Polysaccharide\nNAP‑3 Synergistically Enhances\nthe Efficiency of Metformin in Type 2 Diabetes via Bile Acid/GLP‑1\nAxis through Gut Microbiota Remodeling

The polysaccharides of edible mushrooms are excellent\nphytochemicals\nfor adjuvant treatment of metabolic diseases, but the potential mechanisms\nof synergistic effects are unclear. In this work, we discovered that\nNAP-3 enhanced the efficiency of metformin in lipid and glucose metabolism\nin type 2 diabetic (T2D) mice in a gut microbiome-dependent way. NAP-3\nremodeled the intestinal microbial, resulting in the decreased activity\nof bile salt hydrolases and upregulation of CYP27A1 and CYP7B1 functions\nin the alternative pathway of bile acid synthesis, which leads to\naccumulation of the conjugated bile acids in ileum, specifically TβMCA\nand TUDCA. The accumulated conjugated bile acids either blocked or\nstimulated the nuclear receptors Farnesoid-X-receptor and TGR5, inducing\nthe release of GLP-1 and ultimately enhanced glucose metabolism in\nmice. Collectively, our research indicated that edible mushroom polysaccharide\nNAP-3 may serve as a promising adjunctive oral therapeutic agent for\nT2D.