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<p>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 <i>Lactiplantibacillus plantarum</i> (<i>L. plantarum</i>) KBL396, a strain isolated from a healthy Korean adult. We demonstrate that <i>L. plantarum</i> KBL396 potently induces <i>Tph1</i> gene expression in vitro (<i>p</i> &lt; 0.001),&#xa0;which encodes the rate-limiting enzyme&#xa0;tryptophan hydroxylase&#xa0;1 for 5-hydroxytryptamin (5-HT) synthesis. <i>L. plantarum</i> KBL396 administration ameliorated depressive-like behaviors (<i>p</i> &lt; 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: <i>n</i> = 62; the placebo group: <i>n</i> = 30) showed that <i>L. plantarum</i> KBL396 significantly elevated the serum 5-HT and dopamine level (<i>p</i> &lt; 0.05). <i>L. plantarum</i> KBL396 administration remodeled gut microbiota with the increases of <i>Lactiplantibacillus</i> and <i>Akkermansia</i>. Collectively, our findings preliminarily demonstrate that <i>L. plantarum</i> KBL396 is a psychobiotic candidate that mechanically links gut-derived neurotransmitter production to beneficial mental health-related outcomes across preclinical model and clinical settings.</p> Graphical Abstract <p></p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • 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

摘要

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.

Graphical Abstract