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Buspirone

2026-09-03T01:37:56Z

Tuxedocaspy:Expanded activity of buspirone, with further citations and limited information on mechanism

'''Buspirone''' is an oral [[anxiolytic]] ([[anxiety]]-reducing) drug.<ref name=":0">{{Cite web | url = https://medlineplus.gov/druginfo/meds/a688005.html | title = Buspirone: MedlinePlus Drug Information | website = medlineplus.gov|language=en | access-date = 2019-01-08}}</ref> It has been marketed under the brand name Buspar.<ref name=":0" /> Originally developed as an antipsychotic medication, buspirone's anxiolytic activity and "decreased side-effect profile" have made improved it a favorable choice for treating anxiety as a second-line medication after [[Selective serotonin reuptake inhibitor|selective serotonin reuptake inhibitors]] (SSRIs).<ref name=":1">Wilson TK, Tripp J. Buspirone. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK531477/</nowiki></ref> The [[U.S. Food and Drug Administration]] has approved buspirone for managing anxiety disorders and short-term relief of anxiety symptoms.<ref name=":2">https://www.accessdata.fda.gov/drugsatfda_docs/anda/2001/75-467_Buspirone.pdf</ref> A lack of interaction with [[GABA|gamma-aminobutyric acid]] (GABA) receptors underlies the apparently non-existent risk of physical dependency on buspirone.

Buspirone in the brain acts as a partial agonist for [[serotonin]] 5HT1a receptors, weaker activity at serotonin 5HT2 receptors, but antagonist behavior at [[dopamine]] D2 receptors.<ref name=":1" /> While the mechanism driving clinical effects from this interaction is unknown, 5HT1a activity is thought to be central in providing relief.<ref name=":2" />

==References==
{{reflist}}

{{stub}}

Aspirin

2026-08-31T21:03:57Z

Tuxedocaspy:/* Side Effects */ Expanded the overview of aspirin, and several side effects and adverse effects

{{Stub}}
[[File:Aspirin.jpg|thumb|right|Aspirin tablets with a glass of water]]
[[Aspirin]], also known as acetylsalicylic acid, is a medication used to treat [[pain]], [[fever]], and [[inflammation]].<ref name=drugscom>{{Cite web | url = https://drugs.com/aspirin.html | title = Aspirin | last = | first = | author-link = | date = | website = drugs.com|language=en-US| archive-url = | archive-date = |url-status = | access-date=2021-02-17}}</ref> For pain or fever, effects typically begin within 30 minutes. Aspirin is a nonsteroidal anti-inflammatory drug ([[nonsteroidal anti-inflammatory drug|NSAID]]) and works similar to other NSAIDs but also suppresses the normal functioning of platelets. Unlike other NSAIDs, aspirin irreversibly inhibits cyclooxygenase-1 (COX-1) and alters cyclooxygenase-2 (COX-2) in platelets, which leads to inhibition of clotting.<ref>Arif H, Patel P. Salicylic Acid (Aspirin) [Updated 2026 Jun 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK519032/</nowiki></ref>

==Mast cell diseases ==
Aspirin may also be used as a mast cell stabilizer for people with MCAD or MCAS, but people with high prostaglandin levels must have this supervised by a physician.<ref name="TMS-meds">{{Cite web | url = https://tmsforacure.org/treatments-2/medications-treat-mast-cell-diseases/ | title = Medications to Treat Mast Cell Diseases | last = | first = | author-link = | date = | website = The Mast Cell Disease Society|language=en-US| archive-url = | archive-date = |url-status = | access-date=2021-02-16}}</ref>

==Side Effects==

Commonly reported sides effects include<ref>https://www.nhsinform.scot/tests-and-treatments/medicines-and-medical-aids/types-of-medicine/aspirin/</ref><ref>https://www.nationwidechildrens.org/family-resources-education/health-wellness-and-safety-resources/helping-hands/aspirin</ref><ref>https://www.drugs.com/aspirin.html</ref>:

* Indigestion and stomach aches

* Bleeding and bruising more easily
* Nausea and vomiting
* Drowsiness and mild headache

Adverse effects include:

* Long-lasting pain and swelling
* Ringing in ears or problems hearing
* Bloody, tarry stool (melena) or vomiting blood or dark material that looks like coffe grounds (hematemesis)
* Itchy rashes

== See also ==
*[[Nonsteroidal anti-inflammatory drug|NSAIDs]]
*[[Chronic pain]]
*[[Mast cell activation syndrome]]
*[[Mast cell activation disorder]]

==Learn more==
*[https://drugs.com/aspirin.html Aspirin] - drugs.com
*[https://tmsforacure.org/treatments-2/medications-treat-mast-cell-diseases Medications to Treat Mast Cell Diseases - The Mast Cell Disease Society]

== References ==
{{Reflist}}

[[Category:Potential treatments]]
[[Category:Analgesics]]
[[Category:Anti-inflammatories]]
[[Category:Mast cell stabilizers]]
[[Category:Antipyretics]]
[[Category:Nonsteroidal anti-inflammatory drugs]]

Lyme disease

2026-08-23T23:35:15Z

Tuxedocaspy:/* Later signs and symptoms */ Citation added, increased symptoms section with further details backed by reputable source

'''Lyme Disease''' is caused by members of the spirochete bacteria ''[[Borrelia burgdorferi]]'' in the United States and other members of ''Borrelia'' in Europe and Asia.<ref name=":2">Skar GL, Blum MA, Simonsen KA. Lyme Disease. [Updated 2024 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK431066/</nowiki></ref> The bacterial pathogen is transmitted by infected black legged ticks.<ref name="WebMD">{{Cite news | url=http://www.webmd.com/rheumatoid-arthritis/arthritis-lyme-disease | title = Lyme Disease: Symptoms, Causes, Diagnosis, Treatment, Prevention|work=WebMD|access-date=2018-08-13|language=en-US}}</ref> The bacteria are transferred into tissue following a bite, after which they may disseminate and drive later stages of Lyme Disease. It is treatable but can become [[Chronic Lyme disease|chronic lyme disease]]. A bulls-eye rash can appear at the site of a deer tick bite but can be in different forms<ref>{{Cite news | url=http://www.bayarealyme.org/blog/lyme-disease-bullseye-rash/ | title = Does Everyone Get the Telltale Bullseye Rash? {{!}} Bay Area Lyme Foundation | date = 2014-09-12|work=Bay Area Lyme Foundation|access-date=2018-08-13|language=en-US}}</ref> while some people never recall having a rash; 30% of lyme patients never get a rash.<ref name="WebMD" />

==Symptoms ==
The signs and symptoms of lyme disease vary and usually appear in stages.<ref name="mayo" /> Medical references divide disease progression into Early Localized Disease, Early Disseminated Disease, and Late Disease.<ref name=":2" /> Early Localized Disease, which occurs between 1-28 days following a bite, is notable for the presence of a bulls-eye rash in 70% of patients. The rash may itch or burn, or be asymptomatic. Flu-like symptoms may be concurrent, such as headache and [[myalgia]]. Early Disseminated Disease develops after 3-12 weeks and present with further symptoms. Muscle pain, malaise, fever, neurological symptoms, and 20% of patients present [[central nervous system]] involvement.<ref name=":2" /> Meningitis, peripheral and cranial neuropathies, and rare encephalomyelitis are symptoms. Cardiac and ocular manifestations have also been reported. Late Lyme Disease occurs months after infection, and present with neurological and musculoskeletal issues. Cognitive deficits, personality changes, memory loss, irritability, and depression are common. A population of patients may develop Lyme arthritis, which targets large joints with swelling and stiffness. Another manifestation of the later stages is an atrophic rash on hands and feet known as acrodermatitis chronica atrophicans.
[[File:Lyme Rash.jpg|300px|thumb|right|Classic bulls-eye rash from the bite of a deer tick]]

===Early signs and symptoms===
* Erythema migrans (Bulls-eye rash) (Rash can be in other forms and 30% of the time no rash is present.)<ref name="bayarea">{{Cite news | url=http://www.bayarealyme.org/blog/lyme-disease-bullseye-rash/ | title = Does Everyone Get the Telltale Bullseye Rash? {{!}} Bay Area Lyme Foundation | date = 2014-09-12|work=Bay Area Lyme Foundation|access-date=2018-09-03|language=en-US}}</ref><ref>{{Cite news | url=https://www.webmd.com/rheumatoid-arthritis/arthritis-lyme-disease | title = Lyme Disease: Symptoms, Causes, Diagnosis, Treatment, Prevention|work=WebMD|access-date=2018-09-06|language=en-US}}</ref>
* [[Flu-like symptoms]]
===Later signs and symptoms===
* Erythema migrans
* [[Joint pain]]
* [[Neurological]] problems<ref>Mahajan VK. Lyme Disease: An Overview. Indian Dermatol Online J. 2023 Feb 23;14(5):594-604. doi: 10.4103/idoj.idoj_418_22. PMID: 37727539; PMCID: PMC10506804.</ref>
===Other signs and symptoms===
* [[Nausea]] and [[vomiting]]
* Diffuse [[skin rash|rashes]] (rather than a single bull's-eye rash commonly associated with Lyme disease)<ref name="bayarea" />
===Less common signs and symptoms===
* Heart problems, such as [[arrhythmia|irregular heartbeat]].
* Eye inflammation
* Liver inflammation (hepatitis).
* Severe [[fatigue]]<ref name="mayo">{{Cite news | url=http://www.mayoclinic.org/diseases-conditions/lyme-disease/basics/symptoms/CON-20019701 | title = Lyme disease - Symptoms and causes|work=Mayo Clinic|access-date=2018-09-03|language=en}}</ref>

== Blood and other laboratory tests ==

=== United States ===
* Two-step Laboratory Testing Process<ref>{{Cite web|url=http://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html | title = Two-step Laboratory Testing Process {{!}} Lyme Disease|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-09-03 | date = |last = | first = | authorlink = |archive-url=|archive-date=|url-status=}}</ref>
* Types of Lyme Disease Tests<ref>{{Cite web|url=http://lymediseaseguide.org/types-of-lyme-disease-tests | title = Types of Lyme Disease Tests|last = | first = | date = May 27, 2011 | website = lymediseaseguide.org|language=en-US|archive-url=|archive-date=|url-status=|access-date=2018-09-03}}</ref>
* Laboratory tests that are not recommended<ref>{{Cite web|url=http://www.cdc.gov/lyme/diagnosistesting/LabTest/OtherLab/index.html | title = Laboratory tests that are not recommended {{!}} Lyme Disease|website=[[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-09-03 | date = |last = | first = | authorlink = |archive-url=|archive-date=|url-status=}}</ref>
* [https://www.usatoday.com/story/news/nation/2018/11/16/lyme-disease-congress-report-better-testing/2031063002/ Tests for Lyme disease don't work well enough to diagnose illness early, federal panel says]<ref>{{Cite news | url=https://www.usatoday.com/story/news/nation/2018/11/16/lyme-disease-congress-report-better-testing/2031063002/ | title = Tests for Lyme disease don't work well enough to diagnose illness early, federal panel says|last = Carino|first = Jerry | date = Nov 16, 2018|work=USA TODAY|access-date=2018-11-26|archive-url=|archive-date=|url-status=|language=en}}</ref>

=== United Kingdom ===
* BBC1 Lyme Disease Discussion - Some patients have waited up to 30 years for a correct diagnosis. [[National Health Service]] (NHS) services have only correctly identified the disease in a quarter of the patients. The blood tests are unreliable and often come back negative. The development of an accurate blood test is in need of research funding.<ref>{{Cite web|url=https://www.youtube.com/watch?v=R1-a8kowVkE&app=desktop | title = BBC1 Lyme Disease 27.02.2016|last = Loukas | first = Demetrios | date = Feb 27, 2016 | website = YouTube|publisher=Katherine Allman|via=|archive-url=|archive-date=|url-status=|access-date=}}</ref>

* [[Department of Health and Social Care (UK)]] Testing for Lyme Disease<ref name=":0">{{Cite web|url=http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_106528.pdf | title=Testing for Lyme Disease|last = Donaldson | first = Liam | date = 2009 | website = webarchive.nationalarchives.gov.uk | page = 4|type=PDF|archive-url=|archive-date=|url-status=|access-date=}}</ref>

=== False positives ===
Several herpesviruses including [[varicella zoster virus]]<ref name="Feder1991">{{citation | last1 = Feder | first1 = HM Jr | authorlink = | last2 = Gerber | first2 = MA | authorlink2 = | last3 = Luger | first3 = SW | authorlink3 = | last4 = Ryan | first4 = RW | authorlink4 = | title = False-positive serologic tests for Lyme disease after varicella infection|journal=N Engl J Med|volume=325|issue=26 | page = 1886-7 | date = Dec 1991|pmid=1961232|url=http://www.ncbi.nlm.nih.gov/pubmed/1961232}}</ref><ref name="Woelfle1998">{{citation | last1 = Woelfle | first1 = J | authorlink = | last2 = Wilske | first2 = B | authorlink2 = | last3 = Haverkamp | first3 = F | authorlink3 = | last4 = Bialek | first4 = R | authorlink4 = | title = False-positive serological tests for Lyme disease in facial palsy and varicella zoster meningo-encephalitis|journal=Eur J Pediatr|volume=157|issue=1 | page = 953-4 | date = Nov 1998|pmid=9835449|url=http://www.ncbi.nlm.nih.gov/pubmed/9835449}}</ref>, [[cytomegalovirus]], [[Epstein-Barr virus]],<ref name="Goossens1999">{{citation | last1 = Goossens | first1 = HA | authorlink = | last2 = Nohlmans | first2 = MK | authorlink2 = | last3 = van den Bogaard | first3 = AE | authorlink3 = | title = Epstein-Barr virus and cytomegalovirus infections cause false-positive results in IgM two-test protocol for early Lyme borreliosis|journal=Infection|volume=27|issue=3 | page = 231 | date =May 1999|pmid=10378140|url=http://link.springer.com/article/10.1007%2FBF02561539}}</ref> and [[Herpes simplex virus#HSV-2|HSV-2]]<ref name="Strasfeld2005">{{citation | last1 = Strasfeld | first1 = L | authorlink = | last2 = Romanzi | first2 = L | authorlink2 = | last3 = Seder | first3 = RH | authorlink3 = | last4 = Berardi | first4 = VP | authorlink4 = | title = False-Positive Serological Test Results for Lyme Disease in a Patient with Acute Herpes Simplex Virus Type 2|journal=Clin Infect Dis|volume=41|issue=12 | page = 1826-1827 | date = 2005|pmid=16288417|doi=10.1086/498319|url=http://cid.oxfordjournals.org/content/41/12/1826.full}}</ref> may cause false positives on Lyme Disease tests.

=== News media on unapproved tests ===
* 2005, Unproved Lyme Disease Tests Prompt Warnings<ref>{{Cite news | url=http://www.nytimes.com/2005/08/23/health/policy/unproved-lyme-disease-tests-prompt-warnings.html?_r=0 | title = Unproved Lyme Disease Tests Prompt Warnings|last = Santora | first = Marc | first2 =Dan | last2 =Hurley|publisher =New York Times |access-date=2018-09-03|language=en}}</ref> - New York Times

* 2013, Many tests to diagnose Lyme, but no proof they work<ref>{{Cite news | url=https://www.bostonglobe.com/lifestyle/health-wellness/2013/10/20/many-tests-diagnose-lyme-but-proof-they/ISjAcxmZxkk2disi94ENfI/story.html | title = Many tests to diagnose Lyme, but no proof they do|last = Daley|first = Beth | date = Oct 21, 2013|work=The Boston Globe|access-date=2018-09-03|archive-url=|archive-date=|url-status=|quote=}}</ref> - The Boston Globe

* 2013, Lyme Culture Test Causes Uproar<ref>{{Cite web|url=http://www.medscape.com/viewarticle/778482 | title = Lyme Culture Test Causes Uproar | last = | first = | date = | website = Medscape |url-access=registration|archive-url=|archive-date=|url-status=|access-date=2018-09-03}}</ref> - Medscape

* 2014, Federal Loopholes Compromise Lyme Disease Testing<ref>{{Cite news | url=http://news.wgbh.org/post/federal-loopholes-compromise-lyme-disease-testing | title = Federal Loopholes Compromise Lyme Disease Testing|last = Daley|first = Beth | date = 2014-06-17|work=WGBH 89.7|access-date=2018-09-03|archive-url=|archive-date=|url-status=|language=en}}</ref>

== Treatment ==
[[File:Borrelia burgdorferi-cropped.jpg|225px|thumb|right|Spirochete, or “corkscrew-shaped” bacteria known as Borrelia burgdorferi]]
*[[Centers for Disease Control & Prevention]] (CDC) on Treatment

::Patients treated with appropriate antibiotics in the early stages of Lyme disease usually recover rapidly and completely. Antibiotics commonly used for oral treatment include [[doxycycline]], [[amoxicillin]], or [[cefuroxime axetil]]. Patients with certain neurological or cardiac forms of illness may require intravenous treatment with drugs such as [[ceftriaxone]] or [[penicillin]].<ref name="CDC-treatment">{{Cite web|url=http://www.cdc.gov/lyme/treatment/index.html | title = Treatment {{!}} Lyme Disease {{!}} CDC | date = 2017-12-13 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-08-13}}</ref>

* 2006, [http://cid.oxfordjournals.org/content/43/9/1089.full The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America]<ref name="guidelines2006">{{Cite journal|last = Wormser | first = Gary P. | last2 = Dattwyler | first2 = Raymond J. | last3 = Shapiro | first3 = Eugene D. | last4 = Halperin | first4 = John J. | last5 = Steere | first5 = Allen C. | last6 = Klempner | first6 = Mark S. | last7 = Krause | first7 = Peter J. | last8 = Bakken | first8 = Johan S. | last9 = Strle | first9 = Franc | date = 2006-11-01 | title = The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America|url=https://academic.oup.com/cid/article/43/9/1089/422463|journal=Clinical Infectious Diseases|language=en|volume=43|issue=9|pages=1089–1134|doi=10.1086/508667|issn=1537-6591}}</ref>

== Notable studies ==
*2013, A Manganese-rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia burgdorferi<ref name="Aguirre2013">{{Cite journal | title = A Manganese-rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia burgdorferi* | date = 2013-03-22|url=https://www.jbc.org/article/S0021-9258(19)33493-3/abstract|journal=Journal of Biological Chemistry|volume=288|issue=12 | pages = 8468–8478 | last = Aguirre | first = J. Dafhne | last2 = Clark | first2 = Hillary M. | last3 = McIlvin | first3 = Matthew | last4 = Vazquez | first4 = Christine | last5 = Palmere | first5 = Shaina L. | last6 = Grab | first6 = Dennis J. | last7 = Seshu | first7 = J. | last8 = Hart | first8 = P. John | last9 = Saito | first9 = Mak | last10 = Culotta | first10 = Valeria C.|language=English|doi=10.1074/jbc.M112.433540|pmid=23376276|issn=0021-9258}}</ref> - [https://www.jbc.org/article/S0021-9258(19)33493-3/fulltext (Full text)]

*2016, County-Scale Distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the Continental United States<ref name="Eisen2016">{{Cite journal | title = County-Scale Distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the Continental United States | date = 2016-03-01|url=https://doi.org/10.1093/jme/tjv237|journal=Journal of Medical Entomology|volume=53|issue=2 | pages = 349–386|last = Eisen | first = Rebecca J. | last2 = Eisen | first2 = Lars | last3 = Beard | first3 = Charles B.|doi=10.1093/jme/tjv237|issn=0022-2585}}</ref> - [https://academic.oup.com/jme/article/53/2/349/2459744 (Abstract)]
*2016, Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study<ref name="Pritt2016">{{Cite journal | title = Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study | date = 2016-05-01|url=https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00464-8/abstract|journal=The Lancet Infectious Diseases|volume=16|issue=5 | pages = 556–564 | last = Pritt | first = Bobbi S. | last2 = Mead | first2 = Paul S. | last3 = Johnson | first3 = Diep K. Hoang | last4 = Neitzel | first4 = David F. | last5 = Respicio-Kingry | first5 = Laurel B. | last6 = Davis | first6 = Jeffrey P. | last7 = Schiffman | first7 = Elizabeth | last8 = Sloan | first8 = Lynne M. | last9 = Schriefer | first9 = Martin E. | last10 = Replogle | first10 = Adam J. | last11 = Paskewitz | first11 = Susan M.|language=English|doi=10.1016/S1473-3099(15)00464-8|pmid=26856777|issn=1473-3099}}</ref> - [https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00464-8/fulltext (Abstract)]

*2016, Longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute Lyme disease<ref name="Chiu2016">{{Cite journal | title = Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease | date = 2016-03-02|url=https://journals.asm.org/doi/10.1128/mBio.00100-16|journal=mBio|volume=7|issue=1|last = Bouquet | first = Jerome | last2 = Soloski | first2 = Mark J. | last3 = Swei | first3 = Andrea | last4 = Cheadle | first4 = Chris | last5 = Federman | first5 = Scot | last6 = Billaud | first6 = Jean-Noel | last7 = Rebman | first7 = Alison W. | last8 = Kabre | first8 = Beniwende | last9 = Halpert | first9 = Richard | last10 = Boorgula | first10 = Meher | last11 = Aucott | first11 = John N.|doi=10.1128/mbio.00100-16|pmc=PMC4791844|pmid=26873097|issn=2161-2129}}</ref> - [https://journals.asm.org/doi/10.1128/mBio.00100-16 (Full text)]
*2015, Emerging horizons for tick-borne pathogens: from the 'one pathogen-one disease' vision to the pathobiome paradigm<ref name="VayssierT2015" /> - [http://www.futuremedicine.com/doi/abs/10.2217/fmb.15.114 (Full text)]

==== Pathobiome Paradigm ====
Some future research will focus on a spectrum of pathogens instead of a "one pathogen-one disease" vision.<ref name="VayssierT2015">{{Cite journal | last1 = Vayssier-Taussat | first1 = M | authorlink1 = | last2 = Kazimirova | first2 = M | authorlink2 = | last3 = Hubalek | first3 = Z | authorlink3 = | last4 = Hornok | first4 = S | authorlink4 = | last5 =Farkas | first5 = R | authorlink5 = | last6 = Cosson | first6 = JF | authorlink6 = | last7 = Bonnet | first7 = S | authorlink7 = | last8 = Vourch | first8 = G | authorlink8 = | last9 = Gasqui | first9 = P | authorlink9 = | last10 = Mihalca | first10 = AD | authorlink10 = | last11 = Plantard | first11 = O | authorlink11 = | last12 = Silaghi | first12 = C | authorlink12 = | last13 = Cutler | first13 = S | authorlink13 = | last14 = Rizzlo | first14 = A | authorlink14 = | title = Emerging horizons for tick-borne pathogens: from the 'one pathogen-one disease' vision to the pathobiome paradigm | journal = Future Microbiol | volume = 10 | issue = 12 | page = 2033-43 | date = Nov 19, 2015 | pmid = 26610021 | doi = 10.2217/fmb.15.114 | url = http://www.futuremedicine.com/doi/abs/10.2217/fmb.15.114 }}</ref>

=== United States Congressional Report ===
* 2018, [https://drive.google.com/viewerng/viewer?url=https://www.hhs.gov/sites/default/files/tbdwg-report-to-congress-2018.pdf Tick-Borne Disease Working Group - 2018 Report to Congress]<ref>{{Cite web|url=https://drive.google.com/viewerng/viewer?url=https://www.hhs.gov/sites/default/files/tbdwg-report-to-congress-2018.pdf | title=Tick-Borne Disease Working Group - 2018 Report to Congress | last = Aucott | first = John N | last2 = Honey | first2 = Kristen T | date = 2018 | website = drive.google.com|language=en|others=Allen Richards; Robert Sabatino; Vanila Singh; Patricia Smith; Robert Smith|archive-url=|archive-date=|url-status=|access-date=2018-11-26 | last3 = Adams | first3 = Wendy | last4 = Beard | first4 = Charles Benjamin | last5 = Cooper | first5 = Captain Scott | last6 = Dixon | first6 = Dennis | last7 = Horowitz | first7 = Richard | last8 = Jones | first8 = Captain Estella | last9 = Nigrovic | first9 = Lisa E}}</ref>

==News and articles==
*2016, [http://www.sciencedaily.com/releases/2016/02/160208135440.htm Researchers identify new Borrelia species that causes Lyme disease]
*Apr 23, 2014, [http://www.perthnow.com.au/news/western-australia/lyme-disease-a-ticking-timebomb-that-health-authorities-say-does-not-exist/story-fnhocxo3-1226886911487 Lyme disease — a ticking timebomb that health authorities say does not exist] - PerthNow
*Jul 31, 2016, [http://www.bbc.co.uk/news/magazine-36923336 How I was floored by a tick] - BBC News

==See also==
*[[Alpha-gal allergy]]
*[[Borrelia burgdorferi]]
*[[Chronic Lyme disease]]
*[[Vagus nerve infection hypothesis]]
==Learn more==
*[https://www.nationalgeographic.com/animals/invertebrates/d/deer-tick/ About the Deer Tick] - National Geographic
*[http://www.columbia-lyme.org/ Lyme and Tick-Borne Diseases Research Center] - Columbia Lyme
*[https://blausen.com/en/video/lyme-disease/ Lyme Disease] - Video Short
*[https://www.nejm.org/doi/full/10.1056/NEJMp1807870#.W4x9XYBX_Qg.twitter Tickborne Diseases — Confronting a Growing Threat] - New England Journal of Medicine

== References ==
{{Reflist}}

[[Category:Diagnoses]]
[[Category:Potential comorbidities]]
[[Category:Infectious diseases]]
[[Category:Bacterial diseases]]

Natural killer cell

2026-08-13T04:58:06Z

Tuxedocaspy:/* ME/CFS */ Added an extra study on NK function that provides information for the [citation needed] statement

[[File:Natural killer cell.png|thumb|Natural killer cells are a type of white blood cell.]]
'''Natural killer (NK) cells''' are a type of [[Leucocyte|white blood cell]] that forms part of the [[innate immune system]]. Their function involves the recognition and destruction of tumor and virally infected cells.<ref name="MaleD2007" /> Numerous studies have found evidence of reduced natural killer cell function in patients with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS).<ref name="Barker1994" /><ref name="WhitesideTL1998" /><ref name="BrenuEW2014" /><ref name="FletcherMA2002" /><ref name="BrenuEW2012" />

==Function==
[[File:Nk cell.jpg|thumb|Natural Killer cells]]
The majority of [[lymphocyte]]s, a [[leucocyte]] subgroup, are [[B cell|B]] or [[T cell]]s but approximately 15% of the lymphocyte population lack B or T cell receptors; these are NK cells.<ref name="MaleD2007" /> The latter develop in the [[bone marrow]] and have a half-life of approximately 7 days.<ref name="SompayracL2008" /> Most NK cells are found in the [[blood]], [[spleen]] or [[liver]] and enter tissues at sites of [[inflammation]] following [[infection]]. There are two NK cell subgroups dependent on the expression of either [[CD16]] (FcγRIII) or [[CD56]] [[cell surface receptors]].<ref name="Robson2014" />

NK cells play a major role in eliminating virally infected cells. Following infection, [[Virus|viruses]] block cell synthesis of [[major histocompatibility complex]] class I (MHCI) molecules.<ref name="MaleD2007" /> Presentation of MHC class I molecules at an infected cell’s surface is used by [[Cytotoxicity|cytotoxic]] T cells (Tc cells) to target and destroy the cell. By preventing MHC class I presentation, viruses ensure the cell is unrecognised and escapes elimination by Tc cells: this is where NK cells prove vitally important in the body’s immune response.<ref name="MaleD2007" /> NK cells express specialized receptors – [[killer inhibitory receptors]] (KIRs) – which can identify MHC class I molecules. Following recognition of the MHC class I molecule, the KIR inhibits NK cell cytotoxic activity and destruction of the target.<ref name="MaleD2007" /> Virally infected cells, lacking the surface expression of MHC class I molecules, can be targeted and eliminated by NK cells.

NK cells can also target virally infected cells via expression of the [[IgG]] receptor CD16. This receptor binds antibodies attached to viral molecules on infected cell surfaces in a process called [[antibody-dependent cell mediated cytotoxicity]] (ADCC).<ref name="MaleD2007" />

'''NK Cell Cytotoxic Mechanisms'''

NK cells can terminate an infected cell via several mechanisms including:

*Direct cell-to-cell contact

*Cytokine synthesis and release<ref name="MaleD2007" />

As [[Large Granular Lymphocytes]] (LGLs), NK cells utilize their granular structure to kill infected cells. On fusing with virally infected cells’ [[plasma membranes]], granules release their contents into the cell<ref name="MaleD2007" />. These contents include the [[protein]] [[perforin]], which perforates the infected cell's membrane, enabling entry of specialized ‘suicide’ [[Enzyme|enzymes]], including [[granzyme B]], into the virally infected cell; these initiate apoptosis (programmed cell death).<ref name="MaleD2007" /><ref name="SompayracL2008" /> Granzymes can also damage the infected cell directly and play a vital role in virally infected cell destruction. Apoptosis can also be triggered via the attachment of [[Fas ligands]] (FasL) on the NK cell surface to Fas proteins on the target cell, activating apoptosis-inducing signalling.<ref name="SompayracL2008" />

NK cells express two receptor types:

*Activating

*Inhibitory

[[Activating receptors]] induce NK cells to eliminate infected cells, while [[inhibitory receptors]] block killing mechanisms<ref name="SompayracL2008" />. Resting NK cells synthesize [[Cytokine|cytokines]] and are capable of destroying virally infected cells but activated NK cells produce higher numbers of cytokines and are more efficient at eliminating infected cells<ref name="SompayracL2008" />.

'''Factors Leading to NK cell Activation'''

Several elements can produce NK cell activation, including:

*The detection of [[Lipopolysaccharides|lipopolysaccharide]] (LPS, a bacterial cell wall constituent)

*The release of various cytokines, e.g. [[Interferon alpha|IFN-α]] and [[Interferon beta|IFN-β]], when cells are infected with viruses

LPS is bound by NK cell surface receptors, inducing responses including IFN-γ synthesis, which can prepare [[Macrophage|macrophages]] for activation. Following activation, macrophages synthesize TNF ([[Tumor necrosis factor|tumour necrosis factor]]), which binds a macrophage’s own surface receptors<ref name="SompayracL2008" />. This initiates [[interleukin 12|IL-12]] (interleukin-12) activation. The combination of TNF and IL-12 expression induces increased NK cell synthesis of [[Interferon gamma|IFN-γ]] leading to more macrophage priming, an example of an enhanced immune response via a positive feedback loop<ref name="SompayracL2008" />. TNF synthesis by macrophages also upregulates [[interleukin 2|IL-2]] expression on NK cell surfaces, NK cells respond to their own IL-2 synthesis and undergo rapid division<ref name="SompayracL2008" />.

==In human disease==

===ME/CFS ===
Numerous studies of [[myalgic encephalomyelitis]] and [[chronic fatigue syndrome]] have found evidence of reduced natural killer cell function.<ref name="Barker1994" /><ref name="WhitesideTL1998" /><ref name="BrenuEW2014" /><ref name="FletcherMA2002" /><ref name="BrenuEW2012" /> Some studies have shown natural killer cell function correlates with illness severity.<ref name="OjoAmaize1994" /> One study found increased differentiation in NK cells.<ref name="HuthTK2016" /> A meta-analysis performed to quantify the decrease in NK cytotoxicity in ME/CFS patients compared to controls found NK toxicity was nearly half that of healthy controls.<ref>Baraniuk JN, Eaton-Fitch N, Marshall-Gradisnik S. Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome. Front Immunol. 2024 Oct 17;15:1440643. doi: 10.3389/fimmu.2024.1440643. PMID: 39483457; PMCID: PMC11524851.https://doi.org/10.3389/fimmu.2024.1440643</ref> Combing through 28 studies, the authors noted that steps in the laboratory preparation process such as freezing cells reduced NK toxicity as well, highlighting the need for strict sample handling at risk of increasing variations in measurement when measuring NK function as a consistent [[Diagnostic biomarker|biomarker]] for ME/CFS.

In 2015, [[David Strayer]], et al., published "Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity," in the ''Journal of Clinical & Cellular Immunology.'' The study reviewed previous studies that concluded that the more decreased the natural killer cell [[cytotoxicity]] was in patients, the greater the severity of the disease. The study also reported that ''in vitro'' exposure of peripheral blood mononuclear cells from CFS patients (who fulfilled both the [[Centers for Disease Control and Prevention|CDC]] 1988 and 1994 case definitions) to [[Ampligen]] increased natural killer cell cytotoxicity 100-178%. The conclusion of the study was that low NK cell cytotoxicity is commonly seen in CFS and was associated with increased symptom severity.<ref name="strayer2015" />

==== Causes ====
The following mechanisms have some degree of evidence that they cause NK dysfunction in ME:

* '''Altered MAPK signaling'''.<ref name="Chacko, 2016" /><ref name=":0" />
* '''Calcium channel dysfunction'''.<ref>{{Cite journal|title=Impaired TRPM3-dependent calcium influx and restoration using Naltrexone in natural killer cells of myalgic encephalomyelitis/chronic fatigue syndrome patients|date=2022-02-16|url=https://doi.org/10.1186/s12967-022-03297-8|journal=Journal of Translational Medicine|volume=20|issue=1|pages=94|last=Eaton-Fitch|first=Natalie|last2=Du Preez|first2=Stanley|last3=Cabanas|first3=Hélène|last4=Muraki|first4=Katsuhiko|last5=Staines|first5=Donald|last6=Marshall-Gradisnik|first6=Sonya|doi=10.1186/s12967-022-03297-8|pmc=PMC8848670|pmid=35172836|issn=1479-5876}}</ref>
* '''MicroRNAs'''. Transfecting primary NK cells with microRNAs that were upregulated in ME, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity.<ref name="PettyD2016" />

==== Relevance ====
It's currently unknown what the consequences are of NK dysfunction in ME, and how significant they are. One potential consequences is impaired clearance of pathogens.

===Multiple sclerosis===
In 2009 a team led by Dr Hugh Brady from the Department of Life Sciences at Imperial College London, identified a master gene [[E4bp4]] which causes blood [[stem cells]] to turn into disease-fighting 'Natural Killer' [[autoimmune cells]]. Using a mouse model scientists successfully 'knocked out' the gene known as E4bp4, creating the world's first animal model entirely lacking 'Natural Killer' cells, leaving all other blood cells and immune cells intact. This breakthrough model should help solve the mystery of the role that Natural Killer cells play in autoimmune diseases, such as [[diabetes]] and [[multiple sclerosis]]. This could now lead to new ways of treating these conditions with a drugs which will react with the protein expressed by their E4bp4 gene.<ref name="E4bp4Press">{{Cite web | title = Master gene that switches on disease-fighting cells identified by scientists - Press release | date = September 15, 2009 | website = Imperial College London | url =https://www.imperial.ac.uk/news/73201/master-gene-that-switches-disease-fighting-cells/|access-date=Sep 14, 2022}}</ref><ref name="GascoyneD2009" />

== Brain and spinal cord injury ==
Low NK function is associated with pathologies and experimental models of [[neural strain]].{{Citation needed|reason= | date = 7 July 2020}}, including [[spinal cord injury]].{{Citation needed|reason= | date = 7 July 2020}}
== Modulating NK function ==

=== Probiotics ===

Some [[probiotics]] have been shown to increase NK function, including ''[[Lactobacillus rhamnosus]]'' HN001,<ref name="GillHS2001" /> ''[[Bifidobacterium lactis]]'' HN019<ref name="GillHS2001" /><ref name="ChiangBL2000" /> and ''[[Lactobacillus casei]]'' Shirota<ref name="TakagiA2001" /><ref name="TakedaK2006" /><ref name="MorimotoK2005" />

=== AHCC ===

In animal models, [[Active Hexose Correlated Compound]] (AHCC) has been show to increase NK activity.<ref name="RitzBW2006" /> A randomized, controlled trial of healthy volunteers found no significant effect of AHCC on NK function.<ref name="TerakawaN2008" />

=== Stress ===

There is evidence in humans and animal models that psychological stress<ref name="GlaserR1986" /><ref name="SieberW1992" /> and physical stress, for example surgery,<ref name="PollockRE1991" /><ref name="Pollock1984" /> decreases NK function and promotes tumor development and metastasis.<ref name="Pollock1984" /> Mindfulness based meditation or stress reduction may increase natural killer cell function.<ref name="linda2008" />

=== Smoking ===
Smoking decreases natural killer cell function.<ref name="MorimotoK2005" />

===Ampligen===
In 2015, [[David Strayer]], et al., published a study that ''in vitro'' exposure of peripheral blood mononuclear cells from CFS patients (fulfilling both the CDC 1988 and 1994 case definitions) to [[Ampligen]] increased Natural Killer cell cytotoxicity 100-178%.<ref name="strayer2015" />

===Nutritional deficiencies===
[[Vitamin B12]] deficiency may be associated with decreased natural killer cell activity.<ref name="tamura1999" />

==Notable studies==

*1987, Phenotypic and functional deficiency of natural killer cells in patients with [[chronic fatigue syndrome]] [https://www.ncbi.nlm.nih.gov/pubmed/2824604 (Abstract)]
*2003, Predictive immunophenotypes: Disease-related profile in chronic fatigue syndrome [http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.10034/full (Full Text)]
*2015, Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity [https://www.omicsonline.org/open-access/low-nk-cell-activity-in-chronic-fatigue-syndrome-cfs-and-relationship-to-symptom-severity-2155-9899-1000348.php?aid=59415 (Full Text)]
*May 2015 - [http://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-015-0101-4 Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)], ''BMC Immunology'', 2015 16:35
*May 2015 - [https://journals.sagepub.com/doi/full/10.4137/III.S25147 Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients]<ref>{{Cite journal | last = Marshall-Gradisnik | first = Sonya M. | authorlink = Sonya Marshall-Gradisnik | last2 = Smith | first2 = Peter | authorlink2 = Peter Smith | last3 = Brenu | first3 = Ekua W. | authorlink3 = Ekua Brenu | last4 = Nilius | first4=Bernd | authorlink4 = Bernd Nilius | last5 = Ramos | first5 = Sandra B. | authorlink5 = Sandra Ramos | last6 = Staines | first6 = Donald R. | date = 2015-01-01 | title = Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients|url=https://doi.org/10.4137/III.S25147|journal=[[Immunology and Immunogenetics Insights]]|language=en|volume=7|issue=|pages=III.S25147|doi=10.4137/III.S25147|issn=1178-6345|quote=|via=}}</ref> (small study - 115 people with ME/CFS)
*May 2015 - [http://www.la-press.com/examination-of-single-nucleotide-polymorphisms-snps-in-transient-recep-article-a4824 Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients], ''Immunology and Immunogenetics Insights'', 2015:7 1-6. (small study - 115 people with ME/CFS)

*Dec 2015, [http://onlinelibrary.wiley.com/doi/10.1111/sji.12388/abstract Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis]<ref name="NKcells-2015">{{Cite journal | last = Huth | first = T.K. | authorlink = Teilah Huth | last2 = Brenu | first2 = E.W. | authorlink2 = Ekua Brenu | last3 = Ramos | first3 = S. | authorlink3 = Sandra Ramos | last4 = Nguyen | first4=T. | authorlink4 = Thao Nguyen | last5 = Broadley | first5 = S. | authorlink5 = Simon Broadley | last6 = Staines | first6 = D. | authorlink6 = Donald Staines | last7 = Marshall‐Gradisnik | first7 = S. | authorlink7 = Sonya Marshall-Gradisnik | date = 2016 | title=Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/sji.12388|journal=[[Scandinavian Journal of Immunology]]|language=en|volume=83|issue=1 | pages = 44–51|doi=10.1111/sji.12388|issn=1365-3083|quote=|via=}}</ref> (Abstract)

*Jan 2016, [https://journals.sagepub.com/doi/full/10.4137/III.S37042 Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients]<ref name="Genotype-2016">{{Cite journal | last = Marshall-Gradisnik | first = S.M. | authorlink = Sonya Marshall-Gradisnik | last2 = Chacko | first2 = A. | authorlink2 = A Chacko | last3 = Johnston | first3 = S. | authorlink3 = Samantha Johnston | last4 = Smith | first4 = P. | authorlink4 = Peter Smith | last5 = Nilius | first5 = B. | authorlink5 = B Nilius | last6 = Staines | first6 = D.R. | authorlink6 = Donald Staines | date = 2016-01-01 | title = Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://doi.org/10.4137/III.S37042|journal=Immunology and Immunogenetics Insights|language=en|volume=8|issue=|pages=III.S37042|doi=10.4137/III.S37042|issn=1178-6345|quote=|via=}}</ref> [https://journals.sagepub.com/doi/full/10.4137/III.S37042 (Full text)]

*Apr 2016, [http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0859-z ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients]<ref name=":0">{{Cite journal | last = Huth | first = Teilah Kathryn | authorlink = Teilah Huth | last2 = Staines | first2 = Donald | authorlink2 = Donald Staines | last3 = Marshall-Gradisnik | first3 = Sonya | authorlink3 = Sonya Marshall-Gradisnik | authorlink4 = | authorlink5 = | date = 2016-04-21 | title = ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients|url=https://doi.org/10.1186/s12967-016-0859-z|journal=[[Journal of Translational Medicine]]|volume=14|issue=1 | pages = 97|doi=10.1186/s12967-016-0859-z|issn=1479-5876|pmc=4839077|pmid=27098723|quote=|via=}}</ref> (Full text)

*May 2016, [https://biolres.biomedcentral.com/articles/10.1186/s40659-016-0087-2 Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients]<ref name="TRPM3-2016">{{Cite journal | last = Nguyen | first = T. | authorlink = Thao Nguyen | last2 = Staines | first2 = D. | authorlink2 = Donald Staines | last3 = Nilius | first3 = B. | authorlink3 = B Nilius | last4 = Smith | first4 = P. | authorlink4 = Peter Smith | last5 = Marshall-Gradisnik | first5 = S. | authorlink5 = Sonya Marshall-Gradisnik | date = 2016-05-31 | title = Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients|url=https://doi.org/10.1186/s40659-016-0087-2|journal=[[Biological Research (journal)|Biological Research]]|volume=49|issue=1|pages=27|doi=10.1186/s40659-016-0087-2|issn=0717-6287|pmc=4888729|pmid=27245705|quote=|via=}}</ref> (Full text)

*2016, Dysregulation of Protein Kinase Gene Expression in NK Cells from [[ME/CFS|Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]] Patients<ref name="Chacko, 2016" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003121/ (Full Text)]
*2016, Natural killer cells and single nucleotide polymorphisms of specific ion channels and receptor genes in myalgic encephalomyelitis/chronic fatigue syndrome [https://www.dovepress.com/natural-killer-cells-and-single-nucleotide-polymorphisms-of-specific-i-peer-reviewed-fulltext-article-TACG (Full Text)]
*2016, Killer Cell Immunoglobulin-like Receptor [[Genotype]] and [[Haplotype]] Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients [http://journals.sagepub.com/doi/full/10.4137/GRSB.S39861 (Full Text)]
*2016, [[MicroRNA|MicroRNAs]] [[hsa-miR-99b]], [[hsa-miR-330]], [[hsa-miR-126]] and [[hsa-miR-30c]]: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME)<ref name="PettyD2016" />
*2018, Association of [[T cell|T]] and NK cell phenotype with the diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="Rivas, 2018" /> [https://www.frontiersin.org/articles/10.3389/fimmu.2018.01028/abstract (Abstract)]
*2018, [[Rituximab]] impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation<ref name="Eaton, 2018" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870391/ (Full Text)]

*Aug 2018, Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients<ref>{{Cite journal | last = Cabanas | first = Hélène | authorlink = Hélène | last2 = Muraki | first2 = Katsuhiko | authorlink2 = Katsuhiko Muraki | last3 = Eaton | first3 = Natalie | authorlink3 = Natalie Eaton-Fitch | last4 = Balinas | first4=Cassandra | authorlink4 = Cassandra Balinas | last5 = Staines | first5 = Donald | authorlink5 = Donald Staines | last6 = Marshall-Gradisnik | first6 = Sonya | authorlink6 = Sonya Marshall-Gradisnik | date = 2018-08-14 | title = Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092868/|journal=Molecular Medicine|volume=24|issue=|pages=|doi=10.1186/s10020-018-0046-1|issn=1076-1551|pmc=6092868|pmid=30134818|quote=|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092868/#__ffn_sectitle (Full text)]

*May 2019, Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients<ref>{{Cite journal | last = Cabanas | first = H. | authorlink = Hélène Cabanas | last2 = Muraki | first2 = K. | authorlink2 = Katsuhiko Muraki | last3 = Balinas | first3 = C. | authorlink3 = Cassandra Balinas | last4 = Eaton-Fitch | first4 = N. | authorlink4 = Natalie Eaton-Fitch | last5 = Staines | first5 = D. | authorlink5 = Donald Staines | last6 = Marshall-Gradisnik | first6 = S. | authorlink6 = Sonya Marshall-Gradisnik | date = 2019-04-23 | title = Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480905/|journal=[[Molecular Medicine]]|volume=25|issue=|pages=|doi=10.1186/s10020-019-0083-4|issn=1076-1551|pmc=6480905|pmid=31014226|quote=|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480905/ (Full text)]

==Learn more==

*[https://en.wikipedia.org/wiki/Natural_killer_cell Wikipedia - Natural killer cell]
*[https://www.youtube.com/watch?v=GIJK3dwCWCw&feature=youtu.be Crash Course - The Immune System Part 1]
*2016, [https://www.actionforme.org.uk/resources/questions-and-answers/what-was-the-research-into-immune-responses-in-cfs/m.e.-you-funded-about/ What was the research into immune responses in CFS/M.E. you funded about?]
*2016, [http://www.wehi.edu.au/news/immune-cell-switch-discovery-raises-hopes-cancer-fight Immune cell 'switch' discovery raises hopes in cancer fight]<ref name="WEHIMR20160226" />

==See also==

*[[GcMAF]]
*[[Immune system]]
*[[TRPM3]]
*[[Diagnostic biomarker]]

==References==
<references>
<ref name="Barker1994">{{Cite journal | last1 = Barker | first1 = Edward | authorlink1 = | last2 = Fujimura | first2 = Sue F. | authorlink2 = | last3 = Fadem | first3 = Mitchell B. | authorlink3 = | last4 = Landay | first4 = Alan L. | authorlink4 = | last5 = Levy | first5 = Jay A. | authorlink5 = Jay Levy | title = Immunologic Abnormalities Associated with Chronic Fatigue Syndrome | journal = Clin Infect Dis. | date = 1994 | volume = 18 | issue = Suppl 1 | pages = S136-S141 | doi = 10.1093/clinids/18.Supplement_1.S136 | url = http://cid.oxfordjournals.org/content/18/Supplement_1/S136.short }}</ref>
<ref name="BrenuEW2012">{{citation | last1 = Brenu | first1 = Ekua W | authorlink1 = Ekua Brenu | last2 = van Driel | first2 = Mieke L | authorlink2 = | last3 = Staines | first3 = Donald R | authorlink3 = Donald Staines | last4 = Ashton | first4 = Kevin J | authorlink4 = | last5 = Hardcastle | first5 = Sharni L | authorlink5 = Sharni Hardcastle | last6 = Keane | first6 = James | authorlink6 = | last7 = Tajouri | first7 = Lotti | authorlink7 = | last8 = Peterson | first8 = Daniel | authorlink8 = Daniel Peterson | last9 =Ramos | first9 = Sandra B | authorlink9 = Sandra Ramos | last10 = Marshall-Gradisnik | first10 = Sonya M | authorlink10 = Sonya Marshall-Gradisnik | title = Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis | journal = Journal of Translational Medicine | date = 2012 | volume = 10 | issue = | pages = 88 | doi = 10.1186/1479-5876-10-88 | url = http://www.translational-medicine.com/content/10/1/88 }}</ref>
<ref name="BrenuEW2014">{{Cite journal | last1 = Brenu | first1 = EW | authorlink1 = Ekua Brenu | last2 = Huth | first2 = TK | authorlink2 = Teilah Huth | last3 = Hardcastle | first3 = SL | authorlink3 = Sharni Hardcastle | last4 = Fuller | first4 = K | authorlink4 = | last5 = Kaur | first5 = M | authorlink5 = | last6 = Johnston | first6 = S | authorlink6 = | last7 = Ramos | first7 = S | authorlink7 = Sandra Ramos | last8 = Staines | first8 = D | authorlink8 = Donald Staines | last9 =Marshall-Gradisnik | first9 = S | authorlink9 = Sonya Marshall-Gradisnik | title = The Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis | journal = International Immunology | date = 2014 | volume = 26 | issue = 4 | pages = 233-42 | pmid = 24343819 | doi = 10.1093/intimm/dxt068 }}</ref>
<ref name="Chacko, 2016">{{Cite journal | last1 = Chacko | first1 = Anu | authorlink1 = | last2 = Staines | first2 = Donald R. | authorlink2 = Donald Staines | last3 = Johnston | first3 = Samantha C. | authorlink3 = | last4 = Marshall-Gradisnik | first4 = Sonya M. | authorlink4 = Sonya Marshall-Gradisnik | title = Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients | journal = Gene Regulation and System Biology | volume = | issue = 10 | pages = 85–93 | date = 2016 | pmid = 27594784 | doi = 10.4137/GRSB.S40036 }}</ref>
<ref name="ChiangBL2000">{{citation | last1 = Chiang | first1 = BL | authorlink1 = | last2 = Sheih | first2 = YH | authorlink2 = | last3 = Wang | first3 = LH | authorlink3 = | last4 = Liao | first4 = CK | authorlink4 = | last5 = Gill | first5 = HS | authorlink5 = | title = Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium (Bifidobacterium lactis HN019): optimization and definition of cellular immune responses] | journal = European Journal of Clinical Nutrition | date = 2000 | volume = 54 | issue =11 | pages = 849-855 | doi = 10.1038/sj.ejcn.1601093 | url = http://europepmc.org/abstract/med/11114680 }}</ref>
<ref name="FletcherMA2002">{{citation | last1 = Fletcher | first1 = Mary Ann | authorlink1 = Mary Ann Fletcher | last2 = Maher | first2 = Kevin J | authorlink2 = | last3 = Klimas | first3 = Nancy | authorlink3 = Nancy Klimas | title = Natural killer cell function in chronic fatigue syndrome | journal = Clinical and Applied Immunology Reviews | volume = 2 | issue = 2 | date = April 2002 | pages = 129–139 | doi = 10.1016/S1529-1049(01)00047-2 | url = http://www.sciencedirect.com/science/article/pii/S1529104901000472 }}</ref>
<ref name="Eaton, 2018">{{citation | last1 = Eaton | first1 = Natalie | authorlink1 = | last2 = Cabanas | first2 = Hélène | authorlink2 = | last3 = Balinas | first3 = Cassandra | authorlink3 = | last4 = Klein | first4 = Anne | authorlink4 = | last5 = Staines | first5 = Donald R. | authorlink5 = Donald Staines | last6 = Marshall-Gradisnik | first6 = Sonya | authorlink6 = Sonya Marshall-Gradisnik | title = Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation | journal = BMC Pharmacology & Toxicology | date = 2018 | volume = 19 | issue = 12 | pages = | pmid = 29587879 | doi = 10.1186/s40360-018-0203-8 }}</ref>
<ref name="GascoyneD2009">{{citation | last1 = Gascoyne | first1 = Duncan M | authorlink1 = Duncan M Gascoyne | last2 = Long | first2 = Elaine | authorlink2 = Elaine Long | last3 = Veiga-Fernandes | first3 = Henrique | authorlink3 = Henrique Veiga-Fernandes | last4 = de Boer | first4 = Jasper | authorlink4 = Jasper de Boer | last5 = Williams | first5 = Owen | authorlink5 = Owen Williams | last6 = Seddon | first6 = Benedict | authorlink6 = Benedict Seddon | last7 = Coles | first7 = Mark | authorlink7 = Mark Coles | last8 = Kioussis | first8 = Dimitris | authorlink8 = Dimitris Kioussis | last9 =Brady | first9 = Hugh JM | authorlink9 = Hugh JM Brady | title = The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development | journal = Nature Immunol | volume = 10 | issue =| pages = 1118-1124 | date = Sep 13, 2009 | pmid = 19749763 | doi = 10.1038/ni.1787 | url = http://www.nature.com/ni/journal/v10/n10/full/ni.1787.html }}</ref>
<ref name="GillHS2001">{{citation | last1 = Gill | first1 = HS | authorlink1 = | last2 = Rutherfurd | first2 = KJ | authorlink2 = | last3 = Cross | first3 = ML | authorlink3 = | title = Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes | journal = J Clin Immunol | date = Jul 2001 | volume = 21 | issue = 4 | pages = 264-71 | pmid = 11506196 }}</ref>
<ref name="GlaserR1986">{{citation | last1 = Glaser | first1 = Ronald | authorlink1 = Ronald Glaser | last2 = Rice | first2 = John | authorlink2 = | last3 = Speicher | first3 = Carl E. | authorlink3 = | last4 = Stout | first4 = Julie C. | authorlink4 = | last5 = Kiecolt-Glaser | first5 = Janice K. | authorlink5 = | title = Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity. | journal = Behavioral Neuroscience | volume = 100 | issue =5 | date = Oct 1986 | pages = 675-678 | doi = 10.1037/0735-7044.100.5.675 | url = http://psycnet.apa.org/psycinfo/1987-06499-001 }}</ref>
<ref name="HuthTK2016">{{citation | last1 = Huth | first1 = TK | authorlink1 = Teilah Huth | last2 = Brenu | first2 = EW | authorlink2 = Ekua Brenu | last3 = Ramos | first3 = S | authorlink3 = Sandra Ramos | last4 = Nguyen | first4 = T | authorlink4 = | last5 = Broadley | first5 = S | authorlink5 = | last6 = Staines | first6 = D | authorlink6 = Donald Staines | last7 = Marshall-Gradisnik | first7 = S | authorlink7 = Sonya Marshall-Gradisnik | title = Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis | journal = Scand J Immunol | date = Jan 2016 | volume = 83 | issue = 1 | pages = 44-51 | pmid = 26381393 | doi = 10.1111/sji.12388 | url = https://www.ncbi.nlm.nih.gov/pubmed/26381393 }}</ref>
<ref name="MaleD2007">{{citation | author = Male, D | date = 2007 | title = Immunology | isbn =
| location = Milton Keynes| publisher =The Open University }}</ref>
<ref name="MorimotoK2005">{{citation | last1 = Morimoto | first1 = Kanehisa | authorlink1 = | last2 = Takeshita | first2 = Tatsuya | authorlink2 = | last3 = Nanno | first3 = Masanobu | authorlink3 = | last4 = Tokudome | first4 = Shinkan | authorlink4 = | last5 = Nakayama | first5 = Kunio| authorlink5 = | title = Modulation of natural killer cell activity by supplementation of fermented milk containing Lactobacillus casei in habitual smokers | journal = Preventive Medicine | volume = 40 | issue = 5 | date = May 2005 | pages = 589–594 | doi = 10.1016/j.ypmed.2004.07.019 | url = http://www.sciencedirect.com/science/article/pii/S0091743504004177 }}</ref>
<ref name="OjoAmaize1994">{{citation | last1 = Ojo-Amaize | first1 = Emmanuel A. | authorlink1 = | last2 = Conley | first2 = Edward J. | authorlink2 = | last3 = Peter | first3 = James B. | authorlink3 = | title = Decreased Natural Killer Cell Activity Is Associated with Severity of Chronic Fatigue Immune Dysfunction Syndrome | journal = Clin Infect Dis | date = 1994 | volume = 18 | issue = Supplement 1 | pages = S157-S159 | doi = 10.1093/clinids/18.Supplement_1.S157 | url = http://cid.oxfordjournals.org/content/18/Supplement_1/S157.short }}</ref>
<ref name="PettyD2016">{{Cite journal | last1 = Petty | first1 = Robert D. | authorlink1 = Robert Petty | last2 = McCarthy | first2 = Neil E. | authorlink2 = Neil McCarthy | last3 = Le Dieu | first3 = Rifca | authorlink3 = Rifca Le Dieu | last4 = Kerr | first4 = Jonathan R. | authorlink4 = Jonathan Kerr | title = MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) | journal = PLOS One | date = 2016 | volume = | issue = | pages = | pmid = 26967895 | doi = 10.1371/journal.pone.0150904 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586059/ }}</ref>
<ref name="PollockRE1991">{{citation | last1 = Pollock | first1 = Raphael E. | authorlink1 = | last2 = Lotzová | first2 = Eva| authorlink2 = | last3 = Stanford | first3 = Susan D. | authorlink3 = | title = Mechanism of Surgical Stress Impairment of Human Perioperative Natural Killer Cell Cytotoxicity | journal = Arch Surg | date = 1991 | volume = 126 | issue = 3 | pages = 338-342 | doi = 10.1001/archsurg.1991.01410270082013 | url = http://archsurg.jamanetwork.com/article.aspx?articleid=595011 }}</ref>
<ref name="RitzBW2006">{{citation | last1 = Ritz | first1 = Barry W. | authorlink1 = | last2 = Nogusa | first2 = Shoko| authorlink2 = | last3 = Ackerman | first3 = Elizabeth A. | authorlink3 = | last4 = Gardner | first4 = Elizabeth M. | authorlink4 = | title = Supplementation with Active Hexose Correlated Compound Increases the Innate Immune Response of Young Mice to Primary Influenza Infection | journal = J. Nutr. | date = Nov 2006 | volume = 136 | issue = 11 | pages = 2868-2873 | pmid = 17056815 | url = http://jn.nutrition.org/content/136/11/2868.full }}</ref>
<ref name="Rivas, 2018">{{citation | last1 = Rivas | first1 = Jose Luis | authorlink1 = | last2 = Palencia | first2 = Teresa | authorlink2 = | last3 = Fernandez | first3 = Guerau | authorlink3 = | last4 = Garcia | first4 = Milagros | authorlink4 = | title = Association of T and NK cell phenotype with the diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | journal = Frontiers in Immunology | volume = | issue = |pages = | date = 2018 | doi = 10.3389/fimmu.2018.01028 }}</ref>
<ref name="Robson2014">{{citation | last1 = Robson | first1 = NC | authorlink1 = | last2 = Hidalgo | first2 = L | authorlink2 = | last3 = McAlpine | first3 = T | authorlink3 = | last4 = Wei | first4 = H | authorlink4 = | last5 = Martínez | first5 = VG | authorlink5 = | last6 = Entrena | first6 = A | authorlink6 = | last7 = Melen | first7 = GJ | authorlink7 = | last8 = MacDonald | first8 = AS | authorlink8 = | last9 =Phythian-Adams | first9 = A | authorlink9 = | last10 = Sacedón | first10 = R | author-link10 = | last11 = Maraskovsky | first11 = E | authorlink11 = | last12 = Cebon | first12 = J | authorlink12 = | last13 = Ramírez | first13 = M | authorlink13 = | last14 = Vicente | first14 = A | authorlink14 = | last15 = Varas | first15 = A | authorlink15 = | date = 2014 | title = Optimal Effector Functions in Human Natural Killer Cells rely upon Autocrine Bone Morphogenetic Protein Signaling | journal = Cancer Res. | volume = 74 | issue = 18 | pages = 5019-5031 | doi = 10.1158/0008-5472.CAN-13-2845 }}</ref>
<ref name="SieberW1992">{{citation | last1 = Sieber | first1 = William J. | authorlink1 = | last2 = Rodin | first2 = Judith | authorlink2 = | last3 = Larson | first3 = Lynn | authorlink3 = | last4 = Ortega | first4 = Susan | authorlink4 = | last5 = Cummings | first5 = Nancy | authorlink5 = | last6 = Levy | first6 = Sandra | authorlink6 = | last7 = Whiteside | first7 = Theresa | authorlink7 = | last8 = Herberman | first8 = Ronald | authorlink8 = | title = Modulation of human natural killer cell activity by exposure to uncontrollable stress | date = June 1992 | journal = Brain, Behavior, and Immunity | volume = 6 | issue = 2 | pages = 141–156 | doi = 10.1016/0889-1591(92)90014-F | url = http://www.sciencedirect.com/science/article/pii/088915919290014F }}</ref>
<ref name="SompayracL2008">{{Cite book | author = Sompayrac, L | date = 2008 | title = How the Immune System Works
| publisher = Oxford, Blackwell Publishing | isbn =| location = }}</ref>
<ref name="TakagiA2001">{{citation | last1 = Takagi | first1 = Akimitsu | authorlink1 = | last2 = Matsuzaki | first2 = Takeshi | authorlink2 = | last3 = Sato | first3 = Mikiko | authorlink3 = | last4 = Nomoto | first4 = Koji | authorlink4 = | last5 = Morotomi | first5 = Masami | authorlink5 = | last6 = Yokokura | first6 = Teruo | authorlink6 = | title = Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism | journal = Carcinogenesis | date = 2001 | volume = 22 | issue = 4 | pages = 599-605 | doi = 10.1093/carcin/22.4.599 | url = http://carcin.oxfordjournals.org/content/22/4/599.long }}</ref>
<ref name="TakedaK2006">{{citation | last1 = Takeda | first1 = K | authorlink1 = | last2 = Suzuki | first2 = T | authorlink2 = | last3 = Shimada | first3 = SI | authorlink3 = | last4 = Shida | first4 = K | authorlink4 = | last5 = Nanno | first5 = M | authorlink5 = | last6 = Okumura | first6 = K | authorlink6 = | title = Interleukin‐12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota | journal = Clin Exp Immunol | date = Oct 2006 | volume = 146 | issue =1 | pages = 109-15 | pmid = 16968405 | url = https://www.ncbi.nlm.nih.gov/pubmed/16968405 }}</ref>
<ref name="TerakawaN2008">{{citation | last1 = Terakawa | first1 = Naoyoshi | authorlink1 = | last2 = Matsui | first2 = Yoichi | authorlink2 = | last3 = Satoi | first3 = Sohei | authorlink3 = | last4 = Yanagimoto | first4 = Hiroaki | authorlink4 = | last5 = Takahashi | first5 = Kanji | authorlink5 = | last6 = Yamamoto | first6 = Tomohisa | authorlink6 = | last7 = Yamao | first7 = Jun | authorlink7 = | last8 = Takai | first8 = Soichiro | authorlink8 = | last9 = Kwon | first9 = A-Hon | authorlink9 = | last10 = Kamiyama | first10 = Yasuo | authorlink10 = | url = http://www.tandfonline.com/doi/abs/10.1080/01635580801993280 | title = Immunological Effect of Active Hexose Correlated Compound (AHCC) in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial | journal = Nutrition and Cancer | volume = 60 | issue = 5 | pages = | date = 2008| doi = 10.1080/01635580801993280 }}</ref>
<ref name="WEHIMR20160226">{{citation | author = Walter & Eliza Hall Institute of Medical Research | title = Immune cell 'switch' discovery raises hopes in cancer fight | date = Feb 26, 2016 | url = http://www.wehi.edu.au/news/immune-cell-switch-discovery-raises-hopes-cancer-fight }}</ref>
<ref name="WhitesideTL1998">{{citation | last1 = Whiteside | first1 = TL | last2 = Friberg | first2 = D | title = Natural killer cells and natural killer cell activity in chronic fatigue syndrome. | journal = Am J Med | date = 1998 | volume= 105 | issue= 3A | pages = 27S-34S | pmid = 9790479 | doi= }}</ref>
<ref name="Pollock1984">{{Citation| issn = 0008-5472| volume = 44 | issue = 9| pages = 3888–3891| last1 = Pollock | first1 = Raphael E. | last2 = Babcock | first2 = George F. | last3 = Romsdahl | first3 = Marvin M. | last4 = Nishioka | first4 = Kenji | title = Surgical Stress-mediated Suppression of Murine Natural Killer Cell Cytotoxicity| journal = Cancer Research| access-date = 2016-12-19| date = 1984-09-01| url = http://cancerres.aacrjournals.org/content/44/9/3888 | pmid = 6744305}}</ref>
<ref name="linda2008">{{Citation| doi = 10.1016/j.bbi.2008.01.012| issn = 0889-1591| volume = 22 | issue = 6| pages = 969–981| last1 = Witek-Janusek | first1 = Linda | last2 = Albuquerque | first2 = Kevin | last3 = Chroniak | first3 = Karen Rambo | last4 = Chroniak | first4 = Christopher | last5 = Durazo | first5 = Ramon | last6 = Mathews | first6 = Herbert L.| title = Effect of Mindfulness Based Stress Reduction on Immune Function, Quality of Life and Coping In Women Newly Diagnosed with Early Stage Breast Cancer| journal = Brain, behavior, and immunity | date = August 2008| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586059/| pmid = 18359186}}</ref>
<ref name="strayer2015">{{Citation| doi = 10.4172/2155-9899.1000348| issn = 2155-9899| volume = | issue =| pages = 1–9| last1 = Strayer | first1 = David | last2 = Scott | first2 = Victoria | last3 = Carter | first3 = William| title = Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity| journal = Journal of Clinical & Cellular Immunology| access-date = 2016-12-19| date = 2015-07-29| url = http://www.omicsonline.org/open-access/low-nk-cell-activity-in-chronic-fatigue-syndrome-cfs-and-relationship-to-symptom-severity-2155-9899-1000348.php?aid=59415}}</ref>
<ref name="tamura1999">{{Citation| doi = 10.1046/j.1365-2249.1999.00870.x| issn = 1365-2249| volume = 116 | issue = 1| pages = 28–32| last1 = Tamura | first1 = J. | last2 = Kubota | first2 = K. | last3 = Murakami | first3 = H. | last4 = Sawamura | first4 = M. | last5 = Matsushima | first5 = T. | last6 = Tamura | first6 = T. | last7 = Saitoh | first7 = T. | last8 = Kurabayshi | first8 = H. | last9 = Naruse | first9 = T.| title = Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment| journal = Clinical & Experimental Immunology| access-date = 2016-12-19| date = 1999-04-01| url = http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2249.1999.00870.x/abstract}}</ref>
</references>

[[Category:Body systems]]
[[Category:Immunology]]
[[Category:Immune cells]]
[[Category:Blood components]]

Transient receptor potential melastatin 3

2026-08-12T07:07:05Z

Tuxedocaspy:/* Function */ Began writing for Function, basic characterization, description, complete with sources.

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'''Transient Receptor Potential Melastatin 3''' or '''TRPM3''' is a non-selective [[ion channel]] permeable to both calcium and magnesium. Impaired activity of TRPM3 function is a potential biomarker for [[ME/CFS]].<ref name="Cabanas2019" /> TRPM3 may also be used to refer to the gene for TRPM3.

==Function==
Members of the Transient Receptor Potential family, including TRPM3, are cation-selective channel proteins which allow the transport of cations across cell membranes into cells.<ref>[https://www.ncbi.nlm.nih.gov/gene/80036 https://www.ncbi.nlm.nih.gov/gene/80036https://www.ncbi.nlm.nih.gov/gene/80036]</ref> Calcium plays a crucial role in cellular processes, and the importance of TRP proteins in brain homeostasis and dysregulation in pathology is well-known.<ref>https://journals.sagepub.com/doi/10.1089/ars.2010.3359</ref> Structurally, TRP proteins consist of four adjacent subunits which form pores for ion transport. The Transient Receptor Potential Melastatin subfamily is a subdivision of TRPs with identified roles in regulating senses, including vision (TRPM1), taste (TRPM5), and nociception (TRPM2, TRPM3, TRPM8).<ref name=":0">https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.635659/full</ref> In comparison, TRPM3 is less well-studied in terms of function, but mutations in the protein have been increasingly recognized as playing a role in developmental and epileptic encephalopathies. Of note, TRPM3 has many subunit-forming isoforms, which are variants produced by alternative splicing of exons from the mRNA transcribed from the ''Trpm3'' gene. Characterization of the TRPM3 proteoform family is difficult due to the number of variants, with different combinations of subunits altering permability and selectivity for ions such as calcium, magnesium, zinc, and other molecules which serve as agonists or antagonists.<ref name=":0" />

==ME/CFS==

==Notable studies==
*2021, Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment<ref name="Cabanas2021">{{Cite journal | title = Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment | date = 2021|url=https://www.frontiersin.org/articles/10.3389/fimmu.2021.687806|journal=Frontiers in Immunology|volume=12|issue= | pages = 687806 | last =Cabanas | first = Helene | author-link = Hélène Cabanas | last2 = Muraki | first2 = Katsuhiko|author-link2 = | last3 = Eaton-Fitch | first3 = Natalie | author-link3 = Natalie Eaton-Fitch | last4 = Staines | first4=Donald Ross | authorlink4 = Donald Staines| last5 = Marshall-Gradisnik | first5 = Sonya | authorlink5 = Sonya Marshall-Gradisnik|doi=10.3389/fimmu.2021.687806|pmc=PMC8313851|pmid=34326841|access-date=|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2021.687806/full (Full text)]

*2019, Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients<ref name="Cabanas2019">{{Cite journal | last =Cabanas | first = H. | author-link = Hélène Cabanas | last2 = Muraki | first2 = K.|author-link2 = | last3 = Balinas | first3=C. | author-link3 = Cassandra Balinas | last4 = Eaton-Fitch | first4 = N. | authorlink4 = Natalie Eaton-Fitch| last5 = Staines | first5 = D. | authorlink5 = Donald Staines | last6 = Marshall-Gradisnik | first6 = S. | authorlink6 = Sonya Marshall-Gradisnik | date = Dec 2019 | title = Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients|url=https://molmed.biomedcentral.com/articles/10.1186/s10020-019-0083-4|journal=Molecular Medicine|language=en|volume=25|issue=14|pages=|doi=10.1186/s10020-019-0083-4|issn=1076-1551|quote=|via=|pmc=|pmid=|access-date=}}</ref> - [https://link.springer.com/article/10.1186/s10020-019-0083-4 (Full text)]
* 2019, [[Low dose naltrexone|Naltrexone]] restores impaired transient receptor potential melastatin 3 ion channel function in natural killer cells from myalgic encephalomyelitis/chronic fatigue syndrome patients<ref name="Cabanas2019LDN">{{Cite journal | last =Cabanas | first = Helene | author-link = Hélène Cabanas | last2 = Muraki | first2 = Katsuhiko|author-link2 = | last3 = Staines | first3=Donald | author-link3 = Donald Staines | last4 = Marshall-Gradisnik | first4 = Sonya | author-link4 = Sonya Marshall-Gradisnik | date = Oct 14, 2019 | title = Naltrexone restores impaired transient receptor potential melastatin 3 ion channel function in natural killer cells from myalgic encephalomyelitis/chronic fatigue syndrome patients|url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.02545/abstract|journal=Frontiers in Immunology|volume=|issue=|pages=|doi=10.3389/fimmu.2019.02545|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2019.02545/abstract (Abstract)]

*2018, Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients<ref name="Cabanas2018">{{Cite journal | last =Cabanas | first = Hélène | author-link = Hélène Cabanas | last2 = Muraki | first2 = Katsuhiko | authorlink2 = Katsuhiko Muraki | last3 = Eaton | first3=Natalie | author-link3 = Natalie Eaton-Fitch | last4 = Balinas | first4=Cassandra | author-link4 = Cassandra Balinas| last5 = Staines | first5 = Donald | authorlink5 = Donald Staines | last6 = Marshall-Gradisnik | first6 = Sonya | authorlink6 = Sonya Marshall-Gradisnik | date = 2018-08-14 | title = Loss of Transient Receptor Potential Melastatin 3 ion channel function in Natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092868/|journal=Molecular Medicine|volume=24|issue=2|pages=|doi=10.1186/s10020-018-0046-1|issn=1076-1551|pmc=6092868|pmid=30134818|quote=|via=}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092868/#__ffn_sectitle (Full text)]
*2018, Decreased Expression of TRPM3 and mAChRM3 in the Small Intestine in [[ME/CFS|Chronic Fatigue Syndrome/Myalgic Encephalomyelitis]]<ref name="Marshall2018">{{Cite journal | last =Marshall-Gradisnik | first = Sonya | authorlink = Sonya Marshall-Gradisnik | last2 = Fretel | first2 = Marshall | author-link2 = | last3 = Eaton | first3=Natalie | author-link3 = Natalie Eaton | first4=Helene | last4 = Cabanas | authorlink4 = Hélène Cabanas| last5 = Balinas | first5 = Cassandra | authorlink5 = | last6 = Gopalan | first6 = Vinod | author-link6 = | last7 = Petersen | first7 = Daniel | authorlink7 = Daniel Peterson | last8 = Passmore | first8 = Rachel | last9 = Tang | first9 = Kevin | last10 = Haque | first10 = Mazhar | authorlink10 = | last11 = Lam | first11 = Alfred | authorlink11 = | last12 = Staines | first12 = Donald | authorlink12 = Donald Staines | date = 2018-05-31|access-date=| title=Decreased Expression of TRPM3 and mAChRM3 in the Small Intestine in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis|url=http://www.scirp.org/journal/PaperInformation.aspx?PaperID=85005&#abstract|journal=International Journal of Clinical Medicine|language=en|volume=09|issue=05|pages=467|doi=10.4236/ijcm.2018.95040|via=|pmc=|pmid=|quote=}}</ref> - [http://file.scirp.org/Html/11-2101759_85005.htm (Full text)]

*2016, Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients<ref name="Marshall2016">{{Cite journal | last =Marshall-Gradisnik | first = S.M. | author-link = Sonya Marshall-Gradisnik | last2 = Chacko | first2 = A. | authorlink2 = A Chacko | last3 = Johnston | first3=S. | author-link3 = Samantha Johnston | last4 = Smith | first4 = P. | authorlink4 = Peter Smith| last5 = Nilius | first5 = B. | authorlink5 = B Nilius | last6 = Staines | first6 = D.R. | authorlink6 = Donald Staines | date = 2016-01-01 | title = Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients|url=https://doi.org/10.4137/III.S37042|journal=Immunology and Immunogenetics Insights|language=en|volume=8|issue=|pages=III.S37042|doi=10.4137/III.S37042|issn=1178-6345|quote=|via=}}</ref> - [https://journals.sagepub.com/doi/full/10.4137/III.S37042 (Full text)]
*2016, ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients<ref name="Huth2016">{{Cite journal | last =Huth | first = Teilah Kathryn | author-link = Teilah Huth | last2 = Staines | first2=Donald | authorlink2 = Donald Staines | last3 = Marshall-Gradisnik | first3 = Sonya | author-link3 = Sonya Marshall-Gradisnik | date = 2016-04-21 | title = ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56dimCD16+ and CD56brightCD16dim/− natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients|url=https://doi.org/10.1186/s12967-016-0859-z|journal=Journal of Translational Medicine|volume=14|issue=1 | pages = 97|doi=10.1186/s12967-016-0859-z|issn=1479-5876|pmc=4839077|pmid=27098723|quote=|via=}}</ref> - [http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-016-0859-z (Full text)
*2016, Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients<ref name="Nguyen2016">{{Cite journal | last =Nguyen | first = T. | author-link = Thao Nguyen | last2 = Staines | first2= D. | authorlink2 = Donald Staines | last3 = Nilius | first3=B. | author-link3 = B Nilius | last4 = Smith | first4 = P. | authorlink4 = Peter Smith| last5 = Marshall-Gradisnik | first5 = S. | authorlink5 = Sonya Marshall-Gradisnik | date = 2016-05-31 | title = Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients|url=https://doi.org/10.1186/s40659-016-0087-2|journal=Biological Research|volume=49|issue=1|pages=27|doi=10.1186/s40659-016-0087-2|issn=0717-6287|pmc=4888729|pmid=27245705|quote=|via=}}</ref> - [https://biolres.biomedcentral.com/articles/10.1186/s40659-016-0087-2 (Full text)]

*2015, Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients]<ref name="Marshall2015">{{Cite journal | last =Marshall-Gradisnik | first = Sonya M. | author-link = Sonya Marshall-Gradisnik | last2 = Smith | first2 = Peter | authorlink2 = Peter Smith | last3 = Brenu | first3 = Ekua W. | author-link3 = Ekua Brenu | last4 = Nilius | first4=Bernd | author-link4 = Bernd Nilius| last5 = Ramos | first5 = Sandra B. | authorlink5 = Sandra Ramos | last6 = Staines | first6 = Donald R. | date = 2015-01-01 | title = Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients|url=https://doi.org/10.4137/III.S25147|journal=Immunology and Immunogenetics Insights|language=en|volume=7|issue=|pages=III.S25147|doi=10.4137/III.S25147|issn=1178-6345|quote=|via=}}</ref> - [https://journals.sagepub.com/doi/full/10.4137/III.S25147 (Abstract)] - small study - 115 people with ME/CFS
*2015, Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis<ref name="NKcells-2015">{{Cite journal | last =Huth | first = T.K. | authorlink = Teilah Huth | last2 = Brenu | first2 = E.W. | authorlink2 = Ekua Brenu | last3 = Ramos | first3=S. | author-link3 = Sandra Ramos | last4 = Nguyen | first4=T. | authorlink4 = Thao Nguyen| last5 = Broadley | first5 = S. | authorlink5 = Simon Broadley | last6 = Staines | first6 = D. | authorlink6 = Donald Staines | last7 = Marshall‐Gradisnik | first7 = S. | authorlink7 = Sonya Marshall-Gradisnik | date = 2016 | title=Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/sji.12388|journal=Scandinavian Journal of Immunology|language=en|volume=83|issue=1|pages=44–51|doi=10.1111/sji.12388|issn=1365-3083|quote=|via=}}</ref> - [https://onlinelibrary.wiley.com/doi/10.1111/sji.12388/abstract (Abstract)

==News and blogs==
* Dec 19, 2019, [http://simmaronresearch.com/2019/12/naltrexone-natural-killer-cells-chronic-fatigue-syndrome/ Finally Found – A Natural Killer Cell Enhancer for ME/CFS?] - Cort Johnson

==See also ==
*[[Transient receptor potential melastatin 2]]
*[[Ion channel]]
*[[Diagnostic biomarker]]
*[[Natural killer cell]]
*[[Plasma]]
*[[Ion transportation]]
*[[Transient receptor potential]]
*[[Channelopathy]]
*[[National Centre for Neuroimmunology and Emerging Diseases]]

==Learn more ==

==References ==
{{Reflist}}

[[Category:Immunology]]
[[Category:Anatomy]]
[[Category:Genes]]
[[Category:Biochemistry and cell biology]]
[[Category:Channelopathy]]
[[Category:Energy system]]

Low dose naltrexone

2026-08-05T21:54:07Z

Tuxedocaspy:/* Do not take with */ Added citations to clarify contraindications and other findings of taking LDN with other substances. Used sources to change and provide nuance for substances previously listed as advised against on the page.

'''Low Dose Naltrexone''' (LDN) refers to very small doses of the drug '''naltrexone hydrochloride''', which at higher doses treats drug or [[alcohol]] dependence. Low dose naltrexone may reduce [[pain]], or potentially [[Nervous system|neurological]] symptoms. Brand names of naltrexone include '''ReViva''', '''Depade''', and '''Vivitrol'''.<ref name="brands">{{Cite web|url=https://www.drugs.com/ingredient/naltrexone.html | title = Naltrexone - brand name list from Drugs.com|website=Drugs.com|language=en|access-date=2022-01-17}}</ref>
LDN use other for treating drug dependence is considered off-label. Some patients report that LDN helps reduce their symptoms of [[ME/CFS]], [[Long COVID]], [[fibromyalgia]] (FMS), [[multiple sclerosis]] (MS), or [[autoimmune disease]].<ref>{{Cite journal|title=Low-dose naltrexone as a treatment for chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/31911410/|journal=BMJ case reports|date=2020-01-06|issn=1757-790X|pmc=6954765|pmid=31911410|pages=e232502|volume=13|issue=1|doi=10.1136/bcr-2019-232502|first=Monica Jane|last=Bolton|first2=Bryan Paul|last2=Chapman|first3=Harm|last3=Van Marwijk}}</ref><ref>{{Cite journal|title=Low-dose naltrexone use for the management of post-acute sequelae of COVID-19|url=https://www.sciencedirect.com/science/article/pii/S1567576923012912|journal=International Immunopharmacology|date=2023-11-01|issn=1567-5769|pmc=11028858|pmid=37804660|pages=110966|volume=124|doi=10.1016/j.intimp.2023.110966|language=en-US|first=Hector|last=Bonilla|first2=Lu|last2=Tian|first3=Vincent C.|last3=Marconi|first4=Robert|last4=Shafer|first5=Grace A.|last5=McComsey|first6=Mitchel|last6=Miglis|first7=Philip|last7=Yang|first8=Andres|last8=Bonilla|first9=Lauren|last9=Eggert|first10=Linda N.|last10=Geng}}</ref><ref>{{Cite journal|title=Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization|date=2018-09-21|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313374/|journal=Medical Sciences|volume=6|issue=4|pages=82|last=Toljan|first=Karlo|last2=Vrooman|first2=Bruce|doi=10.3390/medsci6040082|pmc=6313374|pmid=30248938|issn=2076-3271}}</ref><ref>{{Cite journal|title=Efficacy of Low-Dose Naltrexone and Predictors of Treatment Success or Discontinuation in Fibromyalgia and Other Chronic Pain Conditions: A Fourteen-Year, Enterprise-Wide Retrospective Analysis|url=https://www.mdpi.com/2227-9059/11/4/1087|journal=Biomedicines|date=2023-04-03|issn=2227-9059|pmc=PMC10135963|pmid=37189705|pages=1087|volume=11|issue=4|doi=10.3390/biomedicines11041087|language=en|first=C. Noelle|last=Driver|first2=Ryan S.|last2=D’Souza}}</ref><ref>{{Cite web|url=https://ldnresearchtrust.org/sites/default/files/LDN_Side_Effects_Results_2021.pdf|title=Results of the LDN Side Effects Survey|last=Brook|first=Jill|website=LDN Research Trush|access-date=2024-06-07}}</ref> Although its mechanism of action is unclear, some have speculated that it may act as an anti-inflammatory.<ref name="Younger2014" />

==Prescription forms ==
LDN is typically prescribed using generic naltrexone hydrochloride or branded naltrexone, divided into much smaller doses. LDN may be taken in the form of liquid solution/syrup, sublingual doses or 1.5mg capsules, or a compounding pharmacy can create smaller sized capsules or tablets. LDN in the form of naltrexone cream, subcutaneous injections, IV naltrexone and eye drops (for [[Sjögren's syndrome|dry eyes]]) are also available.<ref name="forms">{{Cite web|url=https://ldnresearchtrust.org/types-of-ldn | title = Types of LDN | last = | first = | authorlink = | date = | website = LDN Research Trust |language=en|archive-url=|archive-date=|url-status=|access-date=2022-01-17}}</ref>

== VLDN and ULDN ==
'''Very Low Dose Naltrexone''' (VLDN) and '''Ultra-Low Dose Naltrexone''' (ULDN) have recently been used in limited trials, both VLDN and ULDN involve doses of naltrexone significantly below 1mg.<ref>{{Cite journal | last = Toljan | first = Karlo | author-link =Karlo Toljan | last2 = Vrooman | first2 = Bruce | authorlink2 = Bruce Vrooman | date = Sep 21, 2018 | title = Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313374/|journal=Medical Sciences|volume=6|issue=4|pages=|doi=10.3390/medsci6040082|issn=2076-3271|pmc=|pmid=30248938|quote=|via=}}</ref>

Very Low Dose Naltrexone is increasingly being used under 1mg for people who cannot titrate from 0.5mg to find their individual optimal dose.
==Evidence==
[[File:LDN-Fibro2014.jpg|alt=Data shows a graph with 10% worse after treatment, 57% improved or much improved, and 12% very much improved. Darker colors are the most improved sections.|thumb|350x350px|Low Dose Naltrexone results for 29 patients with [[Fibromyalgia]]. Fibromyalgia participants’ (N = 29) self-reported improvement in symptoms after daily LDN treatment.
Source: Clin Rheumatol 2014; 33(4):452-459. Fig 1.<ref name="Younger2014" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/figure/Fig1/ PMC3962576] ]]

[[Jarred Younger]] published a small study that concluded "...low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia".<ref name="Younger2009" /><ref name="Mackey2009" />

A second study concluded that "specific and clinically beneficial impact on fibromyalgia pain".<ref name="Younger2013" /><ref>{{Cite web|url=https://med.stanford.edu/pain/snapl/completed-research/naltrexone2.html | title = Low Dose Naltrexone for Fibromyalgia|website=Systems Neuroscience and Pain Lab {{!}} Stanford Medicine|language=en|access-date=2018-10-04 | date = |last = | first = | authorlink = |archive-url=|archive-date=|url-status=}}</ref>

A 2014 review by Stanford researchers suggests that "LDN may operate as a novel anti-inflammatory agent in the [[central nervous system]], via action on [[microglia]]l cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on [[opioid]] receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated."<ref name="Younger2014" />
[[File:LDN-Fibro-ESR.jpg|thumb|420x420px|Relationship between ESR, a marker inflammation, and LDN treatment in 29 patients with [[Fibromyalgia]]. ]]
The [[FDA]] approved naltrexone HCL in 1984 to treat opioid addiction. Low-dose naltrexone is typically given at about 1/10th the typical dose of naltrexone. By blocking opioid receptors, naltrexone can increase pain, but at very low doses naltrexone has both pain-reducing ([[analgesic]]) and anti-inflammatory properties.

In 2012 [[Solve ME/CFS Initiative]] contracted [[Biovista]] to use drug models to identify existing drugs that may be worth investigating for treatment. The results suggested Naltrexone was worth considering.<ref>{{Cite web|url=http://solvecfs.org/biovista-work-released | title = Biovista work released|last = Solve ME/CFS Initiative | first = | authorlink = Solve ME/CFS Initiative | date = |website=|archive-url=|archive-date=|access-date=|url-status=live}}</ref>

Jarred Younger's research suggests that people with an [[Erythrocyte sedimentation rate|Erythrocyte Sedimentation Rate]] (ESR) over 40 millimeters an hour, tend to be strong responders to LDN, and that there may be other predictive factors for success.<ref name="Younger20160329sh" />

==News articles==
* 2019, [https://www.npr.org/sections/health-shots/2019/09/23/741783834/in-tiny-doses-an-addiction-medication-moonlights-as-a-treatment-for-chronic-pain In Tiny Doses, An Addiction Medication Moonlights As A Treatment For Chronic Pain] - NPR, All Things Considered
* September 9, 2021<nowiki/>https://www.empr.com/home/news/drugs-in-the-pipeline/low-dose-naltrexone-designated-orphan-drug-for-complex-regional-pain-syndrome/

==Clinical use==

Naltrexone is a prescription drug in many countries including the [[United States]].<ref name="naltrexonecompliance">{{Cite journal | last = Feeney|first = G. F. X. | last2 = Connor | first2 = J.P. | last3 = Young | first3 = R. McD | last4 = Tucker | first4 = J. | last5 = Czajkowski | first5 = F. | date = 2001 | title = Adherence with naltrexone prescription advice in hospital outpatient alcohol rehabilitation programme|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2710.2001.00326.x|journal=Journal of Clinical Pharmacy and Therapeutics|language=en|volume=26|issue=1 | pages = 73–79|doi=10.1111/j.1365-2710.2001.00326.x|issn=1365-2710}}</ref> Compounding chemists or compounding pharmacists can mix naltrexone with a powder filler or dilute in into a liquid to create the lower dose.

=== Fast-release fillers only ===
The LDN Research Trust advises that:
"Pharmacies should be instructed NOT to provide LDN in an "SR" or slow-release or timed-release form. Unless the low dose of naltrexone is in an unaltered form, which permits it to reach a prompt "spike" in the blood stream, its therapeutic effects may be inhibited."<ref name="leaflet2014" /> and states that calcium carbonate filler should NOT be used because they reduce absorption, instead Avicel, lactose, or sucrose fillers as alternative fast-release fillers."<ref name="leaflet2014">{{Cite web|url=https://ldnresearchtrust.org/sites/default/files/Doctors-info-pack-US.pdf | title=Low-dose Naltrexone (LDN) Fact Sheet 2014 | website = LDN Research Trust | date = 2014}}</ref>

===Do not take with===
In general, Low Dose Naltrexone (LDN) should not be taken concurrently with opioid-containing drugs (opioid receptors in brain are blocked by LDN).<ref>https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf</ref> LDN blocks the effect of opioid drugs.<ref name="chronicpain">{{Cite web|url=https://www.ldnresearchtrust.org/content/low-dose-naltrexone-and-chronic-pain-pradeep-chopra-md | title = Low Dose Naltrexone and chronic pain | first = Pradeep |last =Chopra|website=LDN Research Trust|access-date=2019-01-31}}</ref> Some opioid drugs are [[codeine]], [[oxycodone]], [[vicodin]], [[hydrocodone]], [[fentanyl]] and [[morphine]]. Alcohol consumption is not contraindicated by naltrexone, and the FDA cites potential benefits in treating alcoholism with standard doses of naltrexone. The American Addiction Center also claims no significant effects when the two are taken together.<ref>https://americanaddictioncenters.org/alcohol/rehab-treatment/mixing-with-naltrexone</ref> The LDN Research Trust Org states LDN can be taken with immunosuppressive drugs, with some people finding LDN mitigating adverse effects of immunosuppressants.<ref>https://ldnresearchtrust.org/can-i-take-ldn-immune-suppressants</ref> LDN is itself an immunomodulator<ref>{{Cite journal|title=Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy|date=2018-08|url=https://doi.org/10.1016/j.intimp.2018.05.020|journal=International Immunopharmacology|volume=61|pages=178–184|last=Li|first=Zijian|last2=You|first2=Yue|last3=Griffin|first3=Noreen|last4=Feng|first4=Juan|last5=Shan|first5=Fengping|doi=10.1016/j.intimp.2018.05.020|issn=1567-5769}}</ref>, and its combined use with other immunomodulators falls under more scrutiny. Studies have demonstrated little pharmokinetic interactions with other medications, but caution and monitoring are suggested in certain cases.<ref>https://healthrx.com/low-dose-naltrexone/drug-drug-interactions#immunosuppressants-and-immunomodulators</ref>

Some people include tramadol in the list of opioid containing drugs, but tramadol works differently. Per Skip Lenz, a pharmacist and LDN expert -

From the Q&A section of the first LDN Book:

"It should be well known that LDN cannot be taken with opiate pain medications such as oxycontin or morphine. However, I have long recommended that patients who must take pain medications consider tramadol, which is not an opiate, but works on similar receptors. The only problem can be with the amount of tramadol you can take over a period of a day. Large amounts, that is, over 300 mg per day, have been reported to be problematic, but to my knowledge, lower doses (50 mg taken two or three times a day) have not presented any problems for patients while are on LDN."

This situation would only apply to people well established on LDN, as would using opioids with LDN at the opposite ends of the day.

==Pharmacies ==

=== Australia ===
''Compounding Pharmacies'' are able to fill these prescriptions, and post if needed.

=== UK ===
LDN suppliers in the UK include '''Dickson Chemist''' in Glasgow, '''Roseway Labs''', and Specialist Pharmacy (The London Specialist Pharmacy Ltd). All these are compounding pharmacies and require a prescription, they are usually able to put patients in contact with private doctors who will consider writing a prescription, and can post medications to you.<ref name="RosewayLabs">{{Cite web |url = https://rosewaylabs.com/compounding-processes-regulations | title = Compounding processes regulations/|website =Roseway Labs}}</ref> Compounding pharmacies are regulated by the UK's General Pharmaceutical Council.<ref name="RosewayLabs" />

===United States===
Neighborhood ''Compounding Pharmacies'' are able to fill these prescriptions and mail if needed. Your prescribing doctor can help you locate a compounding pharmacy in your area/state or you can look online.<ref>[http://www.wikihow.com/Find-a-Compounding-Pharmacy Finding a Compounding Pharmacy - WIKI How]</ref>

===Other countries ===
'''Roseway Labs''' supplies LDN in the EU. The LDN Research Trust lists pharmacies in multiple countries.<ref name="sources">{{Cite web |url = https://ldnresearchtrust.org/ldn-pharmacists|website=LDN Research Trust|title =LDN Pharmacists |access-date =}}</ref>

== Clinical trials ==
A large number of clinical trials have been completed for LDN recently, including ones that have looked at the effect of LDN on symptoms of [[myalgic encephalomyelitis]]/[[chronic fatigue syndrome]]. Research has also been carried out on patients with MS, [[Chronic Regional Pain Syndrome]], FMS, [[Irritable bowel syndrome|Irritable Bowel Syndrome]] (IBS), Ulcerative Colitis, Skin Disorders and a range of other illnesses.<ref name="trials">{{Cite web|url=https://www.ldnresearchtrust.org/ldn-clinical-trials | title = Clinical Trials|website=LDN Research Trust|access-date=2019-01-21}}</ref>

==When, How To Take ==
Dr Whitaker states that the ideal dose is different for each person. Some doctors recommend starting at 1mg.<ref name="LDN-now">{{Cite web|url=http://www.ldnnow.com/48591/90512.html | title = LDN Dosing|last = LDN Now|first = | authorlink = | date = | website = |access-date=2018-02-01}}</ref> Common dosages are 1.5mg, 3mg, 4.5mg.<ref>{{Cite web|url=https://www.amymyersmd.com/2017/05/low-dose-naltrexone/ | title = Low-Dose Naltrexone for Autoimmunity? | last = Myers | date = 2017-05-02 | website = Amy Myers MD|language=en-US|access-date=2019-02-02|first = Amy | authorlink = |archive-url=|archive-date=|url-status=}}</ref><ref name=":1">{{Cite web|url=https://www.drwhitaker.com/what-is-low-dose-naltrexone | title = What is Low-Dose Naltrexone?|last = Dr Whitaker | first = | authorlink = | date = | website = drwhitaker.com|language=en|archive-url=|archive-date=|access-date=2019-01-21}}</ref><ref name="chronicpain" /> When beginning use of LDN, the drug must be stepped up over 6-8+ weeks as it may keep you awake; discuss how best to do this with your doctor and pharmacist.<ref name=":1" /><ref>{{Cite web|url=https://collierdrug.com/low-dose-naltrexone-ldn/ | title = Low Dose Naltrexone (LDN) – Collier Drug Store|last = | first = | authorlink = | date = | website = collierdrug.com|at=What dose of Low Dose Naltrexone (LDN) is best?|archive-url=|archive-date=|access-date=2019-02-02}}</ref><ref name="chronicpain" />

LDN is usually taken at bedtime. Some people take LDN in the morning to minimize [[Sleep dysfunction|sleep disturbance]], [[insomnia]], and vivid dreams.<ref name="chronicpain" />

== Talks and webinars==
*2012, [https://www.youtube.com/watch?v=z0p0ykSzy9o LDNscience® Presents - How LDN (Low Dose Naltrexone) Works]<ref>{{Cite web|url=https://www.youtube.com/watch?v=z0p0ykSzy9o | title = LDNscience® Presents - How LDN (Low Dose Naltrexone) Works|last = | first = | authorlink = | date = Dec 20, 2012 | website = YouTube|publisher=LDNscience|archive-url=|archive-date=|access-date=}}</ref>
<embedvideo service="youtube" dimensions="400" alignment="center" container="frame" description="''LDNscience® Presents - How LDN (Low Dose Naltrexone) Works'' By LDNscience">https://www.youtube.com/watch?v=z0p0ykSzy9o</embedvideo>

*2015, [https://www.youtube.com/watch?v=8a-ULCaarCQ Functional Medicine & LDN (low-dose naltrexone) with Drs Carnahan and Vasquez]<ref>{{Cite web|url=https://www.youtube.com/watch?v=8a-ULCaarCQ | title = Functional Medicine & LDN (low-dose naltrexone) with Drs Carnahan and Vasquez|last = Carnahan | first = Jill | authorlink= | last2 = Vasquez | first2 = Alex | authorlink2 = | date = Nov 30, 2015 | website = YouTube|publisher=Alex Vasquez|archive-url=|archive-date=|access-date=}}</ref>
<embedvideo service="youtube" dimensions="400" alignment="center" container="frame" description="''Functional Medicine & LDN (low-dose naltrexone) with Drs Carnahan and Vasquez '' By Alex Vasquez">https://www.youtube.com/watch?v=8a-ULCaarCQ</embedvideo>

*2015, [https://www.youtube.com/watch?v=Qnr51yU9ih8 Is Low Dose Naltrexone (LDN) for you?]<ref>{{Cite web|url=https://www.youtube.com/watch?v=Qnr51yU9ih8 | title = 1:05 / 7:05 Is Low Dose Naltrexone (LDN) for you?|last = | first = | authorlink = | date = Oct 11, 2015 | website = YouTube | archive-url=|archive-date=|access-date=}}</ref>
<embedvideo service="youtube" dimensions="400" alignment="center" container="frame" description="''Is Low Dose Naltrexone (LDN) for you?'' By Integrative Health Solutions">https://www.youtube.com/watch?v=Qnr51yU9ih8</embedvideo>

==Notable studies==
* 2009, Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study<ref>{{Cite journal|last = Younger | first = Jarred | authorlink = Jarred Younger | last2 = Mackey | first2 = Sean | authorlink2 = | date = May 2009 | title = Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study|url=https://academic.oup.com/painmedicine/article-lookup/doi/10.1111/j.1526-4637.2009.00613.x|journal=Pain Medicine|language=en|volume=10|issue=4 | pages = 663–672|doi=10.1111/j.1526-4637.2009.00613.x|issn=1526-2375|pmc=2891387|pmid=19453963|access-date=|quote=|via=}}</ref> - [[pmc:2891387/|(Full text)]]
* 2013, Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels<ref name="Younger2013" /> - [https://onlinelibrary.wiley.com/doi/full/10.1002/art.37734 (Full text)]
* 2014, The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain<ref name="Younger2014" /> - [http://link.springer.com/article/10.1007%2Fs10067-014-2517-2 (Full text)]
*2018, Double-blinded placebo-controlled cross-over pilot trial of naltrexone to treat [[Gulf War Illness]]<ref name="Brewer, 2018" /> - [https://www.tandfonline.com/doi/full/10.1080/21641846.2018.1477034 (Abstract)]

* 2018, Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization<ref>{{Cite journal | last = Toljan | first = Karlo | last2 = Vrooman | first2 = Bruce | date = 2018-09-21 | title = Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization | url = http://www.mdpi.com/2076-3271/6/4/82|journal=Medical Sciences|language=en|volume=6|issue=4 | pages = 82|doi=10.3390/medsci6040082|issn=2076-3271|pmc=6313374|pmid=30248938}}</ref> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313374/#!po=19.1057 (Full text)]

* 2019, Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)<ref name="Polo2019">{{Cite journal | last = Polo|first = Olli | authorlink = Olli Polo | last2 = Pesonen | first2 = Pia | authorlink2 = | last3 = Tuominen | first3 = Essi | authorlink3 = | date = 2019-11-19 | title = Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2019.1692770|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=7|issue=4|pages=207-217|doi=10.1080/21641846.2019.1692770|issn=2164-1846|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.tandfonline.com/doi/abs/10.1080/21641846.2019.1692770?journalCode=rftg20 (Abstract)]
* 2020, Low-dose naltrexone as a treatment for chronic fatigue syndrome<ref>{{Cite journal|last = Bolton | first = Monica Jane | authorlink = | last2 = Chapman | first2 = Bryan Paul | authorlink2 = | last3 = Van Marwijk | first3 = Harm | authorlink3 = | date = Jan 2020 | title = Low-dose naltrexone as a treatment for chronic fatigue syndrome|url=http://casereports.bmj.com/lookup/doi/10.1136/bcr-2019-232502|journal=BMJ Case Reports|language=en|volume=13|issue=1| pages = e232502|doi=10.1136/bcr-2019-232502|issn=1757-790X|pmc=6954765|pmid=31911410|access-date=|quote=|via=}}</ref> - [https://casereports.bmj.com/content/bmjcr/13/1/e232502.full.pdf (Full text)]
*2021, Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment<ref name="Cabanas2021">{{Cite journal | title = Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment | date = 2021|url=https://www.frontiersin.org/articles/10.3389/fimmu.2021.687806|journal=Frontiers in Immunology|volume=12|issue= | pages = 687806|last = Cabanas | first = Helene | authorlink = Hélène Cabanas | last2 = Muraki | first2 = Katsuhiko | authorlink2 = | last3 = Eaton-Fitch | first3 = Natalie | authorlink3 = Natalie Eaton-Fitch | last4 = Staines | first4 = Donald Ross | authorlink4 = Donald Staines | last5 = Marshall-Gradisnik | first5 = Sonya | authorlink5 = Sonya Marshall-Gradisnik|doi=10.3389/fimmu.2021.687806|pmc=PMC8313851|pmid=34326841|access-date=|issn=1664-3224|quote=|via=}}</ref> - [https://www.frontiersin.org/articles/10.3389/fimmu.2021.687806/full (Full text)]

==See also==
*[[Endorphin]]
*[[Brain#Microglia|Microglia]]
*[[Oxymatrine]]
*[[The LDN Book]]

==Learn more==
*[https://ldnresearchtrust.org/sites/default/files/Doctors-info-pack-US.pdf Low-dose Naltrexone (LDN) Doctor's Fact Sheet 2014] - LDN Research Trust
*[https://www.ldnresearchtrust.org LDN Research Trust]<ref>{{Cite web|url=https://www.ldnresearchtrust.org/ | title = Low Dose Naltrexone {{!}}|website=LDN Research Trust|access-date=2019-02-02}}</ref>
*[https://www.ldnresearchtrust.org/content/low-dose-naltrexone-and-chronic-pain-pradeep-chopra-md Low Dose Naltrexone and chronic pain]<ref name="chronicpain" />
*[https://en.wikipedia.org/wiki/Naltrexone Wikipedia - Naltrexone]
*[http://www.ldnnow.com/ LDN Now]
*[https://www.ldnscience.org/ LDN Science - MedInsight Research Institute]
*2015, [https://www.ncbi.nlm.nih.gov/books/NBK390569/ The Use of Naltrexone in Low Doses Beyond the Approved Indication]<ref name="NBK390569">{{Citation | url = https://www.ncbi.nlm.nih.gov/books/NBK390569/ | title = The Use of Naltrexone in Low Doses Beyond the Approved Indication|last = Ringerike | first = Tove | last2 = Pike | first2 = Eva | last3 = Nevjar | first3 = Janicke | last4 = Klemp | first4 = Marianne|publisher=NIPH| year = 2015 |isbn=|location=}}</ref>
* [https://selfhacked.com/2016/06/20/top-22-scientific-health-benefits-low-dose-naltrexone/ Top 15 Scientific Health Benefits of Low Dose Naltrexone] (2016)
*[https://www.healthrising.org/treating-chronic-fatigue-syndrome/drugs/low-dose-naltrexone-ldn-fibromyalgia-chronic-fatigue-syndrom/ Low Dose Naltrexone Resource Center for Fibromylgia and ME/CFS] (2019)
*2016, [http://www.rheumatologyadvisor.com/fibromyalgia/using-low-dose-naltrexone-in-fibromyalgia/article/478182/ Low-Dose Naltrexone as Adjunctive Pharmacotherapy for Fibromyalgia]
*[[The LDN Book]] - Lisa Elsegood (2016)
*[http://www.cortjohnson.org/blog/2016/02/04/low-dose-naltrexone-combo-chronic-fatigue/ 2016, Low Dose Naltrexone Drug Combination Proposed for Chronic Fatigue Syndrome] - Health Rising, by [[Cort Johnson]] (2016)
*[https://cfsremission.wordpress.com/2016/03/19/review-of-low-dose-naltrexone/ Low dose naltrexone: side effects and efficacy in gastrointestinal disorders] by [[CFS Remission]] (2016)
*Opioid blocking and alcohol - [http://www.well.com/user/woa/revia/reviafaq.htm FAQ About Naltrexone Treatment for Alcoholism - 10.]
*[https://www.cfspharmacy.pharmacy/blog/post/low-dose-naltrexone-for-fibromyalgia Low Dose Naltrexone for Fibromyalgia] (2018)
* [https://www.cfspharmacy.pharmacy/blog/post/low-dose-naltrexone-therapy-for-crohn-s-disease Low Dose Naltrexone Therapy for Crohn's Disease] (2018)
* [https://www.facebook.com/groups/200010163370187 LDN LOW DOSE NALTREXONE FOR ME/CFS MYALGIC ENCEPHALOMYELITIS & FIBROMYALGIA]

==References==
<references>
<ref name="Brewer, 2018">{{Cite journal | last1 = Brewer | first1 = Kori L. | authorlink1 = | last2 = Mainhart | first2 = Allison | authorlink2 = | last3 = Meggs | first3 = William J. | authorlink3 = | title = Double-blinded placebo-controlled cross-over pilot trial of naltrexone to treat Gulf War Illness | journal = Fatigue: Biomedicine, Health & Behavior | volume = 6 | issue = 3 | pages = 132-140 | date = 2018 | pmid = | url = https://ldnresearchtrust.org/double-blinded-placebo-controlled-cross-over-pilot-trial-naltrexone-treat-gulf-war-illness-abstract | doi = 10.1080/21641846.2018.1477034}}</ref>
<ref name="Younger2009">{{Cite journal | last1 = Younger | first1 = Jarred | authorlink1 = Jarred Younger | last2 = Mackey | first2 = Sean | authorlink2 = Sean Mackey | title = Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study | journal = Pain Med | volume = 10 | issue = 4 | pages = 663–672 | date = Apr 22, 2009 | pmid = 2891387 | doi = 10.1111/j.1526-4637.2009.00613.x | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891387/ }}</ref>
<ref name="Younger2013">{{Cite journal | last1 = Younger | first1 = Jarred | authorlink1 = Jarred Younger | last2 = Noor | first2 = Noorulain | authorlink2 = Noorulain Noor | last3 = McCue | first3 = Rebecca| authorlink3 = Rebecca McCue | last4 = Mackey | first4 = Sean | authorlink4 = Sean Mackey | title = Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels | journal = Arthritis Rheum | volume = 65 | issue = 2 | pages = 529-38 | date = Jan 28, 2013 | pmid = 23359310 | doi = 10.1002/art.37734 | url = http://onlinelibrary.wiley.com/enhanced/doi/10.1002/art.37734/}}</ref>
<ref name="Mackey2009">{{Cite web | last1 = Mackey | first1 = Sean | authorlink1 = Sean Mackey | title = An Update on Fibromyalgia
| publisher = Research Channel (USA) | date = May 1, 2009 | url = https://www.youtube.com/watch?v=jtc2JARVpPw}}</ref>
<ref name="Younger2014">{{Cite journal | last1 = Younger | first1 = Jarred | authorlink1 = Jarred Younger | last2 = Parkitny | first2 = Luke | authorlink2 = Luke Parkitny | last3 = McLain | first3 = David | authorlink3 = David McLain | title = The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain | journal = Clin Rheumatol | volume = 33 | issue = 4 | pages = 451-459 | date = Feb 15, 2014 | pmid = 24526250 | doi = 10.1007/s10067-014-2517-2 | url = http://link.springer.com/article/10.1007%2Fs10067-014-2517-2}}</ref>
<ref name="Younger20160329sh">{{Cite web | last1 = Younger | first1 = Jarred | authorlink1 = Jarred Younger | last2 = Cohen | first2 = Joseph M | authorlink2 = Joseph Cohen | title = Dr. Jarred Younger: Cutting Edge Research on CFS, Neuroinflammation, Pain, and Fatigue
| type = video interview with transcript
| publisher = Self Hacked Blog | date = Mar 29, 2016 | url = http://selfhacked.com/2016/03/29/dr-jared-younger-cutting-edge-research-on-cfs-neuroinflammation-pain-and-fatigue/#Leptin_and_Chronic_Fatigue_Syndrome}}</ref>
</references>

[[Category:Potential treatments]]
[[Category:Anti-inflammatories]]
[[Category:Analgesics]]

Lymphocyte

2026-07-24T04:09:40Z

Tuxedocaspy:Expanded differentiation process of lymphocytes and the roles they play in the immune system, with citations

[[File:Lymphocyte.png|thumb|Lymphocyte. Source: University of Michigan, Webscope]]
'''Lymphocytes''' are a category of [[white blood cell]]s and play important roles in both the [[Innate immune system|innate]] and [[adaptive immune system]].<ref>Male, D. (2010). Immunology. 7th ed. [Philadelphia, Pa.]: Mosby Elsevier.</ref> Lymphocytes include [[natural killer cell]]s, [[T cell]]s, and [[B cell]]s.<ref>{{Cite web|url=https://opentextbc.ca/biology/chapter/12-2-innate-immunity/#fig-ch17_02_03 | title = 12.2 Innate Immunity – Concepts of Biology-1st Canadian Edition|website=opentextbc.ca|language=en-US|access-date=2018-10-08}}</ref> Lymphocytes circulate throughout the body via lymphatic fluid, also known as lymph, as part of the [[lymphatic system]].<ref>{{Cite journal|title=The physiology of lymphocyte migration through the single lymph node in vivo|date=1999-04|url=https://doi.org/10.1006/smim.1999.0163|journal=Seminars in Immunology|volume=11|issue=2|pages=73–83|last=Young|first=Alan J.|doi=10.1006/smim.1999.0163|issn=1044-5323}}</ref> Lymph circulates between blood, tissues, and lymph nodes, transporting immature lymphocytes for maturation, relocation of mature lymphocytes during immune surveillance, or distribute activated lymphocytes to respond to pathogens. Lymph nodes act as filters for lymph fluid and house populations of mature lymphocytes. Lymphocytes make up 40% of the immune cell population.<ref>R. Sender, Y. Weiss, Y. Navon, I. Milo, N. Azulay, L. Keren, S. Fuchs, D. Ben-Zvi, E. Noor, & R. Milo, The total mass, number, and distribution of immune cells in the human body, Proc. Natl. Acad. Sci. U.S.A. 120 (44) e2308511120, <nowiki>https://doi.org/10.1073/pnas.2308511120</nowiki> (2023).</ref>

Lymphocytes differentiate from a stem cell progenitor known as the common lymphoid progenitor in the bone marrow. B cells develop and mature in the bone marrow, while T cells mature in the [[thymus]]. During their maturation, both cell types undergo positive and negative selection of their surface B cell and T cell receptors for their respective cell types to ensure proper functionality while also removing cells with "self"-recognition, i.e., the ability to activate in response to the body itself. Positive selection checks if cells can activate in response to threats while negative selection removes autoreactive cells. Mature B and T cells reside in lymph nodes and await presentation of an antigen before activating as part of the adaptive immune system.

Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system and do not require activation prior to their cytotoxic behavior. Instead, they recognize missing [[major histocompatibility complex]] (MHC) class I surface proteins and other receptors to identify tumor cells or cells infected by viruses.<ref name=":0">Paul S, Lal G. The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy. Front Immunol. 2017 Sep 13;8:1124. doi: 10.3389/fimmu.2017.01124. PMID: 28955340; PMCID: PMC5601256.

</ref> Receptors on NK cells are both activating and inhibiting cytotoxicity: receptors binding to MHC I suppress activation, while receptors binding to stress-associated molecules pushes NK cells towards activation. This mechanism not only allows NK cells to respond rapidly, but also target damaged cells evading "killer" T cells by suppressing MHC I expression. Activated NK cells release cytokines to signal further immune involvement, such as [[Interferon gamma|interferon-γ]], [[Tumor necrosis factor alpha|tumor necrosis factor-α]], [[Interleukin]] (IL)-5, IL-10, IL-13.<ref name=":0" /> These cells also play a role in clearing senescent cells.

{{Clear}}
[[File:Lymphocyte-B-cell.png|thumb|200x200px|Lymphocyte B cell (illustration)]]
{{Clear}}
[[File:Lymphocyte-Tcell.png|thumb|200x200px|Lymphocyte T cell (illustration)]]
{{Clear}}

== See also ==
* [[B cell|B cells]]
* [[T cell|T cells]]
* [[Natural killer cell]]
* [[Leucocyte|Leucocytes]] (white blood cells)
* [[Red blood cell|Red blood cells]]
* [[Innate immune system|Innate Immune System]]
* [[Immune system|Adaptive Immune System]]

== Learn more ==
[https://opentextbc.ca/anatomyandphysiology/chapter/18-4-leukocytes-and-platelets/ Leucocytes and platelets] - OpenStax
[https://opentextbc.ca/biology/chapter/12-2-innate-immunity/#fig-ch17_02_03 Innate Immunity] - OpenStax

== References ==
{{Reflist}}

[[Category:Body systems]]
[[Category:Immune cells]]
[[Category:Immunology]]
[[Category:Blood components]]

Catecholamine

2026-07-24T03:13:14Z

Tuxedocaspy:Linked to the orphan beta adrenergic receptor page, included content and a citation, cleaned up redundancies

{{stub}}
A '''catecholamine''' is a [[monoamine]], an organic compound that has a catechol (benzene with two hydroxyl side groups at carbons 1 and 2) and a side-chain amine. They are derived from the amino acid [[tyrosine]], which is sourced from diet, or from hydroxylation of [[phenylalanine]], another amino acid. Tyrosine may be modified first into [[dopamine]], then into [[norepinephrine]], or even further into [[epinephrine]] before being released into blood circulation or act locally. Dopamine is a [[central nervous system]] neurotransmitter and neuromodulator produced in the brain which regulates behavior as well as motor control.<ref>Khalil B, Rosani A, Warrington SJ. Physiology, Catecholamines. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK507716/</nowiki></ref> Norepinephrine and epinephrine, also neurotransmitters and neuromodulators, are released by the [[adrenal gland]] with roles in activating the fight-or-flight response of the [[autonomic nervous system]]. Norepinephrine and epinephrine effect cells through binding both [[Alpha adrenergic receptor|alpha]] and [[Beta adrenergic receptor|beta adrenergic receptors]] on various tissues with different affinities depending on receptor type. Dopamine binds primarily to dopamine receptors, but is also known to bind adrenergic receptors at sufficiently high concentrations.

[[Category:Neurotransmitters and hormones]]

Nicotinamide

2026-07-24T02:43:12Z

Tuxedocaspy:Added citations, minor edits

{{Cleanup/Citations needed | date = Oct 2020}}
'''Nicotinamide''' (niacinamide) is a form of [[niacin|vitamin B3]] (niacin). Nicotinamide, (/ˌnɪkəˈtɪnəmaɪd/) also known as niacinamide, NAA, and nicotinic amide, is the amide of nicotinic acid (niacin). Nicotinamide is a water-soluble [[B vitamin]].

Nicotinic acid is converted to nicotinamide in vivo, and, though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacological and toxic effects as [[niacin]], which occurs incidental to niacin's conversion. Nicotinamide does not reduce cholesterol or cause flushing, although it may be toxic to the liver at doses exceeding 3g/day in adults. In cells, niacin is incorporated into nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), although the pathways for nicotinic acid amide and nicotinic acid are very similar. [[NAD+]] and [[NADP+]] are coenzymes in a wide variety of enzymatic oxidation-reduction reactions. Commercial production of niacin and niacinamide relies on chemical synthesis from methylpyridines and amounted to 34,000 tons of niacin in 2014.<ref>Lisicki D, Nowak K, Orlińska B. Methods to Produce Nicotinic Acid with Potential Industrial Applications. Materials (Basel). 2022 Jan 20;15(3):765. doi: 10.3390/ma15030765. PMID: 35160711; PMCID: PMC8836525.</ref> Uses for bulk-produced niacin include feed additives, pharmaceutical use, and further industrial applications.

[[Small intestinal bacterial overgrowth]] is one known cause of nicotinamide deficiency.<ref>Burnett, B., Young, H., Panas, R., Klein, G., Mah'moud, M., & Anderson, M. (2015). Management of Small Intestinal Bacterial Overgrowth, (SIBO) Through Dietary and Nutritional Intervention: 2401. ''American Journal of Gastroenterology'', ''110'', S997.</ref>

Niacinamide flush-free supports the [[Mitochondrion|mitochondrial]] function.
Nicotinamide riboside improves the [[energy metabolism]]<ref>[https://www.nature.com/articles/ncomms12948 Nicotinamide riboside is uniquely and orally bioavailable in mice and humans]</ref> and [[neuroprotection]]<ref>[https://www.ncbi.nlm.nih.gov/pubmed/24071780 Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection.]</ref>.

It seems that it also works against [[multi-drug resistant germ]]s<ref>[https://www.aerzteblatt.de/nachrichten/51773/Studie-sieht-Nutzen-von-Vitamin-B3-gegen-Krankenhauskeime Study sees benefits of vitamin B3 against hospital germs (Deutsch: Studie sieht Nutzen von Vitamin B3 gegen Krankenhauskeime)]</ref>.

==Purpose==

==Sources==

==Evidence==
*2016, Treatment with the NAD+ precursor nicotinamide riboside (NR) rejuvenates stem cells, allowing better regeneration processes in aged mice. Beneficial for mitochondria, muscle stem cells, neural stem cells, melanocyte stem cells, and increased lifespan.<ref name="Zhang2016"/>

==ME/CFS==

==Learn more==
It is used in the ME/CFS treatment regime of patient [[Katrina Voss]]:
*[http://meversuscfs.blogspot.com/2018/06/arztanfragen-mein-therapieregime-fur.html My antiretroviral Regime for Antiretroviral Treatment of Myalgic Encephalomyelitis (Deutsch: #Arztanfragen - Mein Therapieregime für die antiretrovirale Behandlung bei Myalgischer Enzephalomyelitis)]

==See also==

==References==
<references>

<ref name="Zhang2016">{{citation | last1 = Zhang | first1 = Hongbo | last2 = Ryu | first2 = Dongryeol | last3 = Wu | first3 = Yibo | last4 = Gariani | first4 = Karim | last5 = Wang | first5 = Xu | last6 = Luan | first6 = Peiling | last7 = D’Amico | first7 = Davide | last8 = Ropelle | first8 = Eduardo R | last9 = Lutolf | first9 = Matthias P | last10 = Aebersold | first10 = Ruedi | last11 = Schoonjans | first11 = Kristina | last12 = Menzies | first12 = Keir J | last13 = Auwerx | first13 = Johan | title = NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice | journal = Science | pages = 2693 | date = 28 Apr 2016 | pmid = 27127236 | doi = 10.1126/science.aaf2693
| url = http://science.sciencemag.org/content/early/2016/04/27/science.aaf2693
| lay-url = https://www.sciencedaily.com/releases/2016/04/160428152124.htm }}</ref>

</references>

[[Category:Potential treatments]]
[[Category:Supplements]]
[[Category:Vitamins]]

Lymphocyte

2026-07-20T06:53:56Z

Tuxedocaspy:Added a citation, expanded a little

[[File:Lymphocyte.png|thumb|Lymphocyte. Source: University of Michigan, Webscope]]
'''Lymphocytes''' are a category of [[white blood cell]]s. <ref>Male, D. (2010). Immunology. 7th ed. [Philadelphia, Pa.]: Mosby Elsevier.</ref> Lymphocytes include [[natural killer cell]]s, [[T cell]]s, and [[B cell]]s.<ref>{{Cite web|url=https://opentextbc.ca/biology/chapter/12-2-innate-immunity/#fig-ch17_02_03 | title = 12.2 Innate Immunity – Concepts of Biology-1st Canadian Edition|website=opentextbc.ca|language=en-US|access-date=2018-10-08}}</ref> Lymphocytes circulate throughout the body via lymphatic fluid, also known as lymph, as part of the [[lymphatic system]].<ref>{{Cite journal|title=The physiology of lymphocyte migration through the single lymph node in vivo|date=1999-04|url=https://doi.org/10.1006/smim.1999.0163|journal=Seminars in Immunology|volume=11|issue=2|pages=73–83|last=Young|first=Alan J.|doi=10.1006/smim.1999.0163|issn=1044-5323}}</ref> Lymph and lymphocyte circulates between blood, tissues, and lymph nodes. Lymph nodes act as filters for lymph fluid and are centers for lymphocytes. Lymphocytes make up 40% of the immune cell population.<ref>R. Sender, Y. Weiss, Y. Navon, I. Milo, N. Azulay, L. Keren, S. Fuchs, D. Ben-Zvi, E. Noor, & R. Milo, The total mass, number, and distribution of immune cells in the human body, Proc. Natl. Acad. Sci. U.S.A. 120 (44) e2308511120, <nowiki>https://doi.org/10.1073/pnas.2308511120</nowiki> (2023).</ref>

{{Clear}}
[[File:Lymphocyte-B-cell.png|thumb|200x200px|Lymphocyte B cell (illustration)]]
{{Clear}}
[[File:Lymphocyte-Tcell.png|thumb|200x200px|Lymphocyte T cell (illustration)]]
{{Clear}}

== See also ==
* [[B cell|B cells]]
* [[T cell|T cells]]
* [[Natural killer cell]]
* [[Leucocyte|Leucocytes]] (white blood cells)
* [[Red blood cell|Red blood cells]]
* [[Innate immune system|Innate Immune System]]
* [[Immune system|Adaptive Immune System]]

== Learn more ==
[https://opentextbc.ca/anatomyandphysiology/chapter/18-4-leukocytes-and-platelets/ Leucocytes and platelets] - OpenStax
[https://opentextbc.ca/biology/chapter/12-2-innate-immunity/#fig-ch17_02_03 Innate Immunity] - OpenStax

== References ==
{{Reflist}}

[[Category:Body systems]]
[[Category:Immune cells]]
[[Category:Immunology]]
[[Category:Blood components]]

Alcohol

2026-07-20T06:24:57Z

Tuxedocaspy:Added a citation, added several examples of viruses and bacteria which are deactivated by ethanol

Alcohol is a class of organic, chemical compounds defined by the presence of a hydroxyl group attached to a carbon. Alcohol is not a medical treatment, but is frequently used in health-care settings to disinfectant surfaces in order to prevent the transmission of common [[virus]]es or [[bacteria]].<ref name="CDC-disinfection">{{Cite web | url = https://www.cdc.gov/infectioncontrol/guidelines/disinfection/disinfection-methods/chemical.html | title = Chemical Disinfectants {{!}} Disinfection & Sterilization Guidelines {{!}} Guidelines Library {{!}} Infection Control | date = 2019-04-04 | website = Centers for Disease Control and Prevention|language=en-us | access-date = 2021-12-12}}</ref>

===Ethyl alcohol===
Ethyl alcohol, also known as ethanol, is the active ingredient in alcoholic beverages. Ethanol is a [[central nervous system]] depressant and causes inebriation and intoxication when consumed. Ethanol is also used as a disinfectant against viruses and bacteria, with the most effective concentrations between 60-90% (volume/volume).<ref name="CDC-disinfect" /> The antimicrobial mechanism is based on protein denaturation in viruses and bacteria, leading to their inactivation. Ethanol has broad antibacterial effects that acts immediately, with activity against ''Staphylococcus aureus, Enteroccocus faecium, Mycobacterium tuberculosis'', among others''.''<ref>Kampf G, Kramer A.2004.Epidemiologic Background of Hand Hygiene and Evaluation of the Most Important Agents for Scrubs and Rubs. Clin Microbiol Rev 17:.<nowiki>https://doi.org/10.1128/cmr.17.4.863-893.2004</nowiki></ref> Ethanol is also known to be effective against enveloped viruses, including<ref name="CDC-disinfect" /><ref>{{Cite journal|title=Sensitivity Evaluation of Enveloped and Non-enveloped Viruses to Ethanol Using Machine Learning: A Systematic Review|date=2023-12-05|url=https://doi.org/10.1007/s12560-023-09571-2|journal=Food and Environmental Virology|volume=16|issue=1|pages=1–13|last=Wanguyun|first=Aken Puti|last2=Oishi|first2=Wakana|last3=Sano|first3=Daisuke|language=en|doi=10.1007/s12560-023-09571-2|pmc=PMC10963467|issn=1867-0334}}</ref>:
* the [[severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]] coronavirus that causes [[COVID-19]]
* the [[Severe acute respiratory syndrome coronavirus|SARS-CoV]] virus that causes [[Severe acute respiratory syndrome|SARS]]
* influenza virus
* hepatitus B virus
*[[Human herpes virus]]es including the [[Epstein-Barr virus]]
Ethanol at higher concentrations is also effective against some non-enveloped viruses<ref>Kampf G, Kramer A.2004.Epidemiologic Background of Hand Hygiene and Evaluation of the Most Important Agents for Scrubs and Rubs. Clin Microbiol Rev 17:.<nowiki>https://doi.org/10.1128/cmr.17.4.863-893.2004</nowiki></ref><ref name="CDC-disinfect" />, including:
* [[adenovirus]]es
* [[rhinovirus]]es
* [[rotavirus]]es
* [[Enterovirus|enteroviruses]]
* astroviruses
* echoviruses

One literature review found several viruses that are resistant to ethanol, even at high concentrations, which are polyomavirus, and coxsackievirus B1 and B5<ref>{{Cite journal|title=Efficacy of ethanol against viruses in hand disinfection|date=2018-04|url=https://doi.org/10.1016/j.jhin.2017.08.025|journal=Journal of Hospital Infection|volume=98|issue=4|pages=331–338|last=Kampf|first=G.|doi=10.1016/j.jhin.2017.08.025|pmc=PMC7132458|issn=0195-6701}}</ref>. Other viruses were found to be deactivated only at >95% ethanol, including poliovirus, echovirus, coxsackievirus B3. 80% ethanol is considered to be insufficient to protect against polyomavirus, hepatitis A virus, foot-and-mouth disease virus.

===Isopropyl alcohol===
Isopropyl alcohol, also known as ''isopropyl'', can destroy any virus enveloped in fat, including the coronaviruses that cause [[COVID-19]], [[Severe acute respiratory syndrome|SARS]] when used in the correct concentration, but unlike ethyl alcohol it cannot inactivate non-enveloped viruses.<ref name="CDC-disinfection" />

Isopropyl is also effective against a variety of bacteria, including:
*[[Escherichia coli]] (e-coli)
*[[Staphylococcus]]
*[[Streptococcus]]<ref name="CDC-disinfection" />

===Methanol===
Methanol is not used in healthcare settings due to its low effectiveness against bacteria.<ref name="CDC-disinfection" />

==Limitations of alcohol disinfectants==
Surfaces must be cleaned before disinfecting with alcohol, which will remove the protein-rich materials that alcohol cannot penetrate.<ref name="CDC-coronavirusprevention">{{Cite web | url = https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html | title = COVID-19 and Your Health | last = CDC | date = 2021-11-29 | website = Centers for Disease Control and Prevention|language=en-us | access-date = 2021-12-12}}</ref><ref name="CDC-disinfect" />

Alcohols are not recommended for sterilizing medical and surgical materials principally because they penetrate protein-rich materials, and they cannot inactivate the spores caused by some forms of [[bacteria]].<ref name="CDC-disinfect">{{Cite web | url = https://www.cdc.gov/infectioncontrol/guidelines/disinfection/disinfection-methods/chemical.html | title = Chemical Disinfectants {{!}} Disinfection & Sterilization Guidelines {{!}} Guidelines Library {{!}} Infection Control | website = Centers for Disease Control and Prevention | date = 2019-04-04|language=en-us | access-date = 2021-12-12}}</ref>

==Alcohol-based hand sanitizer==
'''Alcohol-based hand sanitizers''' (ABHS) are effective against many different types of viruses and bacteria; a 60% strength concentration is recommended for the virus causing the 2019-2020 coronavirus pandemic.<ref name="CDC-coronavirusprevention" /> However, washing hands carefully soap and running water is more effective against [[:Category:Coronaviruses|coronaviruses]], including the coronavirus that causes [[COVID-19]].<ref name="CDC-coronavirusprevention" />

Alcohol-based hand sanitizers have limited effectiveness when incorrect technique is used, not enough sanitizer is used, and when they are not used consistently.<ref name="ABSH">{{Cite book | last = Gold | first = Nina A. | last2 = Mirza | first2 = Taaha M. | last3 = Avva | first3 = Usha | date = 2021 | title = Alcohol Sanitizer |url =http://www.ncbi.nlm.nih.gov/books/NBK513254/|location=Treasure Island (FL)| publisher = StatPearls Publishing|pmid=30020626}}</ref>

==Drinking alcohol==
Drinking alcohol does not provide protection against coronaviruses, and drinking alcohol frequently or excessively can be extremely dangerous.<ref name="WHO-Covid-19-mythsacts">{{Cite web | url = https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters | title = COVID-19 Mythbusters | last = World Health Organization | first = | author-link = World Health Organization | date = | website = World Health Organization|language=en| archive-url = | archive-date = |url-status = | access-date=2021-12-12}}</ref>

==ME/CFS==
A number of different alcohol-based disinfectants are effective against common viruses and bacteria which have been reported to trigger [[ME/CFS]].{{citation needed}}

[[Alcohol intolerance]] is also found in a significant proportion of ME/CFS patients. Some ME/CFS patients also develop [[mast cell activation syndrome]], which involves an intolerance to alcohol and many other substances.

==See also==
*[[Severe acute respiratory syndrome coronavirus 2]]
*[[COVID-19]] (Coronavirus disease 19)
*[[Alcohol intolerance]]
*[[Mast cell activation syndrome]]

==Learn more==
*[https://www.cdc.gov/infectioncontrol/guidelines/disinfection/disinfection-methods/chemical.html Disinfection methods: Alcohol] - CDC
*[https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html Coronavirus (COVID-19): Prevent getting sick] - CDC
*[https://www.epa.gov/pesticide-registration/list-n-disinfectants-use-against-sars-cov-2 Products with Emerging Viral Pathogens AND Human Coronavirus claims for use against SARS-CoV-2] - EPA

==References==
{{Reflist}}

[[Category:Disinfectants]]
[[Category:Potential treatments]]
[[Category:Virology]]
[[Category:Antibacterials]]

Acetylcholinesterase

2026-07-19T06:27:58Z

Tuxedocaspy:/* Examples of irreversible inhibitors */ added citation

'''Acetylcholinesterase''' is the enzyme that breaks down [[acetylcholine]].

==Inhibitors==
Aceytlcholinesterase inhibitors inhibit acetylcholinesterase from breaking down [[acetylcholine]], resulting in higher circulating levels of the [[neurotransmitter]].

They are used to treat [[myasthenia gravis]] and [[postural orthostatic tachycardia]], and to improve [[cognitive dysfunction|cognitive function]] in [[Alzheimer's disease]]<ref name="ageing2006">{{Cite journal| doi = 10.1093/ageing/afl027| issn = 0002-0729| volume = 35 | issue = 4| pages = 336–338| last = Tabet | first = N.| title = Acetylcholinesterase inhibitors for Alzheimer’s disease: anti-inflammatories in acetylcholine clothing!| journal = Age and Ageing| access-date = 2016-11-09| date = 2006-07-01| url = http://ageing.oxfordjournals.org/content/35/4/336 | pmid = 16788077}}</ref> and [[Parkinson's disease]].

=== Examples of potential therapeutic inhibitors ===

Compounds which function as reversible competitive or noncompetitive inhibitors of cholinesterase are those most likely to have therapeutic uses. These include:

* [[Tetrahydrocannabinol]], the main active ingredient in [[cannabis]] is a competitive inhibitor of acetylcholinesterase<ref name="marijuana2006">{{Cite journal | doi = 10.1021/mp060066m| issn = 1543-8384| volume = 3 | issue = 6| pages = 773–777| last1 = Eubanks | first1 = Lisa M. | last2 = Rogers | first2 = Claude J. | last3 = Beuscher | first3 = Albert E. | last4 = Koob | first4 = George F. | last5 = Olson | first5 = Arthur J. | last6 = Dickerson | first6 = Tobin J. | last7 = Janda | first7 = Kim D. | title = A molecular link between the active component of marijuana and Alzheimer's disease pathology| journal = Molecular Pharmaceutics| date = December 2006 | pmid = 17140265| pmc = 2562334}}</ref>
* [[Carbamate]]s
** [[Physostigmine]]
** [[Neostigmine]]
** [[Pyridostigmine]]
** [[Ambenonium]]
** [[Demecarium]]
** [[Rivastigmine]]
* [[Phenanthrene]] derivatives
** [[Galantamine]]
* [[Caffeine]] – noncompetitive (also an [[Adenosine]] receptor antagonist)<ref name="Caffeine1991">{{Cite journal | last1 = Karadsheh | first1 = N | last2 = Kussiel | first2 = P | last3 = Linthicum | first3 = DS | title = Inhibition of acetylcholinesterase by caffeine, anabasine, methyl pyrrolidine and their derivatives | journal = Toxicology letters | date = 1991 | volume = 55 | issue = 3 | pages = 335–42 | pmid = 2003276 | doi = 10.1016/0378-4274(91)90015-X }}</ref><ref name="Caffeine2014">{{Cite journal | last1 = Pohanka | first1 = M | title = The effects of caffeine on the cholinergic system. | journal = Mini Reviews in Medicinal Chemistry | date = 2014 | volume = 14 | issue = 6 | pages = 543–549 | pmid = 24873820 | doi= 10.2174/1389557514666140529223436 | url= http://www.eurekaselect.com/122494/article }}</ref>
* [[Rosmarinic acid]] - ester of [[Caffeic acid]]. Found in plants species of Lamiaceae family.<ref name="Lamiaceae2014">{{Cite journal | last1 = Vladimir-Knežević | first1 = Sanda | last2 = Blažeković | first2 = Biljana | last3 = Kindl | first3 = Marija | last4 = Vladić | first4 = Jelena | last5 = Lower-Nedza | first5 = Agnieszka D. | last6 = Brantner | first6 = Adelheid H. | title = Acetylcholinesterase Inhibitory, Antioxidant and Phytochemical Properties of Selected Medicinal Plants of the Lamiaceae Family| journal = Molecules | date = Jan 9, 2014 | volume = 19 | issue = 1 | pages = 767–782 | pmid = 2003276 | doi = 10.3390/molecules19010767 | url = http://www.mdpi.com/1420-3049/19/1/767 }}</ref>
* [[Alpha-Pinene]] - noncompetitive reversible<ref name="bicyclic2005">{{Cite journal | last1 = Miyazawa | first1 = Mitsuo | last2 = Yamafuji | first2 = Chikako | title = Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids | journal = Journal of Agricultural and Food Chemistry | date = Mar 9, 2005 | volume = 53 | issue = 5 | pages = 1765–1768 | issn = 0021-8561 | pmid = 15740071 | doi = 10.1021/jf040019b | url = http://www.ncbi.nlm.nih.gov/pubmed/15740071 }}</ref><ref name="salvia2000">{{Cite journal | last1 = Perry | first1 = Nicolette S.L. | last2 = Houghton | first2 = Peter J. | last3 = Theobald | first3 = Anthony | last4 = Jenner | first4 = Peter | last5 = Perry | first5 = Elaine K. | title = In-vitro Inhibition of Human Erythrocyte Acetylcholinesterase by Salvia lavandulaefolia Essential Oil and Constituent Terpenes | journal = Journal of Pharmacy and Pharmacology | date = Jul 1, 2000 | volume = 52 | issue = 7 | pages = 895–902
| issn = 2042-7158 | pmid = 10933142 | doi = 10.1211/0022357001774598 | url = http://onlinelibrary.wiley.com/doi/10.1211/0022357001774598/abstract }}</ref>[https://www.greenbalance.se/pinen-tallolja-dillolja/]
* [[Piperidine]]s
** [[Donepezil]]
* [[Tacrine]], also known as tetrahydroaminoacridine (THA')
* [[Edrophonium]]
* [[Huperzine A]]<ref>Bauer, Brent A. [http://www.mayoclinic.com/health/huperzine-a/AN02022 Alzheimer's disease]. mayoclinic.com</ref><ref name="Alzheimers1996">{{Cite journal | last1 = Wang | first1 = BS | last2 = Wang | first2 = H | last3 = Wei | first3 = ZH | last4 = Song | first4 = YY | last5 = Zhang | first5 = L | last6 = Chen | first6 = HZ | title = Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis | journal = Journal of neural transmission | date = 2009 | volume = 116 | issue = 4 | pages = 457–465 | pmid = 19221692 | doi = 10.1007/s00702-009-0189-x }}</ref>
* [[Ladostigil]]
* [[Ungeremine]]<ref name="Nerine2004">{{Cite journal | last1 = Rhee | first1 = IK | last2 = Appels | first2 = N | last3 = Hofte | first3 = B | last4 = Karabatak | first4 = B | last5 = Erkelens | first5 = C | last6 = Stark | first6 = LM | last7 = Flippin | first7 = LA | last8 = Verpoorte | first8 = R | title = Isolation of the Acetylcholinesterase Inhibitor Ungeremine from Nerine bowdenii by Preparative HPLC Coupled On-Line to a Flow Assay System | journal = Biological & Pharmaceutical Bulletin | date = Nov 2004 | volume = 27 | issue = 11 | pages = 1804–1809 | pmid = 15516727 | doi = 10.1248/bpb.27.1804 | url = http://www.ncbi.nlm.nih.gov/pubmed/15516727 }}</ref>
* [[Lactucopicrin]]

=== Examples of irreversible inhibitors===

Irreversible inhibitors can lead to muscular [[paralysis]], convulsion and death by asphyxiation. [[Organophosphate]]s, a class of compounds which include [[insecticide]]s and several outlawed nerve agents, are examples of irreversible inhibitors.<ref>Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013 May;11(3):315-35. doi: 10.2174/1570159X11311030006. PMID: 24179466; PMCID: PMC3648782.</ref>

== See also ==

== Learn more ==

== References ==
{{Reflist}}

[[Category:Potential treatments]]
[[Category:Enzymes]]

Acetylcholine

2026-07-19T06:18:46Z

Tuxedocaspy:/* Acetylcholinesterase inhibitors */ Added a citation to a citation needed section and expanded

'''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 = |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=|access-date=|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 [[Herpes simplex virus#HSV-1|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 = [[The MEAction Network]]|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 ==
Anticholinergic medications are used to inhibit ACh activity and target the parasympathetic system, with use cases in treating respiratory disorders, psychiatric disorders, allergies, etc. They are competitive antagonists for the two types of receptors in the cholinergic system: muscarinic receptors are found on cells in the parasympathetic nervous system and nicotinic receptors are located on nerves in the autonomic nervous system.<ref name=":0">Ghossein N, Kang M, Lakhkar AD. Anticholinergic Medications. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK555893/</nowiki>

</ref> At least 600 drugs not classified as anticholinergic may display anticholinergic properties at therapeutic doses in treating other conditions, but this additional effect is considered adverse.<ref>Migirov A, Datta AR. Physiology, Anticholinergic Reaction. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK546589/</nowiki></ref><ref name=":0" /> Psychotropic medications have been identified as likely to display anticholinergic activity.<ref>Chew, M.L., Mulsant, B.H., Pollock, B.G., Lehman, M.E., Greenspan, A., Mahmoud, R.A., Kirshner, M.A., Sorisio, D.A., Bies, R.R. and Gharabawi, G. (2008), Anticholinergic Activity of 107 Medications Commonly Used by Older Adults. Journal of the American Geriatrics Society, 56: 1333-1341. <nowiki>https://doi.org/10.1111/j.1532-5415.2008.01737.x</nowiki></ref> 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]] - A central AChE inhibitor able to cross the blood-brain barrier.<ref>Friedli MJ, Inestrosa NC. Huperzine A and Its Neuroprotective Molecular Signaling in Alzheimer's Disease. Molecules. 2021 Oct 29;26(21):6531. doi: 10.3390/molecules26216531. PMID: 34770940; PMCID: PMC8587556.</ref> The compound is extracted from the Chinese club moss and has been recognized in traditional Chinese medicine.<ref>Tun MK, Herzon SB. The pharmacology and therapeutic potential of (-)-huperzine A. J Exp Pharmacol. 2012 Sep 5;4:113-23. doi: 10.2147/JEP.S27084. PMID: 27186124; PMCID: PMC4863551.</ref>
* 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

2026-07-19T06:05:15Z

Tuxedocaspy:/* Increasing and decreasing acetylcholine */ Adding citations and expanded the sentence and idea which required the citations

'''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 = |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=|access-date=|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 [[Herpes simplex virus#HSV-1|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 = [[The MEAction Network]]|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 ==
Anticholinergic medications are used to inhibit ACh activity and target the parasympathetic system, with use cases in treating respiratory disorders, psychiatric disorders, allergies, etc. They are competitive antagonists for the two types of receptors in the cholinergic system: muscarinic receptors are found on cells in the parasympathetic nervous system and nicotinic receptors are located on nerves in the autonomic nervous system.<ref name=":0">Ghossein N, Kang M, Lakhkar AD. Anticholinergic Medications. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK555893/</nowiki>

</ref> At least 600 drugs not classified as anticholinergic may display anticholinergic properties at therapeutic doses in treating other conditions, but this additional effect is considered adverse.<ref>Migirov A, Datta AR. Physiology, Anticholinergic Reaction. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: <nowiki>https://www.ncbi.nlm.nih.gov/books/NBK546589/</nowiki></ref><ref name=":0" /> Psychotropic medications have been identified as likely to display anticholinergic activity.<ref>Chew, M.L., Mulsant, B.H., Pollock, B.G., Lehman, M.E., Greenspan, A., Mahmoud, R.A., Kirshner, M.A., Sorisio, D.A., Bies, R.R. and Gharabawi, G. (2008), Anticholinergic Activity of 107 Medications Commonly Used by Older Adults. Journal of the American Geriatrics Society, 56: 1333-1341. <nowiki>https://doi.org/10.1111/j.1532-5415.2008.01737.x</nowiki></ref> 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]]

Microbiome

2026-07-19T02:45:06Z

Tuxedocaspy:/* Gut flora */ Completed a brief picture of changes in the microbiome throughout life with citations

{{Cleanup/Citations needed | date = Mar 2021}}
The '''microbiome''' is the community of microorganisms (such as [[bacteria]], [[fungus|fungi]], and [[virus]]es) that inhabit a particular environment, especially the human body.
<ref>{{Cite web|website=Merrian-Webster Medical Dictionary|access-date=2021-02-20 | title = Definition of MICROBIOME|url=https://www.merriam-webster.com/dictionary/microbiome}}</ref> Of the bacterial component, 29% live in the gastrointestinal tract, 26% live in the oral cavity, 21% reside in the skin, and 14% reside in the respiratory tract.<ref>{{Cite journal|title=A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation|date=2024-09-23|url=https://doi.org/10.1038/s41392-024-01946-6|journal=Signal Transduction and Targeted Therapy|volume=9|issue=1|last=Ma|first=Ziqi|last2=Zuo|first2=Tao|last3=Frey|first3=Norbert|last4=Rangrez|first4=Ashraf Yusuf|language=en|doi=10.1038/s41392-024-01946-6|pmc=PMC11418828|issn=2059-3635}}</ref>

==Anatomical areas==
The microorganisms 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]].<ref>{{Cite journal|title=Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome|date=2017-04-26|url=https://pubmed.ncbi.nlm.nih.gov/28441964/|journal=Microbiome|volume=5|issue=1|pages=44|last=Nagy-Szakal|first=Dorottya|last2=Williams|first2=Brent L.|last3=Mishra|first3=Nischay|last4=Che|first4=Xiaoyu|last5=Lee|first5=Bohyun|last6=Bateman|first6=Lucinda|last7=Klimas|first7=Nancy G.|last8=Komaroff|first8=Anthony L.|last9=Levine|first9=Susan|last10=Montoya|first10=Jose G.|last11=Peterson|first11=Daniel L.|doi=10.1186/s40168-017-0261-y|pmc=5405467|pmid=28441964|issn=2049-2618}}</ref>

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. Around 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].<ref>{{Cite journal|title=Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens|date=October 2003|url=https://www.sciencedirect.com/science/article/abs/pii/S1369527403001176|journal=Current Opinion in Microbiology|volume=6|issue=5|pages=457-461|last=Vendantam|first=Gayatari|last2=Hecht|first2=David}}</ref>

An individual's gut microbiome begins as a sample from the maternal microbiome taken during childbirth. While proportions and specific diversities of bacteria vary between individuals, scientific evidence shows delivery method influences the founding population of intestinal bacteria. Vaginal births are seeded with bacteria found in the birth canal, including ''Bacteroides'', ''Actinobacteria, Lactobacillus, Bifidobacteria.'' Caesarean section births are taken from microbes found on the skin and in the environment, ranging from ''Staphylococcus, Enterococcus, Clostridium, Streptococcus''.<ref>Coelho GDP, Ayres LFA, Barreto DS, Henriques BD, Prado MRMC, Passos CMD. Acquisition of microbiota according to the type of birth: an integrative review. Rev Lat Am Enfermagem. 2021 Jul 19;29:e3446. doi: 10.1590/1518.8345.4466.3446. PMID: 34287544; PMCID: PMC8294792.</ref> Gut microbiomes founded by c-section births are less phylogenetically diverse and alter colonization of normal gut microbiota during early infancy,<ref>Nicholas A. Bokulich ''et al.'', Antibiotics, birth mode, and diet shape microbiome maturation during early life.''Sci. Transl. Med.'''''8''',343ra82-343ra82(2016).DOI:10.1126/scitranslmed.aad7121</ref> with studied links to immune conditions such as allergies and asthma.<ref>Zhang C, Li L, Jin B, Xu X, Zuo X, Li Y, Li Z. The Effects of Delivery Mode on the Gut Microbiota and Health: State of Art. Front Microbiol. 2021 Dec 23;12:724449. doi: 10.3389/fmicb.2021.724449. PMID: 35002992; PMCID: PMC8733716.</ref> Bacterial populations are known to stimulate immune development within infants during a period of plasticity, when immune elements are immature. Metabolites prime immune cells during their maturation process, such as small-chain fatty acids promoting intestinal regulatory T-cells.<ref>Sanidad KZ, Zeng MY. Neonatal gut microbiome and immunity. Curr Opin Microbiol. 2020 Aug;56:30-37. doi: 10.1016/j.mib.2020.05.011. Epub 2020 Jul 4. PMID: 32634598; PMCID: PMC8729197.</ref> Critically, experiments in animal models demonstrate the complete absence of microbiota is associated with numerous defects in intestinal epithelial cells, lymphoid cells, immunomodulatory T-cells, etc. which may be rescued with microbial colonization.<ref>{{Cite journal|title=Interaction between microbiota and immunity in health and disease|date=2020-05-20|url=https://doi.org/10.1038/s41422-020-0332-7|journal=Cell Research|volume=30|issue=6|pages=492–506|last=Zheng|first=Danping|last2=Liwinski|first2=Timur|last3=Elinav|first3=Eran|language=en|doi=10.1038/s41422-020-0332-7|pmc=PMC7264227|issn=1001-0602}}</ref> Interactions in this period not only develop immune cells, but also train them to recognize harmful antigens.<ref>{{Cite journal|title=Gut microbiome and breast-feeding: Implications for early immune development|date=2022-09|url=https://doi.org/10.1016/j.jaci.2022.07.014|journal=Journal of Allergy and Clinical Immunology|volume=150|issue=3|pages=523–534|last=Davis|first=Erin C.|last2=Castagna|first2=Vanessa P.|last3=Sela|first3=David A.|last4=Hillard|first4=Margaret A.|last5=Lindberg|first5=Samantha|last6=Mantis|first6=Nicholas J.|last7=Seppo|first7=Antti E.|last8=Järvinen|first8=Kirsi M.|doi=10.1016/j.jaci.2022.07.014|pmc=PMC9463492|issn=0091-6749}}</ref> Furthermore, these initial, established populations serve to resist colonization by pathogens through occupying space and competing for resources.

At around three years of age, the gut microbiome reaches a more stable composition that persists to adulthood.<ref>{{Cite journal|title=Human gut microbiome viewed across age and geography|date=2012-05-09|url=https://doi.org/10.1038/nature11053|journal=Nature|volume=486|issue=7402|pages=222–227|last=Yatsunenko|first=Tanya|last2=Rey|first2=Federico E.|last3=Manary|first3=Mark J.|last4=Trehan|first4=Indi|last5=Dominguez-Bello|first5=Maria Gloria|last6=Contreras|first6=Monica|last7=Magris|first7=Magda|last8=Hidalgo|first8=Glida|last9=Baldassano|first9=Robert N.|last10=Anokhin|first10=Andrey P.|last11=Heath|first11=Andrew C.|language=en|doi=10.1038/nature11053|pmc=PMC3376388|issn=0028-0836}}</ref><ref>J.E. Koenig, A. Spor, N. Scalfone, A.D. Fricker, J. Stombaugh, R. Knight, L.T. Angenent, & R.E. Ley, Succession of microbial consortia in the developing infant gut microbiome, Proc. Natl. Acad. Sci. U.S.A. 108 (supplement_1) 4578-4585, <nowiki>https://doi.org/10.1073/pnas.1000081107</nowiki> (2011). </ref> This transition is primarily driven by changes in diet during weaning and the introduction of solid foods, resulting in a dominance of ''Bacteroidetes'' and ''Firmicutes.'' The adult microbiome introduces genes capable of breaking down carbohydrates and the biosynthesis of vitamins. The complex communication and symbiosis between the microbiome and the immune system remains through adulthood by continuing to modulate responses and development across innate and adaptive immune arms, both locally to the gut and systemically across the body.<ref name=":0">Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients. 2021 Mar 9;13(3):886. doi: 10.3390/nu13030886. PMID: 33803407; PMCID: PMC8001875.</ref>

Though adult microbiomes are more stable than neo/perinatal populations, each individual's microbiome is largely unique,<ref>{{Cite journal|title=Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease|date=2024-04|url=https://doi.org/10.1016/j.chom.2024.02.012|journal=Cell Host & Microbe|volume=32|issue=4|pages=506–526.e9|last=Zhou|first=Xin|last2=Shen|first2=Xiaotao|last3=Johnson|first3=Jethro S.|last4=Spakowicz|first4=Daniel J.|last5=Agnello|first5=Melissa|last6=Zhou|first6=Wenyu|last7=Avina|first7=Monica|last8=Honkala|first8=Alexander|last9=Chleilat|first9=Faye|last10=Chen|first10=Shirley Jingyi|last11=Cha|first11=Kexin|doi=10.1016/j.chom.2024.02.012|pmc=PMC11022754|issn=1931-3128}}</ref> altered by a host of factors including diet, antibiotics, gender, age, etc throughout life.<ref name=":0" /> Given the importance of the gut microbiome in immune regulation, dysbiosis and perturbations to the gut have been increasingly studied and recognized in disease contexts,<ref>{{Cite journal|title=Correlation between human gut microbiome and diseases|date=2022-09|url=https://doi.org/10.1016/j.imj.2022.08.004|journal=Infectious Medicine|volume=1|issue=3|pages=180–191|last=Madhogaria|first=Barkha|last2=Bhowmik|first2=Priyanka|last3=Kundu|first3=Atreyee|doi=10.1016/j.imj.2022.08.004|pmc=PMC10699709|issn=2772-431X}}</ref> including MECFS.

A 2021 study by Damiano found significant differences in the composition of gut bacteria between CFS/ME patients and healthy controls. People with ME/CFS had:<ref name="Damiano2021" />

* Higher relative abundance of bacteria in the genus ''Bacteroides'' (phylum Bacteriodetes) and the genus ''Phascolarctobacterium'' (phylum Firmicutes)
* Lower relative abundance of bacteria in the genus ''Anaerostipes'' and genus ''Ruminococcus'' (both from phylum Firmicutes)

However, the study authors were unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME, or if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name="Damiano2021" />

Damiano et al. suggest the intestinal microbial profile recorded in their study is consistent with the profiles reported for other autoimmune conditions. For example, a 2021 review on pediatric [[inflammatory bowel disease]] found a reduced abundance of bacteria in genus ''Anaerostipes.''<ref>{{Cite journal|title=Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review|date=2021-02-02|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884334/|journal=Frontiers in Pediatrics|volume=9|pages=626232|last=Zhuang|first=Xiaojun|last2=Liu|first2=Caiguang|last3=Zhan|first3=Shukai|last4=Tian|first4=Zhenyi|last5=Li|first5=Na|last6=Mao|first6=Ren|last7=Zeng|first7=Zhirong|last8=Chen|first8=Minhu|doi=10.3389/fped.2021.626232|pmc=7884334|pmid=33604319|issn=2296-2360}}</ref> A 2014 study found a higher abundance of the genus ''Bacteroides'' in people with [[systemic lupus erythematous]].<ref>{{Cite journal|title=Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus|date=September 30, 2014|url=https://journals.asm.org/doi/10.1128/mbio.01548-14|journal=mBio|volume=5|issue=5|last=Hevia|first=Arancha|last2=Milani|first2=Christian|last3=Lopez|first3=Patricia|last4=Cuervo|first4=Adriana|last5=Arboleya|first5=Silvia|last6=Duranti|first6=Sabrina|last7=Turroni|first7=Francesca|last8=Suarez|first8=Ana|last9=Gueimonde|first9=Miguel|doi=10.1128/mbio.01548-14}}</ref>

===Oral flora===

The microbiome in the oral cavity (mouth and throat) is the second largest after the gut microbiome. The state of your oral microbiome can affect the rest of your body in two major ways<ref>{{Cite journal|title=Oral microbiota in human systematic diseases|date=2022-03-02|url=https://www.nature.com/articles/s41368-022-00163-7|journal=International Journal of Oral Science|volume=14|issue=1|pages=1–11|last=Peng|first=Xian|last2=Cheng|first2=Lei|last3=You|first3=Yong|last4=Tang|first4=Chengwei|last5=Ren|first5=Biao|last6=Li|first6=Yuqing|last7=Xu|first7=Xin|last8=Zhou|first8=Xuedong|language=en|doi=10.1038/s41368-022-00163-7|pmc=8891310|pmid=35236828|issn=2049-3169}}</ref>:

# Microorganisms in the mouth can travel "downstream" to the gut microbiome.
# An oral infection can cause bacteria and their metabolites (digestive byproducts) to enter the bloodstream. This can activate the immune system and cause widespread inflammation.

The 2021 Damiano study above also found differences in the composition of oral bacteria between CFS/ME patients and healthy controls. People with CFS/ME had higher relative abundance of bacteria in the genus ''Rothia'' (phylum Actinobacteria).<ref name="Damiano2021" />

==ME/CFS==

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 [[myalgic encephalomyelitis]]\[[chronic fatigue syndrome]].

===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 [[interleukin 1|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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = | last2 = Venket Rao | first2 = A | authorlink2 = | last3 = Irani | first3 = Dinaz | authorlink3 = | 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 = December 21, 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>{{citation needed | date = 2021 | reason=Add original research}}

===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 ===

Viruses 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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = Ludovic Giloteaux | last2 = Goodrich | first2 = Julia K. | authorlink2 = | last3 = Walters | first3 = William A. | authorlink3 = | last4 = Levine | first4 = Susan M. | authorlink4 = Susan Levine | last5 = Ley | first5 = Ruth E. | authorlink5 = | last6 = Hanson | first6 = Maureen R. | authorlink6 = 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 | authorlink = Amy Proal | last2 = Marshall | first2 = Trevor | authorlink2 = Trevor Marshall | 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="Damiano2021">{{Cite journal | last = Lupo | first = Giuseppe Francesco Damiano | author-link = | last2 = Rocchetti | first2 = Gabriele | authorlink2 = | last3 = Lucini | first3 = Luigi | authorlink3 = | last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso | last5 = Manara | first5 = Elena | authorlink5 = | last6 = Bertelli | first6 = Matteo | authorlink6 = | last7 = Puglisi | first7 = Edoardo | last8 = Capelli | first8 = Enrica | authorlink8 = 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 = Jun 30, 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==
*[[Probiotics]]
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Indoor microbiome]]
*[[Dr Markov's chronic bacterial intoxication syndrome (CBIS) theory of ME/CFS]] (Dr Markov has evidence that ME/CFS is caused by a dysbiosis in the kidneys)

==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="Shukla2015">{{Citation| doi = 10.1371/journal.pone.0145453| issn = 1932-6203| volume = 10 | issue = 12| pages = 0145453| last1 = Shukla | first1 = Sanjay K. | last2 = Cook | first2 = Dane | last3 = Meyer | first3 = Jacob| last4 = Vernon | first4 = Suzanne D. | last5 = Le | first5 = Thao | last6 = Clevidence | first6 = Derek | last7 = Robertson | first7 = Charles E. | last8 = Schrodi | first8 = Steven J. | last9 = Yale | first9 = Steven | last10 = Frank | first10 = Daniel N.| title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)| journal = PLOS ONE| access-date = 2016-12-13 | date = 2015-12-18| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453}}</ref>
<ref name="Jackson2015">{{citation | last1 = Jackson | first1 = Melinda L | authorlink1 = Melinda Jackson | 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 | title = Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study | journal = Sleep Science | volume = 8 | issue = 3 | pages = 124-133 | date = 23 Oct 2015 | pmid = 26779319 | doi = 10.1016/j.slsci.2015.10.001 | url = http://www.sciencedirect.com/science/article/pii/S1984006315000632 }}</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 | title = Support for the Microgenderome: Associations in a Human Clinical Population | journal = Scientific Reports | volume = | pages = | date = 13 Jan 2016 |issue = | pmid = 26757840 | doi = 10.1038/srep19171 | url = http://www.nature.com/articles/srep19171 }}</ref>
<ref name="Maslowski2011">{{Citation| doi = 10.1038/ni0111-5| issn = 1529-2916| volume = 12 | issue = 1| pages = 5–9| last1 = Maslowski | first1 = Kendle M. | last2 = Mackay | first2 = Charles R.| title = Diet, gut microbiota and immune responses| journal = Nature Immunology | date = January 2011 | pmid = 21169997}}</ref>
<ref name="koren2012">{{Citation| doi = 10.1016/j.cell.2012.07.008| issn = 1097-4172| volume = 150 | issue = 3| pages = 470–480| last1 = Koren | first1 = Omry | last2 = Goodrich | first2 = Julia K. | last3 = Cullender | first3 = Tyler C. | last4 = Spor | first4 = Aymé| last5 = Laitinen | first5 = Kirsi | last6 = Bäckhed | first6 = Helene Kling | last7 = Gonzalez | first7 = Antonio | last8 = Werner | first8 = Jeffrey J. | last9 = Angenent | first9 = Largus T. | last10 = Knight | first10 = Rob| last11 = Bäckhed | first11 = Fredrik | last12 = Isolauri | first12 = Erika | last13 = Salminen | first13 = Seppo | last14 = Ley | first14 = Ruth E.| title = Host remodeling of the gut microbiome and metabolic changes during pregnancy| journal = Cell| date = 2012-08-03 | pmid = 22863002}}</ref>
<ref name="Dinan2012">{{Citation| doi = 10.1016/j.psyneuen.2012.03.007| issn = 0306-4530| volume = 37 | issue = 9| pages = 1369–1378| last1 = Dinan | first1 = Timothy G. | last2 = Cryan | first2 = John F.| title = Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology| journal = Psychoneuroendocrinology| access-date = 2016-12-13 | date = September 2012| url = http://www.sciencedirect.com/science/article/pii/S0306453012000935}}</ref>
<ref name="Fremont2013">{{Citation| doi = 10.1016/j.anaerobe.2013.06.002| issn = 1095-8274| volume = 22 | issue = | pages = 50–56| last1 = Frémont | first1 = Marc| last2 = Coomans | first2 = Danny | last3 = Massart | first3 = Sebastien | last4 = De Meirleir | first4 = Kenny| title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients| journal = Anaerobe | date = August 2013 | pmid = 23791918}}</ref>
<ref name="Borody2012">{{Citation| issn = 1328-8040| volume = 31 | issue = 3| pages = 3| last1 = Borody | first1 = Thomas J. | last2 = Nowak | first2 = Anna | last3 = Finlayson | first3 = Sarah| title = The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy| journal = Journal of the Australasian College of Nutritional and Environmental Medicine| access-date = 2016-12-13 | date = December 2012| url = http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/}}</ref>
<ref name="Morris, 2016">{{Citation | last1 = Morris | first1 = Gerwyn | authorlink1 = Gerwyn Morris | last2 = Berk | first2 = Michael | authorlink2 = Michael Berk | last3 = Carvalho | first3 = A.F. | authorlink3 = | last4 = Caso | first4 = J.R. | authorlink4 = | last5 = Sanz | first5 = Y. | authorlink5 = | last6 = Maes | first6 = Michael | authorlink6 = Michael Maes | title = 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. | journal = Current Pharmaceutical Design | volume = | issue = | pages = | date = 2016 | pmid = 27634186 }}</ref>
<ref name="Nagy-Szakal, 2017">{{Citation | last1 = Nagy-Szakal | first1 = Dorottya | authorlink1 = Dorottya Nagy-Szakal | last2 = Williams | first2 = Brent L. | authorlink2 = | last3 = Mishra | first3 = Nischay | authorlink3 = | 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]]

Microbiome

2026-07-17T09:21:28Z

Tuxedocaspy:/* Gut flora */ reminder to cite a needed source

{{Cleanup/Citations needed | date = Mar 2021}}
The '''microbiome''' is the community of microorganisms (such as [[bacteria]], [[fungus|fungi]], and [[virus]]es) that inhabit a particular environment, especially the human body.
<ref>{{Cite web|website=Merrian-Webster Medical Dictionary|access-date=2021-02-20 | title = Definition of MICROBIOME|url=https://www.merriam-webster.com/dictionary/microbiome}}</ref>

==Anatomical areas==
The microorganisms 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]].<ref>{{Cite journal|title=Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome|date=2017-04-26|url=https://pubmed.ncbi.nlm.nih.gov/28441964/|journal=Microbiome|volume=5|issue=1|pages=44|last=Nagy-Szakal|first=Dorottya|last2=Williams|first2=Brent L.|last3=Mishra|first3=Nischay|last4=Che|first4=Xiaoyu|last5=Lee|first5=Bohyun|last6=Bateman|first6=Lucinda|last7=Klimas|first7=Nancy G.|last8=Komaroff|first8=Anthony L.|last9=Levine|first9=Susan|last10=Montoya|first10=Jose G.|last11=Peterson|first11=Daniel L.|doi=10.1186/s40168-017-0261-y|pmc=5405467|pmid=28441964|issn=2049-2618}}</ref>

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. Around 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].<ref>{{Cite journal|title=Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens|date=October 2003|url=https://www.sciencedirect.com/science/article/abs/pii/S1369527403001176|journal=Current Opinion in Microbiology|volume=6|issue=5|pages=457-461|last=Vendantam|first=Gayatari|last2=Hecht|first2=David}}</ref>

An individual's gut microbiome begins as a sample from the maternal microbiome taken during childbirth. While proportions and specific diversities of bacteria vary between individuals, scientific evidence shows delivery method influences the founding population of intestinal bacteria. Vaginal births are seeded with bacteria found in the birth canal, including ''Bacteroides'', ''Actinobacteria, Lactobacillus, Bifidobacteria.'' Caesarean section births are taken from microbes found on the skin and in the environment, ranging from ''Staphylococcus, Enterococcus, Clostridium, Streptococcus''.<ref>Coelho GDP, Ayres LFA, Barreto DS, Henriques BD, Prado MRMC, Passos CMD. Acquisition of microbiota according to the type of birth: an integrative review. Rev Lat Am Enfermagem. 2021 Jul 19;29:e3446. doi: 10.1590/1518.8345.4466.3446. PMID: 34287544; PMCID: PMC8294792.</ref> Gut microbiomes founded by c-section births are less phylogenetically diverse and alter colonization of normal gut microbiota during early infancy,<ref>Nicholas A. Bokulich ''et al.'', Antibiotics, birth mode, and diet shape microbiome maturation during early life.''Sci. Transl. Med.'''''8''',343ra82-343ra82(2016).DOI:10.1126/scitranslmed.aad7121</ref> with studied links to immune disorders such as allergies.<ref>Zhang C, Li L, Jin B, Xu X, Zuo X, Li Y, Li Z. The Effects of Delivery Mode on the Gut Microbiota and Health: State of Art. Front Microbiol. 2021 Dec 23;12:724449. doi: 10.3389/fmicb.2021.724449. PMID: 35002992; PMCID: PMC8733716.</ref> Bacterial populations are known to stimulate immune development within infants during a period of plasticity, with certain metabolites priming immune cells during their maturation process, such as small-chain fatty acids promoting intestinal regulatory T-cells.<ref>Sanidad KZ, Zeng MY. Neonatal gut microbiome and immunity. Curr Opin Microbiol. 2020 Aug;56:30-37. doi: 10.1016/j.mib.2020.05.011. Epub 2020 Jul 4. PMID: 32634598; PMCID: PMC8729197.</ref> Furthermore, these initial, established populations serve to prevent colonization by pathogens.

Compositions change with an infant's dietary transition. At one year, the gut microbiome resembles an adult composition.{{Citation needed}}

A 2021 study by Damiano found significant differences in the composition of gut bacteria between CFS/ME patients and healthy controls. People with ME/CFS had:<ref name="Damiano2021" />

* Higher relative abundance of bacteria in the genus ''Bacteroides'' (phylum Bacteriodetes) and the genus ''Phascolarctobacterium'' (phylum Firmicutes)
* Lower relative abundance of bacteria in the genus ''Anaerostipes'' and genus ''Ruminococcus'' (both from phylum Firmicutes)

However, the study authors were unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME, or if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name="Damiano2021" />

Damiano et al. suggest the intestinal microbial profile recorded in their study is consistent with the profiles reported for other autoimmune conditions. For example, a 2021 review on pediatric [[inflammatory bowel disease]] found a reduced abundance of bacteria in genus ''Anaerostipes.''<ref>{{Cite journal|title=Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review|date=2021-02-02|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884334/|journal=Frontiers in Pediatrics|volume=9|pages=626232|last=Zhuang|first=Xiaojun|last2=Liu|first2=Caiguang|last3=Zhan|first3=Shukai|last4=Tian|first4=Zhenyi|last5=Li|first5=Na|last6=Mao|first6=Ren|last7=Zeng|first7=Zhirong|last8=Chen|first8=Minhu|doi=10.3389/fped.2021.626232|pmc=7884334|pmid=33604319|issn=2296-2360}}</ref> A 2014 study found a higher abundance of the genus ''Bacteroides'' in people with [[systemic lupus erythematous]].<ref>{{Cite journal|title=Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus|date=September 30, 2014|url=https://journals.asm.org/doi/10.1128/mbio.01548-14|journal=mBio|volume=5|issue=5|last=Hevia|first=Arancha|last2=Milani|first2=Christian|last3=Lopez|first3=Patricia|last4=Cuervo|first4=Adriana|last5=Arboleya|first5=Silvia|last6=Duranti|first6=Sabrina|last7=Turroni|first7=Francesca|last8=Suarez|first8=Ana|last9=Gueimonde|first9=Miguel|doi=10.1128/mbio.01548-14}}</ref>

===Oral flora===

The microbiome in the oral cavity (mouth and throat) is the second largest after the gut microbiome. The state of your oral microbiome can affect the rest of your body in two major ways<ref>{{Cite journal|title=Oral microbiota in human systematic diseases|date=2022-03-02|url=https://www.nature.com/articles/s41368-022-00163-7|journal=International Journal of Oral Science|volume=14|issue=1|pages=1–11|last=Peng|first=Xian|last2=Cheng|first2=Lei|last3=You|first3=Yong|last4=Tang|first4=Chengwei|last5=Ren|first5=Biao|last6=Li|first6=Yuqing|last7=Xu|first7=Xin|last8=Zhou|first8=Xuedong|language=en|doi=10.1038/s41368-022-00163-7|pmc=8891310|pmid=35236828|issn=2049-3169}}</ref>:

# Microorganisms in the mouth can travel "downstream" to the gut microbiome.
# An oral infection can cause bacteria and their metabolites (digestive byproducts) to enter the bloodstream. This can activate the immune system and cause widespread inflammation.

The 2021 Damiano study above also found differences in the composition of oral bacteria between CFS/ME patients and healthy controls. People with CFS/ME had higher relative abundance of bacteria in the genus ''Rothia'' (phylum Actinobacteria).<ref name="Damiano2021" />

==ME/CFS==

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 [[myalgic encephalomyelitis]]\[[chronic fatigue syndrome]].

===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 [[interleukin 1|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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = | last2 = Venket Rao | first2 = A | authorlink2 = | last3 = Irani | first3 = Dinaz | authorlink3 = | 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 = December 21, 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>{{citation needed | date = 2021 | reason=Add original research}}

===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 ===

Viruses 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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = Ludovic Giloteaux | last2 = Goodrich | first2 = Julia K. | authorlink2 = | last3 = Walters | first3 = William A. | authorlink3 = | last4 = Levine | first4 = Susan M. | authorlink4 = Susan Levine | last5 = Ley | first5 = Ruth E. | authorlink5 = | last6 = Hanson | first6 = Maureen R. | authorlink6 = 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 | authorlink = Amy Proal | last2 = Marshall | first2 = Trevor | authorlink2 = Trevor Marshall | 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="Damiano2021">{{Cite journal | last = Lupo | first = Giuseppe Francesco Damiano | author-link = | last2 = Rocchetti | first2 = Gabriele | authorlink2 = | last3 = Lucini | first3 = Luigi | authorlink3 = | last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso | last5 = Manara | first5 = Elena | authorlink5 = | last6 = Bertelli | first6 = Matteo | authorlink6 = | last7 = Puglisi | first7 = Edoardo | last8 = Capelli | first8 = Enrica | authorlink8 = 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 = Jun 30, 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==
*[[Probiotics]]
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Indoor microbiome]]
*[[Dr Markov's chronic bacterial intoxication syndrome (CBIS) theory of ME/CFS]] (Dr Markov has evidence that ME/CFS is caused by a dysbiosis in the kidneys)

==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="Shukla2015">{{Citation| doi = 10.1371/journal.pone.0145453| issn = 1932-6203| volume = 10 | issue = 12| pages = 0145453| last1 = Shukla | first1 = Sanjay K. | last2 = Cook | first2 = Dane | last3 = Meyer | first3 = Jacob| last4 = Vernon | first4 = Suzanne D. | last5 = Le | first5 = Thao | last6 = Clevidence | first6 = Derek | last7 = Robertson | first7 = Charles E. | last8 = Schrodi | first8 = Steven J. | last9 = Yale | first9 = Steven | last10 = Frank | first10 = Daniel N.| title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)| journal = PLOS ONE| access-date = 2016-12-13 | date = 2015-12-18| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453}}</ref>
<ref name="Jackson2015">{{citation | last1 = Jackson | first1 = Melinda L | authorlink1 = Melinda Jackson | 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 | title = Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study | journal = Sleep Science | volume = 8 | issue = 3 | pages = 124-133 | date = 23 Oct 2015 | pmid = 26779319 | doi = 10.1016/j.slsci.2015.10.001 | url = http://www.sciencedirect.com/science/article/pii/S1984006315000632 }}</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 | title = Support for the Microgenderome: Associations in a Human Clinical Population | journal = Scientific Reports | volume = | pages = | date = 13 Jan 2016 |issue = | pmid = 26757840 | doi = 10.1038/srep19171 | url = http://www.nature.com/articles/srep19171 }}</ref>
<ref name="Maslowski2011">{{Citation| doi = 10.1038/ni0111-5| issn = 1529-2916| volume = 12 | issue = 1| pages = 5–9| last1 = Maslowski | first1 = Kendle M. | last2 = Mackay | first2 = Charles R.| title = Diet, gut microbiota and immune responses| journal = Nature Immunology | date = January 2011 | pmid = 21169997}}</ref>
<ref name="koren2012">{{Citation| doi = 10.1016/j.cell.2012.07.008| issn = 1097-4172| volume = 150 | issue = 3| pages = 470–480| last1 = Koren | first1 = Omry | last2 = Goodrich | first2 = Julia K. | last3 = Cullender | first3 = Tyler C. | last4 = Spor | first4 = Aymé| last5 = Laitinen | first5 = Kirsi | last6 = Bäckhed | first6 = Helene Kling | last7 = Gonzalez | first7 = Antonio | last8 = Werner | first8 = Jeffrey J. | last9 = Angenent | first9 = Largus T. | last10 = Knight | first10 = Rob| last11 = Bäckhed | first11 = Fredrik | last12 = Isolauri | first12 = Erika | last13 = Salminen | first13 = Seppo | last14 = Ley | first14 = Ruth E.| title = Host remodeling of the gut microbiome and metabolic changes during pregnancy| journal = Cell| date = 2012-08-03 | pmid = 22863002}}</ref>
<ref name="Dinan2012">{{Citation| doi = 10.1016/j.psyneuen.2012.03.007| issn = 0306-4530| volume = 37 | issue = 9| pages = 1369–1378| last1 = Dinan | first1 = Timothy G. | last2 = Cryan | first2 = John F.| title = Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology| journal = Psychoneuroendocrinology| access-date = 2016-12-13 | date = September 2012| url = http://www.sciencedirect.com/science/article/pii/S0306453012000935}}</ref>
<ref name="Fremont2013">{{Citation| doi = 10.1016/j.anaerobe.2013.06.002| issn = 1095-8274| volume = 22 | issue = | pages = 50–56| last1 = Frémont | first1 = Marc| last2 = Coomans | first2 = Danny | last3 = Massart | first3 = Sebastien | last4 = De Meirleir | first4 = Kenny| title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients| journal = Anaerobe | date = August 2013 | pmid = 23791918}}</ref>
<ref name="Borody2012">{{Citation| issn = 1328-8040| volume = 31 | issue = 3| pages = 3| last1 = Borody | first1 = Thomas J. | last2 = Nowak | first2 = Anna | last3 = Finlayson | first3 = Sarah| title = The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy| journal = Journal of the Australasian College of Nutritional and Environmental Medicine| access-date = 2016-12-13 | date = December 2012| url = http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/}}</ref>
<ref name="Morris, 2016">{{Citation | last1 = Morris | first1 = Gerwyn | authorlink1 = Gerwyn Morris | last2 = Berk | first2 = Michael | authorlink2 = Michael Berk | last3 = Carvalho | first3 = A.F. | authorlink3 = | last4 = Caso | first4 = J.R. | authorlink4 = | last5 = Sanz | first5 = Y. | authorlink5 = | last6 = Maes | first6 = Michael | authorlink6 = Michael Maes | title = 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. | journal = Current Pharmaceutical Design | volume = | issue = | pages = | date = 2016 | pmid = 27634186 }}</ref>
<ref name="Nagy-Szakal, 2017">{{Citation | last1 = Nagy-Szakal | first1 = Dorottya | authorlink1 = Dorottya Nagy-Szakal | last2 = Williams | first2 = Brent L. | authorlink2 = | last3 = Mishra | first3 = Nischay | authorlink3 = | 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]]

Microbiome

2026-07-17T09:19:59Z

Tuxedocaspy:/* Gut flora */ Further updates to initial gut microbiota

{{Cleanup/Citations needed | date = Mar 2021}}
The '''microbiome''' is the community of microorganisms (such as [[bacteria]], [[fungus|fungi]], and [[virus]]es) that inhabit a particular environment, especially the human body.
<ref>{{Cite web|website=Merrian-Webster Medical Dictionary|access-date=2021-02-20 | title = Definition of MICROBIOME|url=https://www.merriam-webster.com/dictionary/microbiome}}</ref>

==Anatomical areas==
The microorganisms 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]].<ref>{{Cite journal|title=Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome|date=2017-04-26|url=https://pubmed.ncbi.nlm.nih.gov/28441964/|journal=Microbiome|volume=5|issue=1|pages=44|last=Nagy-Szakal|first=Dorottya|last2=Williams|first2=Brent L.|last3=Mishra|first3=Nischay|last4=Che|first4=Xiaoyu|last5=Lee|first5=Bohyun|last6=Bateman|first6=Lucinda|last7=Klimas|first7=Nancy G.|last8=Komaroff|first8=Anthony L.|last9=Levine|first9=Susan|last10=Montoya|first10=Jose G.|last11=Peterson|first11=Daniel L.|doi=10.1186/s40168-017-0261-y|pmc=5405467|pmid=28441964|issn=2049-2618}}</ref>

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. Around 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].<ref>{{Cite journal|title=Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens|date=October 2003|url=https://www.sciencedirect.com/science/article/abs/pii/S1369527403001176|journal=Current Opinion in Microbiology|volume=6|issue=5|pages=457-461|last=Vendantam|first=Gayatari|last2=Hecht|first2=David}}</ref>

An individual's gut microbiome begins as a sample from the maternal microbiome taken during childbirth. While proportions and specific diversities of bacteria vary between individuals, scientific evidence shows delivery method influences the founding population of intestinal bacteria. Vaginal births are seeded with bacteria found in the birth canal, including ''Bacteroides'', ''Actinobacteria, Lactobacillus, Bifidobacteria.'' Caesarean section births are taken from microbes found on the skin and in the environment, ranging from ''Staphylococcus, Enterococcus, Clostridium, Streptococcus''.<ref>Coelho GDP, Ayres LFA, Barreto DS, Henriques BD, Prado MRMC, Passos CMD. Acquisition of microbiota according to the type of birth: an integrative review. Rev Lat Am Enfermagem. 2021 Jul 19;29:e3446. doi: 10.1590/1518.8345.4466.3446. PMID: 34287544; PMCID: PMC8294792.</ref> Gut microbiomes founded by c-section births are less phylogenetically diverse and alter colonization of normal gut microbiota during early infancy,<ref>Nicholas A. Bokulich ''et al.'', Antibiotics, birth mode, and diet shape microbiome maturation during early life.''Sci. Transl. Med.'''''8''',343ra82-343ra82(2016).DOI:10.1126/scitranslmed.aad7121</ref> with studied links to immune disorders such as allergies.<ref>Zhang C, Li L, Jin B, Xu X, Zuo X, Li Y, Li Z. The Effects of Delivery Mode on the Gut Microbiota and Health: State of Art. Front Microbiol. 2021 Dec 23;12:724449. doi: 10.3389/fmicb.2021.724449. PMID: 35002992; PMCID: PMC8733716.</ref> Bacterial populations are known to stimulate immune development within infants during a period of plasticity, with certain metabolites priming immune cells during their maturation process, such as small-chain fatty acids promoting intestinal regulatory T-cells.<ref>Sanidad KZ, Zeng MY. Neonatal gut microbiome and immunity. Curr Opin Microbiol. 2020 Aug;56:30-37. doi: 10.1016/j.mib.2020.05.011. Epub 2020 Jul 4. PMID: 32634598; PMCID: PMC8729197.</ref> Furthermore, these initial, established populations serve to prevent colonization by pathogens.

Compositions change with an infant's dietary transition. At one year, the gut microbiome resembles an adult composition.

A 2021 study by Damiano found significant differences in the composition of gut bacteria between CFS/ME patients and healthy controls. People with ME/CFS had:<ref name="Damiano2021" />

* Higher relative abundance of bacteria in the genus ''Bacteroides'' (phylum Bacteriodetes) and the genus ''Phascolarctobacterium'' (phylum Firmicutes)
* Lower relative abundance of bacteria in the genus ''Anaerostipes'' and genus ''Ruminococcus'' (both from phylum Firmicutes)

However, the study authors were unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME, or if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name="Damiano2021" />

Damiano et al. suggest the intestinal microbial profile recorded in their study is consistent with the profiles reported for other autoimmune conditions. For example, a 2021 review on pediatric [[inflammatory bowel disease]] found a reduced abundance of bacteria in genus ''Anaerostipes.''<ref>{{Cite journal|title=Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review|date=2021-02-02|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884334/|journal=Frontiers in Pediatrics|volume=9|pages=626232|last=Zhuang|first=Xiaojun|last2=Liu|first2=Caiguang|last3=Zhan|first3=Shukai|last4=Tian|first4=Zhenyi|last5=Li|first5=Na|last6=Mao|first6=Ren|last7=Zeng|first7=Zhirong|last8=Chen|first8=Minhu|doi=10.3389/fped.2021.626232|pmc=7884334|pmid=33604319|issn=2296-2360}}</ref> A 2014 study found a higher abundance of the genus ''Bacteroides'' in people with [[systemic lupus erythematous]].<ref>{{Cite journal|title=Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus|date=September 30, 2014|url=https://journals.asm.org/doi/10.1128/mbio.01548-14|journal=mBio|volume=5|issue=5|last=Hevia|first=Arancha|last2=Milani|first2=Christian|last3=Lopez|first3=Patricia|last4=Cuervo|first4=Adriana|last5=Arboleya|first5=Silvia|last6=Duranti|first6=Sabrina|last7=Turroni|first7=Francesca|last8=Suarez|first8=Ana|last9=Gueimonde|first9=Miguel|doi=10.1128/mbio.01548-14}}</ref>

===Oral flora===

The microbiome in the oral cavity (mouth and throat) is the second largest after the gut microbiome. The state of your oral microbiome can affect the rest of your body in two major ways<ref>{{Cite journal|title=Oral microbiota in human systematic diseases|date=2022-03-02|url=https://www.nature.com/articles/s41368-022-00163-7|journal=International Journal of Oral Science|volume=14|issue=1|pages=1–11|last=Peng|first=Xian|last2=Cheng|first2=Lei|last3=You|first3=Yong|last4=Tang|first4=Chengwei|last5=Ren|first5=Biao|last6=Li|first6=Yuqing|last7=Xu|first7=Xin|last8=Zhou|first8=Xuedong|language=en|doi=10.1038/s41368-022-00163-7|pmc=8891310|pmid=35236828|issn=2049-3169}}</ref>:

# Microorganisms in the mouth can travel "downstream" to the gut microbiome.
# An oral infection can cause bacteria and their metabolites (digestive byproducts) to enter the bloodstream. This can activate the immune system and cause widespread inflammation.

The 2021 Damiano study above also found differences in the composition of oral bacteria between CFS/ME patients and healthy controls. People with CFS/ME had higher relative abundance of bacteria in the genus ''Rothia'' (phylum Actinobacteria).<ref name="Damiano2021" />

==ME/CFS==

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 [[myalgic encephalomyelitis]]\[[chronic fatigue syndrome]].

===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 [[interleukin 1|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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = | last2 = Venket Rao | first2 = A | authorlink2 = | last3 = Irani | first3 = Dinaz | authorlink3 = | 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 = December 21, 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>{{citation needed | date = 2021 | reason=Add original research}}

===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 ===

Viruses 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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = Ludovic Giloteaux | last2 = Goodrich | first2 = Julia K. | authorlink2 = | last3 = Walters | first3 = William A. | authorlink3 = | last4 = Levine | first4 = Susan M. | authorlink4 = Susan Levine | last5 = Ley | first5 = Ruth E. | authorlink5 = | last6 = Hanson | first6 = Maureen R. | authorlink6 = 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 | authorlink = Amy Proal | last2 = Marshall | first2 = Trevor | authorlink2 = Trevor Marshall | 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="Damiano2021">{{Cite journal | last = Lupo | first = Giuseppe Francesco Damiano | author-link = | last2 = Rocchetti | first2 = Gabriele | authorlink2 = | last3 = Lucini | first3 = Luigi | authorlink3 = | last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso | last5 = Manara | first5 = Elena | authorlink5 = | last6 = Bertelli | first6 = Matteo | authorlink6 = | last7 = Puglisi | first7 = Edoardo | last8 = Capelli | first8 = Enrica | authorlink8 = 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 = Jun 30, 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==
*[[Probiotics]]
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Indoor microbiome]]
*[[Dr Markov's chronic bacterial intoxication syndrome (CBIS) theory of ME/CFS]] (Dr Markov has evidence that ME/CFS is caused by a dysbiosis in the kidneys)

==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="Shukla2015">{{Citation| doi = 10.1371/journal.pone.0145453| issn = 1932-6203| volume = 10 | issue = 12| pages = 0145453| last1 = Shukla | first1 = Sanjay K. | last2 = Cook | first2 = Dane | last3 = Meyer | first3 = Jacob| last4 = Vernon | first4 = Suzanne D. | last5 = Le | first5 = Thao | last6 = Clevidence | first6 = Derek | last7 = Robertson | first7 = Charles E. | last8 = Schrodi | first8 = Steven J. | last9 = Yale | first9 = Steven | last10 = Frank | first10 = Daniel N.| title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)| journal = PLOS ONE| access-date = 2016-12-13 | date = 2015-12-18| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453}}</ref>
<ref name="Jackson2015">{{citation | last1 = Jackson | first1 = Melinda L | authorlink1 = Melinda Jackson | 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 | title = Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study | journal = Sleep Science | volume = 8 | issue = 3 | pages = 124-133 | date = 23 Oct 2015 | pmid = 26779319 | doi = 10.1016/j.slsci.2015.10.001 | url = http://www.sciencedirect.com/science/article/pii/S1984006315000632 }}</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 | title = Support for the Microgenderome: Associations in a Human Clinical Population | journal = Scientific Reports | volume = | pages = | date = 13 Jan 2016 |issue = | pmid = 26757840 | doi = 10.1038/srep19171 | url = http://www.nature.com/articles/srep19171 }}</ref>
<ref name="Maslowski2011">{{Citation| doi = 10.1038/ni0111-5| issn = 1529-2916| volume = 12 | issue = 1| pages = 5–9| last1 = Maslowski | first1 = Kendle M. | last2 = Mackay | first2 = Charles R.| title = Diet, gut microbiota and immune responses| journal = Nature Immunology | date = January 2011 | pmid = 21169997}}</ref>
<ref name="koren2012">{{Citation| doi = 10.1016/j.cell.2012.07.008| issn = 1097-4172| volume = 150 | issue = 3| pages = 470–480| last1 = Koren | first1 = Omry | last2 = Goodrich | first2 = Julia K. | last3 = Cullender | first3 = Tyler C. | last4 = Spor | first4 = Aymé| last5 = Laitinen | first5 = Kirsi | last6 = Bäckhed | first6 = Helene Kling | last7 = Gonzalez | first7 = Antonio | last8 = Werner | first8 = Jeffrey J. | last9 = Angenent | first9 = Largus T. | last10 = Knight | first10 = Rob| last11 = Bäckhed | first11 = Fredrik | last12 = Isolauri | first12 = Erika | last13 = Salminen | first13 = Seppo | last14 = Ley | first14 = Ruth E.| title = Host remodeling of the gut microbiome and metabolic changes during pregnancy| journal = Cell| date = 2012-08-03 | pmid = 22863002}}</ref>
<ref name="Dinan2012">{{Citation| doi = 10.1016/j.psyneuen.2012.03.007| issn = 0306-4530| volume = 37 | issue = 9| pages = 1369–1378| last1 = Dinan | first1 = Timothy G. | last2 = Cryan | first2 = John F.| title = Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology| journal = Psychoneuroendocrinology| access-date = 2016-12-13 | date = September 2012| url = http://www.sciencedirect.com/science/article/pii/S0306453012000935}}</ref>
<ref name="Fremont2013">{{Citation| doi = 10.1016/j.anaerobe.2013.06.002| issn = 1095-8274| volume = 22 | issue = | pages = 50–56| last1 = Frémont | first1 = Marc| last2 = Coomans | first2 = Danny | last3 = Massart | first3 = Sebastien | last4 = De Meirleir | first4 = Kenny| title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients| journal = Anaerobe | date = August 2013 | pmid = 23791918}}</ref>
<ref name="Borody2012">{{Citation| issn = 1328-8040| volume = 31 | issue = 3| pages = 3| last1 = Borody | first1 = Thomas J. | last2 = Nowak | first2 = Anna | last3 = Finlayson | first3 = Sarah| title = The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy| journal = Journal of the Australasian College of Nutritional and Environmental Medicine| access-date = 2016-12-13 | date = December 2012| url = http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/}}</ref>
<ref name="Morris, 2016">{{Citation | last1 = Morris | first1 = Gerwyn | authorlink1 = Gerwyn Morris | last2 = Berk | first2 = Michael | authorlink2 = Michael Berk | last3 = Carvalho | first3 = A.F. | authorlink3 = | last4 = Caso | first4 = J.R. | authorlink4 = | last5 = Sanz | first5 = Y. | authorlink5 = | last6 = Maes | first6 = Michael | authorlink6 = Michael Maes | title = 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. | journal = Current Pharmaceutical Design | volume = | issue = | pages = | date = 2016 | pmid = 27634186 }}</ref>
<ref name="Nagy-Szakal, 2017">{{Citation | last1 = Nagy-Szakal | first1 = Dorottya | authorlink1 = Dorottya Nagy-Szakal | last2 = Williams | first2 = Brent L. | authorlink2 = | last3 = Mishra | first3 = Nischay | authorlink3 = | 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]]

Microbiome

2026-07-17T08:59:09Z

Tuxedocaspy:/* Gut flora */ Expanding on establishment of gut microbiota

{{Cleanup/Citations needed | date = Mar 2021}}
The '''microbiome''' is the community of microorganisms (such as [[bacteria]], [[fungus|fungi]], and [[virus]]es) that inhabit a particular environment, especially the human body.
<ref>{{Cite web|website=Merrian-Webster Medical Dictionary|access-date=2021-02-20 | title = Definition of MICROBIOME|url=https://www.merriam-webster.com/dictionary/microbiome}}</ref>

==Anatomical areas==
The microorganisms 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]].<ref>{{Cite journal|title=Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome|date=2017-04-26|url=https://pubmed.ncbi.nlm.nih.gov/28441964/|journal=Microbiome|volume=5|issue=1|pages=44|last=Nagy-Szakal|first=Dorottya|last2=Williams|first2=Brent L.|last3=Mishra|first3=Nischay|last4=Che|first4=Xiaoyu|last5=Lee|first5=Bohyun|last6=Bateman|first6=Lucinda|last7=Klimas|first7=Nancy G.|last8=Komaroff|first8=Anthony L.|last9=Levine|first9=Susan|last10=Montoya|first10=Jose G.|last11=Peterson|first11=Daniel L.|doi=10.1186/s40168-017-0261-y|pmc=5405467|pmid=28441964|issn=2049-2618}}</ref>

===Gut flora===

The [[gut microbiome]] is a complex community of trillions of microorganisms residing in the intestines. Around 99% of bacteria in the gut are [[Anaerobic bacteria|anaerobes]].<ref>{{Cite journal|title=Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens|date=October 2003|url=https://www.sciencedirect.com/science/article/abs/pii/S1369527403001176|journal=Current Opinion in Microbiology|volume=6|issue=5|pages=457-461|last=Vendantam|first=Gayatari|last2=Hecht|first2=David}}</ref>

An individual's gut microbiome begins as a sample from the maternal microbiome taken during childbirth. While proportions and specific diversities of bacteria vary between individuals, scientific evidence shows delivery method influences the founding population of intestinal bacteria. Vaginal births are seeded with bacteria found in the birth canal, including ''Bacteroides'', ''Actinobacteria, Lactobacillus, Bifidobacteria.'' Caesarean section births are taken from microbes found on the skin and in the environment, ranging from ''Staphylococcus, Enterococcus, Clostridium, Streptococcus''.<ref>Coelho GDP, Ayres LFA, Barreto DS, Henriques BD, Prado MRMC, Passos CMD. Acquisition of microbiota according to the type of birth: an integrative review. Rev Lat Am Enfermagem. 2021 Jul 19;29:e3446. doi: 10.1590/1518.8345.4466.3446. PMID: 34287544; PMCID: PMC8294792.</ref> Gut microbiomes founded by c-section births are less phylogenetically diverse and alter colonization of normal gut microbiota during early infancy.

A 2021 study by Damiano found significant differences in the composition of gut bacteria between CFS/ME patients and healthy controls. People with ME/CFS had:<ref name="Damiano2021" />

* Higher relative abundance of bacteria in the genus ''Bacteroides'' (phylum Bacteriodetes) and the genus ''Phascolarctobacterium'' (phylum Firmicutes)
* Lower relative abundance of bacteria in the genus ''Anaerostipes'' and genus ''Ruminococcus'' (both from phylum Firmicutes)

However, the study authors were unable to determine if the alteration of the microbiome is a cause or a consequence of the onset of CFS/ME, or if the changes in the microbial composition are related to any of the several secondary symptoms.<ref name="Damiano2021" />

Damiano et al. suggest the intestinal microbial profile recorded in their study is consistent with the profiles reported for other autoimmune conditions. For example, a 2021 review on pediatric [[inflammatory bowel disease]] found a reduced abundance of bacteria in genus ''Anaerostipes.''<ref>{{Cite journal|title=Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review|date=2021-02-02|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884334/|journal=Frontiers in Pediatrics|volume=9|pages=626232|last=Zhuang|first=Xiaojun|last2=Liu|first2=Caiguang|last3=Zhan|first3=Shukai|last4=Tian|first4=Zhenyi|last5=Li|first5=Na|last6=Mao|first6=Ren|last7=Zeng|first7=Zhirong|last8=Chen|first8=Minhu|doi=10.3389/fped.2021.626232|pmc=7884334|pmid=33604319|issn=2296-2360}}</ref> A 2014 study found a higher abundance of the genus ''Bacteroides'' in people with [[systemic lupus erythematous]].<ref>{{Cite journal|title=Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus|date=September 30, 2014|url=https://journals.asm.org/doi/10.1128/mbio.01548-14|journal=mBio|volume=5|issue=5|last=Hevia|first=Arancha|last2=Milani|first2=Christian|last3=Lopez|first3=Patricia|last4=Cuervo|first4=Adriana|last5=Arboleya|first5=Silvia|last6=Duranti|first6=Sabrina|last7=Turroni|first7=Francesca|last8=Suarez|first8=Ana|last9=Gueimonde|first9=Miguel|doi=10.1128/mbio.01548-14}}</ref>

===Oral flora===

The microbiome in the oral cavity (mouth and throat) is the second largest after the gut microbiome. The state of your oral microbiome can affect the rest of your body in two major ways<ref>{{Cite journal|title=Oral microbiota in human systematic diseases|date=2022-03-02|url=https://www.nature.com/articles/s41368-022-00163-7|journal=International Journal of Oral Science|volume=14|issue=1|pages=1–11|last=Peng|first=Xian|last2=Cheng|first2=Lei|last3=You|first3=Yong|last4=Tang|first4=Chengwei|last5=Ren|first5=Biao|last6=Li|first6=Yuqing|last7=Xu|first7=Xin|last8=Zhou|first8=Xuedong|language=en|doi=10.1038/s41368-022-00163-7|pmc=8891310|pmid=35236828|issn=2049-3169}}</ref>:

# Microorganisms in the mouth can travel "downstream" to the gut microbiome.
# An oral infection can cause bacteria and their metabolites (digestive byproducts) to enter the bloodstream. This can activate the immune system and cause widespread inflammation.

The 2021 Damiano study above also found differences in the composition of oral bacteria between CFS/ME patients and healthy controls. People with CFS/ME had higher relative abundance of bacteria in the genus ''Rothia'' (phylum Actinobacteria).<ref name="Damiano2021" />

==ME/CFS==

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 [[myalgic encephalomyelitis]]\[[chronic fatigue syndrome]].

===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 [[interleukin 1|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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = | last2 = Venket Rao | first2 = A | authorlink2 = | last3 = Irani | first3 = Dinaz | authorlink3 = | 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 = December 21, 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>{{citation needed | date = 2021 | reason=Add original research}}

===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 ===

Viruses 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. | authorlink = | last2 = Wettenhall | first2 = Richard E. H. | authorlink2 = | last3 = Scanlon | first3 = Denis | authorlink3 = | last4 = Gooley | first4 = Paul R. | authorlink4 = Paul Gooley | last5 = Lewis | first5 = Donald P. | authorlink5 = Donald Lewis | last6 = McGregor | first6 = Neil | authorlink6 = Neil McGregor | last7 = Stapleton | first7 = David I. | last8 = Butt | first8 = Henry L. | authorlink8 = Henry Butt | last9 = De Meirleir | first9 = Kenny L. | authorlink9 = 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 | authorlink = Ludovic Giloteaux | last2 = Goodrich | first2 = Julia K. | authorlink2 = | last3 = Walters | first3 = William A. | authorlink3 = | last4 = Levine | first4 = Susan M. | authorlink4 = Susan Levine | last5 = Ley | first5 = Ruth E. | authorlink5 = | last6 = Hanson | first6 = Maureen R. | authorlink6 = 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 | authorlink = Amy Proal | last2 = Marshall | first2 = Trevor | authorlink2 = Trevor Marshall | 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="Damiano2021">{{Cite journal | last = Lupo | first = Giuseppe Francesco Damiano | author-link = | last2 = Rocchetti | first2 = Gabriele | authorlink2 = | last3 = Lucini | first3 = Luigi | authorlink3 = | last4 = Lorusso | first4 = Lorenzo | authorlink4 = Lorenzo Lorusso | last5 = Manara | first5 = Elena | authorlink5 = | last6 = Bertelli | first6 = Matteo | authorlink6 = | last7 = Puglisi | first7 = Edoardo | last8 = Capelli | first8 = Enrica | authorlink8 = 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 = Jun 30, 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==
*[[Probiotics]]
*[[Gastrointestinal system]]
*[[Helminthic therapy]]
*[[Ken Lassesen's model]]
*[[Nasal microbiome]]
*[[Oral microbiome]]
*[[Indoor microbiome]]
*[[Dr Markov's chronic bacterial intoxication syndrome (CBIS) theory of ME/CFS]] (Dr Markov has evidence that ME/CFS is caused by a dysbiosis in the kidneys)

==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="Shukla2015">{{Citation| doi = 10.1371/journal.pone.0145453| issn = 1932-6203| volume = 10 | issue = 12| pages = 0145453| last1 = Shukla | first1 = Sanjay K. | last2 = Cook | first2 = Dane | last3 = Meyer | first3 = Jacob| last4 = Vernon | first4 = Suzanne D. | last5 = Le | first5 = Thao | last6 = Clevidence | first6 = Derek | last7 = Robertson | first7 = Charles E. | last8 = Schrodi | first8 = Steven J. | last9 = Yale | first9 = Steven | last10 = Frank | first10 = Daniel N.| title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)| journal = PLOS ONE| access-date = 2016-12-13 | date = 2015-12-18| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453}}</ref>
<ref name="Jackson2015">{{citation | last1 = Jackson | first1 = Melinda L | authorlink1 = Melinda Jackson | 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 | title = Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study | journal = Sleep Science | volume = 8 | issue = 3 | pages = 124-133 | date = 23 Oct 2015 | pmid = 26779319 | doi = 10.1016/j.slsci.2015.10.001 | url = http://www.sciencedirect.com/science/article/pii/S1984006315000632 }}</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 | title = Support for the Microgenderome: Associations in a Human Clinical Population | journal = Scientific Reports | volume = | pages = | date = 13 Jan 2016 |issue = | pmid = 26757840 | doi = 10.1038/srep19171 | url = http://www.nature.com/articles/srep19171 }}</ref>
<ref name="Maslowski2011">{{Citation| doi = 10.1038/ni0111-5| issn = 1529-2916| volume = 12 | issue = 1| pages = 5–9| last1 = Maslowski | first1 = Kendle M. | last2 = Mackay | first2 = Charles R.| title = Diet, gut microbiota and immune responses| journal = Nature Immunology | date = January 2011 | pmid = 21169997}}</ref>
<ref name="koren2012">{{Citation| doi = 10.1016/j.cell.2012.07.008| issn = 1097-4172| volume = 150 | issue = 3| pages = 470–480| last1 = Koren | first1 = Omry | last2 = Goodrich | first2 = Julia K. | last3 = Cullender | first3 = Tyler C. | last4 = Spor | first4 = Aymé| last5 = Laitinen | first5 = Kirsi | last6 = Bäckhed | first6 = Helene Kling | last7 = Gonzalez | first7 = Antonio | last8 = Werner | first8 = Jeffrey J. | last9 = Angenent | first9 = Largus T. | last10 = Knight | first10 = Rob| last11 = Bäckhed | first11 = Fredrik | last12 = Isolauri | first12 = Erika | last13 = Salminen | first13 = Seppo | last14 = Ley | first14 = Ruth E.| title = Host remodeling of the gut microbiome and metabolic changes during pregnancy| journal = Cell| date = 2012-08-03 | pmid = 22863002}}</ref>
<ref name="Dinan2012">{{Citation| doi = 10.1016/j.psyneuen.2012.03.007| issn = 0306-4530| volume = 37 | issue = 9| pages = 1369–1378| last1 = Dinan | first1 = Timothy G. | last2 = Cryan | first2 = John F.| title = Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology| journal = Psychoneuroendocrinology| access-date = 2016-12-13 | date = September 2012| url = http://www.sciencedirect.com/science/article/pii/S0306453012000935}}</ref>
<ref name="Fremont2013">{{Citation| doi = 10.1016/j.anaerobe.2013.06.002| issn = 1095-8274| volume = 22 | issue = | pages = 50–56| last1 = Frémont | first1 = Marc| last2 = Coomans | first2 = Danny | last3 = Massart | first3 = Sebastien | last4 = De Meirleir | first4 = Kenny| title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients| journal = Anaerobe | date = August 2013 | pmid = 23791918}}</ref>
<ref name="Borody2012">{{Citation| issn = 1328-8040| volume = 31 | issue = 3| pages = 3| last1 = Borody | first1 = Thomas J. | last2 = Nowak | first2 = Anna | last3 = Finlayson | first3 = Sarah| title = The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy| journal = Journal of the Australasian College of Nutritional and Environmental Medicine| access-date = 2016-12-13 | date = December 2012| url = http://www.cdd.com.au/pdf/publications/All%20Publications/2013%20-%20The%20GI%20microbiome%20and%20its%20role%20in%20CFS%20-%20ACNEM%20paper.pdf/}}</ref>
<ref name="Morris, 2016">{{Citation | last1 = Morris | first1 = Gerwyn | authorlink1 = Gerwyn Morris | last2 = Berk | first2 = Michael | authorlink2 = Michael Berk | last3 = Carvalho | first3 = A.F. | authorlink3 = | last4 = Caso | first4 = J.R. | authorlink4 = | last5 = Sanz | first5 = Y. | authorlink5 = | last6 = Maes | first6 = Michael | authorlink6 = Michael Maes | title = 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. | journal = Current Pharmaceutical Design | volume = | issue = | pages = | date = 2016 | pmid = 27634186 }}</ref>
<ref name="Nagy-Szakal, 2017">{{Citation | last1 = Nagy-Szakal | first1 = Dorottya | authorlink1 = Dorottya Nagy-Szakal | last2 = Williams | first2 = Brent L. | authorlink2 = | last3 = Mishra | first3 = Nischay | authorlink3 = | 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]]

MEpedia:Sample page

2026-07-17T06:23:13Z

Tuxedocaspy:Editing practice

Welcome to the '''sample page'''! This page has been created for anyone who wants to practice some edits on the site. Have a go, play around. Leave your edits behind for the next person who comes along to see.

=='''Introduction'''==111111111
this is new to me\

Hello world

== New Editor Questions ==

==Generic questions:==

===What is your favourite movie?===
Harold and Maude{{Citation needed|reason=We need documentation supporting this statement about a cat. | date=2018}}

===What is something that always makes you laugh?===

John Waters{{Citation needed|reason=We need documentation supporting this statement about a cat. | date=2018}}

===What is the weather currently like where you are?===

* previous editor: Early winter in drought-stricken California; 5-15 degrees Celsius and often-cloudy in daytime, 3-10 degrees at night, occasional drizzle/rain when we should be getting frequent rain, with occasionally drenching rainstorms.
* ChaiTea: The sky is green.{{Citation needed|date=28 October 2025}}

===Where in the world are you right now, and where would you most like to be?===
In California. Would love to be in New Zealand, Norway, Switzerland, or the Czech Republic.

===What are a few of your favorite things?===

* previous editor: Music, Fredo, crickets at night, autumn, my husband, being in water, water skiing
* L.Berlin: Funny cat videos, especially Siberian cats; laughing babies; any effective attack on Russia's war infrastructure, by Ukraine's home-grown missiles
* ChaiTea: Autumn, cats, logic puzzles

=== What are your favourite books? ===

* L.Berlin: Asimov's Treasury of Humor<ref>{{Cite book|title=Asimov's Treasury of Humor|date=1991|publisher=Houghton Mifflin|last=Asimov|first=Isaac|quote=A lifetime collection of favorite jokes, anecdotes, and limericks with copious notes on how to tell them and why}}</ref>
* next editor:

==An inspiring blog post==

* previous editor: My new blog.
* ChaiTea: A few posts by [[Whitney Dafoe]].

==Notable studies==

==Online resources==
All [[Welcome to MEpedia|MEpedia]] [[Special:AllPages|pages here!]]

== See also ==
* [[MEpedia:Article outlines|MEpedia article outlines]]
* [[MEpedia:Help desk|Help desk]]
* [[Help:Tutorial|Help Tutorial]]

==References==
<ref>{{Citation | last1 = Mendelson | first1 = Scott| authorlink1 = Scott Mendelson | last2 = Smith | first2 = Scott
| display-authors = 1 | title = Star Wars: The Force Awakens: A Look at Its Record-Breaking Box Office Run
}}
</ref>
<references />
[[Category:MEpedia documentation]]