Free radical biology & medicineDec 31, 2022

Gut bacteria and bile acids partly help fibroblast growth factor 21 improve fatty liver disease caused by a methionine-choline-deficient diet in mice

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

Patients with non-alcoholic fatty liver disease (NAFLD) exhibited higher serum FGF21 levels and altered fecal microbiota compositions.

NAFLD is associated with hepatic steatosis, inflammation, fibrosis, and gut microbiota dysbiosis.
In NAFLD mouse models, FGF21 treatment led to significant reductions in steatohepatitis and collagen deposition.
FGF21 treatment also restored intestinal structure and modified gut microbiota composition.
The benefits of FGF21 may be partially attributed to changes in gut microbiota and bile acid metabolism.
Antibiotic treatment reduced hepatic and intestinal damage in NAFLD mice when combined with FGF21.
Fecal microbiota transplantation from FGF21-treated mice yielded similar improvements as FGF21 therapy.

Simplified

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. Fibroblast growth factor 21 (FGF21), which regulates glucose and lipid metabolism, has been proven to have a good effect on NAFLD. However, the modulating process between FGF21 and gut microbiota remains unclear in treating NAFLD. Here, the fecal microbiota composition of 30 patients with NAFLD who had undergone liver biopsy and 29 matched healthy participants were studied, together with the fecal bile acid (BA) profile. Treatment with FGF21 was given in methionine-choline-deficient (MCD) diet-induced NAFLD model C57BL/6 mice. An antibiotic cocktail and fecal microbiota transplantation were used to further confirm the benefits of FGF21 that were partially attributable to the change in gut microbiota. Patients with NAFLD had higher serum FGF21 levels and dysregulated fecal microbiota compositions and fecal BA profiles. In NAFLD mice, FGF21 significantly reduced steatohepatitis and collagen deposition in vivo and restored intestinal structure. FGF21 treatment also changed gut microbiota composition and regulated dysbiosis in BA metabolism. After treatment with an antibiotic cocktail, FGF21 partially alleviated hepatic and intestinal damage in NAFLD mice. Furthermore, fecal microbiota transplantation from FGF21-treated mice showed benefits similar to FGF21 therapy. The improvement using FGF21 in MCD diet-induced NAFLD mice is partially mediated via gut microbiota and BA. Gut microbiota-regulated BA metabolism may be a potential target of FGF21 in improving NAFLD.

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Gut bacteria and bile acids partly help fibroblast growth factor 21 improve fatty liver disease caused by a methionine-choline-deficient diet in mice

Abstract

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