A polysaccharide isolated from Ganoderma lucidum ameliorates hyperglycemia through modulating gut microbiota in type 2 diabetic mice

In this study, we reported a thermal stable and non-toxic heteropolysaccharide F31, which decreased the blood glucose of diabetic mice (21.75 mmol/L) induced by high-fat diet (HFD) and streptozotocin (STZ) to 12.56 and 15.18 mmol/L (P < 0.01) at 180 and 60 mg/kg, depicting remarkable hypoglycemic effects of 42.25 and 30.21%. Moreover, F31 repaired islet cells and increased insulin secretion, promoted the synthesis and storage of glycogen in liver and improved activities of antioxidant enzymes and insulin resistances, declining HOMA-IR (43.77 mmol/mU) of diabetic mice (P < 0.01) to 17.32 and 20.96 mmol/mU at both doses. 16S rRNA gene sequencing revealed that F31 significantly decreased Firmicutes (44.92%, P < 0.01) and enhanced Bacteroidetes (33.73%, P < 0.01) and then increased B/F ratio of diabetic mice to 0.6969 (P < 0.01), even being close to normal control (P = 0.9579). F31 enriched Lactobacillus, Bacteroides and Ruminococcaceae, which may relieve glucose, insulin resistance and inflammation through decreasing the release of endotoxins into the circulation from intestine, carbohydrate fermentation in gut and activation of the intestine-brain axis. Functionally, F31 improved metabolism of gut microbiota to a normal state. These results may provide novel insights into the beneficial effect of F31 against hyperglycemia.