| Summary: | Gut microbiota plays an important role in the pathophysiology of obesity. Fungal polysaccharide can improve obesity, but the potential mechanism needs further study. This experiment studied the potential mechanism of polysaccharides from <i>Sporisorium reilianum</i> (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. At the genus level, the abundance of Lactobacillus increased and that of Bacteroides decreased. At the species level, the abundance of <i>Lactobacillus crispatus</i>, <i>Lactobacillus helveticus</i>, and <i>Lactobacillus acidophilus</i> increased, while the abundance of <i>Lactobacillus reuteri</i> and <i>Staphylococcus xylosus</i> decreased. The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. The untargeted metabolomics indicated that 36 metabolites were related to the anti-obesity effect of SRP. Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity.
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