Autonomic modulation following fecal microbiota transplantation in chronic insomnia

Objective To determine whether fecal microbiota transplantation (FMT) modulates autonomic function in chronic insomnia disorder and whether autonomic rebalancing mediates sleep improvement.Methods This prespecified exploratory analysis was embedded within a multicenter, double-blind, randomized, placebo-controlled trial of FMT for chronic insomnia. The original trial was designed to evaluate the efficacy and safety of the FMT-based treatment protocol, with polysomnography-measured sleep efficiency at 1 month as the primary endpoint. Eighty adults were randomly assigned to receive either FMT (n = 40) or placebo capsules (n = 40). Overnight polysomnography was conducted at baseline and 1 month, and heart rate variability indices were derived to quantify autonomic regulation. Sleep outcomes included PSG-derived metrics and validated subjective questionnaires. Associations between changes in autonomic parameters and sleep outcomes were examined using correlation analyses. Mediation analysis was performed to evaluate whether autonomic changes statistically mediated FMT-associated improvements in sleep. Gut microbiota composition was profiled using 16S rRNA gene sequencing.Results In the original trial, the FMT-based treatment met its prespecified primary endpoint, with significantly improved polysomnography-measured sleep efficiency at 1 month. In this exploratory analysis, FMT significantly reduced the LF/HF ratio (−0.10; 95% CI, −0.18 to −0.02; p = 0.010). A reduction in LF/HF was associated with longer TST (β = −0.41; p = 0.004). Mediation analysis showed that LF/HF accounted for 49.7% of the FMT effect on TST (ACME = 19.44 min; p = 0.018). FMT induced microbial compositional remodeling associated with the nocturnal LF/HF ratio, including enrichment of Lachnospira eligens, Christensenellaceae R-7 group, Ruminococcaceae, and Coprococcus, and depletion of Prevotella copri, Streptococcus, and Faecalibacterium.Conclusions These findings provide clinical exploratory evidence for autonomic system as a potential pathway through which microbiota-targeted interventions may alleviate insomnia. Further studies are needed to determine the durability and clinical significance of these findings.Clinical trial registration ClinicalTrials.gov: NCT05917379 (June 23, 2023).