Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway

• DOI: 10.1016/j.cell.2024.03.034
• Publication Date: 2024-04-22T14:37:07Z
• Authors: Qixing Nie; Xi Luo; Kai Wang; Yong Ding; Shumi Jia; Qixiang Zhao; Meng Li; Jinxin Zhang; Yingying Zhuo; Jun Lin; Chenghao Guo; Zhiwei Zhang; Huiying Liu; Guangyi Zeng; Jie You; Lulu Sun; Hua Lu; Ming Ma; Yanxing Jia; Ming-Hua Zheng; Yanli Pang; Jie Qiao; Changtao Jiang
• Keywords: Akkermansia muciniphila; Steatohepatitis; Akkermansia

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but mechanisms have not established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage patients liver-tissue-biopsy-proven fatty disease (MAFLD). By screening human bacterial isolates, Bacteroides uniformis strains as effective producers 3-sucCA both vitro and vivo. activity-based protein purification identification, enzyme annotated β-lactamase B. responsible for biosynthesis. Furthermore, that lumen-restricted metabolite alleviates MASH promoting growth Akkermansia muciniphila. Together, our data offer new insights into microbiota-liver axis may be leveraged augment management MASH.