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

Imourana Alassane-Kpembi (1, 2) , Juliana Rubira Gerez (1, 3) , Anne Marie Cossalter (4) , Manon Neves (1) , Joëlle Laffitte (5) , Claire Naylies (6) , Yannick Lippi (6) , Martine Kolf-Clauw (1) , Ana-Paula Loureiro-Bracarense (1) , Philippe Pinton (5) , Isabelle P. Oswald (5)

1 ToxAlim - ToxAlim
2 Hôpital d'Instruction des Armées Camp Guézo
3 Department of Veterinary Preventive Medicine, Laboratory of Animal Pathology
4 Ezop - Plateforme Ezop
5 ToxAlim-BioToMyc - Biosynthèse & Toxicité des Mycotoxines
6 E23 TRiX - Transcriptomic impact of Xenobiotics

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.

Mots clés: toxicologie alimentaire; mycotoxine; fusarenone x

Domaines: Sciences du Vivant [q-bio]

Imourana Alassane-Kpembi, Juliana Rubira Gerez, Anne Marie Cossalter, Manon Neves, Joëlle Laffitte, et al.. Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways. Scientific Reports, 2017, 7, 14 p. ⟨10.1038/s41598-017-07155-2⟩. ⟨hal-01608391⟩