Delphine Payros1,2, Imourana Alassane-Kpembi3, Joelle Laffitte1, Corine Lencina1, Manon Neves1, Ana Paula Bracarense4, Philippe Pinton1, Sandrine Ménard1,2, Isabelle P Oswald1. 1. Research center in Food Toxicology, Université de Toulouse, INRAE, ENVT, INP- PURPAN, UPS, Toxalim, Toulouse, F-31027, France. 2. Université de Toulouse, INSERM, INRAE, ENVT, UPS, IRSD, Toulouse, France. 3. Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, Université de Montréal, 3200, Rue Sicotte, Saint-Hyacinthe, Québec, J2S 2M2, Canada. 4. Universidade Estadual de Londrina, Laboratory of Animal Pathology, Londrina, Parana, CP 6001, Brazil.
Abstract
INTRODUCTION: The food contamination by mycotoxins is of increasing public health concerns. Deoxynivalenol (DON), a mycotoxin contaminating cereals, has been associated with the exacerbation of inflammatory bowel diseases (IBD), thereby raising the question of its role in the development of IBD. Moreover, the effect of DON on the colon is poorly described. METHODS AND RESULTS: Wistar rats exposed (1-4 weeks) to low doses of DON (2 or 9 mg kg-1 feed) show microscopic alterations of colonic tissue (dilated lymphatic vessels, luminal debris, and cubic and flattened enterocytes). Ingestion of DON also alters colonic functions by increasing paracellular permeability while reducing the expression of the tight junction proteins and increased apoptosis in colonic tissue. Pro-apoptotic factors Bax/Bak, cytochrome C, and caspase 9 are upregulated, whereas expression of anti-apoptotic protein Bcl2 tends to decrease for the mitochondrial pathway. An increased expression of FasR and caspase-8 is observed for the extrinsic pathway. An increase in the pro-inflammatory markers TNFα, IL-17, and myeloperoxidase is also observed. CONCLUSION: These results indicate that the dietary exposure to low levels of DON in food targets the colon inducing a health-threatening breakdown of the colonic barrier, highlighting oral exposure to DON as a potential risk factor in triggering IBD.
INTRODUCTION: The food contamination by mycotoxins is of increasing public health concerns. Deoxynivalenol (DON), a mycotoxin contaminating cereals, has been associated with the exacerbation of inflammatory bowel diseases (IBD), thereby raising the question of its role in the development of IBD. Moreover, the effect of DON on the colon is poorly described. METHODS AND RESULTS: Wistar rats exposed (1-4 weeks) to low doses of DON (2 or 9 mg kg-1 feed) show microscopic alterations of colonic tissue (dilated lymphatic vessels, luminal debris, and cubic and flattened enterocytes). Ingestion of DON also alters colonic functions by increasing paracellular permeability while reducing the expression of the tight junction proteins and increased apoptosis in colonic tissue. Pro-apoptotic factors Bax/Bak, cytochrome C, and caspase 9 are upregulated, whereas expression of anti-apoptotic protein Bcl2 tends to decrease for the mitochondrial pathway. An increased expression of FasR and caspase-8 is observed for the extrinsic pathway. An increase in the pro-inflammatory markers TNFα, IL-17, and myeloperoxidase is also observed. CONCLUSION: These results indicate that the dietary exposure to low levels of DON in food targets the colon inducing a health-threatening breakdown of the colonic barrier, highlighting oral exposure to DON as a potential risk factor in triggering IBD.