EVICTION

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EVICTION

EVICTION

Mycotoxins are toxic secondary metabolites produced by a range of fungi and are common contaminants of agricultural crops. These toxins are stable and able to remain active for long periods while withstanding most agricultural decontamination processes. Consequently, mycotoxins are able to enter into the food chain. Many of these mycotoxins have the capacity to cause numerous adverse health effects. Of the currently more than 300 known mycotoxins, the Fusarium toxins that have the largest adverse impact on human and animal health are deoxynivalenol (DON), zearalenone and fumonisin B. Among them, DON is the most prevalent one with a incidence rate of 59 and 43% in raw and processed cereal products respectively. In France, around 1% of adults and between 5 and 10% of children are exposed to DON at levels greater than the toxicological threshold of 1μg/kg bw/d.

Because of its toxicity and widespread occurrence, DON has received particular attention in recent years. Many outbreaks of acute human diseases have been attributed to consumption of DON-contaminated grains. In animals, DON causes many toxic effects on growth, immune response, reproduction, development. At the intestinal level, DON has been demonstrated to affect key immune functions such as intestinal barrier or mucus production. DON toxic effects can be reduced in vivo via two main metabolic pathways, one achieved by gut bacteria (de-epoxidation). Preliminary results in mice showed that DON, orally administered at a dose below the usually considered safe No Observable Adverse Effect Level, could lead to the induction and/or persistence of intestinal inflammation. These observations together with the literature suggest that DON could predispose to intestinal chronic diseases such as Inflammatory Bowel Diseases. But this hypothesis has not yet been investigated so far.

OBJECTIVES

We hypothesize that DON might be an environmental risk factor for IBD. We propose to focus on the human relevance of the gut effects of DON by studying its exposure, metabolism and adverse effects in health and disease, focusing on IBD patients. Alterations of gut microbiota composition and detoxification mechanisms have been observed in IBD patients. We propose that an improper detoxification activity, implicating gut microbiota and/or endogenous enzymes, might lead to an increased susceptibility to DON toxicity in IBD patients.

microbiote

The objectives of this project are to compare, in healthy and IBD suffering individuals, the cartography of DON absorption, distribution, metabolism and excretion (Task 1), the detoxification of DON by the gut and the consequences of DON exposure in term of immune homeostasis (Task 2), the effects of DON on the gut microbiota composition and the reciprocal effect of the gut microbiota on DON metabolism studied in vitro (Task 3). The study of consequences of oral subchronic exposure of DON in humanized gnotobiotic mice colonized with a healthy or an IBD patient microbiota will be the objective of the fourth Task.

PARTNERS

  • LIRIC (Lille Inflammatory Research International Center) UMR 995 : Pr Pierre Desreumaux, Dr Cécile Vignal, Dr Mathilde Body-Malapel (Coordination)
  • ANSES de Fougères : Dr Michel Laurentie
  • GIP Labocea : Eric Marengue
  • MEDiS UMR 454 : Pr Monique Alric, Dr Sylvain Denis, Carine Mazal – Task 3

FINANCEMENT

ANR AAP Générique 2017 – Challenge 4 – PRC (ANR- 17-CE34-0011)

ANR

Date de modification : 24 mai 2023 | Date de création : 02 avril 2020 | Rédaction : sd