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

09/09/2026

AI Summary

FGF21 deficiency exacerbates alcoholic liver disease in mice, causing more severe liver injury and higher hepatic triglyceride accumulation under ethanol exposure.
Administration of rhFGF21 markedly reduces hepatic triglyceride content and attenuates liver injury in both wild-type and Fgf21 knockout mice.
FGF21 reshapes gut microbiota, restoring Firmicutes, decreasing Proteobacteria and Bacteroidetes, lowering serum LPS, linking microbiota modulation to ALD improvement.

AI Summary

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 analysis showed that FGF21 significantly altered gut microbiota β-diversity in mice (adjusted 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.

Basic summary

Zhonghua Gan Zang Bing Za Zhi. 2026 Aug 20;34(8):748-756. doi: 10.3760/cma.j.cn501113-20260318-00116.

ABSTRACT

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.