Oral Administration of Lactiplantibacillus plantarum KBL396 Regulates Serum 5-Hydroxytryptamine and Gut Microbiota: Evidence from a Preclinical Mouse Model and a Randomized Controlled Human Trial.
- 2025-11-17
- Probiotics and antimicrobial proteins 18(4)
- Woojae Myung
- Sung Jae Jang
- Giljae Lee
- Cheonghoon Lee
- Kiuk Lee
- Sung Hyun Moon
- Yunsun Jeong
- Woon-Ki Kim
- SungJun Park
- Hyungjin Lee
- Yun Seong Park
- Sangah Shin
- Tae-Wook Nam
- Hong Jin Jeon
- GwangPyo Ko
- PubMed: 41249723
- DOI: 10.1007/s12602-025-10811-z
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 62
- Population
- 62 adults in KBL396 group and 30 adults in placebo group
- Methods
- Randomized, double-blind, placebo-controlled trial, 8 weeks of L. plantarum KBL396 administration
- Blinding
- Double-blind
- Duration
- 8 weeks
- Funding
- Unclear
- Rigorous Journal
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 < 0.001), which encodes the rate-limiting enzyme tryptophan hydroxylase 1 for 5-hydroxytryptamin (5-HT) synthesis. L. plantarum KBL396 administration ameliorated depressive-like behaviors (p < 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 weeks of randomized, double-blind, placebo-controlled trial (the KBL396 group: n = 62; the placebo group: n = 30) showed that L. plantarum KBL396 significantly elevated the serum 5-HT and dopamine level (p < 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.