Novel selenium-enriched Pichia kudriavzevii as a dietary supplement to alleviate dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota and host metabolism.

Inflammatory bowel disease (IBD) poses persistent challenges due to its chronic and recurrent nature, exacerbated by the unsatisfactory outcomes of the traditional treatment approaches. In this study, we developed a dietary supplement, selenium-enriched Pichia kudriavzevii (SeY), to alleviate dextran sulfate sodium-induced colitis in mice. The newly developed functional food shows dual-functional activity, acting both as a probiotic and a reliable source of organic selenium. This study aimed to investigate the preventive effects of SeY against dextran sulfate sodium-induced colitis in mice and elucidate the underlying mechanisms. Results showed that SeY, especially at high doses (HSeY), significantly ameliorated colitis symptoms, reduced colonic damage, attenuated inflammatory responses, and mitigated oxidative stress. Furthermore, HSeY strengthened intestinal barrier function by increasing goblet cell numbers, upregulating MUC2 expression, and enhancing tight junction proteins (ZO-1, claudin-1, and occludin). Additionally, HSeY alleviated gut microbiota dysbiosis by promoting the colonization of beneficial bacteria such as norank-f-Muribaculaceae and Bacteroides, while suppressing harmful microorganisms such as norank-f-norank-o-Clostridia-UCG-014. The altered gut microbiota also affected gut metabolism, with differential metabolites primarily associated with amino acids, such as tryptophan metabolism, contributing to the mitigation of oxidative stress and inflammatory responses. Further studies involving antibiotic-mediated depletion of gut flora and fecal microbiota transfer trials corroborated that the preventive effect of HSeY against IBD relied on the gut microbiota. This study provides vital insights into colitis prevention and advances selenium-enriched fortified food-targeted nutritional interventions.