Transcriptomic fingerprint of the type B trichothecene mycotoxins on the intestine. Sus scrofa

We employed whole genome gene expression analysis to characterize the intestinal exposure to 5 closely related food contaminants belonging to the type B trichocene mycotoxins groups The few data available on fusarenon-X (FX) do no support derivation of health-based guidance values for this mycotoxin, although preliminary results suggest higher toxicity compared to other regulated trichothecenes. Using histo-morphological analysis and whole-transcriptome profiling, the present study was designed to get a global view of intestinal alterations induced by FX. The well-described trichothecene deoxynivalenol (DON) served as a benchmark. FX exposure induced more severe intestinal histological alterations compared to DON. Intestinal inflammation was the hallmark of the molecular toxicity of DON, but also of FX. The dose-response analysis for FX revealed that benchmark doses for up-regulation of key-inflammatory genes expression were 4 to 45-fold higher than the previously reported ones for DON. Transcriptome analysis revealed that both mycotoxins down-regulated PPAR and LXR-RXR signaling pathways controlling lipid metabolism. Interestingly, several pathways including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling were specific to FX and thus, discriminate the intestinal transcriptomic fingerprint of the two mycotoxins. Altogether, these results demonstrate that FX induces a more potent intestinal inflammation than DON. This study also reveals specific FX-targeted pathways, indicating that the toxicity of DON cannot serve as a benchmark for FX, and that toxicity evaluation of each trichothecene should be conducted separately. Overall design: Jejunal explants from 4 pigs were exposed to 2µM or 10 µM deoxynivalenol, nivalenol, fusarenon-x, 3-acetyldeoxynivalenol or 15-acetyl deoxynivalenol, to vehicle (DMSO).