Gut Microbiota‐Bile Acid Metabolism Axis Drive Anti‐Diabetic Effects of <i>Polygonatum cyrtonema</i> Polysaccharide on Glycolipid Metabolism and Intestinal Inflammation

ABSTRACT 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.