title: The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota.
abstract: An increasing number of human beings from developed countries are colonized byEscherichia colistrains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food-especially cereal products-in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of theE. colistrains producing colibactin.In vitro, intestinal epithelial cells were coexposed to DON andE. coliproducing colibactin.In vivo, newborn rats colonized at birth withE. coliproducing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of theE. coliproducing colibactin in a time- and dose-dependent mannerin vitroAlthough DON had no effect on the composition of the gut microbiota, and especially on the number ofE. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized byE. colistrains producing colibactin and coexposed to DON compared to animals colonized withE. colistrains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity ofE. colistrains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis.IMPORTANCEAn increasing number of human beings from developed countries are colonized byEscherichia colistrains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food-especially cereal products-in Europe and North America. Ourin vitroandin vivoresults demonstrate that the intestinal DNA damage induced by colibactin-producingE. colistrains was exacerbated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis.
authors.affiliation: Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Payros
authors.affiliation: Institute of Hygiene, University of Münster, Münster, Germany.|Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany.
authors.forename: Ulrich
authors.identifier: 0000-0001-9949-1898
authors.initials: U
authors.lastname: Dobrindt
authors.affiliation: CHU Toulouse, Service de Bactériologie-Hygiène, Institut Fédératif de Biologie, TSA, Toulouse, France.|Institut de Recherche en Santé Digestive (IRSD), Université de Toulouse, INSERM, INRA, ENVT, UPS, CS, Toulouse, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
authors.affiliation: Institut de Recherche en Santé Digestive (IRSD), Université de Toulouse, INSERM, INRA, ENVT, UPS, CS, Toulouse, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Secher
authors.affiliation: Laboratorio Patologia Animal, CP, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Ana Paula F L
authors.initials: AP
authors.lastname: Bracarense
authors.affiliation: Institut de Recherche en Santé Digestive (IRSD), Université de Toulouse, INSERM, INRA, ENVT, UPS, CS, Toulouse, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Boury
authors.affiliation: Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Laffitte
authors.affiliation: Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pinton
authors.affiliation: CHU Toulouse, Service de Bactériologie-Hygiène, Institut Fédératif de Biologie, TSA, Toulouse, France.|Institut de Recherche en Santé Digestive (IRSD), Université de Toulouse, INSERM, INRA, ENVT, UPS, CS, Toulouse, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Oswald
authors.affiliation: Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France isabelle.oswald@inra.fr.
authors.forename: Isabelle P
authors.identifier: 0000-0001-9918-227X
authors.initials: IP
authors.lastname: Oswald
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D004249:DNA Damage / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006657:Histones / Q000032:analysis; D009153:Mutagens / Q000633:toxicity*; D010455:Peptides / Q000633:toxicity*; D061065:Polyketides / Q000633:toxicity*; D051381:Rats; D014255:Trichothecenes / Q000378:metabolism*
chemical_list: D006657:Histones; D009153:Mutagens; D010455:Peptides; D061065:Polyketides; D014255:Trichothecenes; C569566:colibactin; C007262:deoxynivalenol