Almond Polysaccharide Ameliorates DSS‐Induced Ulcerative Colitis in Mice by Restoring Intestinal Barrier Function and Modulating Gut Microbiota and SCFAs Metabolism

ABSTRACT The development of new therapeutic strategies for ulcerative colitis (UC) requires the targeting of multiple pathogenic factors, including disruption of the colonic mucosal barrier, dysregulated inflammation, and gut microbiota imbalance. This study aimed to investigate the protective mechanisms of almond polysaccharide (AP1) against dextran sulfate sodium (DSS)‐induced UC in mice. Administration of AP1 significantly restored DSS‐induced reductions in goblet cells and inhibited epithelial apoptosis, thereby preserving colonic mucosal barrier integrity. In addition, AP1 decreased the levels of proinflammatory cytokines and oxidative stress markers in colonic tissues. Gut microbiota analysis revealed that AP1 effectively restored microbial composition and diversity. Furthermore, AP1 increased the relative abundance of beneficial bacteria while reducing pathogenic taxa, thereby contributing to the restoration of intestinal microbial balance in UC mice. Metabolomic analysis of short‐chain fatty acids (SCFAs) demonstrated that DSS‐induced UC significantly depleted major SCFAs (acetic acid, propionic acid, n‐butyric acid) and disrupted branched‐chain fatty acid (i‐butyric acid and i‐valeric acid) metabolism, whereas AP1 intervention reestablished SCFA profiles. Correlation analysis showed Bacteroides negatively correlated with multiple SCFAs, whereas Alistipes positively correlated with propionic acid. Collectively, these findings underscore the role of AP1 in rescuing microbiota‐derived SCFA metabolism. In summary, AP1 was shown to alleviate UC symptoms through multiple mechanisms, including the preservation of mucosal barrier integrity, suppression of oxidative stress and inflammation, and modulation of gut microbiota composition and the intestinal microenvironment. These results support the therapeutic potential of AP1 as a natural polysaccharide‐based agent for UC treatment.