subsp.Bbm-19 ameliorates insomnia by remodeling the gut microbiota and restoring γ-aminobutyric acid and serotonin signaling.

Abstract

Insomnia is associated with dysregulation of the gut-brain axis, yet microbiome-targeted interventions remain underexplored. In this study, we investigated the effects ofsubsp.Bbm-19 (Bbm-19), a strain isolated from human breast milk, in a 4-chloro-DL-phenylalanine-induced mouse model of insomnia. Using integrated behavioral, neurochemical, immunological, and multi-omics approaches, this study demonstrates that insomnia is characterized by shortened sleep duration, prolonged sleep latency, anxiety-like behaviors, and reduced levels of serotonin and gamma-aminobutyric acid in the gut, serum, and brain. Administration of Bbm-19 significantly improved sleep parameters, reduced anxiety-like behaviors, and increased survival. Metagenomic and metabolomic analyses revealed that Bbm-19 restored gut microbiota balance, enriched beneficial taxa, includingbacterium andsp., and reprogrammed microbial metabolic modules, particularly those involved in amino acid metabolism (including alanine, aspartate, glutamate, arginine, proline, and tryptophan pathways). Targeted metabolomics confirmed increased levels of gamma-aminobutyric acid and serotonin in fecal and brain tissues, along with normalization of inflammatory cytokine profiles. Spearman correlation analysis linked Bbm-19-enriched taxa to improved neurotransmitter levels and sleep outcomes. Notably, Bbm-19 outperformed lorazepam in modulating gut-specific metabolic functions and synergistically enhanced its effects when co-administered. These findings demonstrate that Bbm-19 ameliorates insomnia through coordinated regulation of the gut microbiota, host metabolism, and neuroimmune signaling, highlighting its potential as a targeted psychobiotic intervention for sleep disorders.