Glucuronolactone Promotes Mucin Sulfation to Alleviate Deoxynivalenol‐Induced Intestinal Injury via Microbiota‐Dependent and ‐Independent AHR Activation

ABSTRACT Deoxynivalenol (DON), a prevalent trichothecene mycotoxin, poses a global threat to the gut health of both humans and livestock. This study investigates the protective effects and underlying mechanisms of glucuronolactone (GLU) against DON‐induced intestinal injury. In a piglet model, GLU effectively alleviated DON‐induced intestinal injury and inflammation. Transcriptomic analysis revealed that GLU promotes mucin sulfation, a critical process for fortifying the intestinal mucus barrier. On the one hand, integrated microbiome and metabolomics analyses uncovered that GLU increased probiotic Lactobacillus amylovorus abundance and luminal indole‐3‐acetic acid level, thereby facilitating mucin sulfation. On the other hand, GLU itself directly boosted mucin sulfation in a microbiota‐independent manner. Mechanistically, both the microbiota‐dependent and ‐independent pathways through which GLU promoted mucin sulfation converged on the activation of aryl hydrocarbon receptor (AHR). Activated AHR transcriptionally up‐regulated the expression of the sulfotransferase GAL3ST3 , which drove mucin sulfation. This study identifies GLU as a promising nutritional intervention against DON‐induced intestinal injury and reveals AHR‐mediated mucin sulfation as a vital mechanism for maintaining intestinal barrier homeostasis.