Selenized Probiotic L. brevis 23017 Alleviates Colitis by Modulating the Nrf2-GPX4 Axis to Inhibit Ferroptosis.

Ulcerative colitis (UC) constitutes a principal subtype of inflammatory bowel disease (IBD) and exhibits escalating global incidence. This study elucidates the therapeutic efficacy and mechanistic basis of novel selenized probiotic, Lactobacillus brevis 23017 (Se-Lb23017), and biogenic selenium nanoparticles (SeNPs) in a dextran sodium sulfate (DSS)-induced colitis murine model. The investigation specifically probed ferroptosis inhibition and activation of the Nrf2-GPX4-HO-1 signaling axis. The results demonstrated 80 µg/mL of Na2SeO3 is optimal for preparing Se-Lb23017. Both Se-Lb23017 and SeNPs exhibited typical morphology under scanning electron microscopy (SEM). In vivo experiments showed that administration of either Se-Lb23017 or SeNPs, especially Se-Lb23017 effectively mitigated key features of colitis, including elevated disease activity index (DAI) scores, weight loss, tissue damage, and colon shortening. In vitro, both Se-Lb23017 and SeNPs, especially Se-Lb23017 significantly reduced the expression of pro-inflammatory mediators (TNF-α, IL-1β, IL-6) and enhanced levels of anti-inflammatory cytokine IL-10. Mechanistically, the protective effects were associated with reduced oxidative stress and ferroptosis suppression via Nrf2-GPX4-HO-1 axis activation and subsequent reduction in lipid peroxidation. Collectively, these findings demonstrate that Se-Lb23017 and SeNPs ameliorate experimental colitis through synergistic anti-inflammatory and antioxidant effects, providing cytoprotection via Nrf2-dependent ferroptosis inhibition. This study highlights selenized probiotics as a promising therapeutic strategy for ulcerative colitis by targeting a novel cell death modality.