Regulatory effects of polysaccharides from Houttuynia cordata Thunb. on gut microbiota and hyperglycemia in type 2 diabetes mellitus mice.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired insulin secretion. In this study, a novel polysaccharide (HCP) was isolated from Houttuynia cordata Thunb. (H. cordata) and its hypoglycemic effects and underlying mechanisms were investigated. Structural characterization revealed that HCP with a molecular weight of 16.163 kDa is mainly composed of Man, Gal, Glc, and GalA, with predominant (1 → 4) and (1 → 6) glycosidic linkages. HCP intervention significantly improved glycemic control, pancreatic islet function, and alleviated dyslipidemia in T2DM mice. Furthermore, HCP enriched beneficial gut microbiota, such as Ruminiclostridium, Faecalibaculum, and promoted short-chain fatty acids (SCFAs) production. Spearman correlation analysis confirmed strong associations between these bacteria and hypoglycemic metrics. Moreover, HCP upregulated hepatic expression of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2), suggesting that its hypoglycemic effect may occur via the gut microbiota-SCFAs-AKT-1/GLUT-2 axis. These findings provide novel mechanistic insights into the antidiabetic potential of HCP and support its further development as a functional food ingredient.