Lactiplantibacillus plantarum LP15-1 alleviates deoxynivalenol-induced intestinal injury in mice by inhibiting ferroptosis and modulating the gut microbiota.

Deoxynivalenol (DON), a major mycotoxin contaminating grain-based feed, poses a severe threat to intestinal health. Lactiplantibacillus plantarum, as a probiotic, is increasingly recognized for its positive impact on various aspects of animal health. However, the mechanism by which Lactiplantibacillus plantarum LP15-1 alleviates DON-induced intestinal injury remains unclear. In this study, six-week-old male mice were divided into control, DON group (2 mg/kg/day), and LP + DON group (108 CFU/day LP15-1 and 2 mg/kg/day DON). The experiment consisted of a 14-day pre-treatment with LP15-1, followed by a 7-day co-treatment with both LP15-1 and DON, for a total of 21 days. The present study demonstrated that LP15-1 supplementation improved feed conversion efficiency in mice. LP15-1 effectively alleviated DON-induced intestinal damage by restoring villus morphology and intestinal barrier integrity. LP15-1 significantly suppressed DON-induced elevation of serum IL-6 and restored TGF-β levels. Meanwhile, it reduced Ly6G-positive cells in intestinal tissues, thereby attenuating intestinal inflammation. Furthermore, LP15-1 enhanced intestinal antioxidant capacity, increasing T-AOC, SOD, and GSH while reducing MDA. Mechanistically, LP15-1 effectively counteracted DON-induced intestinal ferroptosis by restoring iron storage (FTH1), enhancing antioxidant defense (GPX4, GSS), and suppressing lipid peroxidation execution (ACSL4) and related inflammation (PTGS2) in jejunum. 16S rRNA sequencing showed that LP15-1 reversed DON-induced gut microbiota dysbiosis, restoring a control-like microbial community. The abundances of LP15-1-enriched genera were positively correlated with antioxidant, anti-inflammatory, and ferroptosis-suppressive parameters, and negatively correlated with pro-inflammatory cytokine levels, indicating that the alleviation of DON-induced intestinal injury by LP15-1 is closely associated with gut microbiota remodeling.