metformin attenuates hepatic fibrosis in mice by altering the gut microbiota

Background: metformin is a first-line drug widely used in the treatment of type 2 diabetes. it has been shown to improve liver fibrosis; however, the underlying mechanism remains unclear. objectives: this study investigates the relationship between metformin and gut microbiota in the treatment of liver fibrosis.methods: carbon tetrachloride (ccl₄) was injected intraperitoneally to induce liver fibrosis in mice, followed by metformin treatment for 4 weeks. a ccl₄-induced hepatic fibrosis mouse model was established. the mice were divided into two groups: metformin treatment and control groups. hematoxylin-eosin (he) staining was used to evaluate the overall liver condition, sirius red staining to assess the degree of hepatic fibrosis, α-smooth muscle actin (α-sma) immunohistochemical staining to determine the activation of hepatic stellate cells (hscs), oil red o staining to observe intracellular lipid droplets in hepatocytes, and 16srna sequencing to analyze fecal microbiota. results: in the untreated ccl₄-induced hepatic fibrosis model, hepatic tissue exhibited edema, degeneration, intracellular lipid deposition in hepatocytes, and inflammatory cell infiltration between lobules. metformin treatment attenuated hepatic fibrosis (area reduced from 1.383% to 0.669%, p < 0.001), decreased inflammatory cell infiltration, reduced intracellular lipid accumulation in hepatocytes (area reduced from 0.457% to 0.086%, p < 0.001), and decreased α-sma protein expression (area reduced from 1.509% to 0.598%, p < 0.05). additionally, metformin reduced harmful bacteria and increased the abundance of beneficial bacteria in the intestinal tract of the mice.conclusions: these findings indicate that metformin reduces liver inflammation, alleviates liver fibrosis, and alters the intestinal microbiota. the modification of gut flora may be a significant mechanism by which metformin exerts its therapeutic effects on liver fibrosis.