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The food contaminant, deoxynivalenol, modulates the Thelper/Treg balance and increases inflammatory bowel diseases

Abstract

The incidence of inflammatory bowel diseases (IBD) is increasing in both Western and developing countries. IBD are multifactorial disorders involving complex interactions between genetic, immune, and environmental factors such as exposure to food contaminants. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food and induces intestinal breakdown and inflammatory response. To delineate the role of DON oral exposure in IBD, we used a Dextran sulfate sodium (DSS) colitis model in rats fed with a DON-contaminated diet or a control diet for 4 weeks. Colitis was induced in the 4th week by increasing concentrations of DSS in the drinking water (0, 2, 3 or 5%). DON exacerbated body weight loss and accelerated the appearance of symptoms in animals treated with DSS. DON increased morphological damage, pro-inflammatory markers (myeloperoxidase, CXCL-1 and IL-1β) and immune cell responses. In lamina propria of the rat with colitis, DON increased adaptive and innate immune responses after anti-CD3/28 or LPS stimulation, respectively. In the spleen, DON increased IFNγ secretion and reduced Treg populations. Interestingly, De-epoxy-DON (DOM-1) a detoxified form of DON did not have any consequences on colitis. These results suggest that DON is a risk factor in the onset of IBD.

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Acknowledgements

We thank G. Schatzmayr and D. Moll from the BIOMIN Research Center in Tulln (Austria) for the DOM-1 product. We are grateful to Dr L. Guzylack-Piriou and T. Gauthier from Toxalim (Toulouse, France) for their scientific input and help with flow cytometry experiments and analysis. The authors wish to thank the staff of the team EZOP for animal care. We are grateful to the UPAE (Unité de Préparation des Aliments Expérimentaux, UE0300, Jouy-en-Josas, France) for the preparation of the diets. Thank you to M. Gosselin, L. Murate for excellent technical help. This work was supported by grants from the French National Research Agency (projects CaDON 15-CE21-0001 and Genofood 19-CE34).

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Correspondence to Isabelle P. Oswald.

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Payros, D., Ménard, S., Laffitte, J. et al. The food contaminant, deoxynivalenol, modulates the Thelper/Treg balance and increases inflammatory bowel diseases. Arch Toxicol 94, 3173–3184 (2020). https://doi.org/10.1007/s00204-020-02817-z

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  • DOI: https://doi.org/10.1007/s00204-020-02817-z

Keywords

  • Mycotoxin
  • De-epoxy-DON: DOM-1
  • Intestine
  • Spleen
  • Colitis
  • Immune response