Metformin alleviates insulin resistance in obese-induced mice via remodeling gut microbiota and intestinal metabolites

Metformin is widely used to surmount insulin resistance (IR) and diabetes. Evidence indicates that metformin remodels gut microbiota but the underlying mechanism remain unclear. Present results showed that metformin effectively improved insulin sensitivity and alleviated liver inflammation and oxidative stress in high fat diet (HFD)-induced mice. Metabolomics analysis showed that metformin increased taursodeoxycholic acid (TUDCA) production by increasing the expression of bile acid synthase and . In the palmitic acid (PA)-induced cell, TUDCA activated NRF2/ARE pathway, thereby reducing intracellular ROS and improving insulin signaling. Further gut microbiota analysis showed that metformin increased the proportion of in the HFD-fed mice, while TUDCA promoted the proliferation of but metformin did not. These findings reveal that metformin remodels the gut microbiota, reduces oxidative stress and enhances insulin sensitivity by increasing the production of TUDCA. This provides a novel mechanism by which metformin alleviates diet-induced IR and improves metabolism.