Fecal microbiota transplantation-based treatment protocol for chronic insomnia disorder: A randomized, double-blind, placebo-controlled trial

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Abstract

OBJECTIVE: Chronic insomnia disorder is common and burdensome, and current treatments remain limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to determine whether a fecal microbiota transplantation (FMT)-based treatment protocol improves sleep outcomes in adults with chronic insomnia disorder. METHODS: Participants were randomly assigned 1:1 to receive short-course antibiotic pretreatment followed by donor microbiota capsules (n = 40) or placebo capsules without antibiotic pretreatment (n = 40). Within each group, participants were further randomized to receive synbiotic supplementation or matched placebo for prespecified exploratory subgroup analyses. The primary outcome was polysomnography-measured sleep efficiency (SE) at 1 month after treatment. Secondary outcomes included other polysomnographic parameters, patient-reported sleep outcomes, and safety; microbiota analyses were exploratory. RESULTS: Compared with placebo, the FMT-based treatment protocol improved SE (adjusted between-group difference, 13.9 percentage points; 95% CI 7.29-20.41; p = 0.003) and reduced wake after sleep onset. Synbiotic assignment did not suggest meaningful differences in SE. Insomnia Severity Index and Pittsburgh Sleep Quality Index scores showed sustained improvement from 2 to 6 months. Treatment was well tolerated, with mild, self-limited adverse events and no serious adverse events. The intervention increased microbial richness and diversity and altered community structure; responders and non-responders showed similar posttreatment β-diversity change but differed in baseline microbiota composition. CONCLUSION: In adults with chronic insomnia disorder, an FMT-based treatment protocol incorporating antibiotic pretreatment improved objective sleep continuity and sustained subjective insomnia outcomes. Baseline microbial composition may contribute to treatment heterogeneity and merits further investigation.

Abstract as published, via PubMed.