Scleroglucan from Agroathelia rolfsii ameliorates glucolipid metabolic dysfunction in high-fat diet-fed mice and is associated with gut microbiota and metabolite changes.

Obesity is closely associated with glucolipid dysregulation, hepatic steatosis, and gut microbiota dysbiosis. Scleroglucan (Sclg), a microbial β-glucan produced by Agroathelia rolfsii, has attracted increasing interest owing to its distinctive β-(1 → 3)/(1 → 6)-glucan structure, but its metabolic effects remain unclear. In this study, Sclg was characterized as a high-molecular-weight β-(1 → 3)-D-glucan with β-(1 → 6)-linked branches (1239 kDa), and its metabolic effects were evaluated in high-fat diet (HFD)-induced obese mice. Sclg reduced body weight gain and white adipose tissue accumulation, improved glucose tolerance and insulin sensitivity, ameliorated serum lipid abnormalities, and alleviated hepatic steatosis. Hepatic qPCR analysis showed that Sclg decreased lipogenesis-related Srebp1c and Fasn expression and inflammatory Il6 and Il1b expression. Sclg intervention was also associated with a partial improvement in gut microbial diversity and enrichment of Bacteroides, Blautia, and Eisenbergiella. Consistently, Sclg increased fecal acetate, propionate, and butyrate while reducing isobutyrate and isovalerate. Untargeted fecal metabolomics revealed broad changes in lipid- and bile acid-related metabolites, including palmitoleic acid, 3-OH-C16:1-carnitine, bile acid derivatives, sphingolipids, LysoPC(22:6), and PC/PI-related species, with enriched pathways involving glycerophospholipid, sphingolipid, and unsaturated fatty acid metabolism. Sclg also altered hepatic and ileal genes related to enterohepatic bile acid signaling and lipid homeostasis, including Cyp7a1, Fxr, Fgf15, Tgr5, and Cyp27a1. These findings provide new insight into the metabolic effects of Sclg and may inform the development of targeted nutritional strategies using microbial β-glucans for obesity-related metabolic health management.