Unravelling the Microbial Mechanisms Underlying the Psychobiotic Potential of a Bifidobacterium breve Strain

SCOPE The antidepressant-like effect of psychobiotics has been observed in both pre-clinical and clinical studies, but the molecular mechanisms of action are largely unclear. To address this, the psychobiotic strain Bifidobacterium breve CCFM1025 is investigated for its genomic features, metabolic features, and gut microbial and metabolic modulation effect. METHODS AND RESULTS Unlike B. breve FHLJDQ3M5, CCFM1025 significantly decreases the chronically stressed mice's depressive-like behaviors and neurological abnormalities. CCFM1025 has more genes encoding glycoside hydrolases (GHs) when comparing to FHLJDQ3M5's genome, which means CCFM1025 has a superior carbohydrate utilization capacity and living adaptivity in the gut. CCFM1025 also produces higher levels of neuromodulatory metabolites, including hypoxanthine, tryptophan, and nicotinate. The administration of CCFM1025 reshapes the gut microbiome of chronically stressed mice. It results in higher cecal xanthine, tryptophan, short-chain fatty acid levels, and enhances fatty acid and tryptophan biosynthesis capability in the gut-brain interaction (identified by in silico analyses) than FHLJDQ3M5-treated mice. CONCLUSIONS Genomic and metabolic features involving GHs and neuromodulatory metabolites may determine the antidepressant-like effect of B. breve CCFM1025. Psychobiotics' characterization in this manner may provide guidelines for developing novel psychopharmacological agents in the future.