Intestinal Organoid-Based Toxicity Study on Co-exposure to Food Contaminants Deoxynivalenol and Tenuazonic Acid

Abstract Environmental mycotoxins threaten human and animal health. Deoxynivalenol (DON) and emerging tenuazonic acid (TeA) severely contaminate food crops. The intestine is DON’s main toxic target and TeA’s primary exposure site, but TeA’s intestinal risk and their combined toxicity remain understudied. In this study, using an intestinal organoid model, we found that DON and TeA significantly suppressed cell viability (toxicity ratio ∼ 1:20) with synergistic effects under high toxicity, disrupting organoid development and intestinal barrier function (cell cycle arrest, reduced tight junction proteins, increased goblet cells), linked to their ribotoxicity and inducing lipid metabolism disorders (downregulated fatty acid β-oxidation genes) via the PPAR pathway. Single-cell transcriptome revealed that they impaired intestinal cell proliferation/differentiation, inducing ribotoxic stress in stem/TA cells and reducing canonical enterocytes (ECs), and ECs were core targets of their lipid toxicity. In conclusion, DON and TeA share intestinal toxicological characteristics, and their combined exposure potentiates toxicity, requiring targeted measures to mitigate co-exposure risks.