Supernatant of Water Extraction–Ethanol Precipitation of Chaga mushroom Improves Hyperglycemia in Type 2 Diabetes Mellitus and Is Accompanied by Changes in Gut Microbiota Composition

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and inadequate insulin secretion. Prolonged hyperglycemia is associated with disruption of gut microbiota (GM) homeostasis. Although bioactive compounds in Chaga mushroom, such as polysaccharides, have hypoglycemic effects, research on its polysaccharide preparation by-product, the supernatant of water extraction–ethanol precipitation of Chaga mushroom (SWEPC), remains limited. In this study, we investigated the effects of SWEPC on GM composition and its therapeutic potential in alleviating hyperglycemia in T2DM mice. After four weeks of SWEPC intervention (300 mg/kg/day), T2DM mice exhibited significant improvements: fasting blood glucose (FBG) decreased by 52.29% (p < 0.001); the area under the curve of oral glucose tolerance decreased by 37.68% (p < 0.001); glycated serum protein decreased by 65.36% (p < 0.001); the insulin resistance index decreased by 44.42% (p < 0.001); and the insulin sensitivity index increased by 90.24% (p < 0.001). Spearman’s correlation analysis revealed that Anaeroplasma, Anaerotruncus, and Ruminococcus were associated with serum low-density lipoprotein cholesterol (r = 0.75), FBG (r = −0.81), and body weight (r = −0.65), respectively, suggesting their potential involvement in T2DM-related metabolic traits and warranting further investigation. Overall, SWEPC ameliorated hyperglycemic manifestations in T2DM mice, which was accompanied by changes in the GM community.