Deoxynivalenol-induced cellular signal transduction: research progress on toxicological effects, molecular mechanisms, and biological intervention strategies.

Deoxynivalenol (DON) is an important mycotoxin that contaminates cereal grains and poses serious threats to livestock and poultry production and human health. This review systematically summarizes the cytotoxicity of DON in the intestinal, immune, nervous, and reproductive systems. Particular emphasis is placed on the mechanism in which the direct ribotoxic stress response (direct RSR) acts as the initial trigger, followed by an imbalance in signaling networks and secondary amplification of ROS and endoplasmic reticulum (ER) stress. Through crosstalk among the MAPK, PI3K/AKT/mTOR, NF-κB, JAK2/STAT3, Nrf2/Keap1, and Wnt/β-catenin pathways, these processes further amplify mitochondrial damage, inflammation, apoptosis, and ferroptosis. This review also summarizes how probiotics, postbiotics, and their metabolites alleviate DON toxicity by regulating apoptosis, protecting the intestinal barrier, mediating signaling pathways, and releasing bioactive metabolites. Current bottlenecks are highlighted, including the unclear structures and toxicology of degradation products, poor intestinal stability, strong strain specificity, and overestimation of in vitro efficacy. Future directions are then discussed to provide a basis for mechanistic studies on the combined effects of DON and intervention agents.