A starch-like polysaccharide isolated from Hirsutella sinensis mycelia alleviates DSS-induced colitis in mice by strengthening the intestinal barrier, maintaining immune homeostasis, and modulating the gut microbiota and SCFA metabolism

Hirsutella sinensis ( H. sinensis ), a substitute for a valuable edible and medicinal fungus, Cordyceps sinensis , is well known for its various of beneficial pharmacological properties. However, research on the effects of H. sinensis on colitis in mice is limited. In our previous studies, we carried out a systematic classification and structural identification of the polysaccharides in H. sinensis . Here, we utilized a murine model of colitis induced by a 3% dextran sulfate sodium (DSS) administration to investigate the protective effects of the H. sinensis mycelium-derived starch-like polysaccharide (HSWP-1a) on colitis. Our findings demonstrate that HSWP-1a effectively mitigates DSS-induced weight loss, reduces colon tissue damage, increases tight junction protein expression, and restores intestinal barrier function. Notably, during this process, HSWP-1a reversed the DSS-induced increase in M1/M2 macrophage polarization and the Th17/Treg cell balance, ameliorating the DSS-induced decrease in anti-inflammatory cytokine expression while inhibiting the DSS-induced increase in proinflammatory cytokine levels and mediating immune tolerance to maintain local intestinal immune homeostasis. Furthermore, HSWP-1a is capable of regulating the intestinal microbiota, enhancing the abundance of beneficial bacteria such as Lachnospiraceae_NK4A136_group , and reducing the abundance of harmful bacteria like Proteobacteria and Cyanobacteria. HSWP-1a also restores the levels of short-chain fatty acids (SCFA) to maintain the balanced intestinal microenvironment. Overall, HSWP-1a achieves its colitis-protective effects through its ability to strengthen the intestinal barrier, regulate the immune system, and restore gut microbiota interactions. These findings suggest that HSWP-1a has potential as a valuable food supplement or nutritional health product for alleviating colitis.