Alterations in gut microbiota and associated metabolites in patients with chronic fatigue syndrome.
Cheng, Xinxin, Wang, Wenkuan, Xu, Tingting et al. · Scientific reports · 2025 · DOI
Quick Summary
This study looked at the bacteria living in the gut of people with ME/CFS compared to healthy people, and found that ME/CFS patients have fewer types of bacteria and lower levels of helpful compounds called short-chain fatty acids (SCFAs) that bacteria produce. The study found that people with ME/CFS who eat more fiber have higher levels of these beneficial compounds, suggesting diet may help restore some of the bacterial imbalances seen in ME/CFS.
Why It Matters
This study provides biological evidence that ME/CFS involves measurable alterations in gut bacterial composition and metabolism, potentially opening avenues for microbiome-targeted therapeutic interventions. The finding that dietary fiber correlates with improved bacterial metabolites offers patients a potentially modifiable lifestyle factor that may help ameliorate symptom severity.
Observed Findings
ME/CFS patients showed significantly reduced gut microbial diversity compared to healthy controls across multiple diversity indices (ACE, Chao1, Shannon; all P < 0.01).
Fecal levels of four short-chain fatty acids (acetate, butyrate, isobutyrate, isovalerate) were significantly lower in ME/CFS patients after correction for multiple comparisons (all q < 0.05).
Key SCFA-producing bacterial taxa (Faecalibacterium, Subdoligranulum, Ruminococcaceae) showed positive correlation with butyrate levels (r = 0.52-0.56, all q < 0.05).
Reduced bacterial abundances were associated with worse quality-of-life and higher fatigue scores (r = -0.28 to -0.30, q < 0.05).
ME/CFS patients with higher dietary fiber intake had significantly higher acetate and isovalerate levels than those with lower intake (both q < 0.05).
Inferred Conclusions
ME/CFS involves significant gut dysbiosis characterized by reduced microbial diversity and depleted SCFA-producing bacteria.
Reduced abundance of key SCFA-producing taxa directly correlates with reduced short-chain fatty acid production and increased fatigue severity, suggesting a functional mechanistic link.
Dietary fiber supplementation may partially restore impaired SCFA metabolism in ME/CFS patients.
Remaining Questions
Does increasing dietary fiber intake or supplementing SCFAs directly improve ME/CFS symptoms in prospective clinical trials?
What This Study Does Not Prove
This study does not prove that gut dysbiosis causes ME/CFS, only that an association exists—the dysbiosis could be a consequence of the illness rather than a cause. It also does not establish that increasing fiber intake will clinically improve ME/CFS symptoms in individual patients, only that it correlates with improved SCFA levels. The cross-sectional design cannot establish temporal relationships or determine whether interventions targeting these metabolites would reduce fatigue.
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 causes the initial dysbiosis and SCFA depletion in ME/CFS—does the illness itself alter gut bacterial composition, or do other factors (activity restriction, medications, immune activation) drive the changes?
Are specific SCFA-producing bacterial strains therapeutic targets, and would fecal microbiota transplantation or targeted probiotics be clinically beneficial?
How do the observed SCFA deficiencies mechanistically contribute to ME/CFS pathophysiology (e.g., through intestinal barrier integrity, immune regulation, or neurological effects)?