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

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.