Gut Microbiota-Bile Acid Metabolism Axis Drive Anti-Diabetic Effects of Polygonatum cyrtonema Polysaccharide on Glycolipid Metabolism and Intestinal Inflammation

Polygonatum cyrtonema polysaccharide (PCP-80%) is one of the major active ingredients in Polygonatum cyrtonema . By establishing the type 2 diabetes mellitus (T2DM) rat model and applying multi-omics analysis, the present study aimed to explore the potential mechanism of PCP-80% to alleviate T2DM in terms of the interactions between intestinal microbiota and their metabolites. The results suggested that PCP-80% effectively improve the blood glucose and lipids levels, enhance intestinal barrier function. In addition, PCP-80% restored gut microbiota disorders, increased the secretion of short-chain fatty acids (SCFAs), and enhanced bile acid (BA)-converting enzyme-rich microbiota abundance. Furthermore, PCP-80% intervention significantly ameliorated BA dysmetabolism while enhancing metabolic homeostasis in T2DM rats. These changes activated the G protein-coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR), triggering fibroblast growth factor 15 (FGF15) secretion to ameliorate T2DM-induced intestinal barrier dysfunction and glucose/lipid dysregulation. Mechanistically, PCP-80% exerted therapeutic effects through a microbiota-bile acid crosstalk axis, wherein gut microbiota remodeling enhanced bile acid metabolism and amplified TGR5/FXR-FGF15 signaling, ultimately restoring metabolic homeostasis in T2DM rats.