Sporoderm-broken of Ganoderma lucidum spore polysaccharides alleviate dextran sulfate sodium-induced colon inflammation in mice by regulating Th17/Treg homeostasis and restore gut microbiota balance

Sporoderm-Broken Ganoderma lucidum spore polysaccharides (BGLSPs) have demonstrated therapeutic potential in inflammatory bowel disease (IBD), however, their mechanisms of action in colitis remain unclear. This study aimed to identify the active BGLSP fractions with anti-IBD activity and elucidate their underlying mechanisms. We identified BGLSP-B2 as the primary active fraction and characterized its physicochemical properties. It significantly restored intestinal barrier integrity, reduced inflammatory cell infiltration, and upregulated the expression of intestinal barrier proteins (ZO-1, Occludin, and MUC2). Additionally, BGLSP-B2 modulated the levels of key inflammatory cytokines, reduced the abundance of inflammation-associated bacteria, such as Enterobacteriaceae, and promoted the growth of beneficial intestinal bacteria. Transcriptomic analysis revealed that BGLSP-B2 regulated Th17/Treg homeostasis. Specifically, it downregulated the expression of IL-17 and RORγT, while upregulating the expression of FOXP3, thereby correcting the Th17/Treg imbalance. Moreover, 16s RNA sequencing and diversity analysis indicated that BGLSP-B2 regulated dysbiosis of the intestinal microbiota induced by dextran sulfate sodium, restoring the composition of the intestinal flora in IBD mice to levels comparable to those of the control group. In conclusion, BGLSP-B2 alleviated dextran sulfate sodium-induced colitis in mice by modulating the intestinal microbiota and immune pathways, offering a potential therapeutic strategy for IBD. BGLSP-B2 alleviated IBD by modulating gut microbiota balance and Th17/Treg homeostasis. • BGLSP-B2 purified from Sporoderm-Broken Ganoderma lucidum spore polysaccharides which was the primary fraction with anti-IBD activity. • BGLSP-B2 ameliorated the symptoms of DSS-induced IBD mice. • BGLSP-B2 alleviated DSS-induced colitis in mice by modulating intestinal microbiota. • BGLSP-B2 regulated the TH17/Treg imbalance in DSS-induced IBD mice.