Abstract: Objective: Diabetes mellitus is a metabolic disease characterized by hyperglycemia. The gut microbiota play a vital role in its occurrence and development. Therefore, the present study aimed to investigate the protective effect of Ganoderma atrum polysaccharide in type 2 diabetic rats, and its influence on gut microbiota structure and metabolites. Methods: Wistar rats were fed a high-sugar and high-fat diet for 8 weeks, then injected with streptozotocin (STZ) to establish a diabetic animal model. Subsequently, the diabetic rats were separately administered with double-distilled water, metformin, and Ganoderma atrum polysaccharide at three different doses, 100, 50 and 25 mg/kg mb. After 4 weeks of administration, fasting blood glucose (FBG), and the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and insulin (INS) were determined, and intestinal pathological changes were examined. Meanwhile, in order to observe the effect of Ganoderma atrum polysaccharide on the gut microbiota in diabetic rats, feces were collected for 16S rDNA high-throughput sequencing. Moreover, fecal short chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry (GC-MS). Results: Ganoderma atrum polysaccharide protected the intestinal tissue of diabetic rats, and exerted an anti-diabetic effect by regulating blood glucose, lowering blood lipids and ameliorating insulin resistance. Furthermore, it regulated the species composition of the intestinal microbiota in diabetic rats by significantly increasing the relative abundance of Cyanobacteria, up-regulating the abundance of beneficial Lactobacillus, Roseburia, Bifidobacterium, Oscillospira, Ruminococcus and Coprococcus, consequently enhancing the secretion of short-chain fatty acid butyric acid, and down-regulating the relative abundance of Prevotella and CF231, thereby reducing propionic acid content. Conclusion: Ganoderma atrum polysaccharide can regulate blood glucose, blood lipids and insulin resistance in STZ-induced diabetic rats. Its action mechanism may be related to regulation of the gut microbiota structure and consequently the secretion of SCFAs, which can be absorbed by intestinal cells or enter the blood circulation to protect tissues.

Key words: Ganoderma atrum polysaccharide; diabetes; blood sugar; insulin resistance; gut microbiota; short chain fatty acids