Bile salt hydrolase catalyses formation of amine-conjugated bile acids.
Nature
; 626(8000): 859-863, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38326609
ABSTRACT
Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ácidos y Sales Biliares
/
Aciltransferasas
/
Biocatálisis
/
Microbioma Gastrointestinal
/
Amidohidrolasas
/
Aminas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Infant
Idioma:
En
Revista:
Nature
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos