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Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.
- Source :
-
Cell [Cell] 2024 May 23; Vol. 187 (11), pp. 2717-2734.e33. Date of Electronic Publication: 2024 Apr 22. - Publication Year :
- 2024
-
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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Humans
Male
Mice
beta-Lactamases metabolism
Biosynthetic Pathways genetics
Fatty Liver metabolism
Liver metabolism
Mice, Inbred C57BL
Verrucomicrobia metabolism
Akkermansia metabolism
Bacteroides metabolism
Bile Acids and Salts metabolism
Gastrointestinal Microbiome
Symbiosis
Non-alcoholic Fatty Liver Disease metabolism
Non-alcoholic Fatty Liver Disease microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 187
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 38653239
- Full Text :
- https://doi.org/10.1016/j.cell.2024.03.034