Challenges in translational research on probiotic lactobacilli: From in vitro assays to clinical trials

Beneficial Microbes

Volumn 4, Issue 1, 2013, Pages 83-100

  Meijerink, M ^a   Mercenier, A ^a   Wells, J M ^a  

^a WAGENINGEN UNIVERSITY   (Netherlands)

Author keywords

Animal models; Immunomodulation; Intestinal mucosa; Probiotics; Tolerance

Indexed keywords

CHOLERA VACCINE; INFLUENZA VACCINE; ORAL POLIOMYELITIS VACCINE; PROBIOTIC AGENT;

ADAPTIVE IMMUNITY; ALLERGIC ASTHMA; ARTICLE; BACTERIAL GENE; BACTERIAL STRAIN; BIFIDOBACTERIUM; BIFIDOBACTERIUM ANIMALIS; CELL CULTURE; CELL INTERACTION; CYTOKINE RESPONSE; DRUG MECHANISM; DRUG POTENTIATION; FOOD ALLERGY; GENE IDENTIFICATION; HUMAN; IMMUNOMODULATION; IMMUNOSTIMULATION; INFLUENZA; INNATE IMMUNITY; LACTOBACILLUS; LACTOBACILLUS ACIDOPHILUS; LACTOBACILLUS CASEI; LACTOBACILLUS RHAMNOSUS; MUCOSAL IMMUNITY; NONHUMAN; POLLEN ALLERGY; REGULATORY T LYMPHOCYTE; STRAIN DIFFERENCE; TRANSLATIONAL RESEARCH;

EID: 84875232516     PISSN: 18762883     EISSN: 18762891     Source Type: Journal    
DOI: 10.3920/BM2012.0035     Document Type: Article

References (163)

1. Abraham, C. and Medzhitov, R., 2011. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology 140: 1729-1737.
2. Adams, C.A., 2010. The probiotic paradox: live and dead cells are biological response modifiers. Nutrition Research Reviews 23: 37-46.
3. Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., Taniguchi, T., Takeda, K., Hori, S., Ivanov, I.I., Umesaki, Y., Itoh, K. and Honda, K., 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331: 337-341.
4. Barrila, J., Radtke, A.L., Crabbe, A., Sarker, S.F., Herbst-Kralovetz, M.M., Ott, C.M. and Nickerson, C.A., 2010. Organotypic 3D cell culture models: using the rotating wall vessel to study host-pathogen interactions. Nature Reviews Microbiology 8: 791-801.
5. Begue, B., Dumant, C., Bambou, J.C., Beaulieu, J.F., Chamaillard, M., Hugot, J.P., Goulet, O., Schmitz, J., Philpott, D.J., Cerf-Bensussan, N. and Ruemmele, F.M., 2006. Microbial induction of CARD15 expression in intestinal epithelial cells via Toll-like receptor 5 triggers an antibacterial response loop. Journal of Cellular Physiology 209: 241-252.
6. Berg, R.D., 1995. Bacterial translocation from the gastrointestinal tract. Trends in Microbiology 3: 149-154.
7. Berg, R.D., 1999. Bacterial translocation from the gastrointestinal tract. Advances in Experimental Medicine and Biology 473: 11-30.
8. Berg, R.D. and Owens, W.E., 1979. Inhibition of translocation of viable Escherichia coli from the gastrointestinal tract of mice by bacterial antagonism. Infection and Immunity 25: 820-827.
9. Bernardeau, M., Vernoux, J.P., Henri-Dubernet, S. and Gueguen, M., 2008. Safety assessment of dairy microorganisms: the Lactobacillus genus. International Journal of Food Microbiology 126: 278-285.
10. Bernardo, D., Sanchez, B., Al-Hassi, H.O., Mann, E.R., Urdaci, M.C., Knight, S.C. and Margolles, A., 2012. Microbiota/host crosstalk biomarkers: regulatory response of human intestinal dendritic cells exposed to Lactobacillus extracellular encrypted peptide. PloS ONE 7: e36262.
11. Blumer, N., Sel, S., Virna, S., Patrascan, C.C., Zimmermann, S., Herz, U., Renz, H. and Garn, H., 2007. Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring. Clinical and Experimental Allergy 37: 348-357.
12. Boneca, I.G., Dussurget, O., Cabanes, D., Nahori, M.A., Sousa, S., Lecuit, M., Psylinakis, E., Bouriotis, V., Hugot, J.P., Giovannini, M., Coyle, A., Bertin, J., Namane, A., Rousselle, J.C., Cayet, N., Prevost, M.C., Balloy, V., Chignard, M., Philpott, D.J., Cossart, P. and Girardin, S.E., 2007. A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system. Proceedings of the National Academy of Sciences of the USA 104: 997-1002.
13. Bovee-Oudenhoven, I.M., Lettink-Wissink, M.L., Van Doesburg, W., Witteman, B.J. and Van der Meer, R., 2003. Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium. Gastroenterology 125: 469-476.
14. Bron, P.A., Tomita, S., Van Swam, I.I., Remus, D.M., Meijerink, M., Wels, M., Okada, S., Wells, J.M. and Kleerebezem, M., 2012. Lactobacillus plantarum possesses the capability for wall teichoic acid backbone alditol switching. Microbial Cell Factories 11: 123.
15. Brouwer, M.L., Wolt-Plompen, S.A., Dubois, A.E., Van der Heide, S., Jansen, D.F., Hoijer, M.A., Kauffman, H.F. and Duiverman, E.J., 2006. No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial. Clinical and Experimental Allergy 36: 899-906.
16. Chapman, C.M., Gibson, G.R. and Rowland, I., 2011. Health benefits of probiotics: are mixtures more effective than single strains? European Journal of Nutrition 50: 1-17.
17. Chernyshov, P.V., 2007. Integrated treatment of infants, patients with atopic dermatitis. Dermatology 3: 23-26 (in Russian).
18. Chernyshov, P.V., 2009. Randomized, placebo-controlled trial on clinical and immunologic effects of probiotic containing Lactobacillus rhamnosus R0011 and L. helveticus R0052 in infants with atopic dermatitis. Microbial Ecology in Health and Disease 21: 228-232.
19. Claes, I.J., Lebeer, S., Shen, C., Verhoeven, T.L., Dilissen, E., De Hertogh, G., Bullens, D.M., Ceuppens, J.L., Van Assche, G., Vermeire, S., Rutgeerts, P., Vanderleyden, J. and De Keersmaecker, S.C., 2010. Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis. Clinical and Experimental Immunology 162: 306-314.
20. Collier-Hyams, L.S., Zeng, H., Sun, J., Tomlinson, A.D., Bao, Z.Q., Chen, H., Madara, J.L., Orth, K. and Neish, A.S., 2002. Cutting edge: Salmonella AvrA effector inhibits the key proinflammatory, anti-apoptotic NF-kappa B pathway. The Journal of Immunology 169: 2846-2850.
21. Coombes, J.L., Siddiqui, K.R., Arancibia-Carcamo, C.V., Hall, J., Sun, C.M., Belkaid, Y. and Powrie, F., 2007. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. Journal of Experimental Medicine 204: 1757-1764.
22. Crome, S.Q., Wang, A.Y. and Levings, M.K., 2010. Translational mini-review series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clinical and Experimental Immunology 159: 109-119.
23. Davidson, L.E., Fiorino, A.M., Snydman, D.R. and Hibberd, P.L., 2011. Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. European Journal of Clinical Nutrition 65: 501-507.
24. De Roock, S., Van Elk, M., Van Dijk, M.E., Timmerman, H.M., Rijkers, G.T., Prakken, B.J., Hoekstra, M.O. and De Kleer, I.M., 2010. Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans. Clinical and Experimental Allergy 40: 103-110.
25. De Vrese, M., Rautenberg, P., Laue, C., Koopmans, M., Herremans, T. and Schrezenmeir, J., 2005. Probiotic bacteria stimulate virus-specific neutralizing antibodies following a booster polio vaccination. European Journal of Nutrition 44: 406-413.
26. Delcenserie, V., Martel, D., Lamoureux, M., Amiot, J., Boutin, Y. and Roy, D., 2008. Immunomodulatory effects of probiotics in the intestinal tract. Current Issues in Molecular Biology 10: 37-54.
27. Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO), 2001. Report of a Joint FAO/WHO Expert consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Available at: http://www.who.int/foodsafety/publications/fs_management/en/probiotics.pdf.
28. Feng, T. and Elson, C.O., 2011. Adaptive immunity in the host-microbiota dialog. Mucosal Immunology 4: 15-21.
29. Fittipaldi, N., Sekizaki, T., Takamatsu, D., De la Cruz Dominguez-Punaro, M., Harel, J., Bui, N.K., Vollmer, W. and Gottschalk, M., 2008. Significant contribution of the pgdA gene to the virulence of Streptococcus suis. Molecular Microbiology 70: 1120-1135.
30. Foligne, B., Nutten, S., Grangette, C., Dennin, V., Goudercourt, D., Poiret, S., Dewulf, J., Brassart, D., Mercenier, A. and Pot, B., 2007. Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria. World Journal of Gastroenterology 13: 236-243.
31. Folster-Holst, R., Muller, F., Schnopp, N., Abeck, D., Kreiselmaier, I., Lenz, T., Von Ruden, U., Schrezenmeir, J., Christophers, E. and Weichenthal, M., 2006. Prospective, randomized controlled trial on Lactobacillus rhamnosus in infants with moderate to severe atopic dermatitis. British Journal of Dermatology 155: 1256-1261.
32. Forsythe, P., Inman, M.D. and Bienenstock, J., 2007. Oral treatment with live Lactobacillus reuteri inhibits the allergic airway response in mice. American Journal of Respiratory and Critical Care Medicine 175: 561-569.
33. Franchi, L., Kamada, N., Nakamura, Y., Burberry, A., Kuffa, P., Suzuki, S., Shaw, M.H., Kim, Y.G. and Nunez, G., 2012. NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nature Immunology 13: 449-456.
34. Francius, G., Lebeer, S., Alsteens, D., Wildling, L., Gruber, H.J., Hols, P., De Keersmaecker, S., Vanderleyden, J. and Dufrene, Y.F., 2008. Detection, localization, and conformational analysis of single polysaccharide molecules on live bacteria. ACS Nano 2: 1921-1929.
35. Frossard, C.P., Steidler, L. and Eigenmann, P.A., 2007. Oral administration of an IL-10-secreting Lactococcus lactis strain prevents food-induced IgE sensitization. Journal of Allergy and Clinical Immunology 119: 952-959.
36. Fullner, K.J., Lencer, W.I. and Mekalanos, J.J., 2001. Vibrio cholerae-induced cellular responses of polarized T84 intestinal epithelial cells are dependent on production of cholera toxin and the RTX toxin. Infection and Immunity 69: 6310-6317.
37. Gaboriau-Routhiau, V., Rakotobe, S., Lecuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., Eberl, G., Snel, J., Kelly, D. and Cerf-Bensussan, N., 2009. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31: 677-689.
38. Gautreaux, M.D., Deitch, E.A. and Berg, R.D., 1994. Bacterial translocation from the gastrointestinal tract to various segments of the mesenteric lymph node complex. Infection and Immunity 62: 2132-2134.
39. Gebert, A., Fassbender, S., Werner, K. and Weissferdt, A., 1999. The development of M cells in Peyer's patches is restricted to specialized dome-associated crypts. The American Journal of Pathology 154: 1573-1582.
40. Ghadimi, D., Folster-Holst, R., De Vrese, M., Winkler, P., Heller, K.J. and Schrezenmeir, J., 2008. Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects. Immunobiology 213: 677-692.
41. Gluck, U. and Gebbers, J.O., 2003. Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and beta-hemolytic streptococci). The American Journal of Clinical Nutrition 77: 517-520.
42. Grangette, C., Nutten, S., Palumbo, E., Morath, S., Hermann, C., Dewulf, J., Pot, B., Hartung, T., Hols, P. and Mercenier, A., 2005. Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids. Proceedings of the National Academy of Sciences of the USA 102: 10321-10326.
43. Gruber, C., Wendt, M., Sulser, C., Lau, S., Kulig, M., Wahn, U., Werfel, T. and Niggemann, B., 2007. Randomized, placebo-controlled trial of Lactobacillus rhamnosus GG as treatment of atopic dermatitis in infancy. Allergy 62: 1270-1276.
44. Guarner, F., Bourdet-Sicard, R., Brandtzaeg, P., Gill, H.S., McGuirk, P., Van Eden, W., Versalovic, J., Weinstock, J.V. and Rook, G.A., 2006. Mechanisms of disease: the hygiene hypothesis revisited. Nature Clinical Practice Gastroenterology and Hepatology 3: 275-284.
45. Gullberg, E., Keita, A.V., Salim, S.Y., Andersson, M., Caldwell, K.D., Soderholm, J.D. and Artursson, P., 2006. Identification of cell adhesion molecules in the human follicle-associated epithelium that improve nanoparticle uptake into the Peyer's patches. Journal of Pharmacology and Experimental Therapeutics 319: 632-639.
46. Guyonnet, D., Chassany, O., Ducrotte, P., Picard, C., Mouret, M., Mercier, C.H. and Matuchansky, C., 2007. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Alimentary Pharmacology and Therapeutics 26: 475-486.
47. Hacini-Rachinel, F., Gheit, H., Le Luduec, J.B., Dif, F., Nancey, S. and Kaiserlian, D., 2009. Oral probiotic control skin inflammation by acting on both effector and regulatory T cells. PloS ONE 4: e4903.
48. Hall, J.A., Bouladoux, N., Sun, C.M., Wohlfert, E.A., Blank, R.B., Zhu, Q., Grigg, M.E., Berzofsky, J.A. and Belkaid, Y., 2008. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 29: 637-649.
49. Haller, D., Antoine, J.M., Bengmark, S., Enck, P., Rijkers, G.T. and Lenoir-Wijnkoop, I., 2010. Guidance for substantiating the evidence for beneficial effects of probiotics: probiotics in chronic inflammatory bowel disease and the functional disorder irritable bowel syndrome. Journal of Nutrition 140: 690S-697S.
50. Hampe, J., Cuthbert, A., Croucher, P.J., Mirza, M.M., Mascheretti, S., Fisher, S., Frenzel, H., King, K., Hasselmeyer, A., MacPherson, A.J., Bridger, S., Van Deventer, S., Forbes, A., Nikolaus, S., Lennard-Jones, J.E., Foelsch, U.R., Krawczak, M., Lewis, C., Schreiber, S. and Mathew, C.G., 2001. Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. The Lancet 357: 1925-1928.
51. Harata, G., He, F., Hiruta, N., Kawase, M., Kubota, A., Hiramatsu, M. and Yausi, H., 2010. Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses. Letters in Applied Microbiology 50: 597-602.
52. Hatakka, K., Savilahti, E., Ponka, A., Meurman, J.H., Poussa, T., Nase, L., Saxelin, M. and Korpela, R., 2001. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ 322: 1327.
53. Hojsak, I., Abdovic, S., Szajewska, H., Milosevic, M., Krznaric, Z. and Kolacek, S., 2010. Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Pediatrics 125: e1171-1177.
54. Holt, P.G. and Jones, C.A., 2000. The development of the immune system during pregnancy and early life. Allergy 55: 688-697.
55. Holvoet, S., Zuercher, A.W., Julien-Javaux, F., Perrot, M. and Mercenier, A., 2013. Characterization of candidate anti-allergic probiotic strains in a model of Th2-skewed human peripheral blood mononuclear cells. International Archives of Allergy Immunology 161: 142-154.
56. Howell, W.M., Calder, P.C. and Grimble, R.F., 2002. Gene polymorphisms, inflammatory diseases and cancer. Proceedings of the Nutrition Society 61: 447-456.
57. Iliev, I.D., Spadoni, I., Mileti, E., Matteoli, G., Sonzogni, A., Sampietro, G.M., Foschi, D., Caprioli, F., Viale, G. and Rescigno, M., 2009. Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells. Gut 58: 1481-1489.
58. Isolauri, E., Joensuu, J., Suomalainen, H., Luomala, M. and Vesikari, T., 1995. Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine 13: 310-312.
59. Ivanov, I.I., Atarashi, K., Manel, N., Brodie, E.L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K.C., Santee, C.A., Lynch, S.V., Tanoue, T., Imaoka, A., Itoh, K., Takeda, K., Umesaki, Y., Honda, K. and Littman, D.R., 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139: 485-498.
60. Ivory, K., Chambers, S.J., Pin, C., Prieto, E., Arques, J.L. and Nicoletti, C., 2008. Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune responses in allergic rhinitis. Clinical and Experimental Allergy 38: 1282-1289.
61. Jang, S.O., Kim, H.J., Kim, Y.J., Kang, M.J., Kwon, J.W., Seo, J.H., Kim, H.Y., Kim, B.J., Yu, J. and Hong, S.J., 2012. Asthma prevention by Lactobacillus rhamnosus in a mouse model is associated with CD4(+)CD25(+)Foxp3(+) T cells. Allergy, Asthma and Immunology Research 4: 150-156.
62. Kajander, K., Hatakka, K., Poussa, T., Farkkila, M. and Korpela, R., 2005. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Alimentary Pharmacology and Therapeutics 22: 387-394.
63. Kalliomaki, M., Antoine, J.M., Herz, U., Rijkers, G.T., Wells, J.M. and Mercenier, A., 2010. Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics. Journal of Nutrition 140: 713S-721S.
64. Kalliomaki, M., Salminen, S., Arvilommi, H., Kero, P., Koskinen, P. and Isolauri, E., 2001. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. The Lancet 357: 1076-1079.
65. Kalliomaki, M., Salminen, S., Poussa, T., Arvilommi, H. and Isolauri, E., 2003. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. The Lancet 361: 1869-1871.
66. Kalliomaki, M., Salminen, S., Poussa, T. and Isolauri, E., 2007. Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial. Journal of Allergy and Clinical Immunology 119: 1019-1021.
67. Karczewski, J., Troost, F.J., Konings, I., Dekker, J., Kleerebezem, M., Brummer, R.J. and Wells, J.M., 2010. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. American Journal of Physiology - Gastrointestinal and Liver Physiology 298: G851-859.
68. Karimi, K., Inman, M.D., Bienenstock, J. and Forsythe, P., 2009. Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. American Journal of Respiratory and Critical Care Medicine 179: 186-193.
69. Kataria, J., Li, N., Wynn, J.L. and Neu, J., 2009. Probiotic microbes: do they need to be alive to be beneficial? Nutrition Reviews 67: 546-550.
70. Kawase, M., He, F., Kubota, A., Harata, G. and Hiramatsu, M., 2010. Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infection. Letters in Applied Microbiology 51: 6-10.
71. Kim, H., Kwack, K., Kim, D.Y. and Ji, G.E., 2005. Oral probiotic bacterial administration suppressed allergic responses in an ovalbumin-induced allergy mouse model. FEMS Immunology and Medical Microbiology 45: 259-267.
72. Kim, J.Y., Choi, Y.O. and Ji, G.E., 2008. Effect of oral probiotics (Bifidobacterium lactis AD011 and Lactobacillus acidophilus AD031) administration on ovalbumin-induced food allergy mouse model. Journal of Microbiology and Biotechnology 18: 1393-1400.
73. Konstantinov, S.R., Smidt, H., De Vos, W.M., Bruijns, S.C., Singh, S.K., Valence, F., Molle, D., Lortal, S., Altermann, E., Klaenhammer, T.R. and Van Kooyk, Y., 2008. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proceedings of the National Academy of Sciences of the USA 105: 19474-19479
74. Kopp, M.V., Hennemuth, I., Heinzmann, A. and Urbanek, R., 2008. Randomized, double-blind, placebo-controlled trial of probiotics for primary prevention: no clinical effects of Lactobacillus GG supplementation. Pediatrics 121: e850-856.
75. Kotani, Y., Shinkai, S., Okamatsu, H., Toba, M., Ogawa, K., Yoshida, H., Fukaya, T., Fujiwara, Y., Chaves, P.H., Kakumoto, K. and Kohda, N., 2010. Oral intake of Lactobacillus pentosus strain b240 accelerates salivary immunoglobulin A secretion in the elderly: a randomized, placebo-controlled, double-blind trial. Immunity and Ageing 7: 11.
76. Kwon, H.K., Lee, C.G., So, J.S., Chae, C.S., Hwang, J.S., Sahoo, A., Nam, J.H., Rhee, J.H., Hwang, K.C. and Im, S.H., 2010. Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. Proceedings of the National Academy of Sciences of the USA 107: 2159-2164.
77. Lavasani, S., Dzhambazov, B., Nouri, M., Fak, F., Buske, S., Molin, G., Thorlacius, H., Alenfall, J., Jeppsson, B. and Westrom, B., 2010. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PloS ONE 5: e9009.
78. Lebeer, S., Vanderleyden, J. and De Keersmaecker, S.C., 2010. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nature Reviews Microbiology 8: 171-184.
79. Leonard, F., Collnot, E.M. and Lehr, C.M., 2010. A three-dimensional coculture of enterocytes, monocytes and dendritic cells to model inflamed intestinal mucosa in vitro. Molecular Pharmaceutics 7: 2103-2119.
80. Liao, A.P., Petrof, E.O., Kuppireddi, S., Zhao, Y., Xia, Y., Claud, E.C. and Sun, J., 2008. Salmonella type III effector AvrA stabilizes cell tight junctions to inhibit inflammation in intestinal epithelial cells. PloS ONE 3: e2369.
81. Ligaarden, S.C., Axelsson, L., Naterstad, K., Lydersen, S. and Farup, P.G., 2010. A candidate probiotic with unfavourable effects in subjects with irritable bowel syndrome: a randomised controlled trial. BMC Gastroenterology 10: 16.
82. Macho Fernandez, E., Valenti, V., Rockel, C., Hermann, C., Pot, B., Boneca, I.G. and Grangette, C., 2011. Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide. Gut 60: 1050-1059.
83. Macpherson, A.J. and Uhr, T., 2004. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303: 1662-1665.
84. Manicassamy, B., Medina, R.A., Hai, R., Tsibane, T., Stertz, S., Nistal-Villan, E., Palese, P., Basler, C.F. and Garcia-Sastre, A., 2010. Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines. PLoS Pathogens 6: e1000745.
85. Medina, M., Izquierdo, E., Ennahar, S. and Sanz, Y., 2007. Differential immunomodulatory properties of Bifidobacterium longum strains: relevance to probiotic selection and clinical applications. Clinical and Experimental Immunology 150: 531-538.
86. Meijerink, M., Ulluwishewa, D., Anderson, R.C. and Wells, J.M., 2011. Cryopreservation of monocytes or differentiated immature DCs leads to an altered cytokine response to TLR agonists and microbial stimulation. Journal of Immunological Methods 373: 136-142.
87. Meijerink, M., Van Hemert, S., Taverne, N., Wels, M., De Vos, P., Bron, P.A., Savelkoul, H.F., Van Bilsen, J., Kleerebezem, M. and Wells, J.M., 2010. Identification of genetic loci in Lactobacillus plantarum that modulate the immune response of dendritic cells using comparative genome hybridization. PloS ONE 5: e10632.
88. Meijerink, M. and Wells, J., 2010. Probiotic modulation of dendritic cells and T cell responses in the intestine. Beneficial Microbes 1: 317-326.
89. Meijerink, M., Wells, J.M., Taverne, N., De Zeeuw Brouwer, M.L., Hilhorst, B., Venema, K. and Van Bilsen, J., 2012. Immunomodulatory effects of potential probiotics in a mouse peanut sensitization model. FEMS Immunology and Medical Microbiology 65: 488-496.
90. Miettinen M., Matikainen, S., Vuopio-Varkila, J., Pirhonen, J., Varkila, K., Kurimoto, M. and Julkunen, I., 1998. Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human peripheral blood mononuclear cells. Infection and Immunity 66: 6058-6062.
91. Miettinen, M., Vuopio-Varkila, J. and Varkila, K., 1996. Production of human tumor necrosis factor alpha, interleukin-6, and interleukin-10 is induced by lactic acid bacteria. Infection and Immunity 64: 5403-5405.
92. Mileti, E., Matteoli, G., Iliev, I.D. and Rescigno, M., 2009. Comparison of the immunomodulatory properties of three probiotic strains of lactobacilli using complex culture systems: prediction for in vivo efficacy. PloS ONE 4: e7056.
93. Mobili, P., Serradell Mde, L., Trejo, S.A., Aviles Puigvert, F.X., Abraham, A.G. and De Antoni, G.L., 2009. Heterogeneity of S-layer proteins from aggregating and non-aggregating Lactobacillus kefir strains. Antonie Van Leeuwenhoek 95: 363-372.
94. Mohamadzadeh, M., Pfeiler, E.A., Brown, J.B., Zadeh, M., Gramarossa, M., Managlia, E., Bere, P., Sarraj, B., Khan, M.W., Pakanati, K.C., Ansari, M.J., O'Flaherty, S., Barrett, T. and Klaenhammer, T.R., 2011. Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid. Proceedings of the National Academy of Sciences of the USA 108 Suppl. 1: 4623-4630.
95. Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A. and Coffman, R.L., 1986. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. The Journal of Immunology 136: 2348-2357.
96. Nagano, Y., Itoh, K. and Honda, K., 2012. The induction of Treg cells by gut-indigenous Clostridium. Current Opinion in Immunology 24: 392-397.
97. Niers, L.E., Timmerman, H.M., Rijkers, G.T., Van Bleek, G.M., Van Uden, N.O., Knol, E.F., Kapsenberg, M.L., Kimpen, J.L. and Hoekstra, M.O., 2005. Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines. Clinical and Experimental Allergy 35: 1481-1489.
98. Niess, J.H. and Adler, G., 2010. Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditions. The Journal of Immunology 184: 2026-2037.
99. Niess, J.H., Leithauser, F., Adler, G. and Reimann, J., 2008. Commensal gut flora drives the expansion of proinflammatory CD4 T cells in the colonic lamina propria under normal and inflammatory conditions. The Journal of Immunology 180: 559-568.
100. O'Mahony, C., Scully, P., O'Mahony, D., Murphy, S., O'Brien, F., Lyons, A., Sherlock, G., MacSharry, J., Kiely, B., Shanahan, F. and O'Mahony, L., 2008. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathogens 4: e1000112.
101. O'Toole, P.W. and Cooney, J.C., 2008. Probiotic bacteria influence the composition and function of the intestinal microbiota. Interdisciplinary Perspectives on Infectious Diseases 2008, Article ID 175285, 9 pp.
102. Ogura, Y., Bonen, D.K., Inohara, N., Nicolae, D.L., Chen, F.F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R.H., Achkar, J.P., Brant, S.R., Bayless, T.M., Kirschner, B.S., Hanauer, S.B., Nunez, G. and Cho, J.H., 2001. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411: 603-606.
103. Okada, H., Kuhn, C., Feillet, H. and Bach, J.F., 2010. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clinical and Experimental Immunology 160: 1-9.
104. Olah, A., Belagyi, T., Issekutz, A., Gamal, M.E. and Bengmark, S., 2002. Randomized clinical trial of specific Lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis. British Journal of Surgery 89: 1103-1107.
105. Onori, P., Franchitto, A., Sferra, R., Vetuschi, A. and Gaudio, E., 2001. Peyer's patches epithelium in the rat: a morphological, immunohistochemical, and morphometrical study. Digestive Diseases and Sciences 46: 1095-1104.
106. Ouwehand, A.C., Salminen, S. and Isolauri, E., 2002. Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek 82: 279-289.
107. Paineau, D., Carcano, D., Leyer, G., Darquy, S., Alyanakian, M.A., Simoneau, G., Bergmann, J.F., Brassart, D., Bornet, F. and Ouwehand, A.C., 2008. Effects of seven potential probiotic strains on specific immune responses in healthy adults: a double-blind, randomized, controlled trial. FEMS Immunology and Medical Microbiology 53: 107-113.
108. Parlesak, A., Haller, D., Brinz, S., Baeuerlein, A. and Bode, C., 2004. Modulation of cytokine release by differentiated Caco-2 cells in a compartmentalized coculture model with mononuclear leucocytes and nonpathogenic bacteria. Scandinavian Journal of Immunology 60: 477-485.
109. Peran, L., Camuesco, D., Comalada, M., Nieto, A., Concha, A., Diaz-Ropero, M.P., Olivares, M., Xaus, J., Zarzuelo, A. and Galvez, J., 2005. Preventative effects of a probiotic, Lactobacillus salivarius ssp. salivarius, in the TNBS model of rat colitis. World Journal of Gastroenterology 11: 5185-5192.
110. Perdigon, G., Medina, M., Vintini, E. and Valdez, J.C., 2000. Intestinal pathway of internalisation of lactic acid bacteria and gut mucosal immunostimulation. International Journal of Immunopathology and Pharmacology 13: 141-150.
111. Perdigon, G., Vintini, E., Alvarez, S., Medina, M. and Medici, M., 1999. Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria. Journal of Dairy Science 82: 1108-1114.
112. Petersen, E.R., Claesson, M.H., Schmidt, E.G., Jensen, S.S., Ravn, P., Olsen, J., Ouwehand, A.C. and Kristensen, N.N., 2012. Consumption of probiotics increases the effect of regulatory T cells in transfer colitis. Inflammatory Bowel Diseases 18: 131-142.
113. Prescott, S.L. and Bjorksten, B., 2007. Probiotics for the prevention or treatment of allergic diseases. Journal of Allergy and Clinical Immunology 120: 255-262.
114. Rachmilewitz, D., Katakura, K., Karmeli, F., Hayashi, T., Reinus, C., Rudensky, B., Akira, S., Takeda, K., Lee, J., Takabayashi, K. and Raz, E., 2004. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology 126: 520-528.
115. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. and Medzhitov, R., 2004. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118: 229-241.
116. Rayes, N., Seehofer, D., Hansen, S., Boucsein, K., Muller, A.R., Serke, S., Bengmark, S. and Neuhaus, P., 2002. Early enteral supply of Lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients. Transplantation 74: 123-127.
117. Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J.P. and Ricciardi-Castagnoli, P., 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunology 2: 361-367.
118. Rijkers, G.T., Bengmark, S., Enck, P., Haller, D., Herz, U., Kalliomaki, M., Kudo, S., Lenoir-Wijnkoop, I., Mercenier, A., Myllyluoma, E., Rabot, S., Rafter, J., Szajewska, H., Watzl, B., Wells, J., Wolvers, D. and Antoine, J.M., 2010. Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research. Journal of Nutrition 140: 671S-676S.
119. Rimoldi, M., Chieppa, M., Larghi, P., Vulcano, M., Allavena, P. and Rescigno, M., 2005a. Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different. Blood 106: 2818-2826.
120. Rimoldi, M., Chieppa, M., Salucci, V., Avogadri, F., Sonzogni, A., Sampietro, G.M., Nespoli, A., Viale, G., Allavena, P. and Rescigno, M., 2005b. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nature Immunology 6: 507-514.
121. Rodriguez, B., Prioult, G., Hacini-Rachinel, F., Moine, D., Bruttin, A., Ngom-Bru, C., Labellie, C., Nicolis, I., Berger, B., Mercenier, A., Butel, M.J. and Waligora-Dupriet, A.J., 2012. Infant gut microbiota is protective against cow's milk allergy in mice despite immature ileal T-cell response. FEMS Microbiology Ecology 79: 192-202.
122. Rossi, O., Van Baarlen, P. and Wells, J.M., 2011. Host-recognition of pathogens and commensals in the mammalian intestine. Current Topics in Microbiology and Immunology, in press.
123. Round, J.L. and Mazmanian, S.K., 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology 9: 313-323.
124. Round, J.L. and Mazmanian, S.K., 2010. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proceedings of the National Academy of Sciences of the USA 107: 12204-12209.
125. Rousseaux, C., Thuru, X., Gelot, A., Barnich, N., Neut, C., Dubuquoy, L., Dubuquoy, C., Merour, E., Geboes, K., Chamaillard, M., Ouwehand, A., Leyer, G., Carcano, D., Colombel, J.F., Ardid, D. and Desreumaux, P., 2007. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nature Medicine 13: 35-37.
126. Saleh, M. and Elson, C.O., 2011. Experimental inflammatory bowel disease: insights into the host-microbiota dialog. Immunity 34: 293-302.
127. Schabussova, I., Hufnagl, K., Wild, C., Nutten, S., Zuercher, A.W., Mercenier, A. and Wiedermann, U., 2011. Distinctive anti-allergy properties of two probiotic bacterial strains in a mouse model of allergic poly-sensitization. Vaccine 29: 1981-1990.
128. Schiavi, E., Barletta, B., Butteroni, C., Corinti, S., Boirivant, M. and Di Felice, G., 2011. Oral therapeutic administration of a probiotic mixture suppresses established Th2 responses and systemic anaphylaxis in a murine model of food allergy. Allergy 66: 499-508.
129. Schmidt, E.G., Claesson, M.H., Jensen, S.S., Ravn, P. and Kristensen, N.N., 2010. Antigen-presenting cells exposed to Lactobacillus acidophilus NCFM, Bifidobacterium bifidum BI-98, and BI-504 reduce regulatory T cell activity. Inflammatory Bowel Diseases 16: 390-400.
130. Schroder, N.W. and Schumann, R.R., 2005. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. The Lancet Infectious Diseases 5: 156-164.
131. Sharma, R., Schumacher, U. and Adam, E., 1998. Lectin histochemistry reveals the appearance of M-cells in Peyer's patches of SCID mice after syngeneic normal bone marrow transplantation. Journal of Histochemistry and Cytochemistry 46: 143-148.
132. Shida, K., Takahashi, R., Iwadate, E., Takamizawa, K., Yasui, H., Sato, T., Habu, S., Hachimura, S. and Kaminogawa, S., 2002. Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model. Clinical and Experimental Allergy 32: 563-570.
133. Sing, A., Roggenkamp, A., Geiger, A.M. and Heesemann, J., 2002. Yersinia enterocolitica evasion of the host innate immune response by V antigen-induced IL-10 production of macrophages is abrogated in IL-10-deficient mice. The Journal of Immunology 168: 1315-1321.
134. Smits, H.H., Engering, A., Van der Kleij, D., De Jong, E.C., Schipper, K., Van Capel, T.M., Zaat, B.A., Yazdanbakhsh, M., Wierenga, E.A., Van Kooyk, Y. and Kapsenberg, M.L., 2005. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. Journal of Allergy and Clinical Immunology 115: 1260-1267.
135. Snel, J., Vissers, Y.M., Smit, B.A., Jongen, J.M., Van der Meulen, E.T., Zwijsen, R., Ruinemans-Koerts, J., Jansen, A.P., Kleerebezem, M. and Savelkoul, H.F., 2011. Strain-specific immunomodulatory effects of Lactobacillus plantarum strains on birch-pollen-allergic subjects out of season. Clinical and Experimental Allergy 41: 232-242.
136. Spiller, R., 2008. Review article: probiotics and prebiotics in irritable bowel syndrome. Alimentary Pharmacology and Therapeutics 28: 385-396.
137. Sun, C.M., Hall, J.A., Blank, R.B., Bouladoux, N., Oukka, M., Mora, J.R. and Belkaid, Y., 2007. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. Journal of Experimental Medicine 204: 1775-1785.
138. Sun, L., Nava, G.M. and Stappenbeck, T.S., 2011. Host genetic susceptibility, dysbiosis, and viral triggers in inflammatory bowel disease. Current Opinions in Gastroenterology 27: 321-327.
139. Torok, H.P., Glas, J., Tonenchi, L., Bruennler, G., Folwaczny, M. and Folwaczny, C., 2004. Crohn's disease is associated with a Toll-like receptor-9 polymorphism. Gastroenterology 127: 365-366.
140. Trammell, R.A. and Toth, L.A., 2008. Genetic susceptibility and resistance to influenza infection and disease in humans and mice. Expert Review of Molecular Diagnostics 8: 515-529.
141. Troy, E.B. and Kasper, D.L., 2010. Beneficial effects of Bacteroides fragilis polysaccharides on the immune system. Frontiers in Bioscience 15: 25-34.
142. Tsilingiri, K., Barbosa, T., Penna, G., Caprioli, F., Sonzogni, A., Viale, G. and Rescigno, M., 2012. Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. Gut 61: 1007-1015.
143. Tyrer, P., Foxwell, A.R., Cripps, A.W., Apicella, M.A. and Kyd, J.M., 2006. Microbial pattern recognition receptors mediate M-cell uptake of a Gram-negative bacterium. Infection and Immunity 74: 625-631.
144. Tyrer, P., Ruth Foxwell, A., Kyd, J., Harvey, M., Sizer, P. and Cripps, A., 2002. Validation and quantitation of an in vitro M-cell model. Biochemical and Biophysical Research Communications 299: 377-383.
145. Valdez, Y., Ferreira, R.B. and Finlay, B.B., 2009. Molecular mechanisms of Salmonella virulence and host resistance. Current Topics in Microbiology and Immunology 337: 93-127.
146. Van Baarlen, P., Troost, F.J., Van Hemert, S., Van der Meer, C., De Vos, W.M., De Groot, P.J., Hooiveld, G.J., Brummer, R.J. and Kleerebezem, M., 2009. Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proceedings of the National Academy of Sciences of the USA 106: 2371-2376.
147. Van Hemert, S., Meijerink, M., Molenaar, D., Bron, P., De Vos, P., Kleerebezem, M., Wells, J. and Marco, M., 2010. Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells. BMC Microbiology 10: 293.
148. Veenbergen, S. and Samsom, J.N., 2012. Maintenance of small intestinal and colonic tolerance by IL-10-producing regulatory T cell subsets. Current Opinion in Immunology 24: 269-276.
149. Viljanen, M., Savilahti, E., Haahtela, T., Juntunen-Backman, K., Korpela, R., Poussa, T., Tuure, T. and Kuitunen, M., 2005. Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Allergy 60: 494-500.
150. Vissers, Y.M., Snel, J., Zuurendonk, P.F., Smit, B.A., Wichers, H.J. and Savelkoul, H.F., 2010. Differential effects of Lactobacillus acidophilus and Lactobacillus plantarum strains on cytokine induction in human peripheral blood mononuclear cells. FEMS Immunology and Medical Microbiology 59: 60-70.
151. Von Schillde, M.A., Hormannsperger, G., Weiher, M., Alpert, C.A., Hahne, H., Bauerl, C., Van Huynegem, K., Steidler, L., Hrncir, T., Perez-Martinez, G., Kuster, B. and Haller, D., 2012. Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines. Cell Host Microbe 11: 387-396.
152. Wells, J., 2011a. Mucosal vaccination and therapy with genetically modified lactic acid bacteria. Annual Reviews of Food Science and Technology 2: 423-445.
153. Wells, J.M., 2011b. Immunomodulatory mechanisms of lactobacilli. Microbial Cell Factories 10 Suppl. 1: S17.
154. Wells, J.M. and Mercenier, A., 2008. Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria. Nature Reviews Microbiology 6: 349-362.
155. Wells, J.M., Rossi, O., Meijerink, M. and Van Baarlen, P., 2010. Microbes and health sackler colloquium: epithelial crosstalk at the microbiota-mucosal interface. Proceedings of the National Academy of Sciences of the USA 108 Suppl. 1: 4607-4614.
156. Wickens, K., Black, P.N., Stanley, T.V., Mitchell, E., Fitzharris, P., Tannock, G.W., Purdie, G., Crane, J. and Probiotic Study Group, 2008. A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. Journal of Allergy and Clinical Immunology 122: 788-794.
157. Yan, F. and Polk, D.B., 2002. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. Journal of Biological Chemistry 277: 50959-50965.
158. Yaqoob, P., Newsholme, E.A. and Calder, P.C., 1999. Comparison of cytokine production in cultures of whole human blood and purified mononuclear cells. Cytokine 11: 600-605.
159. Yasui, H., Kiyoshima, J. and Hori, T., 2004. Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota. Clinical and Diagnostic Laboratory Immunology 11: 675-679.
160. Ye, Z., Petrof, E.O., Boone, D., Claud, E.C. and Sun, J., 2007. Salmonella effector AvrA regulation of colonic epithelial cell inflammation by deubiquitination. The American Journal of Pathology 171: 882-892.
161. Zakostelska, Z., Kverka, M., Klimesova, K., Rossmann, P., Mrazek, J., Kopecny, J., Hornova, M., Srutkova, D., Hudcovic, T., Ridl, J. and Tlaskalova-Hogenova, H., 2011. Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment. PloS ONE 6: e27961.
162. Zoumpopoulou, G., Foligne, B., Christodoulou, K., Grangette, C., Pot, B. and Tsakalidou, E., 2008. Lactobacillus fermentum ACA-DC 179 displays probiotic potential in vitro and protects against trinitrobenzene sulfonic acid (TNBS)-induced colitis and Salmonella infection in murine models. International Journal of Food Microbiology 121: 18-26.
163. Zuercher, A.W., Weiss, M., Holvoet, S., Moser, M., Moussu, H., Van Overtvelt, L., Horiot, S., Moingeon, P., Nutten, S., Prioult, G., Singh, A. and Mercenier, A., 2012. Lactococcus lactis NCC 2287 alleviates food allergic manifestations in sensitized mice by reducing IL-13 expression specifically in the ileum. Clinical and Developmental Immunology 2012: 485750.