Scleroglucan ameliorates dextran sulfate sodium-induced ulcerative colitis and gut microbiota dysbiosis in mice.

β-1,3/1,6-Glucans exhibit significant potential as therapeutic agents for ulcerative colitis (UC); nevertheless, most existing studies have focused on yeast β-glucans. In the current research, we assessed the therapeutic effects of scleroglucan (SCL), a β-1,3/1,6-glucan produced from the fungus Sclerotium rolfsii, by using a dextran sulfate sodium (DSS)-induced mouse model. SCL treatment significantly attenuated DSS-induced body weight loss from 18.45% to 14.69%, reduced the disease activity index from 3.83 to 3.11, decreased colonic TNF-α and MPO levels, and restored IL-10 concentrations (p < 0.05). SCL also promoted goblet cell proliferation and upregulated Muc2 gene expression (p < 0.05), but had no significant effects on colon length and tight junction proteins. Additionally, SCL significantly increased cecal acetate to 10.82 μmol/g, propionate to 3.87 μmol/g, butyrate to 7.13 μmol/g, and valerate to 1.16 μmol/g, compared with the respective levels of 3.11, 1.61, 1.67, and 0.60 μmol/g in the DSS group. Consistently, enhanced colonic mRNA expression of GPR41, GPR43, and GPR109A was seen with the SCL group than the DSS group (p < 0.05). SCL also remodeled gut microbiota composition, and significantly elevated Bacteroidetes, Lactobacillus and Ruminococcus, and reduced Firmicutes (p < 0.05), a microbial profile associated with attenuated colitis severity. Taken together, these findings indicate that SCL effectively mitigated DSS-induced colitis, emphasizing its potential as a bioactive polysaccharide for developing functional foods to assist UC nutritional intervention.