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

Gao, Teng; Liu, Xiaoxing; Mi, Weifeng; Shi, Le; Wang, Xueqin; Zhu, Daomin; Geng, Feng; Fu, Yixiao et al. · J Intern Med · 2026

rct · Level II

Where this comes from

Abstract

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. 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. 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. 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.