Modulatory effects of isoflavones and zearalenone metabolites on deoxynivalenol induced gut barrier toxicity in vitro

Humans and animals are frequently exposed to dietary compounds that can adversely affect intestinal health. The Fusarium mycotoxin deoxynivalenol (DON) is known to compromise epithelial barrier integrity. DON frequently co-occurs in food and feed with the mycoestrogen zearalenone (ZEN) and soy-derived isoflavones (ISFs) such as genistein (GEN) and daidzein. Therefore, this study investigates the effects of ZEN (10 nM), its metabolites hydrolyzed ZEN (HZEN) and decarboxylated hydrolyzed ZEN (DHZEN) (each 10 nM), and ISFs (GEN and equol (EQ), 10 µM), alone and in combination with DON (10 µM), on intestinal barrier function using the porcine epithelial cell line IPEC-J2. Barrier integrity was assessed via transepithelial electrical resistance (TEER) and paracellular permeability (lucifer yellow). DON (10 µM) significantly reduced barrier integrity, confirming its disruptive effect. Conversely, treatment with ZEN, HZEN, DHZEN, GEN, and EQ did not impair barrier function. Co-exposure of DON with ZEN or HZEN yielded TEER values similar to those observed with DON alone. In contrast, the DHZEN + DON combination resulted in higher TEER values compared to DON alone, suggesting a mitigating effect under the experimental conditions. Quantification of GEN by LC-MS/MS showed consistent levels across treatments, except for reduced basolateral GEN during co-incubation with DHZEN, suggesting altered transport or metabolism. These findings highlight the ability of DHZEN to mitigate the intestinal barrier disruption induced by DON and underscores the complex interaction of maintaining epithelial barrier integrities.