Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles. — ME/CFS Atlas
Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles.
Tobi, Martin, Chaudhari, Diptaraj, Ryan, Elizabeth P et al. · Biomolecules · 2025 · DOI
Quick Summary
Researchers compared gut bacteria and immune molecules in the blood of people with long COVID and chronic fatigue syndrome. They found that people with these conditions have unusual patterns of gut bacteria and different levels of immune signaling molecules compared to healthy controls. These differences suggest the immune system and gut health may play a role in why some people develop long-lasting fatigue after infection.
Why It Matters
This study provides potential biomarkers—gut microbiome composition and specific immune molecules—that could help identify and understand ME/CFS and long COVID. Finding common immune and microbiome signatures across post-viral fatigue conditions strengthens the case that these are genuine biological illnesses with measurable physiological changes, not purely psychological disorders.
Observed Findings
Significant inversion of dominant gut bacterial phyla (Bacillota and Bacteroidota) in PASC and ME/CFS patients compared to controls.
Multiple serum cytokine imbalances in PASC patients, including elevated IL-8 versus TARC (p<0.002) and altered IL-1β/IL-6 ratios (p<0.01).
Differential cytokine patterns unique to COVID-19 infection (e.g., MDC versus MIP-1α; p<0.01) versus PASC.
History of tonsillectomy identified as a correlate in chronic fatigue cases without identified viral etiology.
Inferred Conclusions
Profound and measurable changes in microbiome and serum cytokine expression characterize both PASC and ME/CFS, suggesting a biological basis for post-viral fatigue syndromes.
Immune dysregulation is a likely etiology of at least some cases of chronic fatigue, including cases without clear viral triggers.
Microbiome and cytokine signatures may serve as objective biomarkers for identifying and potentially stratifying post-viral fatigue conditions.
Remaining Questions
Do the altered microbiome and cytokine patterns represent active drivers of symptoms, or are they secondary consequences of the illness state?
Can these biomarkers predict severity, duration, or recovery trajectory in individual patients?
What This Study Does Not Prove
This study does not prove that microbiome or cytokine changes *cause* ME/CFS or long COVID; it only shows associations. The cross-sectional design means the altered immune profile could be a consequence rather than a cause of illness. The study also does not establish whether these biomarkers can predict who will recover or guide treatment decisions.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
What is the mechanism linking tonsillectomy history to immune dysregulation in non-viral chronic fatigue cases?
Do microbiome-targeted interventions (e.g., probiotics, fecal microbiota transplantation) improve outcomes in PASC or ME/CFS, and would baseline microbiome composition predict treatment response?