Background: It is reported that various diseases such as
non-alcoholic fatty liver disease (
NAFLD) are associated with imbalance of microbiome. And FXR has been well investigated in
liver diseases. Purpose: The objective of this study was to identify the role of farnesoid X receptor agonist
obeticholic acid via targeting gut microbiota in
NAFLD. Patients and methods: Male C57BL/6 mice were fed either a normal-chow diet or a high-fat diet (HFD).
Obeticholic acid(30mg/(kg·d)) and/or a combination of
antibiotics were administered orally by gavage to mice for 12 weeks. Gut microbiota profiles were established through
16S rRNA amplicon sequencing. The effects of
obeticholic acid on liver
inflammation, the gut barrier,
endotoxemia, gut microbiome and composition of the
bile acid were also investigated. Results:
Obeticholic acid treatment can significantly improve
obesity, circulation metabolism disorders, liver
inflammation and
fibrosis, and intestinal barrier damage caused by HFD. Removal of normal commensal bacteria can weaken the effect of
obeticholic acid. The gut microbial structure was changed, and abundance of Blautia was increased significantly after treated with
obeticholic acid. After
obeticholic acid treatment, the concentration of
taurine-bound
bile acid caused by HFD was reduced in the liver. Conclusion: Taken together, these data suggest that
obeticholic acid has aprotective effect on
NAFLD via changing the components of gut microbiota, specifically increasing the abundance of Blautia.