ScholarWorks@중앙대학교

초록

Emerging evidence links gut microbiota to major depressive disorder via the gut-brain axis. Here, we provide comprehensive evidence from a preclinical mouse model and a randomized controlled human trial for the psychobiotic potential of Lactiplantibacillus plantarum (L. plantarum) KBL396, a strain isolated from a healthy Korean adult. We demonstrate that L. plantarum KBL396 potently induces Tph1 gene expression in vitro (p&#x2009;<&#x2009;0.001),&#xa0;which encodes the rate-limiting enzyme&#xa0;tryptophan hydroxylase&#xa0;1 for 5-hydroxytryptamin (5-HT) synthesis. L. plantarum KBL396 administration ameliorated depressive-like behaviors (p&#x2009;<&#x2009;0.05), increased serum 5-HT, and modulated immune cell populations in mice with chronic social defeat stress. Critically, these preclinical findings translated to humans: the 8&#xa0;weeks of randomized, double-blind, placebo-controlled trial (the KBL396 group: n&#x2009;=&#x2009;62; the placebo group: n&#x2009;=&#x2009;30) showed that L. plantarum KBL396 significantly elevated the serum 5-HT and dopamine level (p&#x2009;<&#x2009;0.05). L. plantarum KBL396 administration remodeled gut microbiota with the increases of Lactiplantibacillus and Akkermansia. Collectively, our findings preliminarily demonstrate that L. plantarum KBL396 is a psychobiotic candidate that mechanically links gut-derived neurotransmitter production to beneficial mental health-related outcomes across preclinical model and clinical settings. © 2025. The Author(s).

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