Dietary Quercetin Mitigates DON-Induced Intestinal Injury via Inhibiting MAPK/NF-κB-Mediated Pyroptosis and Tight Junction Disruption in Chicken

Deoxynivalenol (DON), a prevalent food-borne mycotoxin, severely compromises intestinal barrier function. Quercetin (QUE) is a dietary flavonoid with a variety of known bioactivities. Our results demonstrated that QUE significantly ameliorated DON-induced structural damage, functional impairment, and oxidative stress in the small intestine. Mechanistically, DON exposure disrupted the intestinal barrier by downregulating tight junction proteins (ZO-1, Occludin, and Claudin-1) and activating the MAPK/NF-κB signaling pathway. This activation triggered the assembly of the NLRP3 inflammasome, leading to caspase-1 activation and pyroptosis, as evidenced by cleavage of GSDMD and elevated secretion of IL-1β and IL-18. Critically, QUE intervention suppressed the entire cascade, primarily by inhibiting the upstream MAPK/NF-κB activation. Our findings elucidate a novel mechanism by which QUE attenuates DON-induced enterotoxicity via blocking the MAPK/NF-κB-NLRP3-pyroptosis axis, providing a solid mechanistic foundation for its application as a novel nutraceutical or feed additive against mycotoxin contamination.