Ferulic Acid Alleviates Intestinal Mucosal Injury Induced by Acrylamide and Ochratoxin A Co-Exposure: An Association with Redox Homeostasis and Mucin O-Glycan Alterations

Co-exposure to AA and OTA disrupts the intestinal mucus barrier, with reduced claudin-1 and MUC2 expression, goblet cell loss, and downregulated GALNT2/COSMC. • Co-exposure-induced redox imbalance is accompanied by decreased PNA-detectable core 1 (Galβ1-3GalNAc) and downregulated glycosyltransferases. • Ferulic acid alleviates intestinal mucus barrier injury, accompanied by improved redox status and O-glycan-related markers. : The small intestine is highly susceptible to foodborne contaminants including acrylamide (AA) and ochratoxin A (OTA). Ferulic acid (FA), a natural bioactive phytochemical, exhibits great potential in preserving intestinal integrity. Here, we report that FA alleviates intestinal mucus barrier injury induced by AA/OTA co-exposure, and this protection is associated with modulation of oxidative stress homeostasis and O-glycan-related alterations—suggesting a previously underexplored association. In vivo , co-exposure of C57BL/6 mice to AA and OTA caused severe intestinal barrier dysfunction, as evidenced by increased intestinal permeability, goblet cell loss, downregulated expression of tight junction proteins and Mucin 2 (MUC2), excessive oxidative stress, and decreased levels of the O-glycan core 1 structure (Galβ1-3GalNAc). Notably, FA supplementation was associated with significant attenuation of these alterations. In the Caco-2/HT29-MTX co-culture model, FA antagonized AA/OTA-induced cytotoxicity, restored transepithelial electrical resistance (TEER), reduced paracellular permeability, and markedly upregulated the levels of the tight junction protein claudin-1 and the mucin MUC2. FA treatment was accompanied by mitigation of oxidative stress and increased expression of key glycosyltransferases, including GALNT2 and COSMC. Collectively, the coordinated changes in redox markers, GALNT2/COSMC expression, the PNA-detectable core 1 signal, and mucus-barrier indices suggest a coordinated association among redox imbalance, O-glycan-related alterations, and mucus-barrier dysfunction during AA/OTA-induced intestinal injury. These findings support further investigation of FA as a food-derived protective compound. Download: Download high-res image (188KB) Download: Download full-size image