Isabelle P Oswald

University of Toulouse, Tolosa de Llenguadoc, Midi-Pyrénées, France

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Publications (128)391.33 Total impact

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    ABSTRACT: In case of mycotoxin contaminations, food and feedstuff are usually contaminated by more than one toxin. However toxicological data concerning the effects of mycotoxin combinations are sparse. The intestinal epithelium is the first barrier against food contaminants and this constantly renewing organ is particularly sensitive to mycotoxins. The aim of this study was to investigate the effects of deoxynivalenol (DON) and four other type B trichothecenes (TCTB), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX) alone or in combination on intestinal epithelial cells. Proliferating, non-transformed IPEC-1 cells were exposed to increasing doses of TCTB, alone or in binary mixtures and mycotoxin-induced cytotoxicity was measured with MTT test. The toxicological interactions were assessed using the isobologram-Combination index method. The five tested mycotoxins and their mixtures had a dose-dependent effect on the proliferating enterocytes. DON-NIV, DON-15-ADON and 15-ADON-3-ADON combinations were synergistic, with magnitude of synergy for 10 % cytotoxicity ranging from 2 to 7. The association between DON and 3-ADON also demonstrated a synergy but only at high doses, at lower doses antagonism was noted. Additivity was observed between NIV and FX, and antagonism between DON and FX. These results indicate that the simultaneous presence of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of TCTB in the diet.
    Archives of toxicology. 07/2014;
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    ABSTRACT: Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin produced by Aspergilli of the section Flavi that may contaminate food, in the field or during storage. Cassava represents an important staple food in sub-Saharan Africa. The analysis of aflatoxigenic fungi in 36 cassava samples obtained from producers in Benin indicated that 40% were contaminated by Aspergilli of the section Flavi. Upon morphological and molecular characterization of the 20 isolates, 16 belonged to Aspergillus flavus, 2 to Aspergillus parvisclerotigenus and 2 to Aspergillus novoparasiticus. This is the first time that this latter species is isolated from food. Although most of these isolates were toxigenic on synthetic media, no AFB1 contamination was observed in these cassava samples. In order to determine the action of cassava on AFB1 synthesis, a highly toxigenic strain of A. flavus, was inoculated onto fresh cassava and despite a rapid development, no AFB1 was produced. The anti-aflatoxin property was observed with cassava from different geographical origins and on other aflatoxigenic strains of the section Flavi, but it was lost after heating, sun drying and freezing. Our data suggest that fresh cassava is safe regarding AFB1 contamination, however, processing may alter its ability to block toxinogenesis leading to secondary contamination.
    Food Microbiology 04/2014; 38:151-9. · 3.41 Impact Factor
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    ABSTRACT: The aim of this study was to analyse gene expression along the small intestine (duodenum, jejunum, ileum) and in the ileal Peyer's patches in four young pigs with no clinical signs of disease by transcriptome sequencing. Multidimensional scaling evidenced that samples clustered by tissue type rather than by individual, thus prefiguring a relevant scenario to draw tissue-specific gene expression profiles. Accordingly, 1,349 genes were found differentially expressed between duodenum and jejunum, and up to 3,455 genes between duodenum and ileum. Additionally, a considerable number of differentially expressed genes were found by comparing duodenum (7,027 genes), jejunum (6,122 genes), and ileum (6,991 genes) with ileal Peyer's patches tissue. Functional analyses revealed that most of the significant differentially expressed genes along small intestinal tissues were involved in the regulation of general biological processes such as cell development, signalling, growth and proliferation, death and survival or cell function and maintenance. These results suggest that the intrinsic large turnover of intestinal tissues would have local specificities at duodenum, ileum and jejunum. In addition, in concordance with their biological function, enteric innate immune pathways were overrepresented in ileal Peyer's patches. The reported data provide an expression map of the cell pathway variation in the different small intestinal tissues. Furthermore, expression levels measured in healthy individuals could help to understand changes in gene expression that occur in dysbiosis or pathological states.
    PLoS ONE 01/2014; 9(2):e88515. · 3.73 Impact Factor
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    ABSTRACT: Inflammation derived from pathogen infection involves the activation of toll-like receptor (TLR) signaling. Despite the established immunomodulatory activities of probiotics, studies relating the ability of such bacteria to inhibit the TLR signaling pathways are limited or controversial. In a previous study we showed that Lactobacillus amylovorus DSM 16698T, a novel lactobacillus isolated from unweaned pigs, protects the intestinal cells from enterotoxigenic Escherichia coli (ETEC) K88 infection through cytokine regulation. In the present study we investigated whether the ability of L. amylovorus to counteract the inflammatory status triggered by ETEC in intestine is elicited through inhibition of the TLR4 signaling pathway. We used the human intestinal Caco-2/TC7 cells and intestinal explants isolated from 5 week-old crossbreed Pietrain/Duroc/Large-White piglets, treated with ETEC, L. amylovorus or L. amylovorus cell free supernatant, either alone or simultaneously with ETEC. Western blot analysis showed that L. amylovorus and its cell free supernatant suppress the activation of the different steps of TLR4 signaling in Caco-2/TC7 cells and pig explants, by inhibiting the ETEC induced increase in the level of TLR4 and MyD88, the phosphorylation of the IKKα, IKKβ, IκBα and NF-κB subunit p65, as well as the over-production of inflammatory cytokines IL-8 and IL-1β. The immunofluorescence analysis confirms the lack of phospho-p65 translocation into the nucleus. These anti-inflammatory effects are achieved through modulation of the negative regulators Tollip and IRAK-M. We also found that L. amylovorus blocks the up-regulation of the extracellular heat shock protein (Hsp)72 and Hsp90, that are critical for TLR4 function. By using anti-TLR2 antibody, we demonstrate that TLR2 is required for the suppression of TLR4 signaling activation. These results may contribute to develop therapeutic interventions using L. amylovorus in intestinal disorders of piglets and humans.
    PLoS ONE 01/2014; 9(4):e94891. · 3.73 Impact Factor
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    Philippe Pinton, Isabelle P Oswald
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    ABSTRACT: The natural food contaminants, mycotoxins, are regarded as an important risk factor for human and animal health, as up to 25% of the world's crop production may be contaminated. The Fusarium genus produces large quantities of fusariotoxins, among which the trichothecenes are considered as a ubiquitous problem worldwide. The gastrointestinal tract is the first physiological barrier against food contaminants, as well as the first target for these toxicants. An increasing number of studies suggest that intestinal epithelial cells are targets for deoxynivalenol (DON) and other Type B trichothecenes (TCTB). In humans, various adverse digestive symptoms are observed on acute exposure, and in animals, these toxins induce pathological lesions, including necrosis of the intestinal epithelium. They affect the integrity of the intestinal epithelium through alterations in cell morphology and differentiation and in the barrier function. Moreover, DON and TCTB modulate the activity of intestinal epithelium in its role in immune responsiveness. TCTB affect cytokine production by intestinal or immune cells and are supposed to interfere with the cross-talk between epithelial cells and other intestinal immune cells. This review summarizes our current knowledge of the effects of DON and other TCTB on the intestine.
    Toxins. 01/2014; 6(5):1615-1643.
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    ABSTRACT: Immune traits (ITs) are potentially relevant criteria to characterize an individual's immune response. Our aim was to investigate whether the peripheral blood transcriptome can provide a significant and comprehensive view of IT variations in pig. Sixty-day-old Large White pigs classified as extreme for in vitro production of IL2, IL10, IFNgamma and TNFalpha, phagocytosis activity, in vivo CD4-/CD8+ or TCRgammadelta + cell counts, and anti-Mycoplasma antibody levels were chosen to perform a blood transcriptome analysis with a porcine generic array enriched with immunity-related genes. Differentially expressed (DE) genes for in vitro production of IL2 and IL10, phagocytosis activity and CD4-/CD8+ cell counts were identified. Gene set enrichment analysis revealed a significant over-representation of immune response functions. To validate the microarray-based results, a subset of DE genes was confirmed by RT-qPCR. An independent set of 74 animals was used to validate the covariation between gene expression levels and ITs. Five potential gene biomarkers were found for prediction of IL2 (RALGDS), phagocytosis (ALOX12) or CD4-/CD8+ cell count (GNLY, KLRG1 and CX3CR1). On average, these biomarkers performed with a sensitivity of 79% and a specificity of 86%. Our results confirmed that gene expression profiling in blood represents a relevant molecular phenotype to refine ITs in pig and to identify potential biomarkers that can provide new insights into immune response analysis.
    BMC Genomics 12/2013; 14(1):894. · 4.40 Impact Factor
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    ABSTRACT: Patulin is a mycotoxin produced by fungal genera such as Aspergillus, Penicillium and Byssochlamys. It induces neurological, gastrointestinal and immunological effects, which is why patulin belongs to a short list of mycotoxins whose level in food is regulated in many countries around the world. Recently, a cluster gathering 15 genes involved in the biosynthesis of patulin has been identified in Aspergillus clavatus, but so far, only 4 genes encoding 6-methylsalicylic acid synthase, m-cresol hydroxylase, m-hydroxybenzyl alcohol hydroxylase and isoepoxydon dehydrogenase have been characterized. Previous studies have shown the involvement of a decarboxylase in the transformation of 6-methylsalicylic acid, the first stable patulin precursor, into m-cresol. In this study a putative decarboxylase gene, PatG, was identified in the genome sequence of A. clavatus. This gene is located near two P450 cytochrome genes PatH and PatI responsible respectively for the hydroxylation of m-cresol and m-hydroxybenzyl alcohol. This decarboxylase encoded by PatG (ACLA_093620) consists of 325 amino acids. The search for putative conserved domain revealed that the gene product belongs to the AminoCarboxyMuconate Semialdehyde Decarboxylase (ACMSD) related protein family. This family includes decarboxylases such as the γ-resorcylate decarboxylase or o-pyrocatechuate decarboxylase. The substrates of these enzymes display strong structural similarities with 6-methylsalicylic acid. PatG was strongly expressed during patulin production whereas it was very weakly expressed in non-patulin permissive conditions. The coding sequence was used to enable heterologous expression of functional enzymes in Saccharomyces cerevisiae. The presence of decarboxylase was confirmed by Western blot. The bioconversion assays showed that PATG catalyzed the decarboxylation of 6-methylsalicylic acid into m-cresol. These results confirm for the first time that 6-methylsalicylic acid is the substrate for PATG, the 6-methylsalicylic acid decarboxylase. With this study, the four genes involved in the four first steps of patulin biosynthesis pathway (acetate→gentisyl alcohol) are now identified.
    International journal of food microbiology 11/2013; 171C:77-83. · 3.01 Impact Factor
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    ABSTRACT: a b s t r a c t Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin produced by Aspergilli of the section Flavi that may contaminate food, in the field or during storage. Cassava represents an important staple food in sub-Saharan Africa. The analysis of aflatoxigenic fungi in 36 cassava samples obtained from producers in Benin indicated that 40% were contaminated by Aspergilli of the section Flavi. Upon morphological and molecular characterization of the 20 isolates, 16 belonged to Aspergillus flavus, 2 to Aspergillus parvi-sclerotigenus and 2 to Aspergillus novoparasiticus. This is the first time that this latter species is isolated from food. Although most of these isolates were toxigenic on synthetic media, no AFB1 contamination was observed in these cassava samples. In order to determine the action of cassava on AFB1 synthesis, a highly toxigenic strain of A. flavus, was inoculated onto fresh cassava and despite a rapid development, no AFB1 was produced. The anti-aflatoxin property was observed with cassava from different geographical origins and on other aflatoxigenic strains of the section Flavi, but it was lost after heating, sun drying and freezing. Our data suggest that fresh cassava is safe regarding AFB1 contamination, however, processing may alter its ability to block toxinogenesis leading to secondary contamination.
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    ABSTRACT: Characterization of fungal secondary metabolomes has become a challenge due to the industrial applications of many of these molecules, and also due to the emergence of fungal threats to public health and natural ecosystems. Given that, the aim of the present study was to develop an untargeted method to analyze fungal secondary metabolomes by combining high accuracy mass spectrometry and double isotopic labeling of fungal metabolomes. The strain NRRL 35693 of Aspergillus fumigatus, an important fungal pathogen, was grown on three wheat grain substrates: (1) naturally enriched grains (99% 12C), (2) grains enriched 96.8% with 13C, (3) grains enriched with 53.4% with 13C and 96.8% with 15N. Twenty one secondary metabolites were unambiguously identified by HPLC-HRMS analysis. AntiBase 2012 was used to confirm the identity of these metabolites. Additionally, based on MSn experiments, it was possible to identify for the first time the formula and the structure of fumigaclavine D, a new member of the fumigaclavines family. Post biosynthesis degradation of tryptoquivaline F by methanol was also identified during HPLC-HRMS analysis by the detection of a carbon atom of non-fungal origin. The interest of this method lies not only on the unambiguous determination of the exact chemical formulas of fungal secondary metabolites, but also on the easy discrimination of non-fungal products. Validation of the method was thus successfully achieved in this study and it can now be applied to other fungal metabolomes, offering great possibilities for the discovery of new drugs or toxins.
    Analytical Chemistry 07/2013; · 5.70 Impact Factor
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    ABSTRACT: Aflatoxin B1 is a carcinogenic mycotoxin that may contaminate spices. Indeed, these ingredients are usually produced in areas where the climatic conditions are favorable to growth of Aspergillus of the Flavi section and the synthesis of mycotoxins. This study aimed to characterize the fungal flora of 80 paprika, cumin and pepper marketed in Morocco with a special focus on Aspergillus section Flavi isolates. After identification to the species level, their toxigenic potential was determined and the related contamination of spice samples was also investigated.We observed a widespread contamination of spices with Aspergilli section Flavi. Among them, 57% were found to be toxigenic. The most frequent chemotypes correspond to isolates able to produce both aflatoxin B and cyclopiazonic acid followed by B aflatoxins only producers. These chemotypes represented 25% and 16% of the isolates respectively. Eight percent of toxigenic isolates (3/36), that produced sclerotia in culture, were found able to synthesis aflatoxin G1. A molecular identification revealed that these isolates belonged to Aspergillus minisclerotigenes species. That is the first report of the presence of such species in spices.The analysis of the contamination of spice samples with AFB1 revealed that paprika is frequently contaminated since 95% were contaminated with that mycotoxin and 40% of samples exceeded European regulation for that contaminant. Therefore, this spice that is widely used for cooking in Morocco, may represent a direct source of exposure to that carcinogenic compound.
    Food Control. 07/2013; 32(1):143–148.
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    ABSTRACT: Mycotoxin mitigation is of major interest as ingestion of mycotoxins results in poor animal health, decreased productivity as well as substantial economic losses. A feed additive (FA) consisting of a combination of bacteria (Eubacterium BBSH797) and enzyme (fumonisin esterase FumD) was tested in pigs for its ability to neutralize the effects of mono- and co-contaminated diets with deoxynivalenol (DON) and fumonisins (FB) on hematology, biochemistry, tissue morphology and immune response. Forty-eight animals, allocated into eight groups, received one of eight diets for 35 days: a control diet, a diet contaminated with either DON (3 mg/kg) or FB (6 mg/kg), or both toxins, and the same four diets with FA. Inclusion of FA restored the circulating number of neutrophils of piglets fed the FB and DON+FB diets. Similarly, FA counteracted the minor changes observed on plasma concentrations of albumin and creatinine. In lung, the lesions induced by the ingestion of FB in mono- and co-contaminated diets were no longer observed after addition of FA in these diets. Lesions recorded in the liver of pigs fed either of the contaminated diets with FA were partly reduced, and the increased hepatocyte proliferation was totally neutralized when FA was present in the co-contaminated diet. After 35 days of exposure, the development of the vaccinal response was significantly improved in animals fed diets supplemented with FA, as shown by results of lymphocyte proliferation, cytokine expression in spleen, and the production of specific Ig. Similarly, in jejunum of animals fed diets with FA, occurrence of lesions and upregulation of pro-inflammatory cytokines were much less obvious. The ameliorative effects provided by FA suggest that this approach would be suitable in the control of DON and FB that commonly co-occur in feed.
    Journal of Agricultural and Food Chemistry 06/2013; · 2.91 Impact Factor
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    ABSTRACT: Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxins mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON≈DON<NIV<FX. Binary or ternary mixtures also showed a dose-dependent effect. At low concentrations (cytotoxic effect between 10 and 30-40 %), mycotoxin combinations were synergistic; however DON-NIV-FX mixture showed antagonism. At higher concentrations (cytotoxic effect around 50 %), the combinations had an additive or nearly additive effect. These results indicate that the simultaneous presence of low doses of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. Considering the frequent co-occurrence of trichothecenes in the diet and the concentrations of toxins to which consumers are exposed, this synergy should be taken into account.
    Toxicology and Applied Pharmacology 06/2013; · 3.98 Impact Factor
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    ABSTRACT: Enniatins, the most prevalent emerging mycotoxins, represent an emerging food safety issue, because of their common co-occurrence with other fusariotoxins such as trichothecenes co-produced by Fusarium spp on field grains and because of their extensive prevalence in grains. In this study, the intestinal toxicity of enniatin B1 (ENN) alone and mixed with the most toxic trichothecene T-2 toxin (T2) was characterized by using two biological models from pig, the most sensitive species: the intestinal cell line IPEC1 (in vitro exposure) and jejunal explants (ex vivo exposure). Dose-dependent decreases in cell proliferation in IPEC1 and in the histopathological scores of explants were observed for ENN at μM-levels and for T2 at nM-levels, with IC50 values for ENN of 15.8 and 29.7 μM, and for T2 of 9.3 and 15.1 nM in vitro and ex vivo, respectively. Interaction analysis by probabilistic and by determinist approaches showed a less than additive effect both in vitro and ex vivo, at IC50 values, with increasing antagonism with decreasing concentrations of toxins. The results obtained by the determinist median-effect dose analysis and by the nonlinear regression analysis were concordant. All the median-effect doses estimated for IPEC cells were included in the IC50 confidence intervals of the nonlinear regression fitting. Given the occurrence of enniatins, potential synergy following the co-occurrence of enniatins and the major fusariotoxins, especially trichothecene B deoxynivalenol should be investigated.
    Archives of Toxicology 05/2013; · 5.22 Impact Factor
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    ABSTRACT: SCOPE: Deoxynivalenol (DON), a mycotoxin produced by Fusarium spp., is toxic to many animal species, with pigs being the most sensitive species to the toxin. The aim of the present study was to determine the effects of DON on pig polymorphonuclear cells (PMNs), the first line of defense against infection. METHODS AND RESULTS: PMNs isolated from pig blood samples were stimulated with LPS to mimic infection. DON (0.5-10 μM) altered three main functions of pig PMNs: LPS-induced secretion of IL-8, chemotaxis, and phagocytosis capability. This alteration of PMN properties was due to apoptotis induced by DON exposure. Using Western blot and flow cytometry, we demonstrated that this process included the permeabilization of the mitochondrial outer membrane and the activation of caspase-3. The effect of DON was mediated by the phosphorylation of the p38 mitogen-activated protein kinase within the first 30 min of exposure. CONCLUSION: This study provides evidence that low concentrations of DON can alter the immune functions of porcine PMNs and suggests the involvement of p38 mitogen-activated protein kinase in the signal transduction pathway. These immunosuppressive effects of DON may have implications for humans and/or animals when eating contaminated food/feed.
    Molecular Nutrition & Food Research 02/2013; · 4.31 Impact Factor
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    ABSTRACT: Trichothecenes induce changes in the intestinal barrier function through decreased expression of cell junction proteins and apoptosis of enterocytes. The mitogen activated protein kinases (MAPK) play an important role in the signaling pathways of cell turnover and differentiation. Using ex vivo and in vivo approaches, the purpose of this study was to investigate the ability of low doses of DON to induce histological changes in the intestine and to activate the MAPK ERK 1/2, p38 and JNK. Twelve weaning piglets received during four weeks a control diet or a DON-contaminated diet (2.3 mg DON/kg feed). Six weaning piglets were used to prepare jejunal explants (ex vivo model). Explants were exposed during 4 h to vehicle, 5 or 10 μM DON. Intestinal changes were graded using a histological score. Pigs fed a DON-diet and explants exposed to DON showed a significant decrease in the jejunal score. In both models, the toxin significantly enhanced phosphorylation of ERK 1/2 and p38, whereas the increased phosphorylation of JNK was non significant. Taken together these results indicate that in vivo or ex vivo exposure of intestinal tissue to DON lead to similar intestinal lesions and activation of MAPK. These effects could impair the homeostasis of intestinal tissue in the aspects of barrier function and immune protection. The similarity of the in vivo and ex vivo results provides also strong evidence that the jejunal explant model is a good alternative for toxicological studies in intestinal tissue.
    Toxicon 02/2013; 66C:31-36. · 2.92 Impact Factor
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    ABSTRACT: Deoxynivalenol (DON) is a mycotoxin produced by Fusarium species which is commonly found in temperate regions worldwide as a natural contaminant of cereals. It is of great concern not only in terms of economic losses but also in terms of animal and public health. The digestive tract is the first and main target of this food contaminant and it represents a major site of immune tolerance. A finely tuned cross-talk between the innate and the adaptive immune systems ensures the homeostatic equilibrium between the mucosal immune system and commensal microorganisms. The aim of this study was to analyze the impact of DON on the intestinal immune response. Non-transformed intestinal porcine epithelial cells IPEC-1 and porcine jejunal explants were used to investigate the effect of DON on the intestinal immune response and the modulation of naive T cells differentiation. Transcriptomic proteomic and flow cytometry analysis were performed. DON induced a pro-inflammatory response with a significant increase of expression of mRNA encoding for IL-8, IL-1α and IL-1β, TNF-α in all used models. Additionally, DON significantly induced the expression of genes involved in the differentiation of Th17 cells (STAT3, IL-17A, IL-6, IL-1β) at the expenses of the pathway of regulatory T cells (Treg) (FoxP3, RALDH1). DON also induced genes related to the pathogenic Th17 cells subset such as IL-23A, IL-22 and IL-21 and not genes related to the regulatory Th17 cells (rTh17) such as TGF-β and IL-10. DON triggered multiple immune modulatory effects which could be associated with an increased susceptibility to intestinal inflammatory diseases.
    PLoS ONE 01/2013; 8(1):e53647. · 3.73 Impact Factor
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    ABSTRACT: The objective of this study was to measure the effects of chronic exposure to fumonisins via the ingestion of feed containing naturally contaminated corn in growing pigs infected or not with Salmonella spp. This exposure to a moderate dietary concentration of fumonisins (11.8 ppm) was sufficient to induce a biological effect in pigs (Sa/So ratio), but no mortality or pathology was observed over 63 days of exposure. No mortality or related clinical signs, even in cases of inoculation with Salmonella (5 × 104 CFU), were observed either. Fumonisins, at these concentrations, did not affect the ability of lymphocytes to proliferate in the presence of mitogens, but after seven days post-inoculation they led to inhibition of the ability of specific Salmonella lymphocytes to proliferate following exposure to a specific Salmonella antigen. However, the ingestion of fumonisins had no impact on Salmonella translocation or seroconversion in inoculated pigs. The inoculation of Salmonella did not affect faecal microbiota profiles, but exposure to moderate concentrations of fumonisins transiently affected the digestive microbiota balance. In cases of co-infection with fumonisins and Salmonella, the microbiota profiles were rapidly and clearly modified as early as 48 h post-Salmonella inoculation. Therefore under these experimental conditions, exposure to an average concentration of fumonisins in naturally contaminated feed had no effect on pig health but did affect the digestive microbiota balance, with Salmonella exposure amplifying this phenomenon.
    Toxins 01/2013; 5(4):841-64. · 2.13 Impact Factor
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    ABSTRACT: The aim of this review is to give a comprehensive overview of the current knowledge on plant metabolites of mycotoxins, also called masked mycotoxins. Mycotoxins are secondary fungal metabolites, toxic to human and animals. Toxigenic fungi often grow on edible plants, thus contaminating food and feed. Plants, as living organisms, can alter the chemical structure of mycotoxins as part of their defence against xenobiotics. The extractable conjugated or non-extractable bound mycotoxins formed remain present in the plant tissue but are currently neither routinely screened for in food nor regulated by legislation, thus they may be considered masked. Fusarium mycotoxins (deoxynivalenol, zearalenone, fumonisins, nivalenol, fusarenon-X, T-2 toxin, HT-2 toxin, fusaric acid) are prone to metabolisation or binding by plants, but transformation of other mycotoxins by plants (ochratoxin A, patulin, destruxins) has also been described. Toxicological data are scarce, but several studies highlight the potential threat to consumer safety from these substances. In particular, the possible hydrolysis of masked mycotoxins back to their toxic parents during mammalian digestion raises concerns. Dedicated chapters of this article address plant metabolism as well as the occurrence of masked mycotoxins in food, analytical aspects for their determination, toxicology and their impact on stakeholders.
    Molecular Nutrition & Food Research 10/2012; · 4.31 Impact Factor
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    ABSTRACT: Mycotoxins are secondary metabolites produced by fungi especially those belonging to the genus Aspergillus, Penicillum and Fusarium. Mycotoxin contamination can occur in all agricultural commodities in the field and/or during storage, if conditions are favourable to fungal growth. Regarding animal feed, five mycotoxins (aflatoxins, deoxynivalenol, zearalenone, fumonisins and ochratoxin A) are covered by EU legislation (regulation or recommendation). Transgressions of these limits are rarely observed in official monitoring programs. However, low level contamination by Fusarium toxins is very common (e.g., deoxynivalenol (DON) is typically found in more than 50% of the samples) and co-contamination is frequently observed. Multi-mycotoxin studies reported 75%-100% of the samples to contain more than one mycotoxin which could impact animal health at already low doses. Co-occurrence of mycotoxins is likely to arise for at least three different reasons (i) most fungi are able to simultaneously produce a number of mycotoxins, (ii) commodities can be contaminated by several fungi, and (iii) completed feed is made from various commodities. In the present paper, we reviewed the data published since 2004 concerning the contamination of animal feed with single or combinations of mycotoxins and highlighted the occurrence of these co-contaminations.
    Toxins 10/2012; 4(10):788-809. · 2.13 Impact Factor
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    ABSTRACT: The intestinal epithelium is the first barrier against food contaminants and is highly sensitive to mycotoxins, especially de oxynivalenol (DON). Consumption of DON-contaminated food is associated with outbreaks of gastroenteritis. In cereals and their byproducts, DON is present together with two acetylated derivatives, 3-ADON and 15-ADON. The aim of this study was to compare the intestinal toxicity of DON and A-DONs, using noncytotoxic doses. The toxicity was assessed using in vitro (intestinal epithelial cell line), ex vivo (intestinal explants), and in vivo (animals exposed to mycotoxin-contaminated diets) models. The effects were studied on cell proliferation, barrier function, and intestinal structure. The mechanism of toxicity was investigated by measuring the expression of the tight junction proteins and of phosphorylated ERK1/2, p38, and JNK, which are effectors of signaling pathway involved in cellular programs including embryogenesis, proliferation, differentiation, and apoptosis. On proliferating cells, 3-ADON was less toxic than DON, which was less toxic than 15-ADON. On differentiated cells, 15-ADON impaired the barrier function, whereas DON and 3-ADON did not have a significant effect. Similarly, ex vivo and in vivo, 15-ADON caused more histological lesions than DON or 3-ADON. At the molecular level, the 15-ADON activated the mitogen-activated protein kinases (MAPK) ERK1/2, p38, and JNK in the intestinal cell line, explants, and the jejunum from exposed animals at lower dose than DON and 3-ADON. Our results show that the higher toxicity of 15-DON is due to its ability to activate the MAPK. Given that cereal-based foods are contaminated with DON and acetylated-DON, the higher toxicity of 15-ADON should be taken into account.
    Toxicological Sciences 08/2012; 130(1):180-90. · 4.33 Impact Factor

Publication Stats

4k Citations
391.33 Total Impact Points


  • 2013–2014
    • University of Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2009–2013
    • École Nationale Vétérinaire de Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2012
    • Biomin Research Center
      Herzogenburg, Lower Austria, Austria
  • 1997–2012
    • French National Institute for Agricultural Research
      • • Génétique Animale et Biologie Intégrative (GABI)
      • • Laboratoire de Génétique Cellulaire
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Universidade Estadual de Londrina
      Londrina, Paraná, Brazil
  • 2002–2010
    • Institutul National de Cercetare-Dezvoltare pentru Biologie si Nutritie Animala
      Baloteşu, Ilfov County, Romania
  • 2007
    • Universidad Nacional Autónoma de México
      • School of Higher Studies (F.E.S.) Cuautitlán
      Mexico City, The Federal District, Mexico
  • 2001–2006
    • L’Institut national de la recherche agronomique (Toulouse)
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2005
    • University of Saskatchewan
      • Western College of Veterinary Medicine
      Saskatoon, Saskatchewan, Canada
    • University of Liège
      • Faculté de Médecine Vétérinaire
      Liège, WAL, Belgium
    • Carleton University
      Ottawa, Ontario, Canada
  • 2004
    • INRAN - Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione
      Roma, Latium, Italy
  • 2003
    • University of Barcelona
      Barcino, Catalonia, Spain
  • 1991–2000
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 1992–1998
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Parasitic Diseases (LPD)
      Maryland, United States
    • National Institutes of Health
      • Section on Molecular and Cell Biology
      Bethesda, MD, United States
  • 1994
    • The University of Tokyo
      Edo, Tōkyō, Japan