Selenomethionine Mitigates Oxidized Soybean Oil-Induced Jejunal Injury via Antioxidant, Metabolic Reprogramming, and Immunomodulatory Pathways

Dietary oxidized soybean oil (OSO) induces intestinal injury, yet the mechanisms underlying selenium (Se)-mediated protection remain unclear. This study explored the therapeutic effects of selenomethionine (Se-Met) against OSO-induced gut damage in C57BL/6J mice. They were allocated into control (0.2 mg/kg Se + fresh soybean oil), OSO (0.2 mg/kg Se + OSO), and OSO + Se (1.0 mg/kg Se + OSO) groups for 10 weeks. We found that Se-Met attenuated OSO-induced growth retardation and jejunal structural damage and restored barrier integrity. It activated Keap1-Nrf2 and glutathione metabolism pathways, reducing the level of OSO-induced oxidative stress. Se-Met rectified the OSO-induced lipid metabolism disorders, redirected PUFA metabolism from proinflammatory n-6 to anti-inflammatory n-3 profiles, and alleviated the OSO-induced immunosuppression by balancing cytokines and innate immune cells. Transcriptomics linked these to redox, lipid, and immune pathway regulation. Additionally, it alleviated the OSO-induced gut microbiota dysbiosis. These findings demonstrate Se-Met's multitarget efficacy against OSO-induced intestinal damage, highlighting its potential as a nutritional intervention for oxidative diet-related gut pathologies.