Integration of bile acid metabolomics with gut metagenome data identified deoxycholic acid 3-sulfate (DCA-3S) as significantly associated with paediatric sepsis progression, with Enterococcus raffinosus identified as its primary producer contributing at least 80% of total DCA-3S production, and DCA-3S administration effectively alleviating sepsis by improving intestinal barrier function and attenuating inflammatory response.
DCA-3S was significantly associated with paediatric sepsis progression in two independent paediatric sepsis cohorts.
Enterococcus raffinosus was identified as the primary producer of DCA-3S in the human gut.
DCA-3S administration effectively alleviated sepsis in mouse and intestinal organoid models.
Gut microbiota-bile acid interplay plays a role in paediatric sepsis progression through microbial bile acid sulfation.
DCA-3S is positioned as both a diagnostic and therapeutic biomarker for paediatric sepsis.
This research suggests that a specific molecule called deoxycholic acid 3-sulfate (DCA-3S), found in the gut, plays an important role in childhood sepsis — a life-threatening condition where the body's response to infection causes widespread organ damage. By analyzing gut bacteria and bile acid profiles from children with sepsis, the researchers found that lower levels of DCA-3S were linked to worse disease progression. They also discovered that a common gut bacterium called Enterococcus raffinosus is responsible for producing most of this molecule (at least 80%), which is surprising because scientists previously thought this type of chemical modification of bile acids happened mainly in the liver. When the researchers gave DCA-3S to mice with sepsis and tested it in laboratory models of the human intestine, it reduced inflammation and helped repair the gut's protective barrier — two key factors in how sepsis causes harm. These results suggest that gut bacteria can produce compounds that directly influence the severity of a serious illness like sepsis, opening a new understanding of how the gut microbiome interacts with the immune system during critical illness. This research suggests that DCA-3S could potentially serve both as a marker to help identify children at risk of worsening sepsis and as a future therapeutic agent. It also reframes how scientists think about bile acid chemistry, showing that gut bacteria — not just the liver — can be major contributors to this process, which may have broader implications for understanding other diseases linked to gut health and inflammation.
Liu X, Zhang H, Wang Y, Tu X, Wen J, Lei S, et al.. (2026). Sulfated bile acid produced by a human gut commensal alleviates paediatric sepsis in mice.. Nature microbiology. https://doi.org/10.1038/s41564-026-02351-1