Skip to main content
SpringerLink
Log in

Intestinal toxicity of deoxynivalenol is limited by Lactobacillus rhamnosus RC007 in pig jejunum explants

  • Biologics
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Probiotics have been explored to stimulate gut health in weaned pigs, when they started to consume solid diet where mycotoxins could be present. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus RC007 on the intestinal toxicity of deoxynivalenol (DON) in an ex vivo model. Jejunal explants, obtained from 5-week-old crossbred castrated male piglets, were kept as control, exposed for 3 h to 10 μM DON, incubated for 4 h with 109 CFU/mL L. rhamnosus, or pre-incubated 1 h with 109 L. rhamnosus and exposed to DON. Histological lesions were observed, para- and transcellular intestinal permeability was measured in Ussing chambers. The expression levels of mRNA encoding six inflammatory cytokines (CCL20, IL-10, IL-1β, TNFα, IL-8 and IL-22) were determined by RT-PCR. The expressions of the phosphorylated MAP kinases p42/p44 and p38 were assessed by immunoblotting. Exposure to DON induced histological changes, significantly increased the expression of CCL20, IL-1β, TNFα, IL-8, IL-22 and IL-10, increased the intestinal paracellular permeability and activated MAP kinases. Incubation with L. rhamnosus alone did not have any significant effect. By contrast, the pre-incubation with L. rhamnosus reduced all the effects of DON: the histological alterations, the pro-inflammatory response, the paracellular permeability and the phosphorylation of MAP kinases. Of note, L. rhamnosus did not adsorb DON and only slightly degrade the toxin. In conclusion, L. rhamnosus RC007 is a promising probiotic which, included as feed additive, can decrease the intestinal toxicity of DON.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (Finland)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Akbari P, Braber S, Gremmels H, Koelink PJ, Verheijden KAT, Garssen J, Fink-Gremmels J (2014) Deoxynivalenol: a trigger for intestinal integrity breakdown. FASEB J 28:2414–2429. doi:10.1096/fj.13-238717

    Article  CAS  PubMed  Google Scholar 

  • Alassane-Kpembi I, Kolf-Clauw M, Gauthier T, Abrami R, Abiola FA, Oswald IP, Puel O (2013) New insight into mycotoxin mixtures: the toxicity of low doses of Type B trichothecenes against intestinal epithelial cells is synergistic. Toxicol Appl Pharmacol 272:191–198. doi:10.1016/j.taap.2013.05.023

    Article  CAS  PubMed  Google Scholar 

  • Alassane-Kpembi I, Puel O, Pinton P, Cossalter AM, Chou TC, Oswald IP (2017) Co-exposure to low doses of the food contaminants deoxynivalenol and nivalenol has a synergistic inflammatory effect on intestinal explants. Arch Toxicol 91:2677–2687. doi:10.1007/s00204-016-1902-9

    Article  CAS  PubMed  Google Scholar 

  • Bennett JW, Klich M (2003) Mycotoxins. Clin Microbiol Rev 16:497–516. doi:10.1128/CMR.16.3.497-516.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cano P, Seeboth J, Meurens F, Cognie J, Abrami R, Oswald IP, Guzylack-Piriou L (2013) Deoxynivalenol as a new factor in the persistence of intestinal inflammatory diseases: an emerging hypothesis through possible modulation of Th17-mediated response. PLoS One 8:e53647. doi:10.1371/journal.pone.0053647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang C, Wang K, Zhou SN, Wang XD, Wu JE (2017) Protective effect of Saccharomyces boulardii on deoxynivalenol-induced injury of porcine macrophage via attenuating p38 MAPK signal pathway. Appl Biochem Biotechnol 182:411–427. doi:10.1007/s12010-016-2335-x

    Article  CAS  PubMed  Google Scholar 

  • de Moreno de LeBlanc A, Chaves S, Carmuega E, Weill R, Antoine J, Perdigón G (2008) Effect of long-term continuous consumption of fermented milk containing probiotic bacteria on mucosal immunity and the activity of peritoneal macrophages. Immunobiology 213:97–108. doi:10.1016/j.imbio.2007.07.002

    Article  PubMed  Google Scholar 

  • Dogi C, Maldonado Galdeano C, Perdigón G (2008) Gut immune stimulation by non-pathogenic Gram (+) and Gram (−) bacteria. Comparison with a probiotic strain. Cytokine 41:223–231. doi:10.1016/j.cyto.2007.11.014

    Article  CAS  PubMed  Google Scholar 

  • Dogi C, Weill F, Perdigón G (2010) Immune response of non-pathogenic Gram (+) and Gram (−) bacteria in inductive sites of the intestinal mucosa. Study of the pathway of signaling involved. Immunobiology 215:60–69. doi:10.1016/j.imbio.2009.01.005

    Article  CAS  PubMed  Google Scholar 

  • Dogi C, Garcia G, de Moreno de LeBlanc A, Greco C, Cavaglieri L (2016) Lactobacillus rhamnosus RC007 intended for feed additive: immune-stimulatory properties and ameliorating effects on TNBS-induced colitis. Benef Microbes 6:1–10. doi:10.3920/BM2015.0147

    Google Scholar 

  • Döll S, Dänicke S (2004) In vivo detoxification of Fusarium toxins. Arch Anim Nutr 58:419–441. doi:10.1080/00039420400020066

    Article  PubMed  Google Scholar 

  • EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), Knutsen HK, Alexander J, Barregård L, Bignami M, Bruschweiler B, Ceccatelli S, Cottrill B, Dinovi M, Grasl-Kraupp B, Hogstrand C, Hoogenboom LR, Nebbia CS, Oswald IP, Petersen A, Rose M, Roudot A-C, Schwerdtle T, Vleminckx C, Vollmer G, Wallace H, De Saeger S, Eriksen GS, Farmer P, Fremy JM, Gong YY, Meyer K, Naegeli H, Parent-Massin D, Rietjens I, van Egmond H, Altieri A, Eskola M, Gergelova P, Ramos Bordajandi L, Benkova B, Dorr B, Gkrillas A, Gustavsson N, van Manen M, Edler L (2017) Scientific opinion on the risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed. EFSA J 15:4718. doi:10.2903/j.efsa.2017.4718

    Google Scholar 

  • Ezema C (2013) Probiotics in animal production: a review. J Vet Med Anim Health 5:308–316. doi:10.5897/JVMAH2013.0201

    CAS  Google Scholar 

  • Galdeano CM, de Moreno de LeBlanc A, Vinderola G, Bonet ME, Perdigón G (2007) Proposed model: mechanisms of immunomodulation induced by probiotic bacteria. Clin Vaccine Immunol 14:485–492. doi:10.1128/CVI.00406-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallo A, Giuberti G, Frisvad JC, Bertuzzi T, Nielsen KF (2015) Review on mycotoxin issues in ruminants: occurrence in forages, effects of mycotoxin ingestion on health status and animal performance and practical strategies to counteract their negative effects. Toxins 7:3057–3111. doi:10.3390/toxins7083057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghareeb K, Awad WA, Bohm J, Zebeli Q (2015) Impacts of the feed contaminant deoxynivalenol on the intestine of monogastric animals: poultry and swine. J Appl Toxicol 35:327–337. doi:10.1002/jat.3083

    Article  CAS  PubMed  Google Scholar 

  • Grenier B, Applegate TJ (2013) Modulation of intestinal functions following mycotoxin ingestion: meta-analysis of published experiments in animals. Toxins 5:396–430. doi:10.3390/toxins5020396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grenier B, Bracarense AP, Schwartz HE, Trumel C, Cossalter AM, Schatzmayr G, Kolf-Clauw M, Moll WD, Oswald IP (2012) The low intestinal and hepatic toxicity of hydrolyzed fumonisin B1 correlates with its inability to alter the metabolism of sphingolipids. Biochem Pharmacol 83:1465–1473. doi:10.1016/j.bcp.2012.02.007

    Article  CAS  PubMed  Google Scholar 

  • Groschwitz KR, Hogan SP (2009) Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol 124:3–20. doi:10.1016/j.jaci.2009.05.038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardy H, Harris J, Lyon E, Beal J, Foey AD (2013) Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology. Nutrients 5:1869–1912. doi:10.3390/nu5061869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jijon H, Backer J, Diaz H, Yeung H, Thiel D, McKaigney C et al (2004) DNA from probiotic bacteria modulates murine and human epithelial and immune function. Gastroenterology 126:1358–1373. doi:10.1053/j.gastro.2004.02.003

    Article  CAS  PubMed  Google Scholar 

  • Joshi S, Platanias LC (2012) Mnk kinases in cytokine signaling and regulation of cytokine responses. Biomol Concepts 3:127–139. doi:10.1515/bmc-2011-2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG, Pettersson S, Conway S (2004) Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-g and RelA. Nat Immunol 5:104–112. doi:10.1038/ni1018

    Article  CAS  PubMed  Google Scholar 

  • Kim HG, Lee SY, Kim NR, Ko MY, Lee JM, Yi TH et al (2008) Inhibitory effects of Lactobacillus plantarum lipoteichoic acid (LTA) on Staphylococcus aureus LTA-induced tumor necrosis factor-a production. J Microbiol Biotechnol 18:1191–1196

    CAS  PubMed  Google Scholar 

  • Koul HK, Pal M, Koul S (2013) Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer 4:342–359. doi:10.1177/1947601913507951

    Article  PubMed  PubMed Central  Google Scholar 

  • Lambert D, Padfield PJ, McLaughlin J, Cannell S, O’Neill CA (2007) Ochratoxin A displaces claudins from detergent resistant membrane microdomains. Biochem Biophys Res Commun 358:632–636. doi:10.1016/j.bbrc.2007.04.180

    Article  CAS  PubMed  Google Scholar 

  • Lucioli J, Pinton P, Callu P, Laffitte J, Grosjean F, Kolf-Clauw M, Oswald IP, Bracarense AP (2013) The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: comparison of in vivo and ex vivo models. Toxicon 66:31–36. doi:10.1016/j.toxicon.2013.01.024

    Article  CAS  PubMed  Google Scholar 

  • Meissonnier GM, Laffitte J, Raymond I, Benoit E, Cossalter AM, Pinton P, Bertin G, Oswald IP, Galtier P (2008) Subclinical doses of T-2 toxin impair acquired immune response and liver cytochrome P450 in pigs. Toxicology 247:46–54. doi:10.1016/j.tox.2008.02.003

    Article  CAS  PubMed  Google Scholar 

  • Menningen R, Nolte K, Rijken E, Utech M, Loeffler B, Senninger N, Bruewer M (2009) Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol 296:G1140–G1149. doi:10.1152/ajpgi.90534.2008

    Article  Google Scholar 

  • Nietfeld JC, Tyler DE, Harrison LR, Cole JR, Latimer KS, Crowell WA (1991) Culture and morphologic features of small intestinal mucosal explants from weaned pigs. Am J Vet Res 52:1142–1146

    CAS  PubMed  Google Scholar 

  • Osman N, Adawi D, Ahrné S, Jeppsson B, Molin G (2008) Probiotics and blueberry attenuate the severity of dextran sulfate sodium (DSS)-induced colitis. Dig Dis Sci 53:2464–2473. doi:10.1007/s10620-007-0174-x

    Article  PubMed  Google Scholar 

  • Pan X, Whitten DA, Wu M, Chan C, Wilkerson CG, Pestka JJ (2013) Early phosphoproteomic changes in the mouse spleen during deoxynivalenol-induced ribotoxic stress. Toxicol Sci 135:129–143. doi:10.1093/toxsci/kft145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pascale M, Panzarini G, Powers S, Visconti A (2014) Determination of deoxynivalenol and nivalenol in wheat by ultra-performance liquid chromatography/photodiode-array. Food Anal Method 7:555–562. doi:10.1007/s12161-013-9653-1

    Article  Google Scholar 

  • Payros D, Alassane-Kpembi I, Pierron A, Loiseau N, Pinton P, Oswald IP (2016) Toxicology of deoxynivalenol and its acetylated and modified forms. Arch Toxicol 90:2931–2957. doi:10.1007/s00204-016-1826-4

    Article  CAS  PubMed  Google Scholar 

  • Pestka JJ (2010) Deoxynivalenol-induced proinflammatory gene expression: mechanisms and pathological sequelae. Toxins (Basel) 2:1300–1317. doi:10.3390/toxins2061300

    Article  CAS  Google Scholar 

  • Pierron A, Mimoun S, Murate LS, Loiseau N, Lippi Y, Bracarense APFL, Schatzmayr G, He J, Zhou T, Moll WD, Oswald IP (2016a) Microbial biotransformation of DON: molecular basis for reduced toxicity. Sci Rep 6:29105. doi:10.1038/srep29105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pierron A, Mimoun S, Murate LS, Loiseau N, Lippi Y, Bracarense APFL, Schatzmayr G, Berthiller F, Moll WD, Oswald IP (2016b) Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside. Arch Toxicol 90:2037–2046. doi:10.1007/s00204-015-1592-8

    Article  CAS  PubMed  Google Scholar 

  • Pinton P, Oswald IP (2014) Effect of deoxynivalenol and other Type B trichothecenes on the intestine: a review. Toxins 6:1615–1643. doi:10.3390/toxins6051615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinton P, Nougayrede JP, del Rio JC, Moreno C, Marin D, Ferrier L, Bracarense AP, Kolf-Clauw M, Oswald IP (2009) The food contaminant, deoxynivalenol, decreases intestinal barrier function and reduces claudin expression. Toxicol Appl Pharmacol 237:41–48. doi:10.1016/j.taap.2009.03.003

    Article  CAS  PubMed  Google Scholar 

  • Pinton P, Tsybulskyy D, Lucioli J, Laffitte J, Callu P, Lyazhri F, Grosjean F, Bracarense AP, Kolf-Clauw M, Oswald IP (2012) Toxicity of deoxynivalenol and its acetylated derivatives on the intestine: differential effects on morphology, barrier function, tight junctions proteins and MAPKinases. Toxicol Sci 130:180–190. doi:10.1093/toxsci/kfs239

    Article  CAS  PubMed  Google Scholar 

  • Pinton P, Graziani F, Pujol A, Nicoletti C, Paris O, Ernouf P, Di Pasquale E, Perrier J, Oswald IP, Maresca M (2015) Deoxynivalenol inhibits the expression by goblet cells of intestinal mucins through a PKR and MAP kinase dependent repression of the resistin-like molecule. Mol Nutr Food Res 59:1076–1087. doi:10.1002/mnfr.201500005

    Article  CAS  PubMed  Google Scholar 

  • Resta-Lenert S, Barrett KE (2006) Probiotics and commensals reverse TNFa- and IFNg-induced dysfunction in human intestinal epithelial cells. Gastroenterology 130:731–746. doi:10.1053/j.gastro.2005.12.015

    Article  CAS  PubMed  Google Scholar 

  • Robert H, Payros D, Pinton P, Théodorou V, Mercier-Bonin M, Oswald IP (2017) Impact of mycotoxins on the intestine: are mucus and microbiota new targets? J Toxicol Environ Health Part B Crit Rev 20:249–275. doi:10.1080/10937404.2017.1326071

    Article  CAS  Google Scholar 

  • Sobrova P, Adam V, Vasatkova A, Beklova M, Zeman L, Kizek R (2010) Deoxynivalenol and its toxicity. Interdiscip Toxicol 3:94–99. doi:10.2478/v10102-010-0019-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Southcott E, Tooley KL, Howart GS, Davidsson GP, Butler RN (2008) Yoghurts containing probiotics reduce disruption of the small intestinal barrier in methotrexate-treated rats. Dig Dis Sci 53:1837–1841. doi:10.1007/s10620-008-0275-1

    Article  CAS  PubMed  Google Scholar 

  • Springler A, Hessenberger S, Schatzmayr G, Mayer E (2016) Early activation of MAPK p44/42 is partially involved in DON-induced disruption of the intestinal barrier function and tight junction network. Toxins 8:264. doi:10.3390/toxins8090264

    Article  PubMed Central  Google Scholar 

  • Turner PC, Hopton RP, Lecluse Y, White KL, Fisher J, Lebailly P (2010) Determinants of urinary deoxynivalenol and de-epoxy deoxynivalenol in male farmers from Normandy, France. J Agric Food Chem 58:5206–5212. doi:10.1021/jf100892v

    Article  CAS  PubMed  Google Scholar 

  • Waché Y, Valat C, Postollec G, Bougeard S, Burel C, Oswald IP, Fravalo P (2009) Impact of deoxynivalenol on the intestinal microflora of pigs. Int J Mol Sci 10:1–17. doi:10.3390/ijms10010001

    Article  PubMed  Google Scholar 

  • Watanabe T, Nishio H, Tanigawa T, Yamagami H, Okazaki H, Watanabe K et al (2009) Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid. Am J Physiol Gastrointest Liver Physiol 297:506–513. doi:10.1152/ajpgi.90553.2008

    Article  Google Scholar 

  • Weaver AC, See MT, Hansen JA, Kim YB, De Souza AL, Middleton TF, Kim SW (2013) The use of feed additives to reduce the effects of aflatoxin and deoxynivalenol on pig growth, organ health and immune status during chronic exposure. Toxins 5:1261–1281. doi:10.3390/toxins5071261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180

    Article  CAS  PubMed  Google Scholar 

  • Yan F, Polk DB (2002) Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem 277:50959–50965. doi:10.1074/jbc.M207050200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang F, Hou C, Zeng X, Qiao S (2015) The use of lactic acid bacteria as a probiotic in swine diets. Pathogens 4:34–45. doi:10.3390/pathogens4010034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. G. R. García and D. Payros equally contributed to this work.

Authors and Affiliations

  1. Departamento de Microbiología e Inmunología, Universidad Nacional de Río Cuarto, Ruta 36 km.601, 5800, Río Cuarto, Córdoba, Argentina

    Gisela Romina García, Cecilia Ana Dogi, María Laura González Pereyra & Lilia Renée Cavaglieri

  2. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Río Cuarto, Argentina

    Gisela Romina García, Cecilia Ana Dogi, María Laura González Pereyra & Lilia Renée Cavaglieri

  3. Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France

    Delphine Payros, Philippe Pinton, Joëlle Laffitte, Manon Neves & Isabelle P. Oswald

Authors
  1. Gisela Romina García
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Delphine Payros
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philippe Pinton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cecilia Ana Dogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joëlle Laffitte
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manon Neves
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. María Laura González Pereyra
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lilia Renée Cavaglieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Isabelle P. Oswald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabelle P. Oswald.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported in part by the French ANR (Agence Nationale de la Recherche) projects ImBio (ANR-13-CESA-0003-03), CaDON (ANR-15-CE21-0001-02) and ANPCYT-PICT1606/12.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 37 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

García, G.R., Payros, D., Pinton, P. et al. Intestinal toxicity of deoxynivalenol is limited by Lactobacillus rhamnosus RC007 in pig jejunum explants. Arch Toxicol 92, 983–993 (2018). https://doi.org/10.1007/s00204-017-2083-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-017-2083-x

Keywords

Search

Navigation