Gut Microbiota Reshaping by Sparassis latifolia Polysaccharides Ameliorates Glucose Metabolism through Microbiota-Mediated Activation of Intestinal Gluconeogenesis.

Gut microbiota dysbiosis is a key contributor to glucose metabolism disorders. Sparassis latifolia polysaccharides (SLPs) may regulate microbiota-host metabolic interactions. Here, we evaluated the hypoglycemic effects of SLPs in mice with high-fat/high-sugar diet and streptozotocin-induced glucose metabolism disorders. SLPs improved glucose tolerance, reduced fasting blood glucose by approximately 40%, alleviated colonic injury, and restored gut microbiota-derived short-chain fatty acids (SCFAs). Metabolomics showed that SLPs mainly normalized purine metabolism, primary bile acid biosynthesis, and vitamin B6 metabolism. SLP treatment also modulated intestinal gluconeogenesis-related genes, proteins, and enzymes, Microbiota and coabundance group analyses indicated increased beneficial taxa, including Muribaculaceae and Bacteroides acidifaciens, and reduced CAG6 and CAG8 (Co-abundance group) taxa associated with impaired glucose tolerance. Cohabitation experiments suggested partial transmissibility of metabolic benefits. These findings suggest that SLPs improve glucose metabolism by remodeling gut microbiota and metabolites and enhancing PXR-SGK2-associated intestinal gluconeogenesis.