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Background <p>Gut microbiota dysbiosis has been implicated in the pathogenesis of depression. Our previous studies identified loganin as a potential antidepressant agent; however, its oral bioavailability is low. Whether loganin alleviates depression via modulation of the gut microbiota remains unclear.</p> Methods <p>Chronic unpredictable stress mice model was used to evaluate the antidepressant-like effects of loganin. To determine the role of gut microbiota, mice were treated with an antibiotic cocktail (ABX) to deplete microbiota. Fecal microbiota transplantation (FMT) from loganin-treated donors and <i>Muribaculum intestinale</i> (<i>M. intestinale</i>) were performed to assess microbial contributions.</p> Results <p>Loganin exerted antidepressant-like effects by modulating gut microbiota, as evidenced by reduced efficacy in ABX-treated mice and behavioral improvements in recipients of FMT from loganin-treated donors. Loganin modulated gut microbiota composition particularly increasing the abundance of <i>Muribaculum</i>, and increased short-chain fatty acids (SCFAs). <i>M. intestinale</i> alleviated depressive-like behaviors, prompted the butyrylation of RORγt, inhibited Th17 cells differentiation, and suppressed M1 microglia polarization. Importantly, overexpression of RORγt attenuated the behavioral benefits of <i>M. intestinale</i>.</p> Conclusion <p>Loganin exerts antidepressant-like effects by enriching <i>Muribaculum</i> and SCFAs, thereby inhibiting Th17 cell differentiation and M1 microglia polarization. <i>M. intestinale</i> may represent a promising microbial-based therapeutic strategy for depression.</p>

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Muribaculum intestinale alleviates depressive-like behaviors by inhibiting Th17 cell differentiation and M1 microglia polarization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月3日

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  • Jun He,
  • Man-Ni Wang,
  • Hong-Jin Chen,
  • Guo-Yan Zuo,
  • Jing-Liang Li,
  • Wei-Feng Yin,
  • Xue-Ge Pan,
  • Yung-Chi Cheng,
  • Cong-Yuan Xia,
  • Jie-Kun Xu,
  • Wei-Ku Zhang

摘要

Background

Gut microbiota dysbiosis has been implicated in the pathogenesis of depression. Our previous studies identified loganin as a potential antidepressant agent; however, its oral bioavailability is low. Whether loganin alleviates depression via modulation of the gut microbiota remains unclear.

Methods

Chronic unpredictable stress mice model was used to evaluate the antidepressant-like effects of loganin. To determine the role of gut microbiota, mice were treated with an antibiotic cocktail (ABX) to deplete microbiota. Fecal microbiota transplantation (FMT) from loganin-treated donors and Muribaculum intestinale (M. intestinale) were performed to assess microbial contributions.

Results

Loganin exerted antidepressant-like effects by modulating gut microbiota, as evidenced by reduced efficacy in ABX-treated mice and behavioral improvements in recipients of FMT from loganin-treated donors. Loganin modulated gut microbiota composition particularly increasing the abundance of Muribaculum, and increased short-chain fatty acids (SCFAs). M. intestinale alleviated depressive-like behaviors, prompted the butyrylation of RORγt, inhibited Th17 cells differentiation, and suppressed M1 microglia polarization. Importantly, overexpression of RORγt attenuated the behavioral benefits of M. intestinale.

Conclusion

Loganin exerts antidepressant-like effects by enriching Muribaculum and SCFAs, thereby inhibiting Th17 cell differentiation and M1 microglia polarization. M. intestinale may represent a promising microbial-based therapeutic strategy for depression.