann Sally Lin|last5=Nacul|first5=Luis|authorlink5=Luis Nacul|last6=Saligan|first6=Leorey|authorlink6=Leorey Saligan|title=NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Common Data Elements (CDE); Fatigue Subgroup Materials|date=Dec 2017|url=https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf}}</ref> - [https://www.commondataelements.ninds.nih.gov/Doc/MECFS/03_Fatigue_Subgroup_CDE_Draft_Recommendations.pdf (Full Text)]
*2017, Editorial - ''Using a participatory approach to develop and implement the UK ME/CFS Biobank''<ref>{{Cite journal|last1=Lacerda|first1=Eliana M.|authorlink1=Eliana Lacerda|last2=Kingdon|first2=Caroline C.|authorlink2=Caroline Kingdon|last3=Bowman|first3=Erinna W.|authorlink3=Erinna Bowman|last4=Nacul|first4=Luis|authorlink4=Luis Nacul|title=Using a participatory approach to develop and implement the UK ME/CFS Biobank|journal=Fatigue: Biomedicine, Health & Behavior|volume= |issue= |page=|date=2017|pmid=|doi=10.1080/21641846.2018.1396021}}</ref>
*2017, Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome<ref>{{Cite journal|title=Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29250461|journal=Fatigue: Biomedicine, Health & Behavior|date=2017|issn=2164-1846|pmc=5730342|pmid=29250461|pages=1–4|volume=5|issue=1|doi=10.1080/21641846.2017.1273863|first=Luis|last=Nacul|first2=Caroline C.|last2=Kingdon|first3=Erinna W.|last3=Bowman|first4=Hayley|last4=Curran|first5=Eliana M.|last5=Lacerda|quote=|author-link=Luis Nacul|author-link2=Caroline Kingdon|author-link3=Erinna Bowman|author-link4=Hayley Curran|author-link5=Eliana Lacerda|via=}}</ref>
* 2017, The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and [[Multiple sclerosis|Multiple Sclerosis]]<ref>{{Cite journal|last=Lacerda|first=Eliana M|author-link=Eliana Lacerda|last2=Bowman|first2=Erinna W|author-link2=Erinna Bowman|last3=Cliff|first3=Jacqueline M|author-link3=Jacqueline Cliff|last4=Kingdon|first4=Caroline C|author-link4=Caroline Kingdon|last5=King|first5=Elizabeth C|author-link5=Elizabeth King|last6=Lee|first6=Ji-Sook|author-link6=Ji-Sook Lee|last7=Clark|first7=Taane G|author-link7=Taane Clark|last8=Dockrell|first8=Hazel M|author-link8=Hazel Dockrell|last9=Riley|first9=Eleanor M|author-link9=Eleanor Riley|last10=Curran|first10=Hayley|author-link10=Hayley Curran|last11= Nacul|first11=Luis|author-link11=Luis Nacul|date=2017-02-20|title=The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis|url=http://openbioresources.metajnl.com/articles/10.5334/ojb.28/|journal=Open Journal of Bioresources|language=en|volume=4|issue=|pages=|doi=10.5334/ojb.28|issn=2056-5542|pmc=5482226|pmid=28649428|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482226/ (Full text)]
*2018, Functional Status and Well-Being in People with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] Compared with People with [[Multiple Sclerosis]] and Healthy Controls<ref>{{Cite journal|last=Kingdon|first=Caroline C.|author-link=Caroline Kingdon|last2=Bowman|first2=Erinna W.|author-link2=Erinna Bowman|last3=Curran|first3=Hayley|author-link3=Hayley Curran|last4=Nacul|first4=Luis|author-link4=Luis Nacul|last5=Lacerda|first5=Eliana M.|author-link5=Eliana Lacerda|date=2018-03-13|title=Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=|issue=|pages=|doi=10.1007/s41669-018-0071-6|issn=2509-4262|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007%2Fs41669-018-0071-6 (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2018, Hand grip strength as a clinical [[Diagnostic biomarker|biomarker]] for ME/CFS and Disease Severity<ref>{{Cite journal|last=Nacul|first=Luis Carlos|author-link=Luis Nacul|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Kingdon|first3=Caroline|author-link3=Caroline Kingdon|last4=Clark|first4=Taane G.|author-link4=Taane Clark|last5=Lacerda|first5=Eliana Mattos|author-link5=Eliana Lacerda|date=2018|title=Hand grip strength as a clinical biomarker for ME/CFS and disease severity|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.00992|issn=1664-2295|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/abstract (Abstract)]
* 2018, The [[CureME|UK ME/CFS Biobank]]: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref>{{Cite journal|last=Lacerda|first=Eliana|author-link=Eliana Lacerda|last2=Mudie|first2=Kathleen|author-link2=Kathleen Mudie|last3=Butterworth|first3=Jack D.|author-link3=Jack Butterworth|last4=Kingdon|first4=Caroline C.|author-link4=Caroline Kingdon|last5=O'Boyle|first5=Shennae|author-link5=Shennae O'Boyle|last6=Nacul|first6=Luis|author-link6=Luis Nacul|date=2018-12-04|title=The UK ME/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full|journal=Frontiers in Neurology|language=English|volume=9|issue=|pages=|doi=10.3389/fneur.2018.01026|issn=1664-2295|pmc=|pmid=30564186|quote=|via=|last7=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fneur.2018.01026/full (Full text)]
* 2019, Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=McDermott|first2=Clare|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Butterworth|first4=Jack|author-link4=|last5=Cliff|first5=Jacqueline M.|author-link5=Jacqueline Cliff|last6=Nacul|first6=Luis|date=2019-01-10|title=Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/hex.12857|journal=Health Expectations|language=en|volume=0|issue=0|pages=|doi=10.1111/hex.12857|issn=1369-7625|pmid=30632248|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/full/10.1111/hex.12857 (Full text)]
* 2019, Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study<ref>{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=de Barros|first2=Barbara|author-link2=|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Cliff|first4=Jacqueline M.|author-link4=Jacqueline Cliff|last5=Clark|first5=Taane G.|author-link5=|last6=Mudie|first6=Kathleen|last7=Dockrell|first7=Hazel M.|author-link7=Hazel Dockrell|last8=Lacerda|first8=Eliana M.|author-link8=Eliana Lacerda|date=2019-04-10|title=Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study|url=https://www.mdpi.com/2075-4418/9/2/41|journal=Diagnostics|language=en|volume=9|issue=2|pages=41|doi=10.3390/diagnostics9020041|issn=2075-4418|quote=|via=}}</ref> - [https://www.mdpi.com/2075-4418/9/2/41 (Abstract)]
* 2019, Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref>{{Cite journal|last=Cliff|first=Jacqueline M.|author-link=Jacqueline Cliff|last2=King|first2=Elizabeth C.|author-link2=|last3=Lee|first3=Ji-Sook|author-link3=|last4=Sepúlveda|first4=Nuno|author-link4=Nuno Sepúlveda|last5=Wolf|first5=Asia-Sophia|author-link5=|last6=Kingdon|first6=Caroline|author-link6=Caroline Kingdon|last7=Bowman|first7=Erinna|author-link7=Erinna Bowman|last8=Dockrell|first8=Hazel M.|author-link8=Hazel Dockrell|last9=Nacul|first9=Luis|author-link9=Luis Nacul|last10=Lacerda|first10=Eliana|author-link10=Eliana Lacerda|last11=Riley|first11=Eleanor|author-link11=Eleanor Riley|date=2019-04-16|title=Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.frontiersin.org/article/10.3389/fimmu.2019.00796/full|journal=Frontiers in Immunology|volume=10|issue=|pages=|doi=10.3389/fimmu.2019.00796|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.00796/full (Full text)]
* 2019, HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome<ref>{{Cite journal|last=Rodrigues|first=Lucas S|author-link=|last2=Nali|first2=Luiz H da Silva|author-link2=|last3=Leal|first3=Cibele O D|author-link3=|last4=Sabino|first4=Ester C|author-link4=|last5=Lacerda|first5=Eliana M|author-link5=Eliana Lacerda|last6=Kingdon|first6=Caroline C|author-link6=Caroline Kingdon|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Romano|first8=Camila M|date=2019-07-05|title=HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome|url=http://biorxiv.org/lookup/doi/10.1101/693465|journal=bioRxiv|volume=|issue=|pages=|doi=10.1101/693465|quote=|via=}}</ref> - [https://www.biorxiv.org/content/10.1101/693465v1.full (Full text)]
* 2019, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory [[T cell|T cells]] and chronic human [[Herpesviruses|herpesvirus]] infections<ref>{{Cite journal|last=Sepúlveda|first=Nuno|author-link=Nuno Sepulveda|last2=Carneiro|first2=Jorge|author-link2=|last3=Eliana M. Lacerda|first3=Eliana M.|author-link3=Eliana Lacerda|last4=Nacul|first4=Luis C.|author-link4=Luis Nacul|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Oct 2019|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a hyper-regulated immune system driven by an interplay between regulatory T cells and chronic human herpesvirus infections|url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract|journal=Frontiers in Immunology|volume=|issue=|pages=|doi=10.3389/fimmu.2019.02684|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.02684/abstract (Abstract)]
* 2019, A logistic regression analysis of risk factors in ME/CFS pathogenesis<ref>{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=Geraghty|first2=Keith|author-link2=Keith Geraghty|last3=Kingdon|first3=Caroline C.|author-link3=Caroline Kingdon|last4=Palla|first4=Luigi|author-link4=|last5=Nacul|first5=Luis|author-link5=Luis Nacul|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Dec 2019|title=A logistic regression analysis of risk factors in ME/CFS pathogenesis|url=https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-019-1468-2|journal=BMC Neurology|language=en|volume=19|issue=1|pages=275|doi=10.1186/s12883-019-1468-2|issn=1471-2377|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1186/s12883-019-1468-2 (Full text)]
*2019, Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Friedberg2019">{{Cite journal|last=Friedberg|first=Fred|author-link=Fred Friedberg|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Nacul|first3=Luis|author-link3=Luis Nacul|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=2020-03-01|title=Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://doi.org/10.1007/s11606-019-05375-y|journal=Journal of General Internal Medicine|language=en|volume=35|issue=3|pages=906–909|doi=10.1007/s11606-019-05375-y|issn=1525-1497|pmc = 7080939|pmid=31637650|access-date=|quote=|via=}}</ref> - [https://link.springer.com/article/10.1007/s11606-019-05375-y (Full text)]
*2019, How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS<ref name="Stages2019">{{Cite journal|last=Nacul|first=Luis|author-link=Luis Nacul|last2=O'Boyle|first2=Shennae|author-link2=|last3=Nacul|first3=Flavio E.|author-link3=|last4=Mudie|first4=Kathleen|author-link4=|last5=Kingdon|first5=Caroline C.|author-link5=Caroline Kingdon|last6=Cliff|first6=Jacqueline M.|author-link6=Jacqueline Cliff|last7=Clark|first7=Taane G.|last8=Dockrell|first8=Hazel M.|last9=Lacerda|first9=Eliana M.|author-link9=Eliana Lacerda|date=2019-09-17|title=How Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) Progresses: A Framework for Research and the Prevention, Treatment, and Rehabilitation in ME/CFS|url=https://www.preprints.org/manuscript/201909.0188/v1|journal=Preprints|language=en|volume=|issue=|pages=|doi=10.20944/preprints201909.0188.v1|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.preprints.org/manuscript/201909.0188/download/final_file (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies<ref>{{Cite journal|last=Malato|first=João|author-link=|last2=Sotzny|first2=Franziska|author-link2=Franziska Sotzny|last3=Bauer|first3=Sandra|author-link3=|last4=Freitag|first4=Helma|author-link4=|last5=Fonseca|first5=André|author-link5=|last6=Grabowska|first6=Anna D|author-link6=|last7=Graça|first7=Luís|last8=Cordeiro|first8=Clara|last9=Nacul|first9=Luís|date=2021-03-24|title=The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: analysis of high-throughput epigenetic and gene expression studies|url=http://medrxiv.org/lookup/doi/10.1101/2021.03.23.21254175|journal=medRxiv|language=en|volume=|issue=|pages=|doi=10.1101/2021.03.23.21254175|pmc=|pmid=33791744|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010776/ (Full text)]

==Talks and interviews==
*2015, Speaker at the 10th [[Invest in ME International ME Conference]] - [http://www.investinme.org/IIMEC10.shtml#dvd DVD available] Speech title - ''Incidence and Prevalence of ME''
*2018, [[CFS/ME Research Collaborative Conference|UK CFS/ME Research Collaborative Conference]] - ''[https://www.youtube.com/watch?v=5FonUVDyc0I&list=PLJV2oZMsotONY3AEkA-c3kVFjtVokLBD7&index=5 The UK ME/CFS Biobank: Accelerating global research in ME/CFS]''

* 13 Mar 2019, [https://mecfsconference.org.au/videos/luis-nacul/ ''Infrastructure & Translational Research in ME/CFS: the Experience of CureME & the UK ME/CFS Biobank''] given at the [[International Research Symposium - Emerge Australia|International Research Symposium]], Geelong, Australia, sponsored by [[Emerge Australia]]
* 21 Sep 2019, ME/FM Society of BC: Presentation by Dr. Luis Nacul - [https://www.youtube.com/watch?v=kupG4a5vJdM ''Has ME/CFS research helped clinicians and patients? Can we do better?'']

==Online presence==

==See also==
*[[CureME]]
*[[EUROMENE]]
*[[NICE guidelines]]
*[[NHS]]

==Learn more==
*[https://www.lshtm.ac.uk/aboutus/people/nacul.luis LSHTM bio]

==References==
<references>
<ref name="de Carvalho Leite, 2011">{{Citation
| last1 = de Carvalho Leite | first1 = JC | authorlink1 = José de Carvalho Leite
| last2 = de L Drachler | first2 = M | authorlink2 = Maria de L Drachler
| last3 = Killett | first3 = A | authorlink3 = Anne Killett
| last4 = Kale | first4 = S | authorlink4 = Swati Kale
| last5 = Nacul | first5 = L | authorlink5 = Luis Nacul
| last6 = McArthur | first6 = M | authorlink6 = Maggie McArthur
| last7 = Hong | first7 = CS | authorlink7 = Chia Hong
| last8 = O'Driscoll | first8 = L | authorlink8 = Lucy Driscoll
| last9 = Pheby | first9 = D | authorlink9 = Derek Pheby
| last10 = Campion | first10 = P | authorlink10 = Peter Campion
| last11 = Lacerda | first11 = E | authorlink11 = Eliana Lacerda
| last12 = Poland | first12 = F | authorlink12 = Fiona Poland
| title = Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis
| journal = International Journal for Equity in Health | volume = 2 | issue = 10 | page = 46
| date = 2011
| pmid =
| doi = 10.1186/1475-9276-10-46
|url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229491/
| pmc = 3229491
}}
</ref>
<ref name="Osoba, 2007">{{Citation
| last1 = Osoba | first1 = Tolu | authorlink1 = Tolu Osoba
| last2 = Pheby | first2 = Derek | authorlink2 = Derek Pheby
| last3 = Gray | first3 = Selena | authorlink3 = Selena Gray
| last4 = Nacul | first4 = Luis | authorlink4 = Luis Nacul
| title = The Development of an Epidemiological Definition for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| journal = Journal of Chronic Fatigue Syndrome | volume = 14 | issue = 4 | page = 61-84
| date = 2007
| pmid =
| doi = 10.3109/10573320802092112
| url = https://doi.org/10.3109%2F10573320802092112
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:UK researchers]]

Magnetic Resonance Spectroscopy (MRS)

2021-06-01T18:50:26Z

Kmdenmark:added see also links and reflist tag

'''Magnetic resonance spectroscopy (MRS)''', also known as nuclear magnetic resonance (NMR), is a diagnostic imaging technique based on the detection of metabolites in tissues. MRS observes the local magnetic fields around atomic nuclei. MRS incorporates a similar model as an [[Magnetic resonance imaging|MRI]]. Similar to [[Positron emission tomography|PET]], MRS can measure the specific concentration of specific biochemicals. Usage of MRS in [[ME/CFS]] patients in relatively new and has advantages and disadvantages over other scanning technologies.<ref name=":0">{{Cite journal|last=VanElzakker|first=Michael B.|last2=Brumfield|first2=Sydney A.|last3=Lara Mejia|first3=Paula S.|date=2019|title=Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full|journal=Frontiers in Neurology|language=English|volume=9|doi=10.3389/fneur.2018.01033|issn=1664-2295|pmc=PMC6335565|pmid=30687207|issue=|pages=|quote=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Michael VanElzakker|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

== MRS and [[PET]] ==
MRS can be used to complement PET for studying neuroinflammation. PET scans are generally more accurate at analyzing specific metabolites. MRS usually reports metabolites as a ratio of one metabolite vs. another, while PET reports an absolute concentration. However, PET scans are invasive as radioligands are injected while MRS is not invasive. <ref name=":0" />MRS is able to produce high-resolution, high contrast images of soft tissue. On the other hand, PET is able to measure the distribution of radiotracers and biochemicals with high sensitivity. Although not many labs have dual MRS-PET scanners, incorporating both techniques into one is able to combine the strengths from MRS and PET.<ref>{{Cite journal|last=Catana|first=Ciprian|last2=Procissi|first2=Daniel|last3=Wu|first3=Yibao|last4=Judenhofer|first4=Martin S.|last5=Qi|first5=Jinyi|last6=Pichler|first6=Bernd J.|last7=Jacobs|first7=Russell E.|last8=Cherry|first8=Simon R.|date=2008-03-11|title=Simultaneous in vivo positron emission tomography and magnetic resonance imaging|url=https://www.pnas.org/content/105/10/3705|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=10|pages=3705–3710|doi=10.1073/pnas.0711622105|issn=0027-8424|pmc=PMC2268792|pmid=18319342}}</ref>

== MRS Studies in ME/CFS ==
MRS's ability to detect metabolites is useful for studying inflammation, metabolism, and overall brain health. Therefore, MRS and MRS-PET has been utilized in ME/CFS patients to analyze neuroinflammation,
* Natelson et al. 2017<ref>{{Cite journal|last=Natelson|first=Benjamin H.|last2=Vu|first2=Diana|last3=Coplan|first3=Jeremy D.|last4=Mao|first4=Xiangling|last5=Blate|first5=Michelle|last6=Kang|first6=Guoxin|last7=Soto|first7=Eli|last8=Kapusuz|first8=Tolga|last9=Shungu|first9=Dikoma C.|date=2017-01-02|title=Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia|url=https://doi.org/10.1080/21641846.2017.1280114|journal=Fatigue: Biomedicine, Health & Behavior|volume=5|issue=1|pages=15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=PMC5754037|pmid=29308330|quote=|author-link=Benjamin Natelson|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
** Found a significant difference between ME/CFS patients and control group when comparing [[lactate]] in the ventricles region

* Van der Schaaf et al. 2017<ref>{{Cite journal|last=van der Schaaf|first=Marieke E.|last2=De Lange|first2=Floris P.|last3=Schmits|first3=Iris C.|last4=Geurts|first4=Dirk E.M.|last5=Roelofs|first5=Karin|last6=van der Meer|first6=Jos W.M.|last7=Toni|first7=Ivan|last8=Knoop|first8=Hans|date=Feb 2017|title=Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0006322316327378|journal=Biological Psychiatry|language=en|volume=81|issue=4|pages=358–365|doi=10.1016/j.biopsych.2016.07.016|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=Jos van der Meer|via=|author-link8=}}</ref>
** Found no significant differences in metabolites between ME/CFS patients and controls

* Shungu et al. 2012<ref>{{Cite journal|last=Shungu|first=Dikoma C.|last2=Weiduschat|first2=Nora|last3=Murrough|first3=James W.|last4=Mao|first4=Xiangling|last5=Pillemer|first5=Sarah|last6=Dyke|first6=Jonathan P.|last7=Medow|first7=Marvin S.|last8=Natelson|first8=Benjamin H.|last9=Stewart|first9=Julian M.|date=Sep 2012|title=Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology: VENTRICULAR LACTATE, OXIDATIVE STRESS AND CEREBRAL BLOOD FLOW IN CFS|url=http://doi.wiley.com/10.1002/nbm.2772|journal=NMR in Biomedicine|language=en|volume=25|issue=9|pages=1073–1087|doi=10.1002/nbm.2772|pmc=|pmid=|quote=|author-link=Dikoma Shungu|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=|author-link8=Benjamin Natelson|author-link9=Julian Stewart}}</ref>
** Found significant differences in lactate and glutathione in the occipital cortex and ventricles

* Murrough et al. 2010<ref>{{Cite journal|last=Murrough|first=James W.|last2=Mao|first2=Xiangling|last3=Collins|first3=Katherine A.|last4=Kelly|first4=Chris|last5=Andrade|first5=Gizely|last6=Nestadt|first6=Paul|last7=Levine|first7=Susan M.|last8=Mathew|first8=Sanjay J.|last9=Shungu|first9=Dikoma C.|date=2010-03-16|title=Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder|url=http://doi.wiley.com/10.1002/nbm.1512|journal=NMR in Biomedicine|language=en|volume=23|issue=6|pages=643–650|doi=10.1002/nbm.1512|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=|author-link7=Susan Levine|author-link9=Dikoma Shungu}}</ref>
** Found a significant difference in lactate between ME/CFS patients and control group in the anterior cingulate cortex, occipital cortex, and ventricles

* Puri et al. 2009<ref>{{Cite journal|last=Puri|first=B.K.|last2=Agour|first2=M.|last3=Gunatilake|first3=K.D.R.|last4=Fernando|first4=K.A.C.|last5=Gurusinghe|first5=A.I.|last6=Treasaden|first6=I.H.|date=Nov 2009|title=An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)|url=https://linkinghub.elsevier.com/retrieve/pii/S0952327809001720|journal=Prostaglandins, Leukotrienes and Essential Fatty Acids|language=en|volume=81|issue=5-6|pages=303–305|doi=10.1016/j.plefa.2009.10.002|pmc=|pmid=|quote=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

* Mathew et al. 2008<ref>{{Cite journal|last=Mathew|first=Sanjay J.|last2=Mao|first2=Xiangling|last3=Keegan|first3=Kathryn A.|last4=Levine|first4=Susan M.|last5=Smith|first5=Eric L. P.|last6=Heier|first6=Linda A.|last7=Otcheretko|first7=Viktor|last8=Coplan|first8=Jeremy D.|last9=Shungu|first9=Dikoma C.|date=Apr 2009|title=Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T 1 H MRS imaging study|url=http://doi.wiley.com/10.1002/nbm.1315|journal=NMR in Biomedicine|language=en|volume=22|issue=3|pages=251–258|doi=10.1002/nbm.1315|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=Susan Levine|author-link5=|author-link6=|via=|author-link9=Dikoma Shungu}}</ref>
** Found a significant difference in lactate between ME/CFS patients and control group in corpus callosum and ventricles

* Puri et al. 2002<ref>{{Cite journal|last=Puri|first=B. K.|last2=Counsell|first2=S. J.|last3=Zaman|first3=R.|last4=Main|first4=J.|last5=Collins|first5=A. G.|last6=Hajnal|first6=J. V.|last7=Davey|first7=N. J.|date=Sep 2002|title=Relative increase in choline in the occipital cortex in chronic fatigue syndrome: Occipital cortex in chronic fatigue syndrome|url=http://doi.wiley.com/10.1034/j.1600-0447.2002.01300.x|journal=Acta Psychiatrica Scandinavica|language=en|volume=106|issue=3|pages=224–226|doi=10.1034/j.1600-0447.2002.01300.x|pmc=|pmid=|quote=|last8=|first8=|author-link=Basant Puri|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
** Found a significant differences in choline between ME/CFS patients and control group in occipital cortex and left motor cortex

* Brooks et al. 2000<ref>{{Cite journal|last=Brooks|first=J C|last2=Roberts|first2=N|last3=Whitehouse|first3=G|last4=Majeed|first4=T|date=Nov 2000|title=Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome.|url=http://www.birpublications.org/doi/10.1259/bjr.73.875.11144799|journal=The British Journal of Radiology|language=en|volume=73|issue=875|pages=1206–1208|doi=10.1259/bjr.73.875.11144799|issn=0007-1285|pmc=|pmid=|quote=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

* Tomoda et al.<ref>{{Cite journal|last=Tomoda|first=Akemi|last2=Miike|first2=Teruhisa|last3=Yamada|first3=Eiji|last4=Honda|first4=Hajime|last5=Moroi|first5=Toshihiro|last6=Ogawa|first6=Masakatsu|last7=Ohtani|first7=Yoshinobu|last8=Morishita|first8=Shoji|date=Jan 2000|title=Chronic fatigue syndrome in childhood|url=https://linkinghub.elsevier.com/retrieve/pii/S0387760499001114|journal=Brain and Development|language=en|volume=22|issue=1|pages=60–64|doi=10.1016/S0387-7604(99)00111-4|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
** Found a significant difference in choline between ME/CFS patients and control group in frontal white matter

==See also==
*[[Brain]]
*[[MRI]]
*[[fMRI]]
*[[SPECT]]

== References ==
{{reflist}}

[[Category:Medical tests]]
[[Category:Neurology]]

Magnetic Resonance Spectroscopy (MRS)

2021-05-30T17:08:50Z

Kmdenmark:reformatted ref dates; added authorlnks, categories, and hyperlinks

'''Magnetic resonance spectroscopy (MRS)''', also known as nuclear magnetic resonance (NMR), is a diagnostic imaging technique based on the detection of metabolites in tissues. MRS observes the local magnetic fields around atomic nuclei. MRS incorporates a similar model as an [[Magnetic resonance imaging|MRI]]. Similar to [[Positron emission tomography|PET]], MRS can measure the specific concentration of specific biochemicals. Usage of MRS in [[ME/CFS]] patients in relatively new and has advantages and disadvantages over other scanning technologies.<ref name=":0">{{Cite journal|last=VanElzakker|first=Michael B.|last2=Brumfield|first2=Sydney A.|last3=Lara Mejia|first3=Paula S.|date=2019|title=Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods|url=https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full|journal=Frontiers in Neurology|language=English|volume=9|doi=10.3389/fneur.2018.01033|issn=1664-2295|pmc=PMC6335565|pmid=30687207|issue=|pages=|quote=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Michael VanElzakker|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

== MRS and [[PET]] ==
MRS can be used to complement PET for studying neuroinflammation. PET scans are generally more accurate at analyzing specific metabolites. MRS usually reports metabolites as a ratio of one metabolite vs. another, while PET reports an absolute concentration. However, PET scans are invasive as radioligands are injected while MRS is not invasive. <ref name=":0" />MRS is able to produce high-resolution, high contrast images of soft tissue. On the other hand, PET is able to measure the distribution of radiotracers and biochemicals with high sensitivity. Although not many labs have dual MRS-PET scanners, incorporating both techniques into one is able to combine the strengths from MRS and PET.<ref>{{Cite journal|last=Catana|first=Ciprian|last2=Procissi|first2=Daniel|last3=Wu|first3=Yibao|last4=Judenhofer|first4=Martin S.|last5=Qi|first5=Jinyi|last6=Pichler|first6=Bernd J.|last7=Jacobs|first7=Russell E.|last8=Cherry|first8=Simon R.|date=2008-03-11|title=Simultaneous in vivo positron emission tomography and magnetic resonance imaging|url=https://www.pnas.org/content/105/10/3705|journal=Proceedings of the National Academy of Sciences|language=en|volume=105|issue=10|pages=3705–3710|doi=10.1073/pnas.0711622105|issn=0027-8424|pmc=PMC2268792|pmid=18319342}}</ref>

== MRS Studies in ME/CFS ==
MRS's ability to detect metabolites is useful for studying inflammation, metabolism, and overall brain health. Therefore, MRS and MRS-PET has been utilized in ME/CFS patients to analyze neuroinflammation,
* Natelson et al. 2017<ref>{{Cite journal|last=Natelson|first=Benjamin H.|last2=Vu|first2=Diana|last3=Coplan|first3=Jeremy D.|last4=Mao|first4=Xiangling|last5=Blate|first5=Michelle|last6=Kang|first6=Guoxin|last7=Soto|first7=Eli|last8=Kapusuz|first8=Tolga|last9=Shungu|first9=Dikoma C.|date=2017-01-02|title=Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia|url=https://doi.org/10.1080/21641846.2017.1280114|journal=Fatigue: Biomedicine, Health & Behavior|volume=5|issue=1|pages=15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=PMC5754037|pmid=29308330|quote=|author-link=Benjamin Natelson|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
** Found a significant difference between ME/CFS patients and control group when comparing [[lactate]] in the ventricles region

* Van der Schaaf et al. 2017<ref>{{Cite journal|last=van der Schaaf|first=Marieke E.|last2=De Lange|first2=Floris P.|last3=Schmits|first3=Iris C.|last4=Geurts|first4=Dirk E.M.|last5=Roelofs|first5=Karin|last6=van der Meer|first6=Jos W.M.|last7=Toni|first7=Ivan|last8=Knoop|first8=Hans|date=Feb 2017|title=Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome|url=https://linkinghub.elsevier.com/retrieve/pii/S0006322316327378|journal=Biological Psychiatry|language=en|volume=81|issue=4|pages=358–365|doi=10.1016/j.biopsych.2016.07.016|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=Jos van der Meer|via=|author-link8=}}</ref>
** Found no significant differences in metabolites between ME/CFS patients and controls

* Shungu et al. 2012<ref>{{Cite journal|last=Shungu|first=Dikoma C.|last2=Weiduschat|first2=Nora|last3=Murrough|first3=James W.|last4=Mao|first4=Xiangling|last5=Pillemer|first5=Sarah|last6=Dyke|first6=Jonathan P.|last7=Medow|first7=Marvin S.|last8=Natelson|first8=Benjamin H.|last9=Stewart|first9=Julian M.|date=Sep 2012|title=Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology: VENTRICULAR LACTATE, OXIDATIVE STRESS AND CEREBRAL BLOOD FLOW IN CFS|url=http://doi.wiley.com/10.1002/nbm.2772|journal=NMR in Biomedicine|language=en|volume=25|issue=9|pages=1073–1087|doi=10.1002/nbm.2772|pmc=|pmid=|quote=|author-link=Dikoma Shungu|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=|author-link8=Benjamin Natelson|author-link9=Julian Stewart}}</ref>
** Found significant differences in lactate and glutathione in the occipital cortex and ventricles

* Murrough et al. 2010<ref>{{Cite journal|last=Murrough|first=James W.|last2=Mao|first2=Xiangling|last3=Collins|first3=Katherine A.|last4=Kelly|first4=Chris|last5=Andrade|first5=Gizely|last6=Nestadt|first6=Paul|last7=Levine|first7=Susan M.|last8=Mathew|first8=Sanjay J.|last9=Shungu|first9=Dikoma C.|date=2010-03-16|title=Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder|url=http://doi.wiley.com/10.1002/nbm.1512|journal=NMR in Biomedicine|language=en|volume=23|issue=6|pages=643–650|doi=10.1002/nbm.1512|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=|author-link7=Susan Levine|author-link9=Dikoma Shungu}}</ref>
** Found a significant difference in lactate between ME/CFS patients and control group in the anterior cingulate cortex, occipital cortex, and ventricles

* Puri et al. 2009<ref>{{Cite journal|last=Puri|first=B.K.|last2=Agour|first2=M.|last3=Gunatilake|first3=K.D.R.|last4=Fernando|first4=K.A.C.|last5=Gurusinghe|first5=A.I.|last6=Treasaden|first6=I.H.|date=Nov 2009|title=An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)|url=https://linkinghub.elsevier.com/retrieve/pii/S0952327809001720|journal=Prostaglandins, Leukotrienes and Essential Fatty Acids|language=en|volume=81|issue=5-6|pages=303–305|doi=10.1016/j.plefa.2009.10.002|pmc=|pmid=|quote=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

* Mathew et al. 2008<ref>{{Cite journal|last=Mathew|first=Sanjay J.|last2=Mao|first2=Xiangling|last3=Keegan|first3=Kathryn A.|last4=Levine|first4=Susan M.|last5=Smith|first5=Eric L. P.|last6=Heier|first6=Linda A.|last7=Otcheretko|first7=Viktor|last8=Coplan|first8=Jeremy D.|last9=Shungu|first9=Dikoma C.|date=Apr 2009|title=Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T 1 H MRS imaging study|url=http://doi.wiley.com/10.1002/nbm.1315|journal=NMR in Biomedicine|language=en|volume=22|issue=3|pages=251–258|doi=10.1002/nbm.1315|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=Susan Levine|author-link5=|author-link6=|via=|author-link9=Dikoma Shungu}}</ref>
** Found a significant difference in lactate between ME/CFS patients and control group in corpus callosum and ventricles

* Puri et al. 2002<ref>{{Cite journal|last=Puri|first=B. K.|last2=Counsell|first2=S. J.|last3=Zaman|first3=R.|last4=Main|first4=J.|last5=Collins|first5=A. G.|last6=Hajnal|first6=J. V.|last7=Davey|first7=N. J.|date=Sep 2002|title=Relative increase in choline in the occipital cortex in chronic fatigue syndrome: Occipital cortex in chronic fatigue syndrome|url=http://doi.wiley.com/10.1034/j.1600-0447.2002.01300.x|journal=Acta Psychiatrica Scandinavica|language=en|volume=106|issue=3|pages=224–226|doi=10.1034/j.1600-0447.2002.01300.x|pmc=|pmid=|quote=|last8=|first8=|author-link=Basant Puri|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
** Found a significant differences in choline between ME/CFS patients and control group in occipital cortex and left motor cortex

* Brooks et al. 2000<ref>{{Cite journal|last=Brooks|first=J C|last2=Roberts|first2=N|last3=Whitehouse|first3=G|last4=Majeed|first4=T|date=Nov 2000|title=Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome.|url=http://www.birpublications.org/doi/10.1259/bjr.73.875.11144799|journal=The British Journal of Radiology|language=en|volume=73|issue=875|pages=1206–1208|doi=10.1259/bjr.73.875.11144799|issn=0007-1285|pmc=|pmid=|quote=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

* Tomoda et al.<ref>{{Cite journal|last=Tomoda|first=Akemi|last2=Miike|first2=Teruhisa|last3=Yamada|first3=Eiji|last4=Honda|first4=Hajime|last5=Moroi|first5=Toshihiro|last6=Ogawa|first6=Masakatsu|last7=Ohtani|first7=Yoshinobu|last8=Morishita|first8=Shoji|date=Jan 2000|title=Chronic fatigue syndrome in childhood|url=https://linkinghub.elsevier.com/retrieve/pii/S0387760499001114|journal=Brain and Development|language=en|volume=22|issue=1|pages=60–64|doi=10.1016/S0387-7604(99)00111-4|pmc=|pmid=|quote=|author-link=|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>
** Found a significant difference in choline between ME/CFS patients and control group in frontal white matter

== References ==

<references />
[[Category:Medical tests]]
[[Category:Neurology]]

Dichloroacetate

2021-05-29T19:15:03Z

Kmdenmark:moved See also section

'''Dichloroacetic acid''' or '''DCA''' is an analogue of acetic acid. Salts of DCA may be used as drugs because they inhibit [[pyruvate dehydrogenase kinase]] and boost or restore the function of mitochondria (cellular power plants).<ref name="pubchem">{{Cite web|url=https://dcaguide.org/dca-information/what-is-dca/|title=What is DCA ?|last=|website=DCA Guide|language=en|access-date=2021-05-27|date=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|url-status=live}}</ref>

The most popular and researched form of DCA is '''Sodium dichloroacetate'''. The same form was used in pilot trials to evaluate whether this substance could improve the condition in those who suffer from ME/CFS. The first open-label pilot trial examined 22 patients (14 women, 8 men, mean age 43.3) suffering from long-lasting ME/CFS. The study found that 10 patients responded well, their score on the Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a">{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/29602463/|title=Treating Patients Suffering From Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) With Sodium Dichloroacetate: An Open-Label, Proof-Of-Principle Pilot Trial|last=Comhaire|first=F|authorlink=|last2=|first2=|authorlink2=|date=May 2018|website=Medical hypotheses|language=en|pmid=29602463|archive-url=|archive-date=|url-status=|access-date=2020-05-21}}</ref>

Soon after the trial, members from of a ME/CFS community forum also shared their experiences with the substance, some of them positive.<ref name=":0">{{Cite web|url=https://forums.phoenixrising.me/threads/treating-patients-suffering-from-me-cfs-with-sodium-dichloroacetate-pilot-trial.58184/|title=DISCUSSION: Treating patients suffering from ME/CFS with sodium dichloroacetate (pilot trial)|website=Phoenix Rising ME/CFS Forums|language=en-US|access-date=2021-05-29}}</ref>

===Molecular formulas===
[[File:DCA molecule.jpg|alt=Molecule of DCA (Sodium dichloroacetate)|left|thumb]]

*{{Chem2|C2H2Cl2O2}}
==Uses==
DCA, salts of dichloracetic acid, have been discovered in the 1960s. Since then the compound has been intensively researched. In 1983 it has been confirmed to be a potential remedy in treating congenital children mitochondrial disorders.<ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Harman|first2=Eloise M.|last3=Curry|first3=Stephen H.|last4=Baumgartner|first4=Thomas G.|last5=Misbin|first5=Robert I.|date=1983-08-18|title=Treatment of Lactic Acidosis with Dichloroacetate|url=http://www.nejm.org/doi/abs/10.1056/NEJM198308183090702|journal=New England Journal of Medicine|language=en|volume=309|issue=7|pages=390–396|doi=10.1056/NEJM198308183090702|issn=0028-4793}}</ref>

Up till now, dozens of studies have proven that DCA can be useful in managing illnesses such as elevated serum cholesterol and triglycerides, diabetes, amyotrophic lateral sclerosis, pulmonary arterial hypertension, chronic fatigue syndrome, endometriosis and cancer.<ref name="Comhaire2018a" /><ref>{{Cite journal|last=Moore|first=George W.|author-link=|last2=Swift|first2=Larry L.|author-link2=|last3=Rabinowitz|first3=David|author-link3=|last4=Crofford|first4=Oscar B.|author-link4=|last5=Oates|first5=John A.|author-link5=|last6=Stacpoole|first6=Peter W.|author-link6=|last7=|first7=|last8=|first8=|date=Jul 1979|title=Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate|url=https://linkinghub.elsevier.com/retrieve/pii/0021915079901801|journal=Atherosclerosis|language=en|volume=33|issue=3|pages=285–293|doi=10.1016/0021-9150(79)90180-1|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Moore|first2=George W.|last3=Kornhauser|first3=David M.|date=1978-03-09|title=Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia|url=http://www.nejm.org/doi/abs/10.1056/NEJM197803092981002|journal=New England Journal of Medicine|language=en|volume=298|issue=10|pages=526–530|doi=10.1056/NEJM197803092981002|issn=0028-4793}}</ref><ref>{{Cite journal|last=Miquel|first=Ernesto|last2=Cassina|first2=Adriana|last3=Martínez-Palma|first3=Laura|last4=Bolatto|first4=Carmen|last5=Trías|first5=Emiliano|last6=Gandelman|first6=Mandi|last7=Radi|first7=Rafael|last8=Barbeito|first8=Luis|last9=Cassina|first9=Patricia|date=2012-04-03|editor-last=Ferreira|editor-first=Sergio T.|title=Modulation of Astrocytic Mitochondrial Function by Dichloroacetate Improves Survival and Motor Performance in Inherited Amyotrophic Lateral Sclerosis|url=https://dx.plos.org/10.1371/journal.pone.0034776|journal=PLoS ONE|language=en|volume=7|issue=4|pages=e34776|doi=10.1371/journal.pone.0034776|issn=1932-6203|pmc=PMC3318006|pmid=22509356}}</ref><ref>{{Cite journal|last=Michelakis|first=Evangelos D.|last2=Gurtu|first2=Vikram|last3=Webster|first3=Linda|last4=Barnes|first4=Gareth|last5=Watson|first5=Geoffrey|last6=Howard|first6=Luke|last7=Cupitt|first7=John|last8=Paterson|first8=Ian|last9=Thompson|first9=Richard B.|date=2017-10-25|title=Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aao4583|journal=Science Translational Medicine|language=en|volume=9|issue=413|pages=eaao4583|doi=10.1126/scitranslmed.aao4583|issn=1946-6234}}</ref><ref>{{Cite journal|last=Leow|first=H. W.|author-link=|last2=Koscielniak|first2=M.|author-link2=|last3=Williams|first3=L.|author-link3=|last4=Saunders|first4=P. T. K.|author-link4=|last5=Daniels|first5=J.|author-link5=|last6=Doust|first6=A. M.|author-link6=|last7=Jones|first7=M-C|last8=Ferguson|first8=G. D.|last9=Bagger|first9=Y.|date=Dec 2021|title=Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC)|url=https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-021-00797-0|journal=Pilot and Feasibility Studies|language=en|volume=7|issue=1|pages=67|doi=10.1186/s40814-021-00797-0|issn=2055-5784|pmc=PMC7953373|pmid=33712086|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Michelakis|first=E. D.|last2=Sutendra|first2=G.|last3=Dromparis|first3=P.|last4=Webster|first4=L.|last5=Haromy|first5=A.|last6=Niven|first6=E.|last7=Maguire|first7=C.|last8=Gammer|first8=T. L.|last9=Mackey|first9=J. R.|date=2010-05-12|title=Metabolic Modulation of Glioblastoma with Dichloroacetate|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.3000677|journal=Science Translational Medicine|language=en|volume=2|issue=31|pages=31ra34–31ra34|doi=10.1126/scitranslmed.3000677|issn=1946-6234}}</ref>

In 1989, Canada approved DCA for applying to the skin for treating warts and for "cauterization and removal of a wide variety of skin and tissue lesions", though this was cancelled post-market.<ref name="drugbank">{{Cite web|url=https://go.drugbank.com/drugs/DB08809|title=Dichloroacetic acid|website=go.drugbank.com|access-date=2021-05-29}}</ref>

Currently DCA (Sodium dichlrooacetate) is approved in Canada as an orphan-drug, the only way of treating children with inborn mitochondrial-errors. It is also used off-label in alternative cancer clinics in North America, South America and Europe.<ref>{{Cite web|url=https://www.arcadia-praxisklinik.de/en/cancer-therapies/|title=Cancer Therapies|website=Arcadia Praxisklinik|language=en-US|access-date=2021-05-29}}</ref>

==Theory==
Sodium dichloroacetate is a molecule that can enter our cells. The living cells of most organisms have specialized structures that make chemical energy in our body, the mitochondria.

Once DCA enters the mitochondria, it inhibits the enzyme [[pyruvate dehydrogenase kinase]]. After this enzyme is halted, it stops blocking the pyruvate dehydrogenase enzyme. As a result this increases the energy output in our cells.<ref>{{Cite web|url=https://dcaguide.org/dca-information/how-dca-works/|title=How DCA works ? – DCA Guide|language=en-US|access-date=2021-05-29}}</ref>

It is thought that many sufferers of ME/CFS have mitochondrial dysfunction resulting from epigenetic, immunologic and inflammatory factors. Restoring the function of impaired mitochondria could potentially alleviate the symptoms of this disease.<ref name="Comhaire2018a" />

==Evidence==
Open-label pilot trial done in Belgium with 22 patients suffering from ME/CFS had favorable results. The Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a" />

Anecdotal evidence from the members of Phoenix Rising forum, the results range from none, to positive or dramatic improvement.<ref name=":0" />

==Risks and safety==
Dichloroacetic acid is a strong acid and should be avoided for internal use. Instead, only salts or the most common form '''Sodium dichloroacetate''' should be used as its near the finish line of getting FDA-approved registration for other indications and has the most extensively studied safety data.<ref>{{Cite web|url=https://grantome.com/grant/NIH/R01-FD005407-02|title=Phase 3 Trial of DCA in PDC Deficiency IND 028,625 (02/04/2015)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=grantome.com|archive-url=|archive-date=|url-status=|access-date=May 29, 2012}}</ref>

==Formula used in the trials==
DCA and its most popular form '''Sodium dichloroacetate''' were used in the trials. Both powder and capsules are acceptable. The DCA purity used in the pilot trial for ME/CFS treatment was 99.9%.

The full nutraceutical formula was never revealed, however, based on the available literature it looked something like this:
* DCA 400 mg
* Vitamin B1 (thiamine) 100 mg
* Alpha-lipoic acid 100 mg
* Oxidoreductase ubiquinone (Q10) 50 mg
The formula was taken for 30 days straight. However, if symptom relief is not achieved after a month, DCA could be taken 5 days straight with a 2 day break at the end of the week. Such cycles should be repeated every week for symptom control.

Nevertheless, additional trials are needed to draw further conclusions.

==Costs and availability==
DCA and its most popular form '''Sodium dichloroacetate''' is available in naturopath clinics, as an off-label drug in Canada or on the internet. It is a non-patentable generic drug that can be freely transported all around the world.

Daily dose of DCA with the additional supplements in the nutraceutical formula cost about $1-2 daily.

==Notable studies and publications==

*2018, Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial<ref name="Comhaire2018a" /> - [[pubmed:29602463|(Full text)]]
* 2018, Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?<ref name="Comhaire2018b">{{Cite journal|last=Comhaire|first=Frank|date=2018-11-01|title=Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?|url=http://www.sciencedirect.com/science/article/pii/S0306987718307734|journal=Medical Hypotheses|language=en|volume=120|pages=65–67|doi=10.1016/j.mehy.2018.08.014|issn=0306-9877}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0306987718307734 (Full text)]

==See also==
*[[Mitochondrion]]

==Learn more==
*[https://pubchem.ncbi.nlm.nih.gov/compound/Dichloroacetic-acid PubChem]
*[https://www.drugbank.ca/drugs/DB08809 Drugbank.ca]
*[https://dcaguide.org/dca-information/ Phoenix Rising DCA thread]
*[https://dcaguide.org/dca-information/ DCAGuide.org]

==References==
{{Reflist}}

[[Category:Potential treatments]]

Dichloroacetate

2021-05-29T19:13:51Z

Kmdenmark:removed stub tag

'''Dichloroacetic acid''' or '''DCA''' is an analogue of acetic acid. Salts of DCA may be used as drugs because they inhibit [[pyruvate dehydrogenase kinase]] and boost or restore the function of mitochondria (cellular power plants).<ref name="pubchem">{{Cite web|url=https://dcaguide.org/dca-information/what-is-dca/|title=What is DCA ?|last=|website=DCA Guide|language=en|access-date=2021-05-27|date=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|url-status=live}}</ref>

The most popular and researched form of DCA is '''Sodium dichloroacetate'''. The same form was used in pilot trials to evaluate whether this substance could improve the condition in those who suffer from ME/CFS. The first open-label pilot trial examined 22 patients (14 women, 8 men, mean age 43.3) suffering from long-lasting ME/CFS. The study found that 10 patients responded well, their score on the Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a">{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/29602463/|title=Treating Patients Suffering From Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) With Sodium Dichloroacetate: An Open-Label, Proof-Of-Principle Pilot Trial|last=Comhaire|first=F|authorlink=|last2=|first2=|authorlink2=|date=May 2018|website=Medical hypotheses|language=en|pmid=29602463|archive-url=|archive-date=|url-status=|access-date=2020-05-21}}</ref>

Soon after the trial, members from of a ME/CFS community forum also shared their experiences with the substance, some of them positive.<ref name=":0">{{Cite web|url=https://forums.phoenixrising.me/threads/treating-patients-suffering-from-me-cfs-with-sodium-dichloroacetate-pilot-trial.58184/|title=DISCUSSION: Treating patients suffering from ME/CFS with sodium dichloroacetate (pilot trial)|website=Phoenix Rising ME/CFS Forums|language=en-US|access-date=2021-05-29}}</ref>

===Molecular formulas===
[[File:DCA molecule.jpg|alt=Molecule of DCA (Sodium dichloroacetate)|left|thumb]]

*{{Chem2|C2H2Cl2O2}}
==Uses==
DCA, salts of dichloracetic acid, have been discovered in the 1960s. Since then the compound has been intensively researched. In 1983 it has been confirmed to be a potential remedy in treating congenital children mitochondrial disorders.<ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Harman|first2=Eloise M.|last3=Curry|first3=Stephen H.|last4=Baumgartner|first4=Thomas G.|last5=Misbin|first5=Robert I.|date=1983-08-18|title=Treatment of Lactic Acidosis with Dichloroacetate|url=http://www.nejm.org/doi/abs/10.1056/NEJM198308183090702|journal=New England Journal of Medicine|language=en|volume=309|issue=7|pages=390–396|doi=10.1056/NEJM198308183090702|issn=0028-4793}}</ref>

Up till now, dozens of studies have proven that DCA can be useful in managing illnesses such as elevated serum cholesterol and triglycerides, diabetes, amyotrophic lateral sclerosis, pulmonary arterial hypertension, chronic fatigue syndrome, endometriosis and cancer.<ref name="Comhaire2018a" /><ref>{{Cite journal|last=Moore|first=George W.|author-link=|last2=Swift|first2=Larry L.|author-link2=|last3=Rabinowitz|first3=David|author-link3=|last4=Crofford|first4=Oscar B.|author-link4=|last5=Oates|first5=John A.|author-link5=|last6=Stacpoole|first6=Peter W.|author-link6=|last7=|first7=|last8=|first8=|date=Jul 1979|title=Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate|url=https://linkinghub.elsevier.com/retrieve/pii/0021915079901801|journal=Atherosclerosis|language=en|volume=33|issue=3|pages=285–293|doi=10.1016/0021-9150(79)90180-1|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Moore|first2=George W.|last3=Kornhauser|first3=David M.|date=1978-03-09|title=Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia|url=http://www.nejm.org/doi/abs/10.1056/NEJM197803092981002|journal=New England Journal of Medicine|language=en|volume=298|issue=10|pages=526–530|doi=10.1056/NEJM197803092981002|issn=0028-4793}}</ref><ref>{{Cite journal|last=Miquel|first=Ernesto|last2=Cassina|first2=Adriana|last3=Martínez-Palma|first3=Laura|last4=Bolatto|first4=Carmen|last5=Trías|first5=Emiliano|last6=Gandelman|first6=Mandi|last7=Radi|first7=Rafael|last8=Barbeito|first8=Luis|last9=Cassina|first9=Patricia|date=2012-04-03|editor-last=Ferreira|editor-first=Sergio T.|title=Modulation of Astrocytic Mitochondrial Function by Dichloroacetate Improves Survival and Motor Performance in Inherited Amyotrophic Lateral Sclerosis|url=https://dx.plos.org/10.1371/journal.pone.0034776|journal=PLoS ONE|language=en|volume=7|issue=4|pages=e34776|doi=10.1371/journal.pone.0034776|issn=1932-6203|pmc=PMC3318006|pmid=22509356}}</ref><ref>{{Cite journal|last=Michelakis|first=Evangelos D.|last2=Gurtu|first2=Vikram|last3=Webster|first3=Linda|last4=Barnes|first4=Gareth|last5=Watson|first5=Geoffrey|last6=Howard|first6=Luke|last7=Cupitt|first7=John|last8=Paterson|first8=Ian|last9=Thompson|first9=Richard B.|date=2017-10-25|title=Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aao4583|journal=Science Translational Medicine|language=en|volume=9|issue=413|pages=eaao4583|doi=10.1126/scitranslmed.aao4583|issn=1946-6234}}</ref><ref>{{Cite journal|last=Leow|first=H. W.|author-link=|last2=Koscielniak|first2=M.|author-link2=|last3=Williams|first3=L.|author-link3=|last4=Saunders|first4=P. T. K.|author-link4=|last5=Daniels|first5=J.|author-link5=|last6=Doust|first6=A. M.|author-link6=|last7=Jones|first7=M-C|last8=Ferguson|first8=G. D.|last9=Bagger|first9=Y.|date=Dec 2021|title=Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC)|url=https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-021-00797-0|journal=Pilot and Feasibility Studies|language=en|volume=7|issue=1|pages=67|doi=10.1186/s40814-021-00797-0|issn=2055-5784|pmc=PMC7953373|pmid=33712086|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Michelakis|first=E. D.|last2=Sutendra|first2=G.|last3=Dromparis|first3=P.|last4=Webster|first4=L.|last5=Haromy|first5=A.|last6=Niven|first6=E.|last7=Maguire|first7=C.|last8=Gammer|first8=T. L.|last9=Mackey|first9=J. R.|date=2010-05-12|title=Metabolic Modulation of Glioblastoma with Dichloroacetate|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.3000677|journal=Science Translational Medicine|language=en|volume=2|issue=31|pages=31ra34–31ra34|doi=10.1126/scitranslmed.3000677|issn=1946-6234}}</ref>

In 1989, Canada approved DCA for applying to the skin for treating warts and for "cauterization and removal of a wide variety of skin and tissue lesions", though this was cancelled post-market.<ref name="drugbank">{{Cite web|url=https://go.drugbank.com/drugs/DB08809|title=Dichloroacetic acid|website=go.drugbank.com|access-date=2021-05-29}}</ref>

Currently DCA (Sodium dichlrooacetate) is approved in Canada as an orphan-drug, the only way of treating children with inborn mitochondrial-errors. It is also used off-label in alternative cancer clinics in North America, South America and Europe.<ref>{{Cite web|url=https://www.arcadia-praxisklinik.de/en/cancer-therapies/|title=Cancer Therapies|website=Arcadia Praxisklinik|language=en-US|access-date=2021-05-29}}</ref>

==Theory==
Sodium dichloroacetate is a molecule that can enter our cells. The living cells of most organisms have specialized structures that make chemical energy in our body, the mitochondria.

Once DCA enters the mitochondria, it inhibits the enzyme [[pyruvate dehydrogenase kinase]]. After this enzyme is halted, it stops blocking the pyruvate dehydrogenase enzyme. As a result this increases the energy output in our cells.<ref>{{Cite web|url=https://dcaguide.org/dca-information/how-dca-works/|title=How DCA works ? – DCA Guide|language=en-US|access-date=2021-05-29}}</ref>

It is thought that many sufferers of ME/CFS have mitochondrial dysfunction resulting from epigenetic, immunologic and inflammatory factors. Restoring the function of impaired mitochondria could potentially alleviate the symptoms of this disease.<ref name="Comhaire2018a" />

==Evidence==
Open-label pilot trial done in Belgium with 22 patients suffering from ME/CFS had favorable results. The Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a" />

Anecdotal evidence from the members of Phoenix Rising forum, the results range from none, to positive or dramatic improvement.<ref name=":0" />

==Risks and safety==
Dichloroacetic acid is a strong acid and should be avoided for internal use. Instead, only salts or the most common form '''Sodium dichloroacetate''' should be used as its near the finish line of getting FDA-approved registration for other indications and has the most extensively studied safety data.<ref>{{Cite web|url=https://grantome.com/grant/NIH/R01-FD005407-02|title=Phase 3 Trial of DCA in PDC Deficiency IND 028,625 (02/04/2015)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=grantome.com|archive-url=|archive-date=|url-status=|access-date=May 29, 2012}}</ref>

==Formula used in the trials==
DCA and its most popular form '''Sodium dichloroacetate''' were used in the trials. Both powder and capsules are acceptable. The DCA purity used in the pilot trial for ME/CFS treatment was 99.9%.

The full nutraceutical formula was never revealed, however, based on the available literature it looked something like this:
* DCA 400 mg
* Vitamin B1 (thiamine) 100 mg
* Alpha-lipoic acid 100 mg
* Oxidoreductase ubiquinone (Q10) 50 mg
The formula was taken for 30 days straight. However, if symptom relief is not achieved after a month, DCA could be taken 5 days straight with a 2 day break at the end of the week. Such cycles should be repeated every week for symptom control.

Nevertheless, additional trials are needed to draw further conclusions.

==Costs and availability==
DCA and its most popular form '''Sodium dichloroacetate''' is available in naturopath clinics, as an off-label drug in Canada or on the internet. It is a non-patentable generic drug that can be freely transported all around the world.

Daily dose of DCA with the additional supplements in the nutraceutical formula cost about $1-2 daily.

==Notable studies and publications==

*2018, Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial<ref name="Comhaire2018a" /> - [[pubmed:29602463|(Full text)]]
* 2018, Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?<ref name="Comhaire2018b">{{Cite journal|last=Comhaire|first=Frank|date=2018-11-01|title=Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?|url=http://www.sciencedirect.com/science/article/pii/S0306987718307734|journal=Medical Hypotheses|language=en|volume=120|pages=65–67|doi=10.1016/j.mehy.2018.08.014|issn=0306-9877}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0306987718307734 (Full text)]

==Learn more==
*[https://pubchem.ncbi.nlm.nih.gov/compound/Dichloroacetic-acid PubChem]
*[https://www.drugbank.ca/drugs/DB08809 Drugbank.ca]
*[https://dcaguide.org/dca-information/ Phoenix Rising DCA thread]
*[https://dcaguide.org/dca-information/ DCAGuide.org]

==See also==
*[[Mitochondrion]]

==References==
{{Reflist}}

[[Category:Potential treatments]]

Dichloroacetate

2021-05-29T19:12:29Z

Kmdenmark:reformatted reference

{{Stub}}
'''Dichloroacetic acid''' or '''DCA''' is an analogue of acetic acid. Salts of DCA may be used as drugs because they inhibit [[pyruvate dehydrogenase kinase]] and boost or restore the function of mitochondria (cellular power plants).<ref name="pubchem">{{Cite web|url=https://dcaguide.org/dca-information/what-is-dca/|title=What is DCA ?|last=|website=DCA Guide|language=en|access-date=2021-05-27|date=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|url-status=live}}</ref>

The most popular and researched form of DCA is '''Sodium dichloroacetate'''. The same form was used in pilot trials to evaluate whether this substance could improve the condition in those who suffer from ME/CFS. The first open-label pilot trial examined 22 patients (14 women, 8 men, mean age 43.3) suffering from long-lasting ME/CFS. The study found that 10 patients responded well, their score on the Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a">{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/29602463/|title=Treating Patients Suffering From Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) With Sodium Dichloroacetate: An Open-Label, Proof-Of-Principle Pilot Trial|last=Comhaire|first=F|authorlink=|last2=|first2=|authorlink2=|date=May 2018|website=Medical hypotheses|language=en|pmid=29602463|archive-url=|archive-date=|url-status=|access-date=2020-05-21}}</ref>

Soon after the trial, members from of a ME/CFS community forum also shared their experiences with the substance, some of them positive.<ref name=":0">{{Cite web|url=https://forums.phoenixrising.me/threads/treating-patients-suffering-from-me-cfs-with-sodium-dichloroacetate-pilot-trial.58184/|title=DISCUSSION: Treating patients suffering from ME/CFS with sodium dichloroacetate (pilot trial)|website=Phoenix Rising ME/CFS Forums|language=en-US|access-date=2021-05-29}}</ref>

===Molecular formulas===
[[File:DCA molecule.jpg|alt=Molecule of DCA (Sodium dichloroacetate)|left|thumb]]

*{{Chem2|C2H2Cl2O2}}
==Uses==
DCA, salts of dichloracetic acid, have been discovered in the 1960s. Since then the compound has been intensively researched. In 1983 it has been confirmed to be a potential remedy in treating congenital children mitochondrial disorders.<ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Harman|first2=Eloise M.|last3=Curry|first3=Stephen H.|last4=Baumgartner|first4=Thomas G.|last5=Misbin|first5=Robert I.|date=1983-08-18|title=Treatment of Lactic Acidosis with Dichloroacetate|url=http://www.nejm.org/doi/abs/10.1056/NEJM198308183090702|journal=New England Journal of Medicine|language=en|volume=309|issue=7|pages=390–396|doi=10.1056/NEJM198308183090702|issn=0028-4793}}</ref>

Up till now, dozens of studies have proven that DCA can be useful in managing illnesses such as elevated serum cholesterol and triglycerides, diabetes, amyotrophic lateral sclerosis, pulmonary arterial hypertension, chronic fatigue syndrome, endometriosis and cancer.<ref name="Comhaire2018a" /><ref>{{Cite journal|last=Moore|first=George W.|author-link=|last2=Swift|first2=Larry L.|author-link2=|last3=Rabinowitz|first3=David|author-link3=|last4=Crofford|first4=Oscar B.|author-link4=|last5=Oates|first5=John A.|author-link5=|last6=Stacpoole|first6=Peter W.|author-link6=|last7=|first7=|last8=|first8=|date=Jul 1979|title=Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate|url=https://linkinghub.elsevier.com/retrieve/pii/0021915079901801|journal=Atherosclerosis|language=en|volume=33|issue=3|pages=285–293|doi=10.1016/0021-9150(79)90180-1|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Moore|first2=George W.|last3=Kornhauser|first3=David M.|date=1978-03-09|title=Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia|url=http://www.nejm.org/doi/abs/10.1056/NEJM197803092981002|journal=New England Journal of Medicine|language=en|volume=298|issue=10|pages=526–530|doi=10.1056/NEJM197803092981002|issn=0028-4793}}</ref><ref>{{Cite journal|last=Miquel|first=Ernesto|last2=Cassina|first2=Adriana|last3=Martínez-Palma|first3=Laura|last4=Bolatto|first4=Carmen|last5=Trías|first5=Emiliano|last6=Gandelman|first6=Mandi|last7=Radi|first7=Rafael|last8=Barbeito|first8=Luis|last9=Cassina|first9=Patricia|date=2012-04-03|editor-last=Ferreira|editor-first=Sergio T.|title=Modulation of Astrocytic Mitochondrial Function by Dichloroacetate Improves Survival and Motor Performance in Inherited Amyotrophic Lateral Sclerosis|url=https://dx.plos.org/10.1371/journal.pone.0034776|journal=PLoS ONE|language=en|volume=7|issue=4|pages=e34776|doi=10.1371/journal.pone.0034776|issn=1932-6203|pmc=PMC3318006|pmid=22509356}}</ref><ref>{{Cite journal|last=Michelakis|first=Evangelos D.|last2=Gurtu|first2=Vikram|last3=Webster|first3=Linda|last4=Barnes|first4=Gareth|last5=Watson|first5=Geoffrey|last6=Howard|first6=Luke|last7=Cupitt|first7=John|last8=Paterson|first8=Ian|last9=Thompson|first9=Richard B.|date=2017-10-25|title=Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aao4583|journal=Science Translational Medicine|language=en|volume=9|issue=413|pages=eaao4583|doi=10.1126/scitranslmed.aao4583|issn=1946-6234}}</ref><ref>{{Cite journal|last=Leow|first=H. W.|author-link=|last2=Koscielniak|first2=M.|author-link2=|last3=Williams|first3=L.|author-link3=|last4=Saunders|first4=P. T. K.|author-link4=|last5=Daniels|first5=J.|author-link5=|last6=Doust|first6=A. M.|author-link6=|last7=Jones|first7=M-C|last8=Ferguson|first8=G. D.|last9=Bagger|first9=Y.|date=Dec 2021|title=Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC)|url=https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-021-00797-0|journal=Pilot and Feasibility Studies|language=en|volume=7|issue=1|pages=67|doi=10.1186/s40814-021-00797-0|issn=2055-5784|pmc=PMC7953373|pmid=33712086|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Michelakis|first=E. D.|last2=Sutendra|first2=G.|last3=Dromparis|first3=P.|last4=Webster|first4=L.|last5=Haromy|first5=A.|last6=Niven|first6=E.|last7=Maguire|first7=C.|last8=Gammer|first8=T. L.|last9=Mackey|first9=J. R.|date=2010-05-12|title=Metabolic Modulation of Glioblastoma with Dichloroacetate|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.3000677|journal=Science Translational Medicine|language=en|volume=2|issue=31|pages=31ra34–31ra34|doi=10.1126/scitranslmed.3000677|issn=1946-6234}}</ref>

In 1989, Canada approved DCA for applying to the skin for treating warts and for "cauterization and removal of a wide variety of skin and tissue lesions", though this was cancelled post-market.<ref name="drugbank">{{Cite web|url=https://go.drugbank.com/drugs/DB08809|title=Dichloroacetic acid|website=go.drugbank.com|access-date=2021-05-29}}</ref>

Currently DCA (Sodium dichlrooacetate) is approved in Canada as an orphan-drug, the only way of treating children with inborn mitochondrial-errors. It is also used off-label in alternative cancer clinics in North America, South America and Europe.<ref>{{Cite web|url=https://www.arcadia-praxisklinik.de/en/cancer-therapies/|title=Cancer Therapies|website=Arcadia Praxisklinik|language=en-US|access-date=2021-05-29}}</ref>

==Theory==
Sodium dichloroacetate is a molecule that can enter our cells. The living cells of most organisms have specialized structures that make chemical energy in our body, the mitochondria.

Once DCA enters the mitochondria, it inhibits the enzyme [[pyruvate dehydrogenase kinase]]. After this enzyme is halted, it stops blocking the pyruvate dehydrogenase enzyme. As a result this increases the energy output in our cells.<ref>{{Cite web|url=https://dcaguide.org/dca-information/how-dca-works/|title=How DCA works ? – DCA Guide|language=en-US|access-date=2021-05-29}}</ref>

It is thought that many sufferers of ME/CFS have mitochondrial dysfunction resulting from epigenetic, immunologic and inflammatory factors. Restoring the function of impaired mitochondria could potentially alleviate the symptoms of this disease.<ref name="Comhaire2018a" />

==Evidence==
Open-label pilot trial done in Belgium with 22 patients suffering from ME/CFS had favorable results. The Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a" />

Anecdotal evidence from the members of Phoenix Rising forum, the results range from none, to positive or dramatic improvement.<ref name=":0" />

==Risks and safety==
Dichloroacetic acid is a strong acid and should be avoided for internal use. Instead, only salts or the most common form '''Sodium dichloroacetate''' should be used as its near the finish line of getting FDA-approved registration for other indications and has the most extensively studied safety data.<ref>{{Cite web|url=https://grantome.com/grant/NIH/R01-FD005407-02|title=Phase 3 Trial of DCA in PDC Deficiency IND 028,625 (02/04/2015)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=grantome.com|archive-url=|archive-date=|url-status=|access-date=May 29, 2012}}</ref>

==Formula used in the trials==
DCA and its most popular form '''Sodium dichloroacetate''' were used in the trials. Both powder and capsules are acceptable. The DCA purity used in the pilot trial for ME/CFS treatment was 99.9%.

The full nutraceutical formula was never revealed, however, based on the available literature it looked something like this:
* DCA 400 mg
* Vitamin B1 (thiamine) 100 mg
* Alpha-lipoic acid 100 mg
* Oxidoreductase ubiquinone (Q10) 50 mg
The formula was taken for 30 days straight. However, if symptom relief is not achieved after a month, DCA could be taken 5 days straight with a 2 day break at the end of the week. Such cycles should be repeated every week for symptom control.

Nevertheless, additional trials are needed to draw further conclusions.

==Costs and availability==
DCA and its most popular form '''Sodium dichloroacetate''' is available in naturopath clinics, as an off-label drug in Canada or on the internet. It is a non-patentable generic drug that can be freely transported all around the world.

Daily dose of DCA with the additional supplements in the nutraceutical formula cost about $1-2 daily.

==Notable studies and publications==

*2018, Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial<ref name="Comhaire2018a" /> - [[pubmed:29602463|(Full text)]]
* 2018, Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?<ref name="Comhaire2018b">{{Cite journal|last=Comhaire|first=Frank|date=2018-11-01|title=Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?|url=http://www.sciencedirect.com/science/article/pii/S0306987718307734|journal=Medical Hypotheses|language=en|volume=120|pages=65–67|doi=10.1016/j.mehy.2018.08.014|issn=0306-9877}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0306987718307734 (Full text)]

==Learn more==
*[https://pubchem.ncbi.nlm.nih.gov/compound/Dichloroacetic-acid PubChem]
*[https://www.drugbank.ca/drugs/DB08809 Drugbank.ca]
*[https://dcaguide.org/dca-information/ Phoenix Rising DCA thread]
*[https://dcaguide.org/dca-information/ DCAGuide.org]

==See also==
*[[Mitochondrion]]

==References==
{{Reflist}}

[[Category:Potential treatments]]

Dichloroacetate

2021-05-29T19:05:49Z

Kmdenmark:reformatted reference

{{Stub}}
'''Dichloroacetic acid''' or '''DCA''' is an analogue of acetic acid. Salts of DCA may be used as drugs because they inhibit [[pyruvate dehydrogenase kinase]] and boost or restore the function of mitochondria (cellular power plants).<ref name="pubchem">{{Cite web|url=https://dcaguide.org/dca-information/what-is-dca/|title=What is DCA ?|last=|website=DCA Guide|language=en|access-date=2021-05-27|date=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|url-status=live}}</ref>

The most popular and researched form of DCA is '''Sodium dichloroacetate'''. The same form was used in pilot trials to evaluate whether this substance could improve the condition in those who suffer from ME/CFS. The first open-label pilot trial examined 22 patients (14 women, 8 men, mean age 43.3) suffering from long-lasting ME/CFS. The study found that 10 patients responded well, their score on the Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a">{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/29602463/|title=Treating Patients Suffering From Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) With Sodium Dichloroacetate: An Open-Label, Proof-Of-Principle Pilot Trial|last=Comhaire|first=F|authorlink=|last2=|first2=|authorlink2=|date=May 2018|website=Medical hypotheses|language=en|pmid=29602463|archive-url=|archive-date=|url-status=|access-date=2020-05-21}}</ref>

Soon after the trial, members from of a ME/CFS community forum also shared their experiences with the substance, some of them positive.<ref name=":0">{{Cite web|url=https://forums.phoenixrising.me/threads/treating-patients-suffering-from-me-cfs-with-sodium-dichloroacetate-pilot-trial.58184/|title=DISCUSSION: Treating patients suffering from ME/CFS with sodium dichloroacetate (pilot trial)|website=Phoenix Rising ME/CFS Forums|language=en-US|access-date=2021-05-29}}</ref>

===Molecular formulas===
[[File:DCA molecule.jpg|alt=Molecule of DCA (Sodium dichloroacetate)|left|thumb]]

*{{Chem2|C2H2Cl2O2}}
==Uses==
DCA, salts of dichloracetic acid, have been discovered in the 1960s. Since then the compound has been intensively researched. In 1983 it has been confirmed to be a potential remedy in treating congenital children mitochondrial disorders.<ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Harman|first2=Eloise M.|last3=Curry|first3=Stephen H.|last4=Baumgartner|first4=Thomas G.|last5=Misbin|first5=Robert I.|date=1983-08-18|title=Treatment of Lactic Acidosis with Dichloroacetate|url=http://www.nejm.org/doi/abs/10.1056/NEJM198308183090702|journal=New England Journal of Medicine|language=en|volume=309|issue=7|pages=390–396|doi=10.1056/NEJM198308183090702|issn=0028-4793}}</ref>

Up till now, dozens of studies have proven that DCA can be useful in managing illnesses such as elevated serum cholesterol and triglycerides, diabetes, amyotrophic lateral sclerosis, pulmonary arterial hypertension, chronic fatigue syndrome, endometriosis and cancer.<ref>{{Cite journal|last=Moore|first=George W.|author-link=|last2=Swift|first2=Larry L.|author-link2=|last3=Rabinowitz|first3=David|author-link3=|last4=Crofford|first4=Oscar B.|author-link4=|last5=Oates|first5=John A.|author-link5=|last6=Stacpoole|first6=Peter W.|author-link6=|last7=|first7=|last8=|first8=|date=Jul 1979|title=Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate|url=https://linkinghub.elsevier.com/retrieve/pii/0021915079901801|journal=Atherosclerosis|language=en|volume=33|issue=3|pages=285–293|doi=10.1016/0021-9150(79)90180-1|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Moore|first2=George W.|last3=Kornhauser|first3=David M.|date=1978-03-09|title=Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia|url=http://www.nejm.org/doi/abs/10.1056/NEJM197803092981002|journal=New England Journal of Medicine|language=en|volume=298|issue=10|pages=526–530|doi=10.1056/NEJM197803092981002|issn=0028-4793}}</ref><ref>{{Cite journal|last=Miquel|first=Ernesto|last2=Cassina|first2=Adriana|last3=Martínez-Palma|first3=Laura|last4=Bolatto|first4=Carmen|last5=Trías|first5=Emiliano|last6=Gandelman|first6=Mandi|last7=Radi|first7=Rafael|last8=Barbeito|first8=Luis|last9=Cassina|first9=Patricia|date=2012-04-03|editor-last=Ferreira|editor-first=Sergio T.|title=Modulation of Astrocytic Mitochondrial Function by Dichloroacetate Improves Survival and Motor Performance in Inherited Amyotrophic Lateral Sclerosis|url=https://dx.plos.org/10.1371/journal.pone.0034776|journal=PLoS ONE|language=en|volume=7|issue=4|pages=e34776|doi=10.1371/journal.pone.0034776|issn=1932-6203|pmc=PMC3318006|pmid=22509356}}</ref><ref>{{Cite journal|last=Michelakis|first=Evangelos D.|last2=Gurtu|first2=Vikram|last3=Webster|first3=Linda|last4=Barnes|first4=Gareth|last5=Watson|first5=Geoffrey|last6=Howard|first6=Luke|last7=Cupitt|first7=John|last8=Paterson|first8=Ian|last9=Thompson|first9=Richard B.|date=2017-10-25|title=Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aao4583|journal=Science Translational Medicine|language=en|volume=9|issue=413|pages=eaao4583|doi=10.1126/scitranslmed.aao4583|issn=1946-6234}}</ref><ref>{{Cite journal|last=Comhaire|first=Frank|author-link=|last2=|first2=|author-link2=|last3=|first3=|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=May 2018|title=Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987718301051|journal=Medical Hypotheses|language=en|volume=114|issue=|pages=45–48|doi=10.1016/j.mehy.2018.03.002|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Leow|first=H. W.|author-link=|last2=Koscielniak|first2=M.|author-link2=|last3=Williams|first3=L.|author-link3=|last4=Saunders|first4=P. T. K.|author-link4=|last5=Daniels|first5=J.|author-link5=|last6=Doust|first6=A. M.|author-link6=|last7=Jones|first7=M-C|last8=Ferguson|first8=G. D.|last9=Bagger|first9=Y.|date=Dec 2021|title=Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC)|url=https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-021-00797-0|journal=Pilot and Feasibility Studies|language=en|volume=7|issue=1|pages=67|doi=10.1186/s40814-021-00797-0|issn=2055-5784|pmc=PMC7953373|pmid=33712086|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Michelakis|first=E. D.|last2=Sutendra|first2=G.|last3=Dromparis|first3=P.|last4=Webster|first4=L.|last5=Haromy|first5=A.|last6=Niven|first6=E.|last7=Maguire|first7=C.|last8=Gammer|first8=T. L.|last9=Mackey|first9=J. R.|date=2010-05-12|title=Metabolic Modulation of Glioblastoma with Dichloroacetate|url=https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.3000677|journal=Science Translational Medicine|language=en|volume=2|issue=31|pages=31ra34–31ra34|doi=10.1126/scitranslmed.3000677|issn=1946-6234}}</ref>

In 1989, Canada approved DCA for applying to the skin for treating warts and for "cauterization and removal of a wide variety of skin and tissue lesions", though this was cancelled post-market.<ref name="drugbank">{{Cite web|url=https://go.drugbank.com/drugs/DB08809|title=Dichloroacetic acid|website=go.drugbank.com|access-date=2021-05-29}}</ref>

Currently DCA (Sodium dichlrooacetate) is approved in Canada as an orphan-drug, the only way of treating children with inborn mitochondrial-errors. It is also used off-label in alternative cancer clinics in North America, South America and Europe.<ref>{{Cite web|url=https://www.arcadia-praxisklinik.de/en/cancer-therapies/|title=Cancer Therapies|website=Arcadia Praxisklinik|language=en-US|access-date=2021-05-29}}</ref>

==Theory==
Sodium dichloroacetate is a molecule that can enter our cells. The living cells of most organisms have specialized structures that make chemical energy in our body, the mitochondria.

Once DCA enters the mitochondria, it inhibits the enzyme [[pyruvate dehydrogenase kinase]]. After this enzyme is halted, it stops blocking the pyruvate dehydrogenase enzyme. As a result this increases the energy output in our cells.<ref>{{Cite web|url=https://dcaguide.org/dca-information/how-dca-works/|title=How DCA works ? – DCA Guide|language=en-US|access-date=2021-05-29}}</ref>

It is thought that many sufferers of ME/CFS have mitochondrial dysfunction resulting from epigenetic, immunologic and inflammatory factors. Restoring the function of impaired mitochondria could potentially alleviate the symptoms of this disease.<ref name="Comhaire2018a" />

==Evidence==
Open-label pilot trial done in Belgium with 22 patients suffering from ME/CFS had favorable results. The Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a" />

Anecdotal evidence from the members of Phoenix Rising forum, the results range from none, to positive or dramatic improvement.<ref name=":0" />

==Risks and safety==
Dichloroacetic acid is a strong acid and should be avoided for internal use. Instead, only salts or the most common form '''Sodium dichloroacetate''' should be used as its near the finish line of getting FDA-approved registration for other indications and has the most extensively studied safety data.<ref>{{Cite web|url=https://grantome.com/grant/NIH/R01-FD005407-02|title=Phase 3 Trial of DCA in PDC Deficiency|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=Grantome|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref>

==Formula used in the trials==
DCA and its most popular form '''Sodium dichloroacetate''' were used in the trials. Both powder and capsules are acceptable. The DCA purity used in the pilot trial for ME/CFS treatment was 99,9%.

The full nutraceutical formula was never revealed, however, based on the available literature it looked something like this:
* DCA 400 mg
* Vitamin B1 (thiamine) 100 mg
* Alpha-lipoic acid 100 mg
* Oxidoreductase ubiquinone (Q10) 50 mg
The formula was taken for 30 days straight. However, if symptom relief is not achieved after a month, DCA could be taken 5 days straight with a 2 day break at the end of the week. Such cycles should be repeated every week for symptom control.

Nevertheless, additional trials are needed to draw further conclusions.

==Costs and availability==
DCA and its most popular form '''Sodium dichloroacetate''' is available in naturopath clinics, as an off-label drug in Canada or on the internet. It is a non-patentable generic drug that can be freely transported all around the world.

Daily dose of DCA with the additional supplements in the nutraceutical formula cost about 1-2$ daily.

==Notable studies and publications==

*2018, Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial<ref name="Comhaire2018a" /> - [[pubmed:29602463|(Full text)]]
* 2018, Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?<ref name="Comhaire2018b">{{Cite journal|last=Comhaire|first=Frank|date=2018-11-01|title=Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?|url=http://www.sciencedirect.com/science/article/pii/S0306987718307734|journal=Medical Hypotheses|language=en|volume=120|pages=65–67|doi=10.1016/j.mehy.2018.08.014|issn=0306-9877}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0306987718307734 (Full text)]

==Learn more==
*[https://pubchem.ncbi.nlm.nih.gov/compound/Dichloroacetic-acid PubChem]
*[https://www.drugbank.ca/drugs/DB08809 Drugbank.ca]
*[https://dcaguide.org/dca-information/ Phoenix Rising DCA thread]
*[https://dcaguide.org/dca-information/ DCAGuide.org]

==See also==
*[[Mitochondrion]]

==References==
{{Reflist}}

[[Category:Potential treatments]]

Dichloroacetate

2021-05-29T18:52:56Z

Kmdenmark:reformatted references

{{Stub}}
'''Dichloroacetic acid''' or '''DCA''' is an analogue of acetic acid. Salts of DCA may be used as drugs because they inhibit [[pyruvate dehydrogenase kinase]] and boost or restore the function of mitochondria (cellular power plants).<ref name="pubchem">{{Cite web|url=https://dcaguide.org/dca-information/what-is-dca/|title=What is DCA ?|last=|website=DCA Guide|language=en|access-date=2021-05-27|date=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|url-status=live}}</ref>

The most popular and researched form of DCA is '''Sodium dichloroacetate'''. The same form was used in pilot trials to evaluate whether this substance could improve the condition in those who suffer from ME/CFS. The first open-label pilot trial examined 22 patients (14 women, 8 men, mean age 43.3) suffering from long-lasting ME/CFS. The study found that 10 patients responded well, their score on the Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a">{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/29602463/|title=Treating Patients Suffering From Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) With Sodium Dichloroacetate: An Open-Label, Proof-Of-Principle Pilot Trial|last=Comhaire|first=F|authorlink=|last2=|first2=|authorlink2=|date=May 2018|website=Medical hypotheses|language=en|pmid=29602463|archive-url=|archive-date=|url-status=|access-date=2020-05-21}}</ref>

Soon after the trial, members from of a ME/CFS community forum also shared their experiences with the substance, some of them positive.<ref>{{Cite web|url=https://forums.phoenixrising.me/threads/treating-patients-suffering-from-me-cfs-with-sodium-dichloroacetate-pilot-trial.58184/|title=DISCUSSION: Treating patients suffering from ME/CFS with sodium dichloroacetate (pilot trial)|website=Phoenix Rising ME/CFS Forums|language=en-US|access-date=2021-05-29}}</ref>

===Molecular formulas===
[[File:DCA molecule.jpg|alt=Molecule of DCA (Sodium dichloroacetate)|left|thumb]]

*{{Chem2|C2H2Cl2O2}}
==Uses==
DCA, salts of dichloracetic acid, have been discovered in the 1960s. Since then the compound has been intensively researched. In 1983 it has been confirmed to be a potential remedy in treating congenital children mitochondrial disorders.<ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Harman|first2=Eloise M.|last3=Curry|first3=Stephen H.|last4=Baumgartner|first4=Thomas G.|last5=Misbin|first5=Robert I.|date=1983-08-18|title=Treatment of Lactic Acidosis with Dichloroacetate|url=http://www.nejm.org/doi/abs/10.1056/NEJM198308183090702|journal=New England Journal of Medicine|language=en|volume=309|issue=7|pages=390–396|doi=10.1056/NEJM198308183090702|issn=0028-4793}}</ref>

Up till now, dozens of studies have proven that DCA can be useful in managing illnesses such as elevated serum cholesterol and triglycerides, diabetes, amyotrophic lateral sclerosis, pulmonary arterial hypertension, chronic fatigue syndrome, endometriosis and cancer.<ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/625308/|title=Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia|last=Kornhauser|first=D.M.|authorlink=|last2=|first2=|authorlink2=|date=|website=National Library of Medicine|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref><ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/22509356/|title=Modulation of astrocytic mitochondrial function by dichloroacetate improves survival and motor performance in inherited amyotrophic lateral sclerosis|last=Cassina|first=Patricia|authorlink=|last2=|first2=|authorlink2=|date=|website=National Library of Medicine|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref><ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/29070699/|title=Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial hypertension in genetically susceptible patients|last=Michelakis|first=Evangelos D.|authorlink=|last2=|first2=|authorlink2=|date=|website=National Library of Medicine|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref><ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/29602463/|title=Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial|last=Comhaire|first=Frank|authorlink=|last2=|first2=|authorlink2=|date=|website=National Library of Medicine|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref><ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953373/|title=Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC)|last=Whitaker|first=L.H.R.|authorlink=|last2=|first2=|authorlink2=|date=|website=National Library of Medicine|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref><ref>{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/20463368/|title=Metabolic modulation of glioblastoma with dichloroacetate|last=Michelakis|first=Evangelos D.|authorlink=|last2=|first2=|authorlink2=|date=|website=National Library of Medicine|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref><ref>{{Cite journal|last=Moore|first=George W.|author-link=|last2=Swift|first2=Larry L.|author-link2=|last3=Rabinowitz|first3=David|author-link3=|last4=Crofford|first4=Oscar B.|author-link4=|last5=Oates|first5=John A.|author-link5=|last6=Stacpoole|first6=Peter W.|author-link6=|last7=|first7=|last8=|first8=|date=Jul 1979|title=Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate|url=https://linkinghub.elsevier.com/retrieve/pii/0021915079901801|journal=Atherosclerosis|language=en|volume=33|issue=3|pages=285–293|doi=10.1016/0021-9150(79)90180-1|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref>{{Cite journal|last=Stacpoole|first=Peter W.|last2=Moore|first2=George W.|last3=Kornhauser|first3=David M.|date=1978-03-09|title=Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia|url=http://www.nejm.org/doi/abs/10.1056/NEJM197803092981002|journal=New England Journal of Medicine|language=en|volume=298|issue=10|pages=526–530|doi=10.1056/NEJM197803092981002|issn=0028-4793}}</ref>

In 1989, Canada approved DCA for applying to the skin for treating warts and for "cauterization and removal of a wide variety of skin and tissue lesions", though this was cancelled post-market.<ref name="drugbank">https://www.drugbank.ca/drugs/DB08809</ref>

Currently DCA (Sodium dichlrooacetate) is approved in Canada as an orphan-drug, the only way of treating children with inborn mitochondrial-errors. It is also used off-label in alternative cancer clinics in North America, South America and Europe.<ref>{{Cite web|url=https://www.arcadia-praxisklinik.de/en/cancer-therapies/|title=Applications for cancer therapy in the Arcadia Praxisklinik|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=Arcadia clinic official home page|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref>

==Theory==
Sodium dichloroacetate is a molecule that can enter our cells. The living cells of most organisms have specialized structures that make chemical energy in our body, the mitochondria.

Once DCA enters the mitochondria, it inhibits the enzyme [[pyruvate dehydrogenase kinase]]. After this enzyme is halted, it stops blocking the pyruvate dehydrogenase enzyme. As a result this increases the energy output in our cells.<ref>{{Cite web|url=https://dcaguide.org/dca-information/how-dca-works/|title=How DCA works ?|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=DCAGuide|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref>

It is thought that many sufferers of ME/CFS have mitochondrial dysfunction resulting from epigenetic, immunologic and inflammatory factors. Restoring the function of impaired mitochondria could potentially alleviate the symptoms of this disease.<ref>{{Cite web|url=https://www.sciencedirect.com/science/article/pii/S0306987718301051|title=Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial|last=Comhaire|first=Frank|authorlink=|last2=|first2=|authorlink2=|date=|website=Science Direct|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref>

==Evidence==
Open-label pilot trial done in Belgium with 22 patients suffering from ME/CFS had favorable results. The Fatigue severity scale decreased at least by 40%.<ref name="Comhaire2018a" />

Anecdotal evidence from the members of Phoenix Rising forum, the results range from none, to positive or dramatic improvement.<ref name=":0">{{Cite web|url=https://forums.phoenixrising.me/threads/treating-patients-suffering-from-me-cfs-with-sodium-dichloroacetate-pilot-trial.58184/|title=Treating patients suffering from ME/CFS with sodium dichloroacetate (pilot trial)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=Phoenix Rising|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref>

==Risks and safety==
Dichloroacetic acid is a strong acid and should be avoided for internal use. Instead, only salts or the most common form '''Sodium dichloroacetate''' should be used as its near the finish line of getting FDA-approved registration for other indications and has the most extensively studied safety data.<ref>{{Cite web|url=https://grantome.com/grant/NIH/R01-FD005407-02|title=Phase 3 Trial of DCA in PDC Deficiency|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=Grantome|archive-url=|archive-date=|url-status=Live|access-date=2021-05-27}}</ref>

==Formula used in the trials==
DCA and its most popular form '''Sodium dichloroacetate''' were used in the trials. Both powder and capsules are acceptable. The DCA purity used in the pilot trial for ME/CFS treatment was 99,9%.

The full nutraceutical formula was never revealed, however, based on the available literature it looked something like this:
* DCA 400 mg
* Vitamin B1 (thiamine) 100 mg
* Alpha-lipoic acid 100 mg
* Oxidoreductase ubiquinone (Q10) 50 mg
The formula was taken for 30 days straight. However, if symptom relief is not achieved after a month, DCA could be taken 5 days straight with a 2 day break at the end of the week. Such cycles should be repeated every week for symptom control.

Nevertheless, additional trials are needed to draw further conclusions.

==Costs and availability==
DCA and its most popular form '''Sodium dichloroacetate''' is available in naturopath clinics, as an off-label drug in Canada or on the internet. It is a non-patentable generic drug that can be freely transported all around the world.

Daily dose of DCA with the additional supplements in the nutraceutical formula cost about 1-2$ daily.

==Notable studies and publications==

*2018, Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial<ref name="Comhaire2018a" /> - [[pubmed:29602463|(Full text)]]
* 2018, Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?<ref name="Comhaire2018b">{{Cite journal|last=Comhaire|first=Frank|date=2018-11-01|title=Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?|url=http://www.sciencedirect.com/science/article/pii/S0306987718307734|journal=Medical Hypotheses|language=en|volume=120|pages=65–67|doi=10.1016/j.mehy.2018.08.014|issn=0306-9877}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0306987718307734 (Full text)]

==Learn more==
*[https://pubchem.ncbi.nlm.nih.gov/compound/Dichloroacetic-acid PubChem]
*[https://www.drugbank.ca/drugs/DB08809 Drugbank.ca]
*[https://dcaguide.org/dca-information/ Phoenix Rising DCA thread]
*[https://dcaguide.org/dca-information/ DCAGuide.org]

==See also==
*[[Mitochondrion]]

==References==
{{Reflist}}

[[Category:Potential treatments]]

Microbiome

2021-05-14T22:45:22Z

Kmdenmark:Copy edit

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}} A 2021 study observed significant differences in several types of bacteria in the saliva and gut in CFS/ME patients compared to controls, but was unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME and if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name=":0" />

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> decreased levels of [[Bifidobacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|author-link=|last2=Venket Rao|first2=A|author-link2=|last3=Irani|first3=Dinaz|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name=":0">{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

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[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2021-05-14T20:16:19Z

Kmdenmark:removed duplicate reference

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}} A 2021 study observed significant differences in several bacterial populations in the saliva and gut in CFS/ME patients compared to external controls, but was unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME and if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name=":0" />

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> decreased levels of [[Bifidobacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|author-link=|last2=Venket Rao|first2=A|author-link2=|last3=Irani|first3=Dinaz|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name=":0">{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

==References==
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| pmid =
| doi = 10.1042/CS20171330
}}
</ref>
</references>

[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2021-05-14T20:14:53Z

Kmdenmark:typo; reformatted ref

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}} A 2021 study observed significant differences in several bacterial populations in the saliva and gut in CFS/ME patients compared to external controls, but was unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME and if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name=":0" />

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> decreased levels of [[Bifidobacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|author-link=|last2=Venket Rao|first2=A|author-link2=|last3=Irani|first3=Dinaz|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name=":0">{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

==References==
<references>
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| last4 = Che | first4 = Xiaoyu | authorlink4 =
| last5 = Lee | first5 = Bohyun | authorlink5 =
| last6 = Bateman | first6 = Lucinda | authorlink6 = Lucinda Bateman
| last7 = Klimas | first7 = Nancy G. | authorlink7 = Nancy Klimas
| last8 = Komaroff | first8 = Anthony L. | authorlink8 = Anthony Komaroff
| last9 = Levine | first9 = Susan | authorlink9 = Susan Levine
| last10 = Montoya | first10 = Jose G. | authorlink10 = Jose Montoya
| last11 = Peterson | first11 = Daniel L. | authorlink11 = Daniel Peterson
| last12 = Ramanan | first12 = Devi | authorlink12 =
| last13 = Jain | first13 = Komal | authorlink13 =
| last14 = Eddy | first14 = Meredith L. | authorlink14 =
| last15 = Hornig | first15 = Mady | authorlink15 = Mady Hornig
| last16 = Lipkin | first16 = W. Ian | authorlink16 = Ian Lipkin
| title = Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome
| journal = Microbiome | volume = 5 | issue = 44 | pages =
| date = 2017
| pmid =
| doi = 10.1186/s40168-017-0261-y
}}
</ref>
<ref name="Newberry, 2018">{{Citation
| last1 = Newberry | first1 = F. | authorlink1 =
| last2 = Hsieh | first2 = S.-Y. | authorlink2 =
| last3 = Wileman | first3 = T. | authorlink3 =
| last4 = Carding | first4 = S. R. | authorlink4 = Simon Carding
| title = Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?
| journal = Clinical Science | volume = 132 | issue = 5 | pages = 523–542
| date = 2018
| pmid =
| doi = 10.1042/CS20171330
}}
</ref>
</references>

[[Category:Body systems]]
[[Category:Microbiome]]

Henry Butt

2021-05-14T20:13:37Z

Kmdenmark:reformatted ref

[[File:Henry Butt.png|200px|thumb|right]]
'''Henry L. Butt''', MSc, PhD, is the Director of Bioscreen (a laboratory specializing in fecal microbial analysis) and a researcher in Newcastle, [[Australia]].

==Books==

*2014, [http://www.academia.edu/11578244/CHAPTER_FIVE_Metabolism_in_Chronic_Fatigue_Syndrome Chapter Five in ''Advances in Clinical Chemistry, Vol. 66,'' published by Elsevier; "Metabolism in Chronic Fatigue Syndrome," by] [[Christopher Armstrong | Christopher W. Armstrong]], [[Neil McGregor | Neil R. McGregor]], Henry L. Butt, and [[Paul Gooley |Paul R. Gooley]]<ref>{{Cite journal|last=Armstrong|first=Christopher W.|author-link=Christopher Armstrong|last2=McGregor|first2=Neil R.|author-link2=Neil McGregor|last3=Butt|first3=Henry L.|author-link3=Henry Butt|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=2014|title=Metabolism in Chronic Fatigue Syndrome|url=https://www.academia.edu/11578244/CHAPTER_FIVE_Metabolism_in_Chronic_Fatigue_Syndrome|journal=Advances in Clinical Chemistry|language=en|volume=|issue=|pages=121–172|doi=|pmc=|pmid=|access-date=|quote=|via=}}</ref>

==Notable studies==

*1996, [https://www.ncbi.nlm.nih.gov/pubmed/8809350 Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome]
*1996, [https://www.ncbi.nlm.nih.gov/pubmed/8733884 Preliminary determination of a molecular basis of chronic fatigue syndrome]
*1997, A Preliminary Assessment of the Association of SCL-90-R Psychological Inventory Responses with Changes in Urinary Metabolites in Patients with Chronic Fatigue Syndrome<ref>[[Neil McGregor|N.R. McGregor]], R.H. Dunstan, H.L. Butt, T.K. Roberts, I.J. Klineberg, and M. Zerbes. (1997). A Preliminary Assessment of the Association of SCL-90-R Psychological Inventory Responses with Changes in Urinary Metabolites in Patients with Chronic Fatigue Syndrome. ''Journal of Chronic Fatigue Syndrome,'' Vol. 3, Iss. 1, pp 17-37. http://dx.doi.org/10.1300/J092v03n01_03</ref>
*1998, Immunological and Haematological Parameters in Patients with Chronic Fatigue Syndrome<ref>{{Cite journal|last=Roberts|first=Timothy K.|last2=McGregor|first2=Neil R.|author-link2=Neil McGregor|last3=Dunstan|first3=R. Hugh|last4=Donohoe|first4=Mark|last5=Murdoch|first5=Raymond N.|last6=Zhang|first6=S.|last7=Hope|first7=D.|last8=Butt|first8=Henry L.|last9=Watkins|first9=Jennifer A.|last10=Taylor|first10=Warren G.|date=1998|title=Immunological and Haematological Parameters in Patients with Chronic Fatigue Syndrome|url=http://dx.doi.org/10.1300/J092v04n04_05|journal=Journal of Chronic Fatigue Syndrome|volume=4|issue=4|pages=51-65|doi=10.1300/J092v04n04_05|via=}}</ref> - [http://dx.doi.org/10.1300/J092v04n04_05 (Abstract)]
*2000, [https://www.ncbi.nlm.nih.gov/pubmed/10905542 Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome]<ref name="Richards, 2000" />
*2000, Erythrocyte Morphology in Rheumatoid Arthritis and Chronic Fatigue Syndrome: A Preliminary Study<ref>R. S. Richards, T. K. Roberts, D. Mathers, R. H. Dunstan, N. R. McGregor & H. L. Butt. (2000). Erythrocyte Morphology in Rheumatoid Arthritis and Chronic Fatigue Syndrome: A Preliminary Study. ''Journal of Chronic Fatigue Syndrome'', Vol. 6, Iss. 1, pp. 23-35. http://dx.doi.org/10.1300/J092v06n01_03</ref>
*2000, Investigation of Erythrocyte Oxidative Damage in Rheumatoid Arthritis and Chronic Fatigue Syndrome<ref>R. S. Richards, T. K. Roberts, D. Mathers, R. H. Dunstan, [[Neil McGregor|N. R. McGregor]] & H. L. Butt. (2000). Investigation of Erythrocyte Oxidative Damage in Rheumatoid Arthritis and Chronic Fatigue Syndrome. ''Journal of Chronic Fatigue Syndrome'', Vol. 6, Iss. 1, pp. 37-46. http://dx.doi.org/10.1300/J092v06n01_04</ref>
*2007, Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome<ref>{{Cite journal|last=Niblett|first=Suzanne H.|last2=King|first2=Katrina E.|last3=Dunstan|first3=R. Hugh|last4=Clifton-Bligh|first4=Phillip|last5=Hoskin|first5=Leigh A.|last6=Roberts|first6=Timothy K.|last7=Fulcher|first7=Greg R.|last8=McGregor|first8=Neil R.|author-link8=Neil McGregor|last9=Dunsmore|first9=Julie C.|last10=Butt|first10=Henry|author-link10=Henry Butt|last11= Klineberg|first11=Iven|last12=Rothkirch|first12=T. B.|date=Sep 2007|title=Hematologic and Urinary Excretion Anomalies in Patients with Chronic Fatigue Syndrome|url=http://journals.sagepub.com/doi/10.3181/0702-RM-44|journal=Experimental Biology and Medicine|language=en|volume=232|issue=8|pages=1041–1049|doi=10.3181/0702-rm-44|issn=1535-3702|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pubmed/17720950 (Abstract)]
*2009, [http://iv.iiarjournals.org/content/23/4/621.long Increased D-Lactic Acid Intestinal Bacteria in Patients with Chronic Fatigue Syndrome]<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref>
*2014, Metabolism in chronic fatigue syndrome<ref>{{Cite journal|last=Armstrong|first=Christopher W.|author-link=Christopher Armstrong|last2=McGregor|first2=Neil R.|author-link2=Neil McGregor|last3=Butt|first3=Henry L.|author-link3=Henry Butt|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|date=2014|title=Metabolism in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/25344988|journal=Advances in Clinical Chemistry|volume=66|pages=121–172|issn=0065-2423|pmid=25344988|via=}}</ref> - [[pubmed:25344988|(Abstract)]]
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study] (Jackson ML, Henry Butt, Ball M, Lewis DP, Bruck D)
*2015, [http://link.springer.com/article/10.1007%2Fs11306-015-0816-5 Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients]<ref name="Armstrong, 2015" />
*2016, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2016.1207400?journalCode=rftg20 Widespread pain and altered renal function in ME/CFS patients]<ref>{{Cite journal|last=McGregor|first=Neil R.|author-link=Neil McGregor|last2=Armstrong|first2=Christopher W.|author-link2=Christopher Armstrong|last3=Lewis|first3=Donald P.|author-link3=Donald Lewis|last4=Butt|first4=Henry L.|author-link4=Henry Butt|last5=Gooley|first5=Paul R.|author-link5=Paul Gooley|date=Jul 2016|title=Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2016.1207400?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|volume=4|issue=3|pages=132-145|doi=10.1080/21641846.2016.1207400|quote=|via=}}</ref>
*2016, Support for the [[Microgenderome]]: Associations in a Human Clinical Population<ref name="Wallis2016" /> - [http://www.nature.com/articles/srep19171 (Full Text)]
*2017, Examining clinical similarities between [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] and d-lactic acidosis: a systematic review<ref name="Wallis2017" /> - [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1229-1 (Full Text)]
*2017, The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome<ref name="Armstrong, 2017" />
*2018, Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons<ref name="Wallis, 2018" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801817/ (Full Text)] [https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1413-y (Correction)]
*2012, NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome<ref name="Armstrong, 2012" /> - [https://www.sciencedirect.com/science/article/pii/S0009898112003270?via%3Dihub (Abstract)]

==Talks and interviews==

==Online presence==

*[https://www.ncbi.nlm.nih.gov/pubmed/?term=Butt%20H%5BAuthor%5D&cauthor=true&cauthor_uid=26779319 PubMed - Henry Butt]

==See also==
* [[Pesticide exposure link to ME/CFS]]

*

==Learn more==

*2000, [http://sacfs.asn.au/publications/talking_point/2000/2_jun/lecture_3.htm Newcastle Team Lecture - Dr Henry Butt]
*2010, [http://www.medscape.com/viewarticle/732378_4 Gut Inflammation in Chronic Fatigue Syndrome]

==References==
<references>
<ref name="Armstrong, 2012">{{Citation
| last1 = Armstrong | first1 = Christopher W. | authorlink1= Christopher Armstrong
| last2 = McGregor | first2 = Neil R. | authorlink2 = Neil McGregor
| last3 = Sheedy | first3 = John R. | authorlink3 =
| last4 = Buttfield | first4 = Ian | authorlink4 =
| last5 = Butt | first5 = Henry L. | authorlink5 = Henry Butt
| last6 = Gooley | first6 = Paul R. | authorlink6 = Paul Gooley
| title = NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome
| journal = Clinica Chimica Acta | volume = 413 | issue = 19–20 | page = 1525–1531
| date = 2012
| doi = 10.1016/j.cca.2012.06.022
}}
</ref>
<ref name="Armstrong, 2015">{{Citation
| last1 = Armstrong | first1 = Christopher W. | authorlink1 = Christopher Armstrong
| last2 = McGregor | first2 = Neil R. | authorlink2 = Neil McGregor
| last3 = Lewis | first3 = Donald P. | authorlink3 = Donald Lewis
| last4 = Butt | first4 = Henry L. | authorlink4 = Henry Butt
| last5 = Gooley | first5 = Paul R. | authorlink5 = Paul Gooley
| title = Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients
| journal = Metabolomics | volume = 11 | issue = 6 | page = 1626–1639
| date = 2015
| doi = 10.1007/s11306-015-0816-5
}}
</ref>
<ref name="Armstrong, 2017">{{Citation
| last1 = Armstrong | first1 = Christopher W. | authorlink1 = Christopher Armstrong
| last2 = McGregor | first2 = Neil R. | authorlink2 = Neil McGregor
| last3 = Lewis | first3 = Donald P. | authorlink3 = Donald Lewis
| last4 = Butt | first4 = Henry L. | authorlink4 = Henry Butt
| last5 = Gooley | first5 = Paul R. | authorlink5 = Paul Gooley
| title = The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome
| journal = Metabolomics | volume = 13 | issue = 1 | page =
| date = 2017
| doi = 10.1007/s11306-016-1145-z
}}
</ref>
<ref name="Richards, 2000">{{Citation
| last1 = Richards | first1 = RS | authorlink1 =
| last2 = Roberts | first2 = TK | authorlink2 =
| last3 = McGregor | first3 = NR | authorlink3 = Neil McGregor
| last4 = Dunstan | first4 = RH | authorlink4 =
| last5 = Butt | first5 = HL | authorlink5 = Henry Butt
| title = Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome
| journal = Redox Report | volume = 5 | issue = 1 | page = 35-41
| date = 2000
| pmid = 10905542
| doi = 10.1179/rer.2000.5.1.35
}}
</ref>
<ref name="Wallis2016">{{citation
| last1 = Wallis | first1 = Amy | authorlink1 = Amy Wallis
| last2 = Butt | first2 = Henry L | authorlink2 = Henry Butt
| last3 = Ball | first3 = Michelle | authorlink3 = Michelle Ball
| last4 = Lewis | first4 = Donald P | authorlink4 = Donald Lewis
| last5 = Bruck | first5 = Dorothy | authorlink5 = Dorothy Bruck
| display-authors =
| title = Support for the Microgenderome: Associations in a Human Clinical Population
| journal = Scientific Reports | volume = 6 | pages = 19171
| date = 13 Jan 2016
| pmid = 26757840 | doi = 10.1038/srep19171
| url = http://www.nature.com/articles/srep19171
}}</ref>
<ref name="Wallis2017">{{citation
| last1 = Wallis | first1 = Amy | authorlink1 = Amy Wallis
| last2 = Ball | first2 = Michelle | authorlink2 = Michelle Ball
| last3 = McKechnie | first3 = Sandra | authorlink3 =
| last4 = Butt | first4 = Henry L | authorlink4 = Henry Butt
| last5 = Lewis | first5 = Donald P | authorlink5 = Donald Lewis
| last6 = Bruck | first6 = Dorothy | authorlink6 = Dorothy Bruck
| title = Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and d-lactic acidosis: a systematic review
| journal = Journal of Translational Medicine | volume = | issue = 15 | page = 129
| date = 2017
| doi = 10.1186/s12967-017-1229-1
}}</ref>
<ref name="Wallis, 2018">{{citation
| last1 = Wallis | first1 = Amy | authorlink1 = Amy Wallis
| last2 = Ball | first2 = Michelle | authorlink2 = Michelle Ball
| last3 = Butt | first3 = Henry L | authorlink3 = Henry Butt
| last4 = Lewis | first4 = Donald P | authorlink4 = Donald Lewis
| last5 = McKechnie | first5 = Sandra | authorlink5 =
| last6 = Paull | first6 = Phillip | authorlink6 =
| last7 = Jaa-Kwee | first7 = Amber | authorlink7 =
| last8 = Bruck | first8 = Dorothy | authorlink8 = Dorothy Bruck
| title = Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons
| journal = Journal of Translational Medicine | volume = 16 | issue = 1 | page = 24
| date = 2018
| doi = 10.1186/s12967-018-1392-z
}}</ref>
</references>
[[Category:Researchers]]
[[Category:Australia researchers]]
[[Category:Clinicians]]
[[Category:Australian clinicians]]

Microbiome

2021-05-14T20:05:32Z

Kmdenmark:added authorlinks

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}} A 2021 study observed significant differences in several bacterial populations in the saliva and gut in CFS/ME patients compared to external controls, but was unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME and if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name=":0" />

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|author-link8=Henry Butt|last9=De Meirleir|first9=Kenny L.|author-link9=Kenny De Meirleir|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> decreased levels of [[Bifidobacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|author-link=|last2=Venket Rao|first2=A|author-link2=|last3=Irani|first3=Dinaz|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref name="Sheedy2009" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name=":0">{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

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[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2021-05-14T20:03:16Z

Kmdenmark:reformatted ref

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}} A 2021 study observed significant differences in several bacterial populations in the saliva and gut in CFS/ME patients compared to external controls, but was unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME and if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name=":0" />

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref>{{Cite journal|last=Sheedy|first=John R.|author-link=|last2=Wettenhall|first2=Richard E. H.|author-link2=|last3=Scanlon|first3=Denis|author-link3=|last4=Gooley|first4=Paul R.|author-link4=Paul Gooley|last5=Lewis|first5=Donald P.|author-link5=Donald Lewis|last6=McGregor|first6=Neil|author-link6=Neil McGregor|last7=Stapleton|first7=David I.|last8=Butt|first8=Henry L.|last9=DE Meirleir|first9=Kenny L.|date=Jul 2009|title=Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/19567398|journal=In Vivo (Athens, Greece)|volume=23|issue=4|pages=621–628|doi=|issn=0258-851X|pmc=|pmid=19567398|access-date=|quote=|via=}}</ref> decreased levels of [[Bifidobacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|author-link=|last2=Venket Rao|first2=A|author-link2=|last3=Irani|first3=Dinaz|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref name="Sheedy2009" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name=":0">{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

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[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2021-05-14T19:57:42Z

Kmdenmark:added copy

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}} A 2021 study observed significant differences in several bacterial populations in the saliva and gut in CFS/ME patients compared to external controls, but was unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME and if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name=":0" />

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref name="Sheedy2009" /> decreased levels of [[Bifidobacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|author-link=|last2=Venket Rao|first2=A|author-link2=|last3=Irani|first3=Dinaz|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref name="Sheedy2009" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref name=":0">{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

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[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2021-05-14T19:47:46Z

Kmdenmark:reformatted citation

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}}

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}''

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref name="Sheedy2009" /> decreased levels of [[Bifidobacteria]],<ref>{{Cite journal|last=Logan|first=Alan C|author-link=|last2=Venket Rao|first2=A|author-link2=|last3=Irani|first3=Dinaz|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|date=Jun 2003|title=Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=https://linkinghub.elsevier.com/retrieve/pii/S0306987703000963|journal=Medical Hypotheses|language=en|volume=60|issue=6|pages=915–923|doi=10.1016/S0306-9877(03)00096-3|pmc=|pmid=|access-date=|quote=|via=}}</ref> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref name="Sheedy2009" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref>{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

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[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2021-05-14T19:41:23Z

Kmdenmark:moved ref

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}}

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref name="Sheedy2009" /> decreased levels of [[Bifidobacteria]],<ref name="Logan2003" /> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref name="Sheedy2009" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref>{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

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| last5 = Lee | first5 = Bohyun | authorlink5 =
| last6 = Bateman | first6 = Lucinda | authorlink6 = Lucinda Bateman
| last7 = Klimas | first7 = Nancy G. | authorlink7 = Nancy Klimas
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| last15 = Hornig | first15 = Mady | authorlink15 = Mady Hornig
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[[Category:Body systems]]
[[Category:Microbiome]]

Lorenzo Lorusso

2021-05-14T19:33:17Z

Kmdenmark:added study and ref

'''Lorenzo Lorusso''', MD, is the Head of the Multiple Sclerosis (SM)/Amyotrophic Lateral Sclerosis (ALS) Centre and a Consultant Neurologist at Mellino Mellini Hospital, Chiari-Brescia, [[Italy]]. He serves on the Scientific Committee of [[Associazione Malati di CFS onlus]], a patient advocacy group for chronic fatigue syndrome in Pavia, Italy and on the scientific committee for creating recommendations for the [[Italian National Agency for Health Regional Service]] (AGENAS) of the [[Italian National Institute of Health]] on CFS/ME.

==EUROMENE==
Dr. Lorusso is a member of the Working Group on dissemination and exploitation, patient involvement, digitalisation on behalf of the [[EUROMENE]], a European Union COST Action CA15111 not-for-profit research organization committed to tackling the cause and treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.<ref>http://www.cost.eu/COST_Actions/ca/CA15111?management</ref>

==Notable studies==
*2004, [[Chronic fatigue syndrome]]: a review<ref name="Carlo-Stella, 2004">{{Citation
| last1 = Carlo-Stella | first1 = N | authorlink1 = Nicoletta Carlo-Stella
| last2 = Lorusso | first2 = L | authorlink2 = Lorenzo Lorusso
| last3 = Candura | first3 = SM | authorlink3 =
| last4 = Cuccia | first4 = M | authorlink4 =
| title = Chronic fatigue syndrome: a review
| journal = Recenti Prog Med | volume = 96 | issue = 11 | page = 546-52
| date = 2004| pmid = 15598093| doi = }}</ref>[https://www.ncbi.nlm.nih.gov/pubmed/15598093 (Abstract)]
*2006, A first study of [[cytokine]] genomic polymorphisms in [[CFS]]: Positive association of TNF-857 and IFNgamma 874 rare alleles.<ref name="Carlo-Stella, Badulli, 2006">{{Citation
| last1 = Carlo-Stella | first1 = N | authorlink1 = Nicoletta Carlo-Stella
| last2 = Badulli | first2 = C | authorlink2 =
| last3 = De Silvestri | first3 = A | authorlink3 =
| last4 = Bazzichi | first4 = L | authorlink4 =
| last5 = Martinetti | first5 = M | authorlink5 =
| last6 = Lorusso | first6 = L | authorlink6 = Lorenzo Lorusso
| last7 = Bombardieri | first7 = S | authorlink7 =
| last8 = Salvaneschi | first8 = L | authorlink8 =
| last9 = Cuccia | first9 = M | authorlink9 =
| title = A first study of cytokine genomic polymorphisms in CFS: Positive association of TNF-857 and IFNgamma 874 rare alleles
| journal = Clinical and Experimental Rheumatology | volume = 24 | issue = 2 | page = 179-82
| date = 2006| pmid = 16762155| doi = }}</ref> [https://pubmed.ncbi.nlm.nih.gov/16762155/ (Full text)]
*2009, Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in [[chronic fatigue syndrome]].<ref name="Carlo-Stella, Bozzini, 2009">{{Citation
| last1 = Carlo-Stella | first1 = N | authorlink1 = Nicoletta Carlo-Stella
| last2 = Bozzini | first2 = S | authorlink2 =
| last3 = De Silvestri | first3 = A | authorlink3 =
| last4 = Sbarsi | first4 = I | authorlink4 =
| last5 = Pizzochero | first5 = C | authorlink5 =
| last6 = Lorusso | first6 = L | authorlink6 = Lorenzo Lorusso
| last7 = Martinetti | first7 = M | authorlink7 =
| last8 = Cuccia | first8 = M | authorlink8 =
| title = Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome
| journal = International Journal of Immunopathology and Pharmacology | volume = 22 | issue = 3 | page = 745-54
| date = 2009| pmid = 19822091
| doi = 10.1177/039463200902200320
}}</ref> [https://pubmed.ncbi.nlm.nih.gov/19822091/ (Abstract)]
*2009, Immunological aspects of [[chronic fatigue syndrome]]<ref name="Lorusso, 2009">{{Citation
| last1 = Lorusso | first1 = Lorenzo | authorlink1 = Lorenzo Lorusso
| last2 = Mikhaylova | first2 = SV | authorlink2 =
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Ferrari | first4 = D | authorlink4 =
| last5 = Ngonga | first5 = GK | authorlink5 =
| last6 = Ricevuti | first6 = Giovanni | authorlink6 =
| title = Immunological aspects of chronic fatigue syndrome
| journal = Autoimmun Rev | volume = 8 | issue = 4 | page = 287-91| date = 2009| pmid = 18801465
| doi = 10.1016/j.autrev.2008.08.003}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/18801465 (Abstract)]
*2010, [Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An Update<ref name="Capelli, 2010">{{Citation
| last1 = Capelli | first1 = Enrica | authorlink1 = Enrica Capelli
| last2 = Zola | first2 = R | authorlink2 =
| last3 = Lorusso | first3 = Lorenzo | authorlink3 = Lorenzo Lorusso
| last4 = Venturini | first4 = Luigi | authorlink4 =
| last5 = Sardi | first5 = F | authorlink5 =
| last6 = Ricevuti | first6 = Giovanni | authorlink6 =
| title = Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]: An Update
| journal = International Journal of Immunopathology and Pharmacology | volume = 23 | issue = 4 | page = 981-989
| date = 2010| pmid = 21244747
| doi = 10.1177/039463201002300402}}</ref>[http://journals.sagepub.com/doi/pdf/10.1177/039463201002300402 (Full Text)]
*2015, [[Chronic fatigue syndrome]]: Features of a population of patients from northern Italy<ref name="Capelli, 2015">{{Citation
| last1 = Capelli | first1 = Enrica | authorlink1 = Enrica Capelli
| last2 = Lorusso | first2 = Lorenzo | authorlink2 = Lorenzo Lorusso
| last3 = Ghitti | first3 = M | authorlink3 =
| last4 = Venturini | first4 = Luigi | authorlink4 =
| last5 = Cusa | first5 = C | authorlink5 =
| last6 = Ricevuti | first6 = Giovanni | authorlink6 =
| title = Chronic fatigue syndrome: Features of a population of patients from northern Italy
| journal = International Journal of Immunopathology and Pharmacology | volume = | issue = | page =
| date = 2015| pmid = | doi = 10.1177/0394632015572074 }}</ref> [http://journals.sagepub.com/doi/full/10.1177/0394632015572074#articleCitationDownloadContainer (Full Text)]
*2016, Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with [[chronic fatigue syndrome]]<ref name="Maltese, 2016">{{citation
| last1 = Maltese | first1 = PE | authorlink1 =
| last2 = Venturini | first2 = L | authorlink2 =
| last3 = Poplavskaya | first3 = E | authorlink3 =
| last4 = Bertelli | first4 = M | authorlink4 =
| last5 = Cecchin | first5 = S | authorlink5 =
| last6 = Granato | first6 = M | authorlink6 =
| last7 = Nikulina | first7 = SY | authorlink7 =
| last8 = Salmina | first8 = A | authorlink8 =
| last9 = Aksyutina | first9 = N | authorlink9 =
| last10 = Capelli | first10 = Enrica | authorlink10 = Enrica Capelli
| last11 = Ricevuti | first11 = Giovanni | authorlink11 =
| last12 = Lorusso | first12 = Lorenzo | authorlink12 = Lorenzo Lorusso
| title = Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with chronic fatigue syndrome
| journal = Genet Mol Res | volume = 15 | issue = 3
| date = 2016| doi = 10.4238/gmr.15038717}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/27525900 (Full Text)]
*2017, [[XMRV]] and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] Appears Unreliable<ref name="Panelli, 2017">{{Citation
| last1 = Panelli | first1 = Simona | authorlink1 =
| last2 = Lorusso | first2 = Lorenzo | authorlink2 = Lorenzo Lorusso
| last3 = Balestrieri | first3 = Alessandro | authorlink3 =
| last4 = Lupo | first4 = Giuseppe | authorlink4 =
| last5 = Capelli | first5 = Enrica | authorlink5 = Enrica Capelli
| title = XMRV and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Appears Unreliable
| journal = Frontiers in Public Health | volume = 5 | issue = 108 | page =
| date = 2017| pmid = 28589117 | pmc= 5439170
| doi = 10.3389/fpubh.2017.00108}}</ref> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772628/ (Full Text)]
*2018, Cardiovascular characteristics of [[chronic fatigue syndrome]]<ref name="Bozzini, 2018">{{Citation
| last1 = Bozzini | first1 = S | authorlink1 =
| last2 = Albergati | first2 = A | authorlink2 =
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso
| last5 = Gazzaruso | first5 = C | authorlink5 =
| last6 = Pelissero | first6 = G | authorlink6 =
| last7 = Falcone | first7 = C | authorlink7 =
| title = Cardiovascular characteristics of chronic fatigue syndrome.
| journal = Biomedical Reports | volume = 8 | issue = 1 | page = 26–30
| date = 2018| pmid = 29399336 | pmc = 5772628
| doi = 10.3892/br.2017.1024}}</ref> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772628/ (Full Text)]
* 2018, Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref name="Estevez-Lope2018">{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology <ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref>{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Talks and interviews==

==Online presence==
*[https://www.ncbi.nlm.nih.gov/pubmed/?term=Lorusso%20L%5BAuthor%5D&cauthor=true&cauthor_uid=29399336 PubMed]
*[http://www.euromene.eu/workinggroups/Lorusso_L_biosketch_CostAction.pdf EUROMENE CV]

==Learn more==

==See also==
*[[EUROMENE]]

==References==
{{Reflist}}

[[Category:Researchers]]
[[Category:Italian clinicians]]

Microbiome

2021-05-14T19:31:56Z

Kmdenmark:alphabetized see also

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}}

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010" /> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref name="Sheedy2009" /> decreased levels of [[Bifidobacteria]],<ref name="Logan2003" /> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref name="Sheedy2009" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref>{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==See also==
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Indoor microbiome]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Probiotics]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

==References==
<references>
<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref>
<ref name="Maes2012">{{Citation| doi = 10.1016/j.jad.2011.09.010| issn = 1573-2517| volume = 136| issue = 3| pages = 909–917| last1 = Maes| first1 = Michael| last2 = Twisk| first2 = Frank N. M.| last3 = Kubera| first3 = Marta| last4 = Ringel| first4 = Karl| last5 = Leunis| first5 = Jean-Claude| last6 = Geffard| first6 = Michel| title = Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome| journal = Journal of Affective Disorders| date = February 2012| pmid = 21967891}}</ref>
<ref name="Sheedy2009">{{Citation| issn = 0258-851X| volume = 23| issue = 4| pages = 621–628| last1 = Sheedy| first1 = John R.| last2 = Wettenhall| first2 = Richard E. H.| last3 = Scanlon| first3 = Denis| last4 = Gooley| first4 = Paul R.| last5 = Lewis| first5 = Donald P.| last6 = McGregor| first6 = Neil| last7 = Stapleton| first7 = David I.| last8 = Butt| first8 = Henry L.| last9 = DE Meirleir| first9 = Kenny L.| title = Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome| journal = In Vivo (Athens, Greece)| date = August 2009| pmid = 19567398}}</ref>
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[[Category:Body systems]]
[[Category:Microbiome]]

Microbiome

2021-05-14T19:29:33Z

Kmdenmark:added copy and study

{{Cleanup/Citations needed|date = Mar 2021}}
The '''microbiome''' is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the [[nose microbiome|nose]], ears, [[oral microbiome|mouth]] and [[gut microbiome|gut]]. [[Dysbiosis]] or an imbalance in this community may play a role in the pathophysiology of [[chronic fatigue syndrome]].{{Citation needed|date=Mar 2021}}

==Anatomical areas==

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].

===Skin flora===

===Nose flora===

===Oral flora===

==Chronic fatigue syndrome==

A growing body of evidence suggests that an [[dysbiosis|altered microbiome]]; [[intestinal permeability|mucosal barrier]] dysfunction;<ref name="Lakhan2010" /> the translocation or crossing of bacteria from the gut into the [[blood|bloodstream]]; and subsequent immune response may pay a role in the pathophysiology of [[chronic fatigue syndrome]].

A 2021 study showed that the intestinal microbial profile recorded in CFS/ME patients is indeed consistent with the reported for other autoimmune conditions, such as Crohn’s disease, Ulcerative Colitis and Systemic Lupus Erythematous.

===Immune response===

A study of 128 [[ME/CFS]] patients found significantly increased [[IgA]] response to [[lipopolysaccharide]]s from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum [[IL-1]], [[TNFα]], [[neopterin]] and [[elastase]]. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.<ref name="Maes2012" />

===Dysbiosis===
:''{{main|page_name =Dysbiosis}}

There is strong evidence that [[dysbiosis]] or an imbalance in the microbial ecology of the gut plays a role in the symptoms of [[ME/CFS]]. ME/CFS patients have higher levels of [[D-lactic acid]] bacteria,<ref name="Sheedy2009" /> decreased levels of [[Bifidobacteria]],<ref name="Logan2003" /> and may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at higher rates.{{citation needed}}

===Exercise===

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the [[gastrointestinal system|intestine]] into the [[blood|bloodstream]] following exercise). In the blood, the study found increased ''[[Clostridium]]'' fifteen minutes after exercise and increased ''[[Bacilli]]'' 48 hours later.<ref name="Shukla2015" /><ref>{{citation |last= Johnson|first= Cort|date= 21 December 2015|title= Exercise Triggers Gut Changes in Chronic Fatigue Syndrome (ME/CFS)|url= http://www.cortjohnson.org/blog/2015/12/21/exercise-gut-chronic-fatigue-syndrome-me-cfs/|newspaper= HealthRising|location= Houston|access-date= 2016-12-12}}</ref>

===Sleep===

In a very small study, CFS patients treated with [[erythromycin]] who had clinical response (i.e., reduced [[streptococcus]]) had improved sleep. Higher [[lactobacillus]] was associated with poorer mood.<ref name="Jackson2015" />

===Gender===

A study of 274 [[ME/CFS]] patients found sex-specific interactions between [[Firmicute]]s ([[Clostridium]], [[Streptococcus]], [[Lactobacillus]] and [[Enterococcus]]) and ME/CFS symptoms (including neurological, immune and mood symptoms) and symptoms in spite of similar overall composition across sexes.<ref name="Wallis2016" />

==Factors affecting microbiome==

=== Diet ===

The food we eat has a considerable effect on the composition of the intestinal microbiota.<ref name="Maslowski2011" />

=== Viral infection ===

Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases [[Lactobacillus]] and [[Lactococcus]] species and increases in [[Enterobacteriaceae]].<ref>{{citation |last= Racaniello|first= Vincent|date= 10 December 2014|title= How influenza virus infection might lead to gastrointestinal symptoms|url= http://www.virology.ws/2014/12/10/how-influenza-virus-infection-might-lead-to-gastrointestinal-symptoms/|newspaper= Virology Blog|location= New York|access-date= 2016-12-12}}</ref>

=== Pregnancy ===

Gut microbiota change dramatically from the first trimester to the third trimester of [[pregnancy]]. During the first trimester, there is an overrepresentation of 18 bacterial groups, mainly [[Faecalibacterium]], a [[butyrate]] producer that has been shown to improve symptoms of [[inflammatory bowel disease]].<ref name="koren2012" />

During the third trimester, populations of pro-inflammatory [[bacteria]] species such as [[proteobacteria]] and [[actinobacteria]] increase and there is a reduction in diversity. Populations of [[Faecalibacterium]] decrease.<ref name="koren2012" /> Overall bacterial load increases over the course of pregnancy.<ref>http://www.scopus.com/record/display.uri?eid=2-s2.0-53849104768&origin=inward&txGid=B73C4858FB9D5F216C9F222F22386A44.iqs8TDG0Wy6BURhzD3nFA%3a2</ref>

===Nervous system===

The intestinal microbiota play a major role in the [[gut-brain axis]] with consequences for both neurological development and host behavior.

=== Stress ===

There is growing evidence that the microbiome plays an important role in the [[stress]] response. Animals raised in a germ-free environment show an exaggerated [[HPA]] response to psychological stress which normalizes when [[Bifidobacterium infantis|''Bifidobacterium infantis'']] is introduced. [[Escherichia coli|''Escherichia coli'']] can activate the HPA.<ref name="Dinan2012" />

Stress also increases [[intestinal permeability]].

==Planned studies==
British patient charity [[Invest in ME]] is raising funds for a gut microbiome study at the University of East Anglia in the United Kingdom led by professor [[Simon Carding]].<ref>[http://www.investinme.org/LDR%20UK%20Gut%20Microbiota.htm Invest in ME – UK gut microbiota research]</ref>

Funds are being raised by patients (originally led by the late [[Vanessa Li]]) for [[Ian Lipkin]] and [[Mady Hornig]] of Columbia University in the United States to perform a study, called the [[ME/CFS Monster Study]], looking at many areas including the gut microbiome in [[ME/CFS]] patients. Fundraising efforts are led by the [[Microbe Discovery Project]].

==Notable studies==
*2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome<ref name="Sheedy2009" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843715/ (Full Text)]
*2010, [https://www.ncbi.nlm.nih.gov/pubmed/20939923 Gut inflammation in chronic fatigue syndrome]<ref name="Lakhan2010" />
*2012, [https://www.ncbi.nlm.nih.gov/pubmed/21967891 Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome]<ref name="Maes2012" />
*2012, [http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/ The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy]<ref name="Borody2012" />
*2013, [https://www.ncbi.nlm.nih.gov/pubmed/23791918 High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients]<ref name="Fremont2013" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26779319 Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study]<ref name="Jackson2015" />
*2015, [https://www.ncbi.nlm.nih.gov/pubmed/26683192 Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)]<ref name="Shukla2015" />
*2016, [https://www.ncbi.nlm.nih.gov/pubmed/27634186 The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome]<ref name="Morris, 2016" />
*2016, [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4 Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome]<ref>{{Cite journal|last=Giloteaux|first=Ludovic|author-link=Ludovic Giloteaux|last2=Goodrich|first2=Julia K.|author-link2=|last3=Walters|first3=William A.|author-link3=|last4=Levine|first4=Susan M.|author-link4=Susan Levine|last5=Ley|first5=Ruth E.|author-link5=|last6=Hanson|first6=Maureen R.|author-link6=Maureen Hanson|date=Dec 2016|title=Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0171-4|journal=Microbiome|language=en|volume=4|issue=1|pages=|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587|quote=|via=}}</ref>
*2016, [http://www.nature.com/articles/srep19171 Support for the Microgenderome: Associations in a Human Clinical Population]<ref name="Wallis2016" />
*2017, Fecal metagenomic profiles in subgroups of patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]]<ref name="Nagy-Szakal, 2017" /> [https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0261-y (Full Text)]
*2018, Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?<ref name="Newberry, 2018" />
*2018, [[Chronic fatigue syndrome]] patients have alterations in their oral microbiome composition and function<ref>{{Cite journal|last=Wang|first=Taiwu|last2=Yu|first2=Lei|last3=Xu|first3=Cong|last4=Pan|first4=Keli|last5=Mo|first5=Minglu|last6=Duan|first6=Mingxiang|last7=Zhang|first7=Yao|last8=Xiong|first8=Hongyan|date=2018-09-11|title=Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203503|doi=10.1371/journal.pone.0203503|issn=1932-6203}}</ref> [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203503 (Full Text)]
*2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host [[metabolism]], [[gene expression]] and [[Immune system|immunity]]<ref>{{Cite journal|last=Proal|first=Amy|author-link=Amy Proal|last2=Marshall|first2=Trevor|author-link2=Trevor Marshall|author-link3=|author-link4=|author-link5=|date=Nov 2018|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the era of the human microbiome: persistent pathogens drive chronic symptoms by interfering with host metabolism, gene expression and immunity|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full|journal=Frontiers in Pediatrics|volume=|issue=|pages=|quote=|via=|doi=10.3389/fped.2018.00373}}</ref> [https://www.frontiersin.org/articles/10.3389/fped.2018.00373/full (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref>{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Commercial testers==
*[[uBiome]]

==Academic projects==
*[[American Gut]]
*[[British Gut Project]]

==Learn more==
*[https://en.wikipedia.org/wiki/Microbiota Wikipedia - Microbiota]
*[[CFS Remission]] ([[Ken Lassesen]]'s blogs about experimental ME/CFS microbiome and probiotic treatments)
*2016, [https://cfsremission.wordpress.com/2016/08/09/what-should-be-in-the-ideal-microbiome-test-for-cfs/ What should be in the ideal microbiome test for CFS] ''[[CFS Remission]]''
*2016, [https://cfstreatment.blogspot.co.uk/2016/07/all-in-your-gut.html It's All in Your Gut] ''[[Onward Through the Fog]]''
*2016, [http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/ Gut Bacteria Are Different in People With Chronic Fatigue Syndrome] ''The New York Times''<ref>{{citation |last= Bakalar|first= Nicholas|date= 7 July 2016|title= Gut Bacteria Are Different in People With Chronic Fatigue Syndrome|url= http://well.blogs.nytimes.com/2016/07/07/gut-bacteria-are-different-in-people-with-chronic-fatigue-syndrome/|newspaper= The New York Times|location= |access-date= 2016-12-13}}</ref>
*2016, [https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/ New study shows chronic fatigue syndrome may have to do with gut microbes] ''The Washington Post''<ref>{{citation |last= Cha|first= Ariana Eunjung|date= 30 June 2016|title= New study shows chronic fatigue syndrome may have to do with gut microbes|url= https://www.washingtonpost.com/news/to-your-health/wp/2016/06/30/new-study-shows-chronic-fatigue-isnt-just-in-your-head-it-may-have-to-do-with-your-gut/|newspaper= The Washington Post|location= |access-date= 2016-12-13}}</ref>
*2016, [http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria Indicator of chronic fatigue syndrome found in gut bacteria] ''Cornell Chronicle''<ref>{{citation |last= Ramanujan|first= Krishna|date= 24 June 2016|title= Indicator of chronic fatigue syndrome found in gut bacteria|url= http://news.cornell.edu/stories/2016/06/indicator-chronic-fatigue-syndrome-found-gut-bacteria|newspaper= Cornell Chronicle|location= New York|access-date= 2016-12-13}}</ref>
*2016, [http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/ Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women] ''[[Health Rising]]''<ref>{{citation |last= Johnson|first= Cort|date= 21 February 2016|title= Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women|url= http://www.cortjohnson.org/blog/2016/02/21/gut-chronic-fatigue-syndrome-gender-differences/|newspaper= HealthRising|location= Houston|access-date= 2016-12-13}}</ref>
*[https://cfsremission.wordpress.com/2016/04/02/vitamin-d-and-the-microbiome/ Vitamin D and the Microbiome] ''[[CFS Remission]]''

==See also==
*[[Nasal microbiome]]
*[[Indoor microbiome]]
*[[Oral microbiome]]
*[[Helminthic therapy]]
*[[Gastrointestinal system]]
*[[Probiotics]]
*[[Ken Lassesen's model]]

==References==
<references>
<ref name="Lakhan2010">{{Citation| doi = 10.1186/1743-7075-7-79| issn = 1743-7075| volume = 7|issue = | pages = 79| last1 = Lakhan| first1 = Shaheen E| last2 = Kirchgessner| first2 = Annette| title = Gut inflammation in chronic fatigue syndrome| journal = Nutrition & Metabolism| access-date = 2016-12-13| date = 2010-10-12| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/| pmid = 20939923}}</ref>
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[[Category:Body systems]]
[[Category:Microbiome]]

Enrica Capelli

2021-05-14T19:21:54Z

Kmdenmark:added authorlinks

[[File:Enrica Capelli.png|200px|thumb|right]]
Professor '''Enrica Capelli''' is the Senior Researcher and Head of the Laboratory of Immunology and Genetic Analyses Department of Earth and Environmental Sciences, University of Pavia in Pavia, Italy. Since 2010, she has been a member of working group on Chronic Fatigue Syndrome (CFS), [[National Agency for Health Regional Service]] (AGENAS) of the [[Italian National Institute of Health]].<ref>http://www.euromene.eu/workinggroups/Enrica%20Capelli%20CV.pdf</ref>

==EUROMENE==
Dr. Capelli is a member of the [[Biomarkers]] Working Group of [[ME/CFS]] across Europe on behalf of [[EUROMENE]], a European Union COST Action CA15111 not-for-profit research organization investigating the cause of and treatment for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]].<ref>http://www.cost.eu/COST_Actions/ca/CA15111?management</ref>

==Notable studies==
*2009, Immunological aspects of chronic fatigue syndrome<ref>{{Cite journal|last=Lorusso|first=Lorenzo|author-link=Lorenzo Lorusso|last2=Mikhaylova|first2=Svetlana V.|last3=Capelli|first3=Enrica|author-link3=Enrica Capelli|last4=Ferrari|first4=Daniela|last5=Ngonga|first5=Gaelle K.|last6=Ricevuti|first6=Giovanni|date=Feb 2009|title=Immunological aspects of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/18801465|journal=Autoimmunity Reviews|volume=8|issue=4|pages=287–291|doi=10.1016/j.autrev.2008.08.003|issn=1873-0183|pmid=18801465|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pubmed/18801465 (Abstract)]
*2010, [[ME/CFS|Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]: An Update<ref name="Capelli, 2010" /> - [http://journals.sagepub.com/doi/pdf/10.1177/039463201002300402 (Full Text)]
*2015, [[Chronic fatigue syndrome]]: Features of a population of patients from northern Italy<ref name="Capelli, 2015" /> - [http://journals.sagepub.com/doi/full/10.1177/0394632015572074#articleCitationDownloadContainer (Full Text)]
*2016, Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with [[chronic fatigue syndrome]]<ref name="Maltese, 2016" /> - [https://www.ncbi.nlm.nih.gov/pubmed/27525900 (Full Text)]
*2017, The European ME/CFS [[Biomarker]] Landscape project: an initiative of the European network EUROMENE<ref>{{Cite journal|last=Scheibenbogen|first=Carmen|author-link=Carmen Scheibenbogen|last2=Freitag|first2=Helma|author-link2=Helma Freitag|last3=Blanco|first3=Julià|author-link3=Julià Blanco|last4=Capelli|first4=Enrica|author-link4=Enrica Capelli|last5=Lacerda|first5=Eliana|author-link5=Eliana Lacerda|last6=Authier|first6=Jerome|author-link6=François Jérôme Authier|last7=Meeus|first7=Mira|author-link7=Mira Meeus|last8=Castro Marrero|first8=Jesus|author-link8=Jesús Castro-Marrero|last9=Nora-Krukle|first9=Zaiga|author-link9=Zaiga Nora-Krukle|last10=Oltra|first10=Elisa|author-link10=Elisa Oltra|last11= Strand|first11=Elin Bolle|author-link11=Elin Bolle Strand|last12= Shikova|first12= Evelina|author-link12= Evelina Shikova|last13= Sekulic|first13=Slobodan|author-link13=Slobodan Sekulic|last14=Murovska|first14=Modra|author-link14=Modra Murovska|date=2017-07-26|title=The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1263-z|journal=Journal of Translational Medicine|language=en|volume=15|issue=1|pages=|doi=10.1186/s12967-017-1263-z|issn=1479-5876|pmc=5530475|pmid=28747192|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530475/ (Full Text)]
*2017, [[XMRV]] and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] Appears Unreliable<ref name="Panelli, 2017" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439170/ (Full Text)]
*2018, [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] – Evidence for an [[autoimmune disease]]<ref name="Sotzny, 2018" /> - [https://www.sciencedirect.com/science/article/pii/S1568997218300880 (Full Text)]
*2018, Cardiovascular characteristics of [[chronic fatigue syndrome]]<ref name="Bozzini, 2018" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772628/ (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology <ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref>{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=Lorenzo Lorusso|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|author-link8=Enrica Capelli|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Talks and interviews==

==Online presence==
*PubMed
*[https://www.researchgate.net/profile/Enrica_Capelli ResearchGate]
*[http://www.euromene.eu/workinggroups/Enrica%20Capelli%20CV.pdf Curriculum Vitae for EUROMENE]

==Learn more==

==See also==
*[[EUROMENE]]

==References==
<references>
<ref name="Bozzini, 2018">{{Citation
| last1 = Bozzini | first1 = S | authorlink1 =
| last2 = Albergati | first2 = A | authorlink2 =
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso
| last5 = Gazzaruso | first5 = C | authorlink5 =
| last6 = Pelissero | first6 = G | authorlink6 =
| last7 = Falcone | first7 = C | authorlink7 =
| title = Cardiovascular characteristics of chronic fatigue syndrome.
| journal = Biomedical Reports | volume = 8 | issue = 1 | page = 26–30
| date = 2018
| pmid = 29399336
| doi = 10.3892/br.2017.1024
}}
</ref>
<ref name="Capelli, 2010">{{Citation
| last1 = Capelli | first1 = Enrica | authorlink1 = Enrica Capelli
| last2 = Zola | first2 = R | authorlink2 =
| last3 = Lorusso | first3 = Lorenzo | authorlink3 = Lorenzo Lorusso
| last4 = Venturini | first4 = Luigi | authorlink4 =
| last5 = Sardi | first5 = F | authorlink5 =
| last6 = Ricevuti | first6 = Giovanni | authorlink6 =
| title = <nowiki>Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]: An Update</nowiki>
| journal = International Journal of Immunopathology and Pharmacology | volume = 23 | issue = 4 | page = 981-989
| date = 2010
| pmid = 21244747
| doi = 10.1177/039463201002300402
}}
</ref>
<ref name="Capelli, 2015">{{Citation
| last1 = Capelli | first1 = Enrica | authorlink1 = Enrica Capelli
| last2 = Lorusso | first2 = Lorenzo | authorlink2 = Lorenzo Lorusso
| last3 = Ghitti | first3 = M | authorlink3 =
| last4 = Venturini | first4 = Luigi | authorlink4 =
| last5 = Cusa | first5 = C | authorlink5 =
| last6 = Ricevuti | first6 = Giovanni | authorlink6 =
| title = Chronic fatigue syndrome: Features of a population of patients from northern Italy
| journal = International Journal of Immunopathology and Pharmacology
| date = 2015
| pmid =
| doi = 10.1177/0394632015572074
}}
</ref>
<ref name="Maltese, 2016">{{citation
| last1 = Maltese | first1 = PE | authorlink1 =
| last2 = Venturini | first2 = L | authorlink2 =
| last3 = Poplavskaya | first3 = E | authorlink3 =
| last4 = Bertelli | first4 = M | authorlink4 =
| last5 = Cecchin | first5 = S | authorlink5 =
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| last7 = Nikulina | first7 = SY | authorlink7 =
| last8 = Salmina | first8 = A | authorlink8 =
| last9 = Aksyutina | first9 = N | authorlink9 =
| last10 = Capelli | first10 = Enrica | authorlink10 = Enrica Capelli
| last11 = Ricevuti | first11 = Giovanni | authorlink11 =
| last12 = Lorusso | first12 = Lorenzo | authorlink12 = Lorenzo Lorusso
| title = Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with chronic fatigue syndrome
| journal = Genet Mol Res | volume = 15 | issue = 3
| date = 2016
| doi = 10.4238/gmr.15038717
}} </ref>
<ref name="Panelli, 2017">{{Citation
| last1 = Panelli | first1 = Simona | authorlink1 =
| last2 = Lorusso | first2 = Lorenzo | authorlink2 = Lorenzo Lorusso
| last3 = Balestrieri | first3 = Alessandro | authorlink3 =
| last4 = Lupo | first4 = Giuseppe | authorlink4 =
| last5 = Capelli | first5 = Enrica | authorlink5 = Enrica Capelli
| title = XMRV and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Appears Unreliable
| journal = Frontiers in Public Health | volume = 5 | issue = 108 | page =
| date = 2017
| pmid =
| doi = 10.3389/fpubh.2017.00108
}}
</ref>
<ref name="Sotzny, 2018">{{Citation
| last1 = Sotzny | first1 = Franziska | authorlink1 = Franziska Sotzny
| last2 = Blanco | first2 = Julià | authorlink2 = Julià Blanco
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero
| last5 = Steiner | first5 = Sophie | authorlink5 =
| last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska
| last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
| journal = Autoimmunity Reviews | volume = | issue = | page =
| date = 2018
| pmid =
| doi = 10.1016/j.autrev.2018.01.009
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:Italy researchers]]

Enrica Capelli

2021-05-14T19:18:31Z

Kmdenmark:added study

[[File:Enrica Capelli.png|200px|thumb|right]]
Professor '''Enrica Capelli''' is the Senior Researcher and Head of the Laboratory of Immunology and Genetic Analyses Department of Earth and Environmental Sciences, University of Pavia in Pavia, Italy. Since 2010, she has been a member of working group on Chronic Fatigue Syndrome (CFS), [[National Agency for Health Regional Service]] (AGENAS) of the [[Italian National Institute of Health]].<ref>http://www.euromene.eu/workinggroups/Enrica%20Capelli%20CV.pdf</ref>

==EUROMENE==
Dr. Capelli is a member of the [[Biomarkers]] Working Group of [[ME/CFS]] across Europe on behalf of [[EUROMENE]], a European Union COST Action CA15111 not-for-profit research organization investigating the cause of and treatment for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]].<ref>http://www.cost.eu/COST_Actions/ca/CA15111?management</ref>

==Notable studies==
*2009, Immunological aspects of chronic fatigue syndrome<ref>{{Cite journal|last=Lorusso|first=Lorenzo|author-link=Lorenzo Lorusso|last2=Mikhaylova|first2=Svetlana V.|last3=Capelli|first3=Enrica|author-link3=Enrica Capelli|last4=Ferrari|first4=Daniela|last5=Ngonga|first5=Gaelle K.|last6=Ricevuti|first6=Giovanni|date=Feb 2009|title=Immunological aspects of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/18801465|journal=Autoimmunity Reviews|volume=8|issue=4|pages=287–291|doi=10.1016/j.autrev.2008.08.003|issn=1873-0183|pmid=18801465|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pubmed/18801465 (Abstract)]
*2010, [[ME/CFS|Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]: An Update<ref name="Capelli, 2010" /> - [http://journals.sagepub.com/doi/pdf/10.1177/039463201002300402 (Full Text)]
*2015, [[Chronic fatigue syndrome]]: Features of a population of patients from northern Italy<ref name="Capelli, 2015" /> - [http://journals.sagepub.com/doi/full/10.1177/0394632015572074#articleCitationDownloadContainer (Full Text)]
*2016, Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with [[chronic fatigue syndrome]]<ref name="Maltese, 2016" /> - [https://www.ncbi.nlm.nih.gov/pubmed/27525900 (Full Text)]
*2017, The European ME/CFS [[Biomarker]] Landscape project: an initiative of the European network EUROMENE<ref>{{Cite journal|last=Scheibenbogen|first=Carmen|author-link=Carmen Scheibenbogen|last2=Freitag|first2=Helma|author-link2=Helma Freitag|last3=Blanco|first3=Julià|author-link3=Julià Blanco|last4=Capelli|first4=Enrica|author-link4=Enrica Capelli|last5=Lacerda|first5=Eliana|author-link5=Eliana Lacerda|last6=Authier|first6=Jerome|author-link6=François Jérôme Authier|last7=Meeus|first7=Mira|author-link7=Mira Meeus|last8=Castro Marrero|first8=Jesus|author-link8=Jesús Castro-Marrero|last9=Nora-Krukle|first9=Zaiga|author-link9=Zaiga Nora-Krukle|last10=Oltra|first10=Elisa|author-link10=Elisa Oltra|last11= Strand|first11=Elin Bolle|author-link11=Elin Bolle Strand|last12= Shikova|first12= Evelina|author-link12= Evelina Shikova|last13= Sekulic|first13=Slobodan|author-link13=Slobodan Sekulic|last14=Murovska|first14=Modra|author-link14=Modra Murovska|date=2017-07-26|title=The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1263-z|journal=Journal of Translational Medicine|language=en|volume=15|issue=1|pages=|doi=10.1186/s12967-017-1263-z|issn=1479-5876|pmc=5530475|pmid=28747192|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530475/ (Full Text)]
*2017, [[XMRV]] and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] Appears Unreliable<ref name="Panelli, 2017" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439170/ (Full Text)]
*2018, [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] – Evidence for an [[autoimmune disease]]<ref name="Sotzny, 2018" /> - [https://www.sciencedirect.com/science/article/pii/S1568997218300880 (Full Text)]
*2018, Cardiovascular characteristics of [[chronic fatigue syndrome]]<ref name="Bozzini, 2018" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772628/ (Full Text)]
* 2018, Prevalence and incidence of [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] in Europe—the Euro-epiME study from the European network [[EUROMENE]]: a protocol for a systematic review<ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Castro-Marrero|first2=Jesus|author-link2=Jesús Castro-Marrero|last3=Wang|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=Andrejs Ivanovs|last6=Nacul|first6=Luis|author-link6=Luis Nacul|last7=Sepúlveda|first7=Nuno|author-link7=Nuno Sepulveda|last8=Strand|first8=Elin B.|author-link8=Elin Strand|last9=Pheby|first9=Derek|author-link9=Derek Pheby|last10=Alegre|first10=José|author-link10=José Alegre|last11=Scheibenbogen|first11=Carmen|author-link11=Carmen Scheibenbogen|last12=Shikova|first12=Evelina|author-link12=Evelina Shikova|last13=Lorusso|first13=Lorenzo|author-link13=Lorenzo Lorusso|last14=Capelli|first14=Enrica|author-link14=Enrica Capelli|last15=Sekulic|first15=Slobodan|author-link15=Slobodan Sekulic|last16=Lacerda|first16=Eliana|author-link16=Eliana Lacerda|last17=Murovska|first17=Modra|author-link17=Modra Murovska|date=2018-09-01|title=Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe—the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review|url=https://bmjopen.bmj.com/content/8/9/e020817|journal=BMJ Open|language=en|volume=8|issue=9|pages=e020817|doi=10.1136/bmjopen-2017-020817|issn=2044-6055|pmc=|pmid=30181183|via=}}</ref> - [https://bmjopen.bmj.com/content/8/9/e020817 (Full text)]
* 2020, Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology <ref>{{Cite journal|last=Estévez-López|first=Fernando|author-link=Fernando Estévez-López|last2=Mudie|first2=Kathleen|author-link2=|last3=Wang-Steverding|first3=Xia|author-link3=Xia Wang-Steverding|last4=Bakken|first4=Inger Johanne|author-link4=Inger Johanne Bakken|last5=Ivanovs|first5=Andrejs|author-link5=|last6=Castro-Marrero|first6=Jesús|author-link6=Jesús Castro-Marrero|last7=Nacul|first7=Luis|author-link7=Luis Nacul|last8=Alegre|first8=Jose|author-link8=José Alegre|last9=Zalewski|first9=Paweł|last10=Słomko|first10=Joanna|author-link10=|last11=Bolle Strand|first11=Elin|author-link11=Elin Bolle Strand|last12=Pheby|first12=Derek|author-link12=Derek Pheby|last13=Shikova|first13=Evelina|author-link13=Evelina Shikova|last14=Lorusso|first14=Lorenzo|author-link14=Lorenzo Lorusso|last15=Capelli|first15=Enrica|author-link15=Enrica Capelli|last16=Sekulic|first16=Slobodan|author-link16=Slobodan Sekulic|last17=Scheibenbogen|first17=Carmen|author-link17=Carmen Scheibenbogen|last18=Sepúlveda|first18=Nuno|author-link18=Nuno Sepúlveda|last19=Murovska|first19=Modra|author-link19=Modra Murovska|last20=Lacerda|first20=Eliana|author-link20=Eliana Lacerda|date=May 2020|title=Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology|url=https://www.mdpi.com/2077-0383/9/5/1557|journal=Journal of Clinical Medicine|language=en|volume=9|issue=5|pages=1557|doi=10.3390/jcm9051557|pmc=|pmid=|quote=|access-date=|via=}}</ref> - [https://www.mdpi.com/2077-0383/9/5/1557/htm (Full text)]
* 2021, Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)<ref>{{Cite journal|last=Lupo|first=Giuseppe Francesco Damiano|author-link=|last2=Rocchetti|first2=Gabriele|author-link2=|last3=Lucini|first3=Luigi|author-link3=|last4=Lorusso|first4=Lorenzo|author-link4=|last5=Manara|first5=Elena|author-link5=|last6=Bertelli|first6=Matteo|author-link6=|last7=Puglisi|first7=Edoardo|last8=Capelli|first8=Enrica|date=March 2021|title=Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)|url=http://www.nature.com/articles/s41598-021-86425-6|journal=Scientific Reports|language=en|volume=11|issue=1|pages=7043|doi=10.1038/s41598-021-86425-6|issn=2045-2322|pmc=|pmid=33782445|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-021-86425-6 (Full text)]

==Talks and interviews==

==Online presence==
*PubMed
*[https://www.researchgate.net/profile/Enrica_Capelli ResearchGate]
*[http://www.euromene.eu/workinggroups/Enrica%20Capelli%20CV.pdf Curriculum Vitae for EUROMENE]

==Learn more==

==See also==
*[[EUROMENE]]

==References==
<references>
<ref name="Bozzini, 2018">{{Citation
| last1 = Bozzini | first1 = S | authorlink1 =
| last2 = Albergati | first2 = A | authorlink2 =
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso
| last5 = Gazzaruso | first5 = C | authorlink5 =
| last6 = Pelissero | first6 = G | authorlink6 =
| last7 = Falcone | first7 = C | authorlink7 =
| title = Cardiovascular characteristics of chronic fatigue syndrome.
| journal = Biomedical Reports | volume = 8 | issue = 1 | page = 26–30
| date = 2018
| pmid = 29399336
| doi = 10.3892/br.2017.1024
}}
</ref>
<ref name="Capelli, 2010">{{Citation
| last1 = Capelli | first1 = Enrica | authorlink1 = Enrica Capelli
| last2 = Zola | first2 = R | authorlink2 =
| last3 = Lorusso | first3 = Lorenzo | authorlink3 = Lorenzo Lorusso
| last4 = Venturini | first4 = Luigi | authorlink4 =
| last5 = Sardi | first5 = F | authorlink5 =
| last6 = Ricevuti | first6 = Giovanni | authorlink6 =
| title = <nowiki>Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]: An Update</nowiki>
| journal = International Journal of Immunopathology and Pharmacology | volume = 23 | issue = 4 | page = 981-989
| date = 2010
| pmid = 21244747
| doi = 10.1177/039463201002300402
}}
</ref>
<ref name="Capelli, 2015">{{Citation
| last1 = Capelli | first1 = Enrica | authorlink1 = Enrica Capelli
| last2 = Lorusso | first2 = Lorenzo | authorlink2 = Lorenzo Lorusso
| last3 = Ghitti | first3 = M | authorlink3 =
| last4 = Venturini | first4 = Luigi | authorlink4 =
| last5 = Cusa | first5 = C | authorlink5 =
| last6 = Ricevuti | first6 = Giovanni | authorlink6 =
| title = Chronic fatigue syndrome: Features of a population of patients from northern Italy
| journal = International Journal of Immunopathology and Pharmacology
| date = 2015
| pmid =
| doi = 10.1177/0394632015572074
}}
</ref>
<ref name="Maltese, 2016">{{citation
| last1 = Maltese | first1 = PE | authorlink1 =
| last2 = Venturini | first2 = L | authorlink2 =
| last3 = Poplavskaya | first3 = E | authorlink3 =
| last4 = Bertelli | first4 = M | authorlink4 =
| last5 = Cecchin | first5 = S | authorlink5 =
| last6 = Granato | first6 = M | authorlink6 =
| last7 = Nikulina | first7 = SY | authorlink7 =
| last8 = Salmina | first8 = A | authorlink8 =
| last9 = Aksyutina | first9 = N | authorlink9 =
| last10 = Capelli | first10 = Enrica | authorlink10 = Enrica Capelli
| last11 = Ricevuti | first11 = Giovanni | authorlink11 =
| last12 = Lorusso | first12 = Lorenzo | authorlink12 = Lorenzo Lorusso
| title = Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with chronic fatigue syndrome
| journal = Genet Mol Res | volume = 15 | issue = 3
| date = 2016
| doi = 10.4238/gmr.15038717
}} </ref>
<ref name="Panelli, 2017">{{Citation
| last1 = Panelli | first1 = Simona | authorlink1 =
| last2 = Lorusso | first2 = Lorenzo | authorlink2 = Lorenzo Lorusso
| last3 = Balestrieri | first3 = Alessandro | authorlink3 =
| last4 = Lupo | first4 = Giuseppe | authorlink4 =
| last5 = Capelli | first5 = Enrica | authorlink5 = Enrica Capelli
| title = XMRV and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Appears Unreliable
| journal = Frontiers in Public Health | volume = 5 | issue = 108 | page =
| date = 2017
| pmid =
| doi = 10.3389/fpubh.2017.00108
}}
</ref>
<ref name="Sotzny, 2018">{{Citation
| last1 = Sotzny | first1 = Franziska | authorlink1 = Franziska Sotzny
| last2 = Blanco | first2 = Julià | authorlink2 = Julià Blanco
| last3 = Capelli | first3 = Enrica | authorlink3 = Enrica Capelli
| last4 = Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero
| last5 = Steiner | first5 = Sophie | authorlink5 =
| last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska
| last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
| journal = Autoimmunity Reviews | volume = | issue = | page =
| date = 2018
| pmid =
| doi = 10.1016/j.autrev.2018.01.009
}}
</ref>
</references>

[[Category:Researchers]]
[[Category:Italy researchers]]

Talk:Bikram malati

2021-05-14T19:06:36Z

Kmdenmark:Kmdenmark moved page Talk:Bikram malati to Talk:Bikram Malati:capitalization

#REDIRECT [[Talk:Bikram Malati]]

Talk:Bikram Malati

2021-05-14T19:06:36Z

Kmdenmark:Kmdenmark moved page Talk:Bikram malati to Talk:Bikram Malati:capitalization

== Does Bikram Malati have ME/CFS? -- [[User:Kmdenmark|Kmdenmark]] ([[User talk:Kmdenmark|talk]]) 19:04, May 14, 2021 (UTC) ==

Is there documentation of his illness? [[User:Kmdenmark|Kmdenmark]] ([[User talk:Kmdenmark|talk]]) 19:04, May 14, 2021 (UTC)

Talk:Bikram Malati

2021-05-14T19:04:27Z

Kmdenmark:/* Does Bikram Malati have ME/CFS? -- ~~~~ */ new section

ME activists and advocates

2021-05-14T18:54:50Z

Kmdenmark:added names

[[File:ME activists or advocates protesting in 2018.png|alt=Photo of two women wearing Missing Millions T-shirts at a protest. One is a young woman sat on the concrete. The other woman is smiling and holding a sign saying "There's around 50,000 people housebound in the UK with ME and missing from the outside world."|thumb|Photo by Richard Lewis.]]
Activists and advocates for patients with [[Myalgic encephalomyelitis|Myalgic Encephalomyelitis]] (ME) or [[Chronic fatigue syndrome|Chronic Fatigue Syndrome]] include patients, their friends and family, researchers and health professionals, politicans, and members of the general public.

A number of activists are [[:Category:Citizen scientists|citizen scientists]] who reviewed or re-analysed existing research, and in some cases have conducted their own research.

==Patient activists==
{{See also|List of open letters from patient advocates and advocacy organizations|Open letters from patient advocates and organizations}}
Notable patient activists with ME or CFS.
*[[Jennifer Brea|Jen Brea]], director of [[Unrest]], co-founder of the [[The MEAction Network|#MEAction Network]]
*[[Robin Brown]], NHS doctor, author, and creator of a major UK treatment petition, also involved in training doctors
*[[Robert Courtney]] (deceased), citizen scientist and who proved that the [[Cochrane]] review of exercise for CFS failed to meet Cochrane's own standards
*[[Keith Geraghty]], researcher and activist who has investigated if ME charities are militant
*[[Ellen Goudsmit]], psychologist and former patron of several ME charities
*[[Tanya Harrison]], [[BRAME]] charity founder, resigned from the 2007 [[NICE guidelines]] group because she could not support the controversial guidelines they developed
*[[Cort Johnson]], founder of both [[Phoenix Rising]] and [[Health Rising]], has won several awards for advocacy, blogs about science and research
*[[Tom Kindlon]], citizen scientist and extremely well known ME advocate
*[[Alem Matthees]], citizen scientist who fought and won a tribunal for the release of the PACE trial data despite being too ill to attend. He is now very severely ill.
*[[Courtney Miller]], member of the Board of Directors and an online writer at [[Simmaron Research]]
*[[Nina Muirhead]], NHS surgeon who has done a number of media interviews and is involved in training doctors
*[[John Peters]], [[PACE trial]] critic and originator of a number of [[Freedom of Information Act]] requests, friend of [[Ben Lake]] MP
*[[Julie Rehmeyer]], math/science journalist, [[:Category:PACE trial critics|PACE trial critic]] and author of memoir about living with ME/CFS
*[[Rivka Solomon]], writer and Million Missing organizer
*[[Frank Twisk|Frank N. M. Twisk]], [[Stichting ME-de-patiënten|ME-de-patiënten Foundation]], an outspoken Dutch activist with over a dozen letters or citizen science articles published, Twisk advocates for ME but not [[chronic fatigue syndrome]]
*[[Mark Vink]], doctor (general practice), patient researcher, former marathon runner and Dutch national hockey captain
*[[Naomi Whittingham]], severely ill since childhood, Naomi featured in [[Voices from the Shadows]] and has a number of media interviews

==Psychologists and psychiatrists ==
*[[Brian Hughes]], psychologist
*[[Ellen Goudsmit]], psychologist and author of the [[London criteria]] for ME, who also has [[Myalgic encephalomyelitis|ME]]
*[[Janet Dafoe]], child psychologist, Vice President of [[Phoenix Rising]], protests at [[Millions Missing protests|Millions Missing]] everyday and full time carer for her very severely ill son [[Whitney Dafoe]]

==ME/CFS researchers ==
{{See also|List of open letters from researchers|Open letters from researchers||||}}
*[[Jonathan Edwards]], well known advocate and infectious diseases specialist, applied to join the UK's NICE guideline development group for [[ME/CFS]]
*[[Ronald Davis|Ron Davis]], whose son Whitney Dafoe has very severe ME
*[[Keith Geraghty]], who has [[Myalgic encephalomyelitis|ME]], and has investigated if patient groups are militant
*[[Ellen Goudsmit]], who has [[ME]], and co-authored the [[London criteria]]
*[[Leonard Jason]], who has also recovered from ME/CFS
*[[Sarah Myhill]], GP, author and researcher, now in private practice treating ME/CFS in Wales, UK

==Journalists ==
*[[David Tuller]], the "PACE man", senior fellow in Public Health in Journalism and contributor to the [[Virology blog]]
==Politicians ==
*[[Countess of Mar]], member of the UK House of Lords, who has recovered from [[ME/CFS]]
*[[Carol Monaghan]], [[:Category:United Kingdom politicians|British MP]] who has arranged several ME debates in UK parliament
*[[Ben Lake]], [[:Category:United Kingdom politicians|British MP]]
*Jamie Raskin, US Congressman from Maryland, introduced legislation to expand NIH budget for post-viral chronic neuroimmune diseases such as ME

==Charity and patient group representatives==
{{See also|List of open letters from patient advocates and advocacy organizations|Open letters from patient groups and patient advocates||||}}
*[[Jane Colby]] of [[Tymes Trust |The Young ME Sufferers Trust]] (Tymes Trust)
*[[Frank Twisk]]
*[[Charles Shepherd]], Medical Advisor at [[The ME Association]]
*[[Nigel Speight]], doctor and charity Medical Advisor
*[[Greg Crowhurst]] of [[Stonebird]], author, carer for his very severely ill wife Linda, and secretary of the [[25 Percent ME Group|25% ME Group]] for the most severely ill

== Friends and family of patients ==
* [[Ronald Davis|Ron Davis]], researcher, father of [[Whitney Dafoe]], who has [[very severe ME]]
* [[Janet Dafoe]], psychiatrist, Vice President of [[Phoenix Rising]], protests at [[Millions Missing protests|Millions Missing]] everyday and full time carer for her very severely ill son [[Whitney Dafoe]]
* [[Greg Crowhurst]], nurse, outspoken activist and full-time carer for his very severely ill wife, some of Greg's views and criticism of [[NICE guidelines|NHS guidelines]] can be found on his [http://www.Stonebird.co.uk Stonebird] blog
* [[Steve Topple]], journalist and carer for his girlfriend

== Notable activist campaigns ==
[[File:ME-activists-advocates-protest.jpg|alt=Too ill to be here banner with footprint sized pieces of paper with handwritten messages from those too ill to go.|thumb|Too ill to be here: Missing Millions activists too ill to attend send in footprint-shaped messages. Photo: Richard Lewis]]
* [[Millions Missing protests|#millionsmissing]] protests - international events run by [[The MEAction Network|The #MEAction Network]]
* [[BedFest|#Bedfest]] - ME awareness for [[Severe and very severe ME|bedbound and housebound]] patients
* [[NICE guidelines review]] - a successful UK petition by the ME Association calling for the CFS/ME guidelines to be reviewed, in protest at the announcement that the guidelines would be moved to the "static" list and not reviewed for another 10 years
* [[Let's Do It for ME]] - Ongoing patient-run campaign to fund a biomedical research center in Norwich, UK, in support of the [[Invest in ME Research]] charity

==Notable studies==

*2008, [https://linkinghub.elsevier.com/retrieve/pii/S0738399108001936 Obstructions for quality care experienced by patients with chronic fatigue syndrome (CFS)—A case study]<ref>{{Cite journal|last=Gilje|first=Ann Marit|author-link=Ann Marit Gilje|last2=Söderlund|first2=Atle|author-link2=Atle Söderlund|last3=Malterud|first3=Kirsti|author-link3=Kirsti Malterud|author-link4=|author-link5=|date=Oct 2008|title=Obstructions for quality care experienced by patients with chronic fatigue syndrome (CFS)—A case study|url=https://linkinghub.elsevier.com/retrieve/pii/S0738399108001936|journal=[[Patient Education and Counseling]]|language=en|volume=73|issue=1|pages=36–41|doi=10.1016/j.pec.2008.04.001|quote=|via=}}</ref>

*2015, [http://www.wakeupcallbeweging.be/pdf/30yearsdisdainsummary.pdf THIRTY YEARS OF DISDAIN: How HHS and A Group of Psychiatrists Buried Myalgic Encephalomyelitis]<ref name="Disdain">{{Cite web|url=http://www.wakeupcallbeweging.be/pdf/30yearsdisdainsummary.pdf|title=THIRTY YEARS OF DISDAIN: How HHS and a group of psychiatrists Buried Myalgic Encephalomyelitis|last=Dimmock|first=Mary|authorlink=Mary Dimmock|last2=Lazell-Fairman|first2=Matthew|authorlink2=Matthew Lazell-Fairman|date=Dec 2015|website=|archive-url=|archive-date=|url-status=|access-date=Nov 5, 2018}}</ref> - Professor Malcolm Hooper

*2016, [http://www.meassociation.org.uk/wp-content/uploads/2015-ME-Association-Illness-Management-Report-No-decisions-about-me-without-me-30.05.15.pdf Illness Management Report: No decisions about ME without me] - results from the ME Association survey on treatment effectiveness, harms and difficulties experienced by patients

*2016, [https://www.research.manchester.ac.uk/portal/en/publications/cognitive-behavioural-therapy-in-the-treatment-of-chronic-fatigue-syndrome-a-narrative-review-on-efficacy-and-informed-consent(987590d0-a62d-473e-8d46-b74b9247e81c).html "Cognitive behavioural therapy in the treatment of chronic fatigue syndrome: A narrative review on efficacy and informed consent"]<ref name="BleaseGeraghty2016a">{{Cite journal
| last1 = Blease | first1 = Charlotte | authorlink1 = Charlotte Blease
| last2 = Geraghty | first2 = Keith | authorlink2 = Keith Geraghty
| title = Cognitive behavioural therapy in the treatment of chronic fatigue syndrome: A narrative review on efficacy and informed consent
| journal = Journal of Health Psychology
| date = Sep 15, 2016
| doi = 10.1177/1359105316667798
|url = https://doi.org/10.1177/1359105316667798
}}</ref>

*2016, [http://bjgp.org/content/66/649/437 "Chronic fatigue syndrome: is the biopsychosocial model responsible for patient dissatisfaction and harm?"]<ref name="Geraghty,Esmail, 2016">{{Cite journal
| last1 = Geraghty | first1 = Keith | authorlink1 = Keith Geraghty
| last2 = Esmail | first2 = Aneez | authorlink2 = Aneez Esmail
| title = Chronic fatigue syndrome: is the biopsychosocial model responsible for patient dissatisfaction and harm?
| journal = British Journal of General Practice | volume = 66 | issue =649 | page = 437-438
| date = 1 Aug 2016
| doi = 10.3399/bjgp16X686473
|url = https://doi.org/10.3399/bjgp16X686473
}}
</ref>

*2016, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675701/ Caring for People with Severe Myalgic Encephalomyelitis: An Interpretative Phenomenological Analysis of Parents’ Experiences]<ref name="Mihelicova">{{Cite journal|last=Mihelicova|first=Martina|author-link=Martina Mihelicova|last2=Siegel|first2=Zachary|author-link2=Zachary Siegel|last3=Evans|first3=Meredyth|author-link3=Meredyth Evans|last4=Brown|first4=Abigail|author-link4=Abigail Brown|last5=Jason|first5=Leonard|author-link5=Leonard Jason|date=Dec 2016|title=Caring for People with Severe Myalgic Encephalomyelitis: An Interpretative Phenomenological Analysis of Parents’ Experiences|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675701/|journal=Journal of health psychology|volume=21|issue=12|pages=2824–2837|doi=10.1177/1359105315587137|issn=1359-1053|pmc=4675701|pmid=26063209|quote=|via=}}</ref>

* 2017, [https://jme.bmj.com/content/43/8/549 Epistemic injustice in healthcare encounters: evidence from chronic fatigue syndrome]<ref name="Blease2017">{{Cite journal|last=Blease|first=Charlotte|author-link=Charlotte Blease|last2=Carel|first2=Havi|author-link2=Havi Carel|last3=Geraghty|first3=Keith|author-link3=Keith Geraghty|author-link4=|author-link5=|date=2017-08-01|title=Epistemic injustice in healthcare encounters: evidence from chronic fatigue syndrome|url=https://jme.bmj.com/content/43/8/549|journal=Journal of Medical Ethics|language=en|volume=43|issue=8|pages=549–557|doi=10.1136/medethics-2016-103691|issn=0306-6800|pmid=27920164|quote=|via=}}</ref>

*2018, [https://www.tandfonline.com/doi/full/10.1080/09638288.2018.1481149 Myalgic encephalomyelitis/chronic fatigue syndrome and the biopsychosocial model: a review of patient harm and distress in the medical encounter]<ref name="Geraghtyharm">{{Cite journal|last=Geraghty|first=Keith J.|author-link=Keith Geraghty|last2=Blease|first2=Charlotte|author-link2=Charlotte Blease|author-link3=|author-link4=|author-link5=|date=2018-06-21|title=Myalgic encephalomyelitis/chronic fatigue syndrome and the biopsychosocial model: a review of patient harm and distress in the medical encounter|url=https://www.tandfonline.com/doi/full/10.1080/09638288.2018.1481149|journal=Disability and Rehabilitation|language=en|volume=|issue=|pages=1–10|doi=10.1080/09638288.2018.1481149|issn=0963-8288|quote=|via=}}</ref>

*2019, [https://onlinelibrary.wiley.com/doi/abs/10.1111/bioe.12559 Ethical classification of ME/CFS in the United Kingdom]<ref>{{Cite journal|last=O'Leary|first=Diane|author-link=Diane O'Leary|author-link2=|author-link3=|author-link4=|author-link5=|date=Feb 2019|title=Ethical classification of ME/CFS in the United Kingdom|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/bioe.12559|journal=Bioethics|language=en|volume=|issue=|pages=|doi=10.1111/bioe.12559|issn=1467-8519|quote=|via=}}</ref>

*2019, [https://www.meassociation.org.uk/wp-content/uploads/NICE-Patient-Survey-Outcomes-CBT-and-GET-Final-Consolidated-Report-03.04.19.pdf Evaluation of a survey exploring the experiences of adults and children with ME/CFS who have participated in CBT and GET interventional programme]<ref name="OxfordBrookesSurvey">{{Cite web|url =https://www.meassociation.org.uk/wp-content/uploads/NICE-Patient-Survey-Outcomes-CBT-and-GET-Final-Consolidated-Report-03.04.19.pdf|title =Evaluation of a survey exploring the experiences of adults and children with ME/CFS who have participated in CBT and GET interventional programmes. FINAL REPORT |last=Oxford Clinical Allied Technology and Trials Services Unit (OxCATTS)|location=Oxford Brookes University|date=Feb 27, 2019}}</ref> - survey commissioned by NICE in the UK for the clinical guidelines review

*2019, [http://www.bioethics.net/articles/faces-of-fatigue-ethical-considerations-on-the-treatment-of-chronic-fatigue-syndrome/ Faces of fatigue: Ethical considerations]<ref>{{Cite web|url=http://www.bioethics.net/articles/faces-of-fatigue-ethical-considerations-on-the-treatment-of-chronic-fatigue-syndrome/|title=Faces of Fatigue: Ethical Considerations on the Treatment of Chronic Fatigue Syndrome {{!}} Bioethics.net|website=www.bioethics.net|access-date=2019-02-10}}</ref>

*2019, [https://25megroup.org/download/2527/ KNOWLEDGE IN THE HOPE OF PROTECTING M.E. SUFFERERS FROM UNNECESSARY SECTIONING] by the Grace Charity for M.E., with the 25% ME Group

*2019, [https://www.tandfonline.com/doi/abs/10.1080/21641846.2020.1718292 Legitimizing myalgic encephalomyelitis/chronic fatigue syndrome: indications of change over a decade]<ref name="Friedberg2019">{{Cite journal|title=Legitimizing myalgic encephalomyelitis/chronic fatigue syndrome: indications of change over a decade|url=https://doi.org/10.1080/21641846.2020.1718292|journal=Fatigue: Biomedicine, Health & Behavior|date=2020-01-02|issn=2164-1846|pages=24–31|volume=8|issue=1|doi=10.1080/21641846.2020.1718292|first=Fred|last=Friedberg|last2=|first2=|pmc=|pmid=|quote=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|author-link=Fred Friedberg|author-link2=|access-date=|author-link3=|author-link4=|author-link5=|author-link6=|via=}}</ref>

==See also==
*[[Intimidation and bullying of PACE trial critics]]
*[[:Category:Advocates or allies |Advocates or allies]] (category)
*[[Ethical issues]]
*[[:Category:PACE trial critics |PACE Trial critics]]
*[[:Category:Psychological paradigm critics |Psychological paradigm critics]]
*[[Primer for journalists]]
*[[:Category:People with ME, CFS, and/or FMS|People with ME, CFS, and/or FMS]]
*[[Biopsychosocial model]]
*[[Wessely school]]

==References==
{{reflist}}
[[Category:Advocates or allies]]
[[Category:People]]