Abstract
Ulcerative colitis (UC) is evolving into a global burden with a substantially increasing incidence in developing countries. It is characterized by inflammation confined to mucosa and is recognized as an intestinal barrier disease. The intestinal microbiota plays a crucial role in UC pathogenesis. N. commune has long been appreciated as a healthy food and supplement worldwide and polysaccharides account for 60%. Here, we examined the amelioration of N. commune polysaccharides against acute colitis in mice induced by DSS and assessed the mediating role of gut microbiota. An integrated analysis of microbiome, metabolomics, and transcriptomics fully elaborated it markedly enhanced intestinal mucosal barrier function, including: increasing the relative abundance of Akkermansia muciniphila, uncultured_bacterium_g__norank_f__Muribaculaceae, and unclassified_g__norank_f__norank_o__Clostridia_UCG-014; decreasing microbiota-derived phosphatidylcholines and thromboxane 2 levels mapped to arachidonic acid metabolism; improving mucin2 biosynthesis and secretion; enhancing ZO-1 and occludin expression; reducing neutrophil infiltration; regulating the level of colitis-related inflammatory cytokines; involving inflammation and immune function-associated signaling pathways. Further, the mediation effect of gut microbiota was evaluated by administering a cocktail of antibiotics. In conclusion, our results demonstrated that N. commune polysaccharides predominantly reinforced the gut microbiota-mediated intestinal mucosal barrier to confer protection against UC and exhibited dramatic prebiotic-like functions, providing an alternative or complementary treatment for UC.