Modulation of the gut microbiota alleviates insulin resistance in type 2 diabetic mice by daucosterol from Eleocharis dulcis peel

Daucosterol, a natural saponin from Eleocharis dulcis peel, exhibited anti-hyperglycemic properties. This study investigated daucosterol's effects on glycemic control, insulin resistance, and gut microbiota in type 2 diabetic mice. The results demonstrated that daucosterol treatment reduced fasting glucose, improved glucose intolerance and pancreatic islet damage. It decreased HOMA-IR and increased ISI, indicating enhanced insulin sensitivity. Daucosterol supplementation enriched gut microbiota diversity, including reducing Firmicutes and Desulfobacterota while increasing Bacteroidia. This involved an increase in Enterococcus, Akkermansia, Alistipes, Clostridium_sensu_stricto_1, and Odoribacter, coupled with decreased Aerococcus, Desulfovibrio, and Blautia, improved gut health. Uncultured_bacterium_g_Clostridium_sensu_stricto_1 and Bifidobacterium_pseudolongum were identified as major biomarkers. PICRUSt analysis revealed daucosterol improved the pathways of glycan biosynthesis and metabolism, lipid metabolism, carbohydrate metabolism, and some organismal systems. Therefore, daucosterol act as a potential anti-hyperglycemic agent, improving insulin resistance and optimizing gut microbiota to alleviate type 2 diabetes.