Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.
Cell
; 187(11): 2717-2734.e33, 2024 May 23.
Article
in En
| MEDLINE
| ID: mdl-38653239
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 ß-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Symbiosis
/
Bacteroides
/
Bile Acids and Salts
/
Non-alcoholic Fatty Liver Disease
/
Gastrointestinal Microbiome
/
Akkermansia
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell
Year:
2024
Document type:
Article