Dietary Exposure to the Food Contaminant Deoxynivalenol Triggers Colonic Breakdown by Activating the Mitochondrial and the Death Receptor Pathways

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.

Exposure of intestinal explants to NX, but not to DON, enriches the secretome in mitochondrial proteins

“…Our results are in agreement with the known toxicity of DON that causes lesions in the intestine and the loss of the intestinal barrier (Pinton et al 2009 , 2012 ; Payros et al 2021b ). Indeed, the enrichment of structural proteins as well as of proteins involved in metabolism known to be present in mature enterocytes in the DON intestinal secretomes reflects increased destruction of the intestinal epithelium, and the release of cytosolic proteins into the medium.…”

Deoxynivalenol Exposure Induced Colon Damage in Mice Independent of the Gut Microbiota

“…DON-contaminated diets led to pathological injury in the colon, decreased the expression of TJPs, and elevated the levels of pro-inflammatory cytokines in rats. [30] In the present study, DON exposure impaired colon pathology and altered the expression of TJPs in colon tissue, which was generally consistent with the conclusions of previous studies. However, there was no significant change in the levels of inflammatory cytokines in colon tissue after DON exposure, demonstrating that the inflammatory damage induced by DON exposure in colon tissue in the present study was not as severe as that reported in previous studies.…”

Real-life exposure to Fusarium toxins deoxynivalenol and zearalenone triggers apoptosis and activates NLRP3 inflammasome in bovine primary theca cells

“…DON induces several types of cell death patterns. We reported both the mitochondrial and the death receptor pathways to be involved in the apoptosis induced by DON (Payros et al, 2021). More recently, pyropoptosis, another pattern of programmed cell death that relates to DON-induced in ammation has also been described (Mao et al, 2022).…”

“…The kinetics of membrane phosphatidylserine translocation and loss of membrane integrity are valuable indicators for the mode of cell death, since apoptosis inducers are expected to produce substantial phosphatidylserine translocation prior to the loss of membrane integrity[28]. In contrast with DON and ZEN that are known apoptosis inducers(Cai et al, 2019;Payros et al, 2021), there was no kinetic difference in the phosphatidylserine release and the loss of membrane integrity in the theca cells exposed to DOM-1. A previous study demonstrated the lack of caspase-3 activation by DOM-1 up to 100µM in the non-transformed porcine intestinal epithelial IPEC-J2 cell line(Springler et al, 2017).…”