The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression.
'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.
Pinton
Philippe
P
INRA: UR66, Toulouse, France.
Nougayrède
Jean-Philippe
JP
Del Rio
Juan-Carlos
JC
Moreno
Carolina
C
Marin
Daniela E
DE
Ferrier
Laurent
L
Bracarense
Ana-Paula
AP
Kolf-Clauw
Martine
M
Oswald
Isabelle P
IP
D000818:Animals; D018938:Caco-2 Cells; D062465:Claudin-3; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D005506:Food Contamination; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity; D010539:Permeability / Q000187:drug effects; D020033:Protein Isoforms; D018709:Statistics, Nonparametric; D013552:Swine; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*
C568122:CLDN3 protein, human; D062465:Claudin-3; D008565:Membrane Proteins; D009183:Mycotoxins; D020033:Protein Isoforms; D014255:Trichothecenes; C007262:deoxynivalenol