[Fibroblast growth factor 21 improves alcoholic liver disease by regulating gut microbiota in mice]

Objective: To investigate whether fibroblast growth factor 21 (FGF21) can improve alcoholic liver disease (ALD) by regulating gut microbiota. Methods: Male C57BL/6J wild-type (WTPF) and Fgf21^-/- (KO) mice were used and divided into control groups (fed with a control liquid diet), ALD model groups (fed with an ethanol-containing liquid diet for 8 weeks), and rhFGF21 treatment groups (administered intraperitoneal injections of rhFGF21 4 mg·kg^-1·day^-1 for 5 days before the end of ALD modeling), totaling six groups. Gut microbiota was analyzed using 16S rRNA sequencing to detect liver histopathology and serum lipopolysaccharide (LPS) levels. Statistical analysis was performed using one-way ANOVA or the Kruskal-Wallis test. Results: The KOPF group showed more severe liver damage and higher triglyceride accumulation compared to the WTPF group under ethanol exposure. Exogenous rhFGF21 administration significantly reduced intracellular liver triglyceride content and degree of liver injury in WTPF and KOPF groups (P<0.05). Gut microbiota analysis showed that FGF21 significantly altered gut microbiota β-diversity in mice (adjusted P<0.05). The WTAF and KOAF groups had a lower abundance of Firmicutes compared to the control group, while the abundance of Proteobacteria, Bacteroidetes, and serum LPS levels was increased. The abundance of Proteobacteria, Bacteroidetes, and serum LPS levels decreased again, while the firmicutes abundance was restored following rhFGF21 administration (P<0.05). Conclusion: FGF21 deficiency worsens gut microbiota dysbiosis in ALD mice, while exogenous rhFGF21 supplementation regulates gut microbiota, lowers serum LPS, and improves ALD.