Effet chez le porcelet d'une exposition à un régime co-contaminé en ...

AUTHOR : Bertrand GRENIERTITLE : Effect in pigs of the exposure to a mycotoxins co-contaminated diet, and evaluation ofcontrol strategiesTHESIS SUPERVISORS : Dr. Isabelle OSWALD and Pr. Martine KOLF-CLAUWABSTRACT :Mycotoxins are secondary metabolites of fungi that are natural contaminants of severalcommodities, in particular cereals. In the present work, we focused on two major mycotoxinsproduced by the Fusarium genus, Deoxynivalenol (DON) and Fumonisin (FB). The main objectives ofthe thesis were to determine the toxic effects of individual and combined DON and FB contaminationin pig, a target species highly sensitive to mycotoxins. The effects on the immune functions followingan antigenic challenge and also on the intestinal functions were evaluated. Besides, within theframework of an industrial partnership, we evaluated in vivo the effects of detoxifying methods bybiotransformation and targeting specifically these two toxins. In pigs, ingestion of contaminatedfeeds with low doses of mycotoxins (DON, 3 mg/kg ; FB, 6 mg/kg) triggered tissular lesions (liver,kidneys and lungs) and strongly impaired the establishment of the antigenic immune response(cytokines expression, lymphocytes proliferation and specific antibodies). Animals consuming the cocontaminateddiet were more affected and the interaction could be considered as additive. Inaddition, changes in morphology, in profile of cytokines secretion and in cell adhesion were observedat intestinal level. The interaction here could be characterized as less than additive. The biologicaldetoxification approaches proposed by the industrial were based on the transformation by enzymaticway of DON and FB, from intact microorganism and enzyme respectively. We paid a particularattention to the strategy of FB removal as this method is not marketed and still in development.Therefore, the toxicity of the hydrolysis product of FB1 (major mycotoxin in the FB group) initiallyobtained by enzymatic way, was compared in vivo to the toxicity of the parent compound FB1.Results showed that the hydrolysis of FB1 strongly reduced the toxicity in piglets at intestinal andhepatic levels. The animal experiment with DON and FB, alone or in combination was then repeatedin order to determine in pigs the hydrolysis efficiency of this process when enzyme was incorporatedin contaminated feeds. In these feeds, the intact microorganism toward DON was also included. Themarked decrease of the biomarker of exposure to FB and the partial or total counteraction of theeffects suggested that the process had greatly reduced the FB bioavailability in the gastrointestinaltract. This observation was also in part confirmed for the method degrading DON. Thebiotransformation method of mycotoxins by enzymatic way represents therefore a promisingbiotechnological strategy in the control of these contaminants.KEY WORDS : Deoxynivalenol, Fumonisin, pig, co-contamination, immune response, intestinalresponse, biomarker of exposure, enzymatic biotransformationDISCIPLINE : Food ToxicologyHEADING AND ADRESS OF THE LABORATORY :Institut National de la Recherche Agronomique – INRAUnité ToxAlim, Equipe d’Immuno-Mycotoxicologie180, chemin de Tournefeuille – BP 9317331027 TOULOUSE Cedex 3 – FRANCE