Abstract
Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi-DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explants, exposure for 4 hours to 10 μM DON induced intestinal lesions not seen in explants treated with deepoxy-DON and 3-epi-DON. A pan-genomic transcriptomic analysis was performed on intestinal explants. 747 probes, representing 323 genes, were differentially expressed, between DON-treated and control explants. By contrast, no differentially expressed genes were observed between control, deepoxy-DON and 3-epi-DON treated explants. Both DON and its biotransformation products were able to fit into the pockets of the A-site of the ribosome peptidyl transferase center. DON forms three hydrogen bonds with the A site and activates MAPKinases (mitogen-activated protein kinases). By contrast deepoxy-DON and 3-epi-DON only form two hydrogen bonds and do not activate MAPKinases. Our data demonstrate that bacterial de-epoxidation or epimerization of DON altered their interaction with the ribosome, leading to an absence of MAPKinase activation and a reduced toxicity.
Highlights
Mycotoxins are toxic secondary metabolites produced by various molds, such as Aspergillus, Penicillium and Fusarium which may contaminate food and feed at all stages of the food/feed chain[1,2]
We have further demonstrated that these microbial metabolites of DON fit into the ribosome pocket but do not elicit ribotoxic stress or activate the MAPKinase pathway
Microbial transformation is of interest but requires demonstration of the absence of toxicity of the metabolites produced
Summary
Mycotoxins are toxic secondary metabolites produced by various molds, such as Aspergillus, Penicillium and Fusarium which may contaminate food and feed at all stages of the food/feed chain[1,2]. Deoxynivalenol (DON) produced by Fusarium species, is commonly detected in cereal crops, including wheat, barley, and maize. It is the most abundant trichothecene in food with a frequent occurrence at toxicologically relevant concentrations worldwide[4,5]. One paper has investigated the effect of 3-epi-DON and demonstrated the lack of toxicity, both in vitro and in vivo, of this DON metabolite[22]. The aim of the current study was to assess the efficacy of microbial transformation through analysis of the intestinal toxicity of deepoxy-DON and 3-epi-DON. Histological and transcriptomic analysis, we have observed reduced toxicity of deepoxy-DON and 3-epi-DON, both for human intestinal epithelial cells and pig intestinal explants. Our paper provides the first molecular insight for the reduced toxicity of deepoxy-DON and 3-epi-DON
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