Potent Intestinal Mucosal Barrier Enhancement of Nostoc commune Vaucher Polysaccharide Supplementation Ameliorates Acute Ulcerative Colitis in Mice Mediated by Gut Microbiota

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. communehas long been appreciated as a healthy food and supplement worldwide and polysaccharides account for 60%. Here, we examined the amelioration ofN. communepolysaccharides 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 ofAkkermansia muciniphila, uncultured_bacterium_g__norank_f__Muribaculaceae, andunclassified_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 thatN. communepolysaccharides 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.Keywords:mucosal barrier;gut microbiota;ulcerative colitis;polysaccharides

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