Effect of Gypenosides on the composition of gut microbiota and metabolic activity in the treatment of CCl4-induced liver injury in rats

Abstract

• To explore the mechanism of GPs in the treatment of liver injury from a microbiome-metabolomics perspective. • 13 differential genera were found to be associated with the development of liver injury and the treatment with GPs. • The biomarkers were mainly involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. Long-term chronic liver damage can lead to serious consequences of cirrhosis or liver failure, so it is crucial to find effective therapeutic drugs. Gypenosides (GPs) has been proved to have therapeutic effects on various liver diseases. To provide an overall description of GPs for the treatment of liver injury, we conducted a combined study of gut microbiota and host metabolism based on metabolomic analysis and 16S rRNA high-throughput sequencing. The results showed that GPs treatment significantly improved the disorder of liver function index, inflammatory index, intestinal barrier index and oxidative damage index induced by liver injury. H&E staining showed that GPs treatment could significantly alleviate liver injury in rats. Metabolomics analysis identified 25, 27 and 31 endogenous metabolites in feces, plasma and urine, respectively. Gut microbiota analysis revealed increased diversity in the model group and significant differences between groups. Metastats analysis identified 13 differential genera. Spearman’s correlation analysis was found that the increase of liver injury-related pathological indices or metabolite showed positive correlation with the genera with increased relative abundance, while the genera with decreased relative abundance showed negative correlation with them. The above results suggest that GPs modulates gut microbiota dysbiosis-metabolic activity disorder to achieve the treatment of liver injury.