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Phd thesis: Investigating Immune Reactivity to the Intestinal Microbiome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Seton, 2022)


Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) pathogenesis is thought to be multisystemic, including the immune and gastrointestinal systems. A proportion of patients experience gastrointestinal disturbances with evidence suggesting a leaky gut. It was hypothesised that a leaky gut and microbial translocation causes a breach in immune tolerance, promoting inflammation and autoimmunity.

Aims: A) determine whether severe ME/CFS patients have increased systemic and mucosal immunoglobulin (Ig) reactivity to the intestinal microbiome, and B) determine which intestinal microbes serum IgG was directed against.

Methods: Serum and stool samples were collected from five pairs of severe ME/CFS patients and matched household controls. Enzyme linked immunosorbent assays were developed to quantify IgG in serum, bound and non-bound IgA in stool and serum IgG levels reactive with autologous and heterologous stool bacteria. Flow cytometry methods were developed to quantify both stool microbial load and the proportion of stool microbes reactive with mucosal IgA and serum IgG. A ‘bug FACS’ method was developed to identify and quantify serum IgG reactivity to stool bacteria and fungi.

Results: The main finding was that severe ME/CFS patients have significantly lower levels of serum IgG reactive to heterologous stool bacteria compared to their matched household controls. In addition, severe ME/CFS patients do not have higher levels of serum IgG reactive to heterologous stool bacteria than autologous stool bacteria. Severe ME/CFS patients also have a non-significant increase of IgG binding to Campylobacter jejuni and Pseudomonas viridiflava compared to their matched household controls. Analysis of mucosal IgA found ME/CFS patients with a long disease duration had higher microbe bound IgA concentrations compared to their matched household controls.

Conclusion: This thesis presents results from the first ME/CFS study to investigate serum IgG immune reactivity to stool microbes. Findings suggest ME/CFS patients have an impaired serum IgG immune response to the intestinal microbiome.



Senior Member
I think this is unlikely to be part of the core dysfunction of ME. If it was a factor, then dietary changes, antibiotics, etc, should have more effects on PWME. I think it's more likely that ME alters immune functions elsewhere in the body, and that in turn can worsen some symptoms of ME for some people.


Senior Member
Interestiing, but I would think that in addition to leaky gut you would have to include Crohn's and EPI to accont for low IgG and subclass deficiency. With Crohn's and EPI any dietary changes and antibiotics would have virtually no effect on the malnutrition induced immune deficiency. With leaky gut you are still absorbing nutrients from food, but (of course) also absorbing bad things in to the digestive tract.