北京大学Changtao Jiang，Jie Qiao，Yanli Pang，Yanxing Jia和温州医科大学第一附属医院Ming-Hua Zheng共同合作，近期取得重要工作进展。他们研究提出，肠道共生体通过次级胆汁酸生物合成途径缓解MASH。相关研究成果2024年4月22日在线发表于《细胞》杂志上。
据介绍，肠道微生物群已被发现在代谢功能障碍相关脂肪性肝炎（MASH）的进展中发挥重要作用，但其机制尚未确定。
通过开发一种基于点击化学的富集策略，研究人员鉴定了几种微生物来源的胆汁酸，包括以前未鉴定的3-琥珀酸（3-ucCA），它与肝组织活检证实的代谢功能障碍相关脂肪肝（MAFLD）患者的肝损伤呈负相关。通过筛选人类细菌分离株，研究人员在体外和体内鉴定出均匀拟杆菌菌株是3-ucCA的有效产生者。通过基于活性的蛋白质纯化和鉴定，研究人员在均匀芽孢杆菌中鉴定了一种注释为β-内酰胺酶的酶，负责3-ucCA的生物合成。
此外，研究人员发现3-ucCA是一种管腔限制性代谢产物，通过促进粘液阿克曼菌的生长来缓解MASH。
总之，这一研究为肠道微生物群-肝轴提供了新的见解，可以用来加强MASH的管理。
附：英文原文
Title: Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway
Author: 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
Issue&Volume: 2024-04-22
Abstract: 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.
DOI: 10.1016/j.cell.2024.03.034
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00350-7