Polysaccharides from Phellinus linteus attenuate type 2 diabetes mellitus in rats via modulation of gut microbiota and bile acid metabolism

Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder. Polysaccharides from Phellinus linteus (PLP) have been found to have anti-diabetes effects, but the mechanism has not been elucidated. The purpose of this study was to investigate the mechanism of PLP on T2DM through the gut microbiota and bile acids metabolism. The T2DM rat model was induced by a high-fat high-carbohydrate (HFHC) diet and streptozocin (30 mg/kg). We found that PLP ameliorated diabetes symptoms. Besides, PLP intervention increased the abundance of g_Bacteroides, g_Parabacteroides, and g_Alistioes, which are associated with the biosynthesis of short-chain fatty acids (SCFAs) and bile acids (BAs) metabolism. Meanwhile, untargeted and targeted metabolomics indicated that PLP could regulate the composition of BAs and increase the levels of SCFAs. Real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were performed to analyze the expression levels of BAs metabolism enzymes in the liver. Finally, the results of correlation analysis and Glucagon-like peptide-1 (GLP-1) showed that PLP stimulated the release of GLP-1 by regulating SCFAs and BAs. In conclusion, this study demonstrated that PLP can regulate gut microbiota and BAs metabolism to promote GLP-1 secretion, thereby increasing insulin release, decreasing blood glucose and attenuating T2DM.