Metabolomics and Lipidomics Reveal the Metabolic Disorders Induced by Single and Combined Exposure of Fusarium Mycotoxins in IEC-6 Cells.

Deoxynivalenol (DON), fumonisin B (FB), and zearalenone (ZEN) are typical fusarium mycotoxins that occur worldwide in foodstuffs, posing significant health hazards to humans and animals. Single and combined exposure of DON, FB, and ZEN leads to intestinal toxicity but the toxicology mechanism research is still limited. In this study, we explored the cytotoxicity effects of DON, FB, ZEN, and their combination in rat intestinal epithelial cell line 6 (IEC-6) cells. Cell viability results showed that the cytotoxicity potency ranking was DON > ZEN > FB. Furthermore, both DON + FB and DON + ZEN presented synergism to antagonism effects based on a combination index (CI)-isobologram equation model. Integrated metabolomics and lipidomics was adopted to explore cell metabolism disorders induced by fusarium mycotoxin exposure. A total of 2011 metabolites and 670 lipids were identified. An overlap of 37 and 62 differential compounds was confirmed after single and combined mycotoxin exposure by multivariate analysis, respectively. Some of the differential compounds were endocellular antioxidants and were significantly downregulated in mycotoxin exposure groups, indicating metabolic disorders as well as antioxidant capacity damage in cells. Pathway enrichment analysis annotated ethanol metabolism production of ROS by CYP2E1 was mainly involved in the disturbance of DON, FB, and ZEN. The results obtained in this study help to define the toxicity effects of DON, FB, and ZEN singly and in co-existence, providing an important scientific basis for combined risk recognition of mycotoxin contamination.