Polysaccharide from Boletus aereus ameliorates DSS-induced colitis in mice by regulating the MANF/MUC2 signaling and gut microbiota

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions characterized by disruptions in the colonic mucus barrier and gut microbiota. In this study, a novel soluble polysaccharide obtained from Boletus aereus (BAP) through water extraction was examined for its structure. The protective effects of BAP on colitis were investigated using a DSS-induced mice model. BAP was found to promote the expression of intestinal mucosal and tight junction proteins, restore the compromised mucus barrier, and suppress the activation of inflammatory signaling. Moreover, BAP reshape the gut microbiota and had a positive impact on the composition of the gut microbiota by reducing inflammation-related microbes. Additionally, BAP decreased cytokine levels through the MANF-BATF2 signaling pathway. Correlation analysis revealed that MANF was negatively correlated with the DAI and the level of cytokines. Furthermore, the depletion of gut microbiota using antibiotic partially inhabited the effect of BAP on the activation of MANF and Muc2, indicating the role of gut microbiota in its protective effect against colitis. In conclusion, BAP had an obvious activation on MANF under gut inflammation. This provides new insights into the prospective use of BAP as a functional food to enhance intestinal health.