Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways

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Alassane-Kpembi, Imourana | Rubira Gerez, Juliana | Cossalter, Anne Marie | Neves, Manon | Laffitte, Joëlle | Naylies, Claire | Lippi, Yannick | Kolf-Clauw, Martine | Loureiro-Bracarense, Ana-Paula | Pinton, Philippe | Oswald, Isabelle P.

Edité par CCSD ; Nature Publishing Group -

Times Cited: 0Alassane-Kpembi, Imourana Gerez, Juliana Rubira Cossalter, Anne-Marie Neves, Manon Laffitte, Joelle Naylies, Claire Lippi, Yannick Kolf-Clauw, Martine Bracarense, Ana Paula L. Pinton, Philippe Oswald, Isabelle P.ANR-CESA project DONCo; PHC Stefanik [35813XM]The authors are grateful to the Bioinformatics platform from Toulouse Midi-Pyrenees genopole (GenoToul) for providing resources for the microarray analysis. This work was supported by the ANR-CESA project DON&Co and PHC Stefanik 35813XM.0. The few data available on fusarenon-X (FX) do not support the derivation of health-based guidance values, although preliminary results suggest higher toxicity than other regulated trichothecenes. Using histo-morphological analysis and whole transcriptome profiling, this study was designed to obtain a global view of the intestinal alterations induced by FX. Deoxynivalenol (DON) served as a benchmark. FX induced more severe histological alterations than DON. Inflammation was the hallmark of the molecular toxicity of both mycotoxins. The benchmark doses for the up-regulation of key inflammatory genes by FX were 4- to 45-fold higher than the previously reported values for DON. The transcriptome analysis revealed that both mycotoxins down-regulated the peroxisome proliferator-activated receptor (PPAR) and liver X receptor - retinoid X receptor (LXR-RXR) signaling pathways that control lipid metabolism. Interestingly, several pathways, including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling, were specific to FX and thus discriminated the transcriptomic fingerprints of the two mycotoxins. These results demonstrate that FX induces more potent intestinal inflammation than DON. Moreover, although the mechanisms of toxicity of both mycotoxins are similar in many ways, this study emphasize specific pathways targeted by each mycotoxin, highlighting the need for specific mechanism-based risk assessments of Fusarium mycotoxins.

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