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<p>Gut microbiota and bile acids have been reported to affect sepsis progression, but the underlying mechanisms remain largely unknown. Here we investigated gut microbiota–bile acid interplay in two paediatric sepsis cohorts. Integration of bile acid-targeted metabolomics with gut metagenome data from paediatric sepsis patients identified deoxycholic acid 3-sulfate (DCA-3S) as significantly associated with paediatric sepsis progression. In vitro and in vivo experiments identified <i>Enterococcus raffinosus</i> as the primary producer of DCA-3S, contributing at least 80% of its total production, challenging the conventional notion of hepato-centric bile acid sulfation pathways. Intervention experiments in mouse and intestinal organoid models revealed that DCA-3S administration effectively alleviated sepsis by improving intestinal barrier function and attenuating inflammatory response. Collectively, our findings highlight a previously unrecognized microbial contribution to bile acid sulfation and position DCA-3S as a promising diagnostic and therapeutic biomarker for paediatric sepsis.</p>

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Sulfated bile acid produced by a human gut commensal alleviates paediatric sepsis in mice

  • 期刊论文

  • 发表日期：

    2026年5月1日

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  • Xiang Liu,
  • Haobo Zhang,
  • Yan-Zhen Wang,
  • Xinyu Tu,
  • Jiejie Wen,
  • Shu Lei,
  • Nian Liu,
  • Xinyi Wei,
  • Changzhen Li,
  • Yiwei Li,
  • Bifeng Liu,
  • Yu-Qi Feng,
  • Quan-Fei Zhu,
  • Xin Liu,
  • Kang Ning

摘要

Gut microbiota and bile acids have been reported to affect sepsis progression, but the underlying mechanisms remain largely unknown. Here we investigated gut microbiota–bile acid interplay in two paediatric sepsis cohorts. Integration of bile acid-targeted metabolomics with gut metagenome data from paediatric sepsis patients identified deoxycholic acid 3-sulfate (DCA-3S) as significantly associated with paediatric sepsis progression. In vitro and in vivo experiments identified Enterococcus raffinosus as the primary producer of DCA-3S, contributing at least 80% of its total production, challenging the conventional notion of hepato-centric bile acid sulfation pathways. Intervention experiments in mouse and intestinal organoid models revealed that DCA-3S administration effectively alleviated sepsis by improving intestinal barrier function and attenuating inflammatory response. Collectively, our findings highlight a previously unrecognized microbial contribution to bile acid sulfation and position DCA-3S as a promising diagnostic and therapeutic biomarker for paediatric sepsis.