ABSTRACT Selenium (Se) is an essential trace element with multiple biological functions, including anti‐inflammatory, antioxidant, growth‐regulating, and immunomodulatory functions. Dysregulation of the arachidonic acid (AA) metabolism‐ferroptosis‐inflammation axis is associated with the progression of intestinal inflammatory diseases, suggesting that its nutritional regulation holds potential for health management. This study explored how selenomethionine (Se‐Met), a bioactive dietary form of Se, regulates this axis to promote gut health using a murine model of AA‐induced colitis. C57BL/6J mice were pre‐fed a diet with Se‐Met (0.2 or 1.0 mg/kg) for 6 weeks, followed by intragastric administration of AA (30 mg/day) for 4 weeks. The results showed that excessive AA intake induced colitis, characterized by intestinal inflammation and barrier dysfunction. Se‐Met supplementation alleviated colitis symptoms, improved intestinal barrier function, and inhibited inflammation. Mechanistically, Se‐Met enhanced antioxidant defenses by upregulating selenoprotein expression, modulated AA metabolism to reduce the production of pro‐inflammatory oxylipins, and inhibited the ferroptosis signaling pathway. Transcriptomics analysis revealed systemic regulatory effects of Se‐Met on pathways related to inflammation and lipid metabolism, whereas 16S rRNA sequencing showed that Se‐Met remodeled the gut microbiota. These findings highlight that Se‐Met alleviates colitis through multi‐targeted regulation of the AA metabolism‐ferroptosis‐inflammation axis, thereby providing experimental support for dietary Se supplementation in gut health protection and informing nutritional strategies for managing inflammatory bowel disease.
Tian et al. (Sat,) studied this question.