Grape Skin Polysaccharides Alleviate Type 2 Diabetic Rats via Gut Microbiota and Nontargeted Metabolism Alterations

This study investigates the therapeutic potential of grape skin polysaccharides (GSP) for type 2 diabetes (T2D). Employing a T2D model developed via a high-fat diet combined with STZ, three intervention groups were established: low-dose GSP (25 mg/kg), high-dose GSP (100 mg/kg), and metformin control (300 mg/kg). Following a 30-day oral administration period, marked enhancements in body weight and glucose/lipid metabolic parameters were noted in both the high-dose GSP group and the metformin-treated cohort. Specifically, compared with the model group, high-dose GSP improved insulin resistance by 48.48%, increased hepatic glycogen content by 63.38% and HDL–C levels by 13.16%, while reducing TG, TC, and LDL–C by 65.5%, 20.80%, and 32.63%, respectively. GSP also enhanced GSH–Px activity by 10.15% and SOD activity by 26.48%, while reducing MDA levels by 30.91%, thereby alleviating pathological damage in the liver, kidneys, and intestines. These results suggested that the regulatory effect of GSP is concentration-dependent. GSP also regulated gut microbiota by not only reducing Thermodesulfobacteriota and increasing Bacillota/Bacteroidetes abundance, but also enhancing acid-producing bacteria to elevate short-chain fatty acid (SCFA) levels, thereby further improving insulin sensitivity. Collectively, these preclinical data support the potential of GSP as a functional food ingredient or adjunct therapy for T2D management, pending further clinical validation.