The combination of epigallocatechin gallate with exopolysaccharides from Bacillus subtilis STB22 alleviates hyperglycemia by regulating gut microbiota and metabolites in type 2 diabetic mice

Diabetes mellitus is a chronic metabolic disorder. Although natural components such as polyphenols and polysaccharides have demonstrated anti-diabetic potential, the in vivo synergistic effects of their combinations remain poorly understood. This study explored the hypoglycemic effects and molecular mechanisms of Bacillus subtilis exopolysaccharides (BS-EPS) and their combination with epigallocatechin gallate (EGCG) in type 2 diabetes mellitus (T2DM) mice. Monotherapy with BS-EPS (200 mg/kg·bw/day) or EGCG (100 mg/kg·bw/day) significantly reduced fasting blood glucose levels by 15.3 % and 15.7 %, respectively, while combination therapy showed a superior reduction of 25.4 %. Moreover, the combined treatment significantly improved insulin sensitivity and alleviated hepatic injury. The combined treatment modulated the gut microbiota composition by enriching beneficial bacteria (including Faecalibaculum , Akkermansia , and Parabacteroides ) while enhancing short-chain fatty acid production, particularly acetate. Metabolomic analysis revealed that the combined treatment altered bile acids and glycerophospholipids profiles, while modulating key metabolic pathways including choline metabolism, glycerophospholipid metabolism, and unsaturated fatty acid biosynthesis. These findings suggest that the combined intervention of BS-EPS and EGCG may synergistically ameliorate hyperglycemia through gut microbiota-metabolite-pathway interactions, supporting their potential as a dietary intervention for T2DM.