Coix Seed Polysaccharide Mitigates Ulcerative Colitis in Mice through the Modulation of Gut Microbiota and Improvement of Intestinal Metabolism Balance

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising incidence globally, whereas existing treatments exhibit significant limitations. Coix seed polysaccharide (CSP), a component of traditional Chinese medicine known for its immunomodulatory and antioxidant properties, has not been thoroughly investigated for its role in UC. In this study, CSP was prepared via water extraction and ethanol precipitation, and its protective effects and mechanisms were evaluated using a dextran sulfate sodium salt (DSS)-induced UC mouse model. The results demonstrated that CSP significantly ameliorated DSS-induced UC symptoms, including weight loss, an elevated Disease Activity Index, colon shortening, increased levels of inflammatory cytokines, and intestinal barrier damage. Moreover, CSP reshaped the DSS-induced gut microbiota dysbiosis by increasing gut microbial diversity and regulating the abundance of specific genera, such as increasing <i>Anaerotruncus</i>. Metabolomic analysis revealed that CSP significantly modulated the levels of 116 metabolites, particularly enhancing the beneficial metabolite 3-hydroxybutyrate. Importantly, the preventive effect of CSP on UC was dependent on the gut microbiota and could be transferred via fecal microbiota transplantation. This study demonstrates that CSP, a microecology-regulating polysaccharide, effectively modulates gut microbiota and alleviates symptoms of UC. These findings support the potential of CSP as a dietary supplement for UC prevention and underscore its value in the development of medicinal foods and functional food applications.