Microbiome

The microbiome is the ecological community of commensal, symbiotic and pathogenic microorganisms that live on the skin and genitals and in the nose, ears, mouth and gut. Dysbiosis or an imbalance in this community may play a role in the pathophysiology of chronic fatigue syndrome.

Gut flora
The gut microbiome is a complex community of trillions of microorganisms residing in the intestines. 99% of bacteria in the gut are anaerobes.

Chronic fatigue syndrome
A growing body of evidence suggests that an altered microbiome; mucosal barrier dysfunction; the translocation or crossing of bacteria from the gut into the bloodstream; and subsequent immune response may pay a role in the pathophysiology of chronic fatigue syndrome.

Immune response
A study of 128 ME/CFS patients found significantly increased IgA response to lipopolysaccharides from the cell walls of commensal bacteria. Increased IgA response was associated with increased serum IL-1, TNFα, neopterin and elastase. The study concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.

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, decreased levels of Bifidobacteria, and may suffer from small intestinal bacterial overgrowth (SIBO) at higher rates.

Exercise
A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the intestine into the bloodstream following exercise). In the blood, the study found increased Clostridium fifteen minutes after exercise and increased Bacilli 48 hours later.

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.

Gender
A study of 274 ME/CFS patients found sex-specific interactions between Firmicutes (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.

Diet
The food we eat has a considerable effect on the composition of the intestinal microbiota.

Viral infection
Viral infection can cause shifts in the gut microbiome.

In mice, the influenza virus leads to injury of both the lungs (the primary site of infection) and the intestinal tract, even when there is no evidence of viral replication in the gut, and causes decreases Lactobacillus and Lactococcus species and increases in Enterobacteriaceae.

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.

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. Overall bacterial load increases over the course of pregnancy.

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 is introduced. Escherichia coli can activate the HPA.

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.

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

 * 2017, Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome (FULL TEXT)"Abstract - Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleep disturbance, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Results: Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. Conclusions: Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups."
 * 2016, 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
 * 2016, Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome
 * 2016, Support for the Microgenderome: Associations in a Human Clinical Population
 * 2015, Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study
 * 2015, Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
 * 2013, High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients
 * 2012, Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome
 * 2012, The GI Microbiome and its Role in Chronic Fatigue Syndrome: A Summary of Bacteriotherapy
 * 2010, Gut inflammation in chronic fatigue syndrome
 * 2009, Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome

Commercial testers

 * uBiome

Academic projects

 * American Gut
 * British Gut Project

Learn more

 * Wikipedia - Microbiota
 * CFS Remission (Ken Lassesen's blogs about experimental ME/CFS microbiome and probiotic treatments)
 * 2016, What should be in the ideal microbiome test for CFS CFS Remission
 * 2016, It's All in Your Gut Onward Through the Fog
 * 2016, Gut Bacteria Are Different in People With Chronic Fatigue Syndrome The New York Times
 * 2016, New study shows chronic fatigue syndrome may have to do with gut microbes The Washington Post
 * 2016, Indicator of chronic fatigue syndrome found in gut bacteria Cornell Chronicle
 * 2016, Gender Gut Wars: Australian ME/CFS Study Suggests Different Gut Treatment Protocols Needed For Men and Women Health Rising
 * Vitamin D and the Microbiome CFS Remission