Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons. — CFSMEATLAS
Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons.
Wallis, Amy, Ball, Michelle, Butt, Henry et al. · Journal of translational medicine · 2018 · DOI
Quick Summary
This study tested whether treating an overgrowth of Streptococcus bacteria in the gut could help ME/CFS patients, particularly those with brain fog and sleep problems. Forty-four patients received alternating weeks of an antibiotic and a probiotic for 4 weeks. The treatment reduced the problematic bacteria and improved several symptoms including sleep quality, attention, and memory, though it did not significantly affect fatigue or mood.
Why It Matters
This study provides preliminary mechanistic evidence that gut dysbiosis—specifically Streptococcus overgrowth—may contribute to specific ME/CFS neurological symptoms, offering a potential therapeutic target beyond symptom management. The findings could guide more personalized treatment approaches and motivate larger controlled trials to clarify whether microbiota-targeted interventions benefit ME/CFS patients.
Observed Findings
Streptococcus viable counts decreased following the 4-week treatment protocol
Total symptom burden improved with treatment
Cognitive outcomes improved, including attention, processing speed, cognitive flexibility, story memory, and verbal fluency
Sleep quality and efficiency improved; nighttime awakenings decreased
Fatigue severity and mood scores remained unchanged; urine D:L lactate ratios did not significantly shift
Inferred Conclusions
Specific gut dysbiosis patterns (elevated Streptococcus) may interact with some—but not all—ME/CFS symptoms, particularly cognitive and sleep dysfunction
Microbiota-targeted treatment may offer therapeutic benefit for neuropsychological symptoms in a subset of ME/CFS patients
Sex-based differences in microbiota-symptom relationships suggest biological heterogeneity in ME/CFS and potential need for sex-stratified or individualized treatment strategies
D-lactate may not be the primary mechanism linking Streptococcus overgrowth to neurological symptoms in this population
Remaining Questions
Does a double-blind, placebo-controlled design confirm the benefit observed in this open-label study, and what is the magnitude of true treatment effect?
What This Study Does Not Prove
This open-label design cannot establish causation or rule out placebo effects, since patients knew they were receiving treatment. The study does not prove that Streptococcus is the primary cause of ME/CFS symptoms, and the lack of change in fatigue and mood suggests the mechanism is incomplete. Sex differences in response require confirmation in larger samples and do not yet explain why microbiota shifts associate differently with outcomes in males versus females.
Why do microbiota shifts correlate with clinical improvement differently in males versus females, and what biological mechanisms underlie this sex difference?
Which concurrent microbial changes (increased Bacteroides/Bifidobacterium, decreased Clostridium) directly cause symptom improvement, and can these be targeted selectively?
Do fatigue and mood respond to different microbiota-targeted interventions, or are these symptoms independent of gut dysbiosis in ME/CFS?