生物
胆汁酸
生物化学
生物合成
微生物学
细胞生物学
基因
作者
Qixing Nie,Xi Luo,Kai Wang,Yong Ding,Shaofeng Jia,Qixiang Zhao,Meng Li,Jinxin Zhang,Yingying Zhuo,Jianhua Lin,Chenghao Guo,Zhiwei Zhang,Huiying Liu,Guangyi Zeng,Jie You,Lulu Sun,Hua Liu,Ming Ma,Yanxing Jia,Mei Zheng,Yanli Pang,Jie Qiao,Changtao Jiang
出处
期刊:Cell
[Elsevier]
日期:2024-04-01
标识
DOI:10.1016/j.cell.2024.03.034
摘要
Summary
The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as β-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.
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