Skip to main content Accessibility help
×
Home

Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets

  • Ana-Paula F. L. Bracarense (a1), Joelma Lucioli (a1), Bertrand Grenier (a2) (a3), Graziela Drociunas Pacheco (a1) (a2), Wulf-Dieter Moll (a3), Gerd Schatzmayr (a3) and Isabelle P. Oswald (a2)...

Abstract

Deoxynivalenol (DON) and fumonisins (FB) are mycotoxins produced by Fusarium species, which naturally co-occur in animal diets. The gastrointestinal tract represents the first barrier met by exogenous food/feed compounds. The purpose of the present study was to investigate the effects of DON and FB, alone and in combination, on some intestinal parameters, including morphology, histology, expression of cytokines and junction proteins. A total of twenty-four 5-week-old piglets were randomly assigned to four different groups, receiving separate diets for 5 weeks: a control diet; a diet contaminated with either DON (3 mg/kg) or FB (6 mg/kg); or both toxins. Chronic ingestion of these contaminated diets induced morphological and histological changes, as shown by the atrophy and fusion of villi, the decreased villi height and cell proliferation in the jejunum, and by the reduced number of goblet cells and lymphocytes. At the end of the experiment, the expression levels of several cytokines were measured by RT-PCR and some of them (TNF-α, IL-1β, IFN-γ, IL-6 and IL-10) were significantly up-regulated in the ileum or the jejunum. In addition, the ingestion of contaminated diets reduced the expression of the adherent junction protein E-cadherin and the tight junction protein occludin in the intestine. When animals were fed with a co-contaminated diet (DON+FB), several types of interactions were observed depending on the parameters and segments assessed: synergistic (immune cells); additive (cytokines and junction protein expression); less than additive (histological lesions and cytokine expression); antagonistic (immune cells and cytokine expression). Taken together, the present data provide strong evidence that chronic ingestion of low doses of mycotoxins alters the intestine, and thus may predispose animals to infections by enteric pathogens.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets
      Available formats
      ×

Copyright

Corresponding author

*Corresponding author: Dr I. P. Oswald, email isabelle.oswald@toulouse.inra.fr

References

Hide All
1 Shephard, GS (2008) Determination of mycotoxins in human foods. Chem Soc Reviews 37, 24682477.
2 Oswald, IP & Comera, C (1998) Immunotoxicity of mycotoxins. Rev Med Vet 149, 585590.
3 Binder, EM, Tan, LM, Chin, LJ, et al. (2007) Worldwide occurrence of mycotoxins in commodities, feeds and feed ingredients. Anim Feed Sci Technol 137, 265282.
4 Schothorst, RC & van Egmond, HP (2004) Report from SCOOP task 3.2.10 ‘collection of occurrence data of Fusarium toxins in food and assessment of dietary intake by the population of EU member states’ – Subtask: trichothecenes. Toxicol Lett 153, 133143.
5 Smith, TK, McMillan, EG & Castillo, JB (1997) Effect of feeding blends of Fusarium mycotoxin-contaminated grains containing deoxynivalenol and fusaric acid on growth and feed consumption of immature swine. J Anim Sci 75, 21842191.
6 Grenier, B & Oswald, IP (2011) Mycotoxin co-contamination of foods and feeds: meta-analysis of publications describing toxicological interactions. World Mycotoxin J 4, 285313.
7 Bouhet, S & Oswald, IP (2005) The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response. Vet Immunol Immunopathol 108, 199209.
8 Maresca, M & Fantini, J (2010) Some food-associated mycotoxins as potential risk factors in humans predisposed to chronic intestinal inflammatory diseases. Toxicon 56, 282294.
9 Voss, KA, Smith, GW & Haschek, WM (2007) Fumonisins: toxicokinetics, mechanism of action and toxicity. Anim Feed Sci Technol 137, 299325.
10 Halloy, DJ, Gustin, PG, Bouhet, S, et al. (2005) Oral exposure to culture material extract containing fumonisins predisposes swine to the development of pneumonitis caused by Pasteurella multocida. Toxicology 213, 3444.
11 Wang, H, Wei, H, Ma, J, et al. (2000) The fumonisin B1 content in corn from North China, a high-risk area of esophageal cancer. J Environ Pathol Toxicol Oncol 19, 139141.
12 Goope, NV, He, Q & Sharma, RP (2003) Fumonisin B1-induced apoptosis is associated with delayed inhibition of protein kinase C, nuclear factor-kappaB and tumor necrosis factor alpha in LLC-PK1 cells. Chem-Biol Interact 146, 131145.
13 Schmelz, EM, Dombrink-Kurtzman, MA, Roberts, PC, et al. (1998) Induction of apoptosis by fumonisin B1 in HT29 cells is mediated by the accumulation of endogenous free sphingoid bases. Toxicol Appl Pharmacol 148, 252260.
14 Bouhet, S, Le Dorze, E, Pérès, SY, et al. (2006) Mycotoxin fumonisin B1 selectively down-regulates the basal IL-8 expression in pig intestine: in vivo and in vitro studies. Food Chem Toxicol 44, 17681773.
15 Taranu, I, Marin, DE, Bouhet, S, et al. (2005) Mycotoxin fumonisin B1 alters the cytokine profile and decreases the vaccinal antibody titer in pigs. Toxicol Sci 84, 301307.
16 Marin, DE, Taranu, I, Pascale, F, et al. (2006) Sex-related differences in the immune response of weanling piglets exposed to low doses of fumonisin extract. Br J Nut 95, 11851192.
17 Pestka, JJ & Smolinski, AT (2005) Deoxynivalenol: toxicology and potential effects on humans. J Toxicol Environ Health B Crit Rev 8, 3969.
18 Pinton, P, Accensi, F, Beauchamp, E, et al. (2008) Ingestion of deoxynivalenol (DON) contaminated feed alters the pig vaccinal immune responses. Toxicol Lett 177, 215222.
19 Accensi, F, Pinton, P, Callu, P, et al. (2006) Ingestion of low doses of deoxynivalenol does not affect hematological, biochemical, or immune responses of piglets. J Anim Sci 84, 19351942.
20 Pestka, JJ, Zhou, HR, Moon, Y, et al. (2004) Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicol Lett 53, 6173.
21 Maresca, M, Yahi, N, Younès-Sakr, L, et al. (2008) Both direct and indirect effects account for the proinflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium:stimulation of interleukin-8 secretion, potentiation of interleukin-1beta effect and increase in the transepithelial passage of commensal bacteria. Toxicol Appl Pharmacol 228, 8492.
22 Pinton, P, Nougayrede, JP, Del Rio, JC, et al. (2009) The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression. Toxicol Appl Pharmacol 237, 4148.
23 Van De Walle, J, Sergent, T, Piront, N, et al. (2010) Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis. Toxicol Appl Pharmacol 245, 291298.
24 Grenier, B, Loureiro-Bracarense, AP, Lucioli, J, et al. (2011) Individual and combined effects of subclinical doses of deoxynivalenol and fumonisins in piglets. Mol Nutr Food Res 55, 761771.
25 Kolf-Clauw, M, Castellote, J, Joly, B, et al. (2009) Development of a pig jejunal explant culture for studying the gastrointestinal toxicity of the mycotoxin deoxynivalenol: Histopathological analysis. Toxicol in vitro 23, 15801584.
26 Pinton, P, Braicu, C, Nougayrede, JP, et al. (2010) Deoxynivalenol impairs porcine intestinal barrier function and decreases the protein expression of claudin-4 through a mitogen activated protein kinase dependent mechanism. J Nut 140, 19561962.
27 Oswald, IP, Dozois, CM, Barlagne, R, et al. (2001) Cytokine mRNA expression in pigs infected with Schistosoma japonicum. Parasitology 122, 299307.
28 Devriendt, B, Gallois, M, Verdonck, F, et al. (2009) The food contaminant fumonisin B-1 reduces the maturation of porcine CD11R1(+) intestinal antigen presenting cells and antigen-specific immune responses, leading to a prolonged intestinal ETEC infection. Vet Res 40, 40.
29 Kubena, LF, Edrington, TS, Harvey, RB, et al. (1997) Individual and combined effects of fumonisin B1 present in Fusarium moniliforme culture material and T-2 toxin or deoxynivalenol in broiler chicks. Poultry Sci 76, 12391247.
30 Bouhet, S & Oswald, IP (2007) The intestine as a possible target for fumonisin toxicity. Mol Nutr Food Res 51, 925931.
31 Wang, E, Norred, WP, Bacon, CW, et al. (1991) Inhibition of shingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. J Biol Chem 266, 1448614490.
32 Awad, WA, Böhm, J, Razzazi-Fazeli, E, et al. (2006) Effects of feeding deoxynivalenol contaminated wheat on growth performance, organ weights and histological parameters of the intestine of broiler chickens. J Anim Physiol Animal Nutr 90, 3237.
33 McGuckin, MA, Linden, SK, Sutton, P, et al. (2011) Mucin dynamics and enteric pathogens. Nat Rev/Microbiol 9, 265278.
34 Piva, A, Casadei, G, Pagliuca, G, et al. (2005) Activated carbon does not prevent the toxicity of culture material containing fumonisin B 1 when fed to weanling piglets. J Anim Sci 83, 19391947.
35 Brown, T, Rottinghaus, G & Williams, M (1992) Fumonisin mycotoxicosis in broilers: performances and pathology. Avian Dis 36, 450454.
36 Theumer, MG, Lopez, AG, Masih, DT, et al. (2002) Immunobiological effects of fumonisin B1 in experimental subchronic mycotoxicoses in rats. Clin Diagn Lab Immunol 9, 149155.
37 Bouhet, S, Hourcade, E, Loiseau, N, et al. (2004) The mycotoxin fumonisin B1 alters the proliferation and the barrier function of porcine intestinal epithelial cells. Toxicol Sci 77, 165171.
38 Chen, F, Ma, Y, Xue, C, et al. (2008) The combination of deoxynivalenol and zearalenone at permitted feed concentrations causes serious physiological effects in young pigs. J Vet Sci 9, 3944.
39 Shifrin, VI & Anderson, P (1999) Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis. J Biol Chem 274, 1398513992.
40 Stadnyk, AW (2002) Intestinal epithelial cells as a source of inflammatory cytokines and chemokines. Can J Gastroenterol 16, 241246.
41 Azcona-Olivera, JI, Ouyang, Y, Murtha, J, et al. (1995) Induction of cytokine mRNAs in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): relationship to toxin distribution and protein synthesis inhibition. Toxicol Appl Pharmacol 133, 109120.
42 Dugyala, RR, Sharma, RP, Tsunoda, M, et al. (1998) Tumor necrosis factor-α as a contributor in fumonisin B1. J Pharmacol Experim Therap 285, 317324.
43 Bhandari, N, Brown, CC & Sharma, RP (2002) Fumonisin B1-induced localized activation of cytokine network in mouse liver. Food Chem Toxicol 40, 14831491.
44 Van Cruchten, S & Van den Broeck, W (2002) Morphological and biochemical aspects of apoptosis, oncosis and necrosis. Anat Histol Embryol 31, 214223.
45 Ye, D, Ma, I & Ma, TY (2006) Molecular mechanism of tumor necrosis factor-α modulation of intestinal epithelial tight junction barrier. Am J Physiol Gastrointest Liver Physiol 290, 496504.
46 Al-Sadi, R, Ye, D, Dokladny, K, et al. (2008) Mechanism of IL-1beta induced increase in intestinal epithelial tight junction permeability. J Immunol 180, 56535661.
47 Hershberg, RM & Mayer, LF (2000) Antigen processing and presentation by intestinal epithelial cell-polarity and complexity. Immunol Today 21, 123128.
48 Soderholm, JD, Olaison, G, Peterson, KH, et al. (2002) Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease. Gut 50, 307313.
49 Luongo, D, De Luna, R, Russo, R, et al. (2008) Effects of four Fusarium toxins (fumonisin B(1), alpha-zearalenol, nivalenol and deoxynivalenol) on porcine whole-blood cellular proliferation. Toxicon 52, 156162.
50 Speijers, GJ & Speijers, MH (2004) Combined toxic effects of mycotoxins. Toxicol Lett 153, 9198.
51 Pinelli, E, Poux, N, Garren, L, et al. (1999) Activation of mitogen-activated protein kinase by fumonisin B(1) stimulates cPLA(2) phosphorylation, the arachidonic acid cascade and cAMP production. Carcinogenesis 20, 16831688.
52 Dong, C, Davis, RJ & Flavell, RA (2002) MAP kinases in the immune response. Annu Rev Immunol 20, 5572.
53 Pestka, JJ & Zhou, HR (2000) Interleukin-6-deficient mice refractory to IgA dysregulation but not anorexia induction by vomitoxin (deoxynivalenol) ingestion. Food Chem Toxicol 38, 565575.
54 Royaee, AR, Husmann, RJ, Dawson, HD, et al. (2004) Deciphering the involvement of innate immune factors in the development of the host response to PRRSV vaccination. Vet Immunol Immunopathol 102, 199216.
55 Meissonnier, GM, Pinton, P, Laffitte, J, et al. (2008) Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression. Toxicol Appl Pharmacol 231, 142149.
56 Meurens, F, Berri, M, Auray, G, et al. (2009) Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops. Vet Res 40, 5.

Keywords

Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets

  • Ana-Paula F. L. Bracarense (a1), Joelma Lucioli (a1), Bertrand Grenier (a2) (a3), Graziela Drociunas Pacheco (a1) (a2), Wulf-Dieter Moll (a3), Gerd Schatzmayr (a3) and Isabelle P. Oswald (a2)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed