A Pueraria lobata root extract alleviates high-fat diet-induced non-alcoholic fatty liver disease by modulating the gut microbiota and associated metabolites

Pueraria lobata root has garnered considerable attention for its remarkable hepatoprotective properties. In this study, we employed a pseudo-germ-free (PGF) mice model treated with antibiotics to investigate the effects of gut microbiota on the therapeutic efficacy of the extract of P. lobata root (PLE) in mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results demonstrated that mice not exposed to antibiotics exhibited significantly improved liver damage and inflammation, as well as a more diverse gut microbiota after PLE treatment compared to mice treated with antibiotics. It is noteworthy that these beneficial effects of PLE were partially attenuated following the administration of antibiotics. Furthermore, the serum of mice not exposed to antibiotics showed a significant increase in the relative abundance of daidzein. Cell experiments demonstrated that daidzein, a gut microbial metabolite of puerarin, is more effective than puerarin in improving cellular lipid deposition and reducing inflammation. In conclusion, our findings substantiate the pivotal role of the gut microbiota in the processes associated with PLE therapy for NAFLD and the gut microbiota may enhance the efficacy of PLE in treating NAFLD by metabolizing parent compounds, such as puerarin, into secondary metabolites, predominantly daidzein. These findings contribute to a deeper understanding of the therapeutic potential of botanical extracts in the management of liver diseases, particularly NAFLD.