Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.
Cell
; 187(11): 2717-2734.e33, 2024 May 23.
Article
en 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Simbiosis
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Bacteroides
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Ácidos y Sales Biliares
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Enfermedad del Hígado Graso no Alcohólico
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Microbioma Gastrointestinal
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Akkermansia
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell
Año:
2024
Tipo del documento:
Article