Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway

Cell. 2024 May 23;187(11):2717-2734.e33. doi: 10.1016/j.cell.2024.03.034. Epub 2024 Apr 22.


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.

Keywords: 3-sucCA; BAS-suc; MAFLD; acylated bile acids; bile acid; biosynthesis; gut microbiota.

MeSH terms

  • Akkermansia* / metabolism
  • Animals
  • Bacteroides* / metabolism
  • Bile Acids and Salts* / metabolism
  • Biosynthetic Pathways / genetics
  • Fatty Liver / metabolism
  • Gastrointestinal Microbiome*
  • Humans
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / microbiology
  • Symbiosis*
  • Verrucomicrobia / metabolism
  • beta-Lactamases / metabolism


  • beta-Lactamases
  • Bile Acids and Salts

Supplementary concepts

  • Akkermansia muciniphila