The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: Contribution of germ-free and gnotobiotic animal models of human diseases

Cellular and Molecular Immunology

Volumn 8, Issue 2, 2011, Pages 110-120

  Tlaskalová Hogenová, Helena ^a   Tpánková, Renata ^a   Kozáková, Hana ^a   Hudcovic, Tomá ^a   Vannucci, Luca ^a   Tuková, Ludmila ^a   Rossmann, Pavel ^a   Hrní, Tomá ^a   Kverka, Miloslav ^a   Zákostelská, Zuzana ^a   Klimeová, Klára ^a   Pibylová, Jaroslava ^a   Bártová, Jiina ^b   Sanchez, Daniel ^a   Fundová, Petra ^a,c   Borovská, Dana ^a   Rtková, Dagmar ^a   Zídek, Zdenk ^d   Schwarzer, Martin ^a   Drastich, Pavel ^e   Funda, David P ^a   more..

^a INSTITUTE OF MICROBIOLOGY   (Czech Republic)

^b CHARLES UNIVERSITY   (Czech Republic)

^c CENTRAL MILITARY HOSPITAL   (Czech Republic)

^d INSTITUTE OF EXPERIMENTAL MEDICINE   (Czech Republic)

^e INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE   (Czech Republic)

Author keywords

allergy; hygiene hypothesis; intestinal permeability; leaky gut; probiotics

Indexed keywords

PREBIOTIC AGENT; PROBIOTIC AGENT;

ADAPTIVE IMMUNITY; ALLERGY; ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; BACTERIAL COLONIZATION; CARDIOVASCULAR DISEASE; CELIAC DISEASE; CROHN DISEASE; DIARRHEA; DISEASE MODEL; ENTERITIS; GENOTYPE ENVIRONMENT INTERACTION; GERMFREE ANIMAL; GNOTOBIOTICS; HUMAN; ILEITIS; IMMUNOLOGICAL TOLERANCE; INFLAMMATORY DISEASE; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; IRRITABLE COLON; MALIGNANT NEOPLASTIC DISEASE; MENTAL DISEASE; METAGENOMICS; MUCOSAL IMMUNITY; NEUROLOGIC DISEASE; NONHUMAN; OBESITY; PATHOGENESIS; POSTNATAL DEVELOPMENT; PROTECTION; REVIEW; RHEUMATIC DISEASE; SYMBIOSIS; TRAVELLER DIARRHEA; ULCERATIVE COLITIS; VIRAL GASTROENTERITIS;

ANIMALS; AUTOIMMUNE DISEASES; DISEASE MODELS, ANIMAL; GASTROINTESTINAL TRACT; GERM-FREE LIFE; HUMANS; IMMUNITY; INFLAMMATION; METAGENOME; MUCOUS MEMBRANE; NEOPLASMS;

ANIMALIA; BACTERIA (MICROORGANISMS); MUS;

EID: 79952384278     PISSN: 16727681     EISSN: None     Source Type: Journal    
DOI: 10.1038/cmi.2010.67     Document Type: Review

References (171)

1. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science 2005; 307: 1915-1920. (Pubitemid 40404694)
2. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M et al. Diversity of the human intestinal microbial flora. Science 2005; 308: 1635-1638. (Pubitemid 40807514)
3. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464: 59-65.
4. Doré J, Leclerc M, Juste C, Lepage P, Blottière H, Corthier G. The human intestinal microbiota: from phylogenetics to functional metagenomics. In: Heidt PJ, Snel J, Midtvedt T, Rusch V, (eds.) Intestinal Microbiomics: Novel Indicators of Health and Disease. Herborn: Old Herborn University Foundation, 2010: 15-22.
5. Martin FP, Sprenger N, Yap IK, Wang Y, Bibiloni R, Rochat F et al. Panorganismal gut microbiome-host metabolic crosstalk. J Proteome Res 2009; 8: 2090-2105.
6. Kleerebezem M. Metagenomic approaches to unravel the composition and function of the human intestinal microbiota. In: Heidt PJ, Snel J, Midtvedt T, Rusch V (eds.) Intestinal Microbiomics: Novel Indicators of Health and Disease. Herborn: Old Herborn University Foundation, 2010: 27-39.
7. Falk PG, Hooper LV, Midtvedt T, Gordon JI. Creating and maintaining the gastrointestinal ecosystem: what we know and need to know from gnotobiology. Microbiol Mol Biol Rev 1998; 62: 1157-1170. (Pubitemid 28558295)
8. Hooper LV, Falk PG, Gordon JI. Analyzingthemolecularfoundationsof commensalism in the mouse intestine. Curr Opin Microbiol 2000; 3: 79-85.
9. Mestecky J, Russel MW, Jackson S, Michalek SM, Tlaskalova-Hogenova H, Sterzl J (eds.) Advances in Mucosal Immunology. New York/London: Plenum Press, 1995.
10. Tlaskalova-Hogenova H, Tuckova L, Lodinova-Zadnikova R, Stepankova R, Cukrowska B, Funda D P et al. Mucosal immunity: its role in defenseand allergy. Int Arch Allergy Immunol 2002; 128: 77-89. (Pubitemid 34639015)
11. Mestecky J, Bienenstock J, Lamm ME, McGhee J, Strober W, Mayer L (eds.))Mucosal Immunology. 3rd ed. Amsterdam: Elsevier-Academic Press, 2005.
12. Garrett WS, Gallini CA, Yatsunenko T, Michaud M, Du Bois A, Delaney ML et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 2010; 8: 292-300.
13. Hill DA, Artis D. Intestinal bacteria and the regulation of immune cell homeostasis. Annu Rev Immunol 2010; 28: 623-667.
14. Chung H, Kasper DL. Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Curr Opin Immunol 2010; 22: 455-460.
15. Russell MW, Ogra PL. Mucosal decisions: tolerance and responsiveness at mucosal surfaces. Immunol Invest 2010; 39: 297-302.
16. Tlaskalova-Hogenova H, Stepankova R, Hudcovic T, Tuckova L, Cukrowska B, Lodinova-Zadnikova R et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 2004; 93: 97-108. (Pubitemid 38678650)
17. Turner JR. Intestinal mucosal barrierfunction inhealthanddisease. Nat Rev Immunol 2009; 9: 799-809.
18. Linden SK, Sutton P, Karlsson NG, Korolik V, McGuckin MA. Mucins in the mucosal barrier to infection. Mucosal Immunol 2008; 1: 183-197. (Pubitemid 351541304)
19. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living l if e on the edge of the wall. Am J Pathol 2008; 173: 1243-1252.
20. Bienenstock J, Collins S. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: psycho-neuroimmunology and the intestinal microbiota: clinical observations and basic mechanisms. Clin Exp Immunol 2010; 160: 85-91.
21. Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev 2000; 173: 89-97. (Pubitemid 30095213)
22. Kobayashi K, Inohara N, Hernandez LD, Galan JE, Nunez G, Janeway CA et al. RICK/Rip2/CARDIAK mediates signallingfor receptorsof the innateand adaptive immune systems. Nature 2002; 416: 194-199. (Pubitemid 34246479)
23. Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttlingofPPAR-gammaandRel A. Nat Immunol 2004; 5: 104-112. (Pubitemid 38081475)
24. Petnicki-Ocwieja T, Hrncir T, Liu YJ, Biswas A, Hudcovic T, Tlaskalova-Hogenova H et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci USA 2009; 106: 15813-15818.
25. Rescigno M, Di Sabatino A. Dendritic cells in intestinal homeostasis and disease. J Clin Invest 2009; 119: 2441-2450.
26. Coombes JL, Powrie F. Dendritic cells in intestinal immune regulation. Nat Rev Immunol 2008; 8: 435-446. (Pubitemid 351733420)
27. Barnes MJ, Powrie F. Regulatory T cells reinforce intestinal homeostasis. Immunity 2009; 31: 401-411.
28. Mestecky J, Russell MW, Elson CO. Intestinal Ig A: novelviewson itsfunction inthe defence of the largest mucosal surface. Gut 1999; 44: 2-5. (Pubitemid 29143269)
29. Holmgren J, Czerkinsky C. Mucosal immunityandvaccines. Nat Med 2005; 11: S45-S53.
30. Brandtzaeg P. Updateon mucosal immunoglobulin A ingastrointestinal disease. Curr Opin Gastroenterol 2010; 26: 554-563.
31. Ogra PL. Developmental aspects of the mucosal immune system: role of external environment, mucosal microflora and milk. Adv Exp Med Biol 2009; 639: 41-56.
32. Hanson LA, Silfverdal SA. The mother's immune system is a balanced threat to the foetus, turningto protection of the neonate. Acta Paediatr 2009; 98: 221-228.
33. Kverka M, Burianova J, Lodinova-Zadnikova R, Kocourkova I, Cinova J, Tuckova L et al. Cytokine profiling in human colostrum and milk by protein array. Clin Chem 2007; 53: 955-962. (Pubitemid 46744254)
34. Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr 2009; 98: 229-238.
35. Tlaskalova-Hogenova H, Cerna J, Mandel L. Peroral immunizationof germfreepiglets: appearance of antibody-forming cells and antibodies of different isotypes. Scand J Immunol 1981; 13: 467-472. (Pubitemid 11143652)
36. Cebra JJ. Influences of microbiota on intestinal immune system development. Am J Clin Nutr 1999; 69: 1046S-1051S. (Pubitemid 29205083)
37. Cebra JJ, Jiang HQ, Boiko N, Tlaskalová-Hogenová H. The roleof mucosal microbiota inthedevelopment, maintenance, andpathologiesofthemucosal immunesystem. In: Mestecky J, Bienenstock J, Lamm ME, McGhee J, Strober W, Mayer L (eds.)Mucosal Immunology. 3rd ed Amsterdam: Elsevier-Academic Press, 2005: 335-368.
38. Sterzl J, Silverstein AM. Developmental aspectsof immunity. Adv Immunol 1967; 6: 337-459.
39. Tlaskalova H, Kamarytova V, Mandel L, Prokesova L, Kruml J, Lanc A et al. The immune response of germ-free piglets after peroral monocontamination with living Escherichia coli strain 086. I. The fate of antigen, dynamics and site of antibody formation, nature of antibodies and formation of heterohaemagglutinins. Folia Biol (Praha) 1970; 16: 177-187.
40. Tlaskalova-Hogenova H, Sterzl J, Stepankova R, Dlabac V, Veticka V, Rossmann P et al. Development of immunological capacity under germfree and conventional conditions. Ann N Y Acad Sci 1983; 409: 96-113. (Pubitemid 13057638)
41. Mandel L, Travnicek J. The minipig as a model in gnotobiology. Nahrung 1987; 31: 613-618.
42. Tlaskalová-Hogenová H. Gnotobiology as a tool\an introduction. In: Lefkovits I (ed.)Immunology Methods Manual: The Comprehensive Sourcebook of Techniques. London: Academic Press Ltd, 1997: 1524-1529.
43. Stepankova R, Sinkora J, Hudcovic T, Kozakova H, Tlaskalova-Hogenova H. Differences in development of lymphocyte subpopulations from gut-associated lymphatic tissue (GALT) of germfree and conventional rats: effect of aging. Folia Microbiol (Praha) 1998; 43: 531-534. (Pubitemid 128439399)
44. Sinkora M, Butler JE. The ontogeny of the porcine immune system. Dev Comp Immunol 2009; 33: 273-283.
45. Hrncir T, Stepankova R, Kozakova H, Hudcovic T, Tlaskalova-Hogenova H. Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice. BMcImmunol 2008; 9: 65.
46. Williams AM, Probert CS, Stepankova R, Tlaskalova-Hogenova H, Phillips A, Bland PW. Effects of microflora on the neonatal development of gut mucosal T cells and myeloid cells in the mouse. Immunology 2006; 119:470-478. (Pubitemid 44722209)
47. Probert CS, Williams AM, Stepankova R, Tlaskalova-Hogenova H, Phillips A, Bland PW. The effect of weaningon theclonalityof alpha beta T-cell receptor Tcells in the intestine of GF and SPF mice. Dev Comp Immunol 2007; 31: 606-617. (Pubitemid 46109039)
48. Kozakova H, Rehakova Z, Kolinska J. Bifidobacterium bifidum monoassociation of gnotobiotic mice: effect on enterocyte brush-border enzymes. Folia Microbiol(Praha) 2001; 46: 573-576. (Pubitemid 33638685)
49. Umesaki Y, Tohyama K, Mutai M. Biosynthesis of microvillus membrane-associated glycoproteins of small intestinal epithelial cells in germ-free and conventionalized mice. J Biochem 1982; 92: 373-379. (Pubitemid 13064759)
50. Bry L, Falk PG, Midtvedt T, Gordon JI. A model of host-microbial interactions in an open mammalian ecosystem. Science 1996; 273: 1380-1383. (Pubitemid 26296524)
51. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 2002; 347: 911-920.
52. Backhed F. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: the normal gut microbiota in health and disease. Clin Exp Immunol 2010; 160: 80-84.
53. Ehlers S, Kaufmann SH. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: lifestyle changes affecting the host-environment interface. Clin Exp Immunol 2010; 160: 10-14.
54. Selmi C, Gershwin ME. The role of environmental factors in primary biliary cirrhosis. Trends Immunol 2009; 30: 415-420.
55. Youinou P, Pers JO, Gershwin ME, Shoenfeld Y. Geo-epidemiology and autoimmunity. J Autoimmun 2010; 34: J163-J167.
56. Israeli E, Grotto I, Gilburd B, Balicer RD, Goldin E, Wiik A et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut 2005; 54: 1232-1236. (Pubitemid 41192480)
57. Shoenfeld Y, Blank M, Abu-Shakra M, Amital H, Barzilai O, Berkun Y et al. Themosaic of autoimmunity: prediction, autoantibodies, and therapy in autoimmune diseases\2008. Isr Med Assoc J 2008; 10: 13-19. (Pubitemid 351649456)
58. Westall FC. Molecular mimicry revisited: gut bacteria and multiple sclerosis. J Clin Microbiol 2006; 44: 2099-2104. (Pubitemid 43902159)
59. Blank M, Barzilai O, Shoenfeld Y. Molecular mimicry and auto-immunity. Clin Rev Allergy Immunol 2007; 32: 111-118. (Pubitemid 46594581)
60. van Eden W, Wick G, Albani S, Cohen I. Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases. Ann NY Acad Sci 2007; 1113: 217-237. (Pubitemid 350015017)
61. Zhernakova A, van Diemen CC, Wijmenga C Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat Rev Genet 2009; 10: 43-55.
62. Hawkins RD, Hon GC, Ren B. Next-generationgenomics: an integrativeapproach. Nat Rev Genet 2010; 11:476-486.
63. Tlaskalova-Hogenova H, Stepankova R, Tuckova L, Farre MA, Funda DP, Verdu EF et al. Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora. Folia Microbiol (Praha) 1998; 43: 545-550. (Pubitemid 128439402)
64. Abt MC, Artis D. The intestinal microbiota in health and disease: the influence of microbial products on immunecell homeostasis. Curr Opin Gastroenterol 2009; 25: 496-502.
65. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev 2010; 90: 859-904.
66. Singh B, Read S, Asseman C, Malmstrom V, Mottet C, Stephens LA et al. Control of intestinal inflammation by regulatoryT cells. Immunol Rev 2001; 182: 190-200. (Pubitemid 33070218)
67. Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B, Stepankova R et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 2006; 25: 309-318.
68. Clavel T, Haller D. Molecular interactions between bacteria, theepithelium, andthe mucosal immunesystem intheintestinaltract: implicationsforchronic inflammation. Curr Issues Intest Microbiol 2007; 8: 25-43.
69. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448: 427-434. (Pubitemid 47123518)
70. Blumberg RS. Inflammation in the intestinal tract: pathogenesis and treatment. Dig Dis 2009; 27: 455-464.
71. Bengmark S. Bioecological control of inflammatory bowel disease. Clin Nutr 2007; 26: 169-181. (Pubitemid 46477826)
72. Mathew CG. New links to the pathogenesis of Crohn disease provided by genome-wide association scans. Nat Rev Genet 2008; 9: 9-14. (Pubitemid 350277296)
73. Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanismsof hostdialoguewiththemicrobiota. Immunol Rev 2005; 206: 260-276. (Pubitemid 41105175)
74. Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 1998; 66: 5224-5231. (Pubitemid 29044613)
75. Dieleman LA, Hoentjen F, Qian BF, Sprengers D, Tjwa E, Torres MF et al. Reduced ratio of protectiveversus proinflammatorycytokine responsesto commensal bacteria in HLA-B27 transgenic rats. Clin Exp Immunol 2004; 136: 30-39. (Pubitemid 38437762)
76. Hudcovic T, Stepankova R, Cebra J, Tlaskalova-Hogenova H. The roleof microflora in the development of intestinal inflammation: acute and chronic colitis induced by dextran sulfate in germ-free and conventionally reared immunocompetent and immunodeficient mice. Folia Microbiol (Praha) 2001; 46: 565-572. (Pubitemid 33638684)
77. + T cells. Inflamm Bowel Dis 2007; 13: 1202-1211. (Pubitemid 47597767)
78. Verdu EF, Bercik P, Cukrowska B, Farre-Castany MA, Bouzourene H, Saraga E et al. Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severityof experimental acutecolitis in BALB/cmice. Clin Exp Immunol 2000; 120: 46-50. (Pubitemid 30176898)
79. Kverka M, Zakostelska Z, Klimesova K, Sokol D, Hudcovic T, Hrncir T et al. Oral administration of Parabacteroides distasonis antigens attenuates experimental murine colitis through modulation of immunity and microbiota composition. Clin Exp Immunol 2010; 163: 250-259.
80. Kucera P, Novakova D, Behanova M, Novak J, Tlaskalova-Hogenova H, Andel M. Gliadin, endomysial and thyroid antibodies in patients with latent autoimmune diabetes of adults (LADA). Clin Exp Immunol 2003; 133: 139-143. (Pubitemid 36791952)
81. Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol 2005; 2: 416-422. (Pubitemid 41486094)
82. Wapenaar MC, Monsuur AJ, van Bodegraven AA, Weersma RK, Bevova MR, Linskens RK et al. Associationswithtightjunction genes PARD3 and MAGI2 in Dutch patients pointtoa common barrier defect forcoeliac diseaseand ulcerativecolitis. Gut 2008; 57: 463-467. (Pubitemid 351442527)
83. Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes. Diabetes Metab Res Rev 2008; 24: 59-63.
84. Plot L, Amital H. Infectiousassociationsof Celiacdisease. Autoimmun Rev 2009; 8: 316-319.
85. Ou G, Hedberg M, Horstedt P, Baranov V, Forsberg G, Drobni M et al. Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease. Am J Gastroenterol 2009; 104: 3058-3067.
86. Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Specific duodenal and faecal bacterialgroupsassociated with paediatriccoeliacdisease. J Clin Pathol 2009; 62: 264-269.
87. de Palma G, Cinova J, Stepankova R, Tuckova L, Sanz Y. Pivotal advance: Bifidobacteria and Gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease. J Leukoc Biol 2010; 87: 765-778.
88. Stepankova R, Tlaskalova-Hogenova H, Sinkora J, Jodl J, Fric P. Changes in jejunal mucosa after long-term feeding of germfree rats with gluten. Scand J Gastroenterol 1996; 31: 551-557. (Pubitemid 26196135)
89. Vaarala O. Leaking gut in type 1 diabetes. Curr Opin Gastroenterol 2008; 24: 701-706.
90. Pozzilli P, Signore A, Williams AJ, Beales PE. N O Dmousecoloniesaroundtheworld\recent facts and figures. Immunol Today 1993; 14: 193-196.
91. Funda D, Fundova P, Harrison L. Microflora-dependency of selected diabetes-preventive diets: germ-free and ex-germ-free monocolonized NOD mice as models for studying environmental factors in type 1 diabetes. 13th International Congress of Immunology, MS-11.4 16 (Brazilian Societyfor Immunology, Rio de Janeiro, 2007).
92. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008;455: 1109-1113.
93. Hoorfar J, Buschard K, Dagnaes-Hansen F. Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Br J Nutr 1993;69:597-607. (Pubitemid 23105495)
94. Funda DP, Kaas A, Bock T, Tlaskalova-Hogenova H, Buschard K. Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev 1999; 15: 323-327. (Pubitemid 29535091)
95. Funda DP, Kaas A, Tlaskalova-Hogenova H, Buschard K. Gluten-free but also gluten-enriched (gluten +) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes. Diabetes Metab Res Rev 2008; 24: 59-63. (Pubitemid 351176001)
96. Jelinkova L, Tuckova L, Cinova J, Flegelova Z, Tlaskalova-Hogenova H. Gliadin stimulates human monocytes to production of IL-8 and TNF-alpha through a mechanism involving NF-kappaB. FEBS Lett 2004; 571: 81-85. (Pubitemid 38992927)
97. Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A et al. Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol 2006; 41: 408-419. (Pubitemid 43675406)
98. Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R et al. Role of the intestinal tightjunction modulatorzonulin inthepathogenesisof typeI diabetes in B Bdiabetic-prone rats. Proc Natl Acad Sci USA 2005; 102: 2916-2921. (Pubitemid 40299891)
99. + B cells and increased intestinal permeability. Dig Dis Sci 1996; 41: 2493-2498. (Pubitemid 27041808)
100. Pender MP. Preventing and curing multiple sclerosis by controlling Epstein-Barr virus infection. Autoimmun Rev 2009; 8: 563-568.
101. Schrijver IA, van Meurs M, Melief MJ, Wim Ang C, Buljevac D, Ravid R et al. Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis. Brain 2001; 124: 1544-1554. (Pubitemid 32726768)
102. Faria AM, Weiner HL. Oral tolerance: therapeutic implications for autoimmune diseases. Clin Dev Immunol 2006; 13: 143-157. (Pubitemid 44950033)
103. Ochoa-Reparaz J, Mielcarz DW, Ditrio LE, Burroughs AR, Foureau DM, Haque-Begum S et al. Role of gut commensal microflora in the development of experimental autoimmuneencephalomyelitis. J Immunol 2009; 183: 6041-6050.
104. Ochoa-Reparaz J, Mielcarz DW, Wang Y, Begum-Haque S, Dasgupta S, Kasper DL et al. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol 2010; 3: 487-495.
105. Collins SM, Bercik P. The relationship between intestinal microbiota and thecentral nervous system in normal gastrointestinal function and disease. Gastroenterology 2009;136:2003-2014.
106. Gershon MD. The enteric nervous system: a second brain. Hosp Pract (Minneap) 1999; 34: 31-32, 35-38, 41-42 passim.
107. Lebouvier T, Chaumette T, Paillusson S, Duyckaerts C, Bruley des Varannes S, Neunlist M et al. The second brain and Parkinson's disease. Eur J Neurosci 2009; 30: 735-741.
108. deMagistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P et al.Alterationsof the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr 2010; 51: 418-424.
109. Theoharides TC, Doyle R. Autism, gut-blood-brain barrier, and mast cells. J Clin Psychopharmacol 2008; 28: 479-483.
110. Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD et al. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 2010; 16: 444-453.
111. Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC, Nicholson JK. Urinarymetabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res 2010; 9: 2996-3004.
112. Maes M, Kubera M, Leunis JC The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett 2008; 29: 117-124.
113. Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nat Neurosci 2010; 13: 1161-1169.
114. Castany MA, Stepankova R, Tlaskalova H, Turner LF, Liu Z, Bures J. Studyof behavior of rats with gluten-induced enteropathy. Int J Neurosci 1995; 83: 7-15. (Pubitemid 3011992)
115. Addolorato G, Di Giuda D, de Rossi G, Valenza V, Domenicali M, Caputo F et al. Regional cerebral hypoperfusion in patients with celiac disease. Am J Med 2004; 116: 312-317. (Pubitemid 38230290)
116. Weber P, Brune T, Ganser G, Zimmer KP. Gastrointestinal symptoms and permeability in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol 2003; 21: 657-662. (Pubitemid 37236464)
117. Rodriguez-Reyna TS, Martinez-Reyes C, Yamamoto-Furusho JK. Rheumatic manifestations of inflammatory bowel disease. World J Gastroenterol 2009; 15: 5517-5524.
118. Toivanen P. Normal intestinal microbiota in the aetiopathogenesis of rheumatoid arthritis. Ann Rheum Dis 2003; 62: 807-811. (Pubitemid 37026488)
119. Ebringer A, Rashid T, Wilson C Rheumatoid arthritis, proteus, anti-CCP antibodies and Karl Popper. Autoimmun Rev 2010; 9: 216-223.
120. Rashid T, Ebringer A. Ankylosing spondylitis is linked to Klebsiella\the evidence. Clin Rheumatol 2007; 26: 858-864. (Pubitemid 46951278)
121. Vaahtovuo J, Munukka E, Korkeamaki M, Luukkainen R, Toivanen P. Fetal microbiota in early rheumatoid arthritis. J Rheumatol 2008; 35: 1500-1505.
122. Rehakova Z, Capkova J, Stepankova R, Sinkora J, Louzecka A, Ivanyi P et al. Germ-free mice do not develop ankylosing enthesopathy, a spontaneous joint disease. Hum Immunol 2000; 61: 555-558. (Pubitemid 30346481)
123. Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 1994; 180: 2359-2364. (Pubitemid 24351619)
124. Rovensky J, Stancikova M, Svik K, Uteseny J, Bauerova K, Jurcovicova J. Treatmentof adjuvant-induced arthritis with the combination of methotrexate and probiotic bacteria Escherichia coli O83 (Colinfant). Folia Microbiol (Praha) 2009; 54: 359-363.
125. Wu HJ, Ivanov, II, Darce J, Hattori K, Shima T, Umesaki Y et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 2010; 32: 815-827.
126. Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlyingthe resistanceto diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA 2007; 104: 979-984. (Pubitemid 46154722)
127. Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK et al. Effectsof the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA 2008; 105: 16767-16772.
128. Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol 2010; 26: 5-11.
129. Ayada K, Yokota K, Kobayashi K, Shoenfeld Y, Matsuura E, Oguma K. Chronic infections and atherosclerosis. Clin Rev Allergy Immunol 2009; 37: 44-48.
130. Sandek A, Anker SD, von Haehling S. Thegut and intestinal bacteria in chronic heart failure. Curr Drug Metab 2009; 10: 22-28.
131. Wright SD, Burton C, Hernandez M, Hassing H, Montenegro J, Mundt S et al. Infectious agents are not necessary for murine atherogenesis. J Exp Med 2000; 191: 1437-1442.
132. Stepankova R, Tonar Z, Bartova J, Nedorost L, Rossman P, Poledne R et al. Absenceof microbiota (germ-free conditions) accelerates the atherosclerosis in Apo E-deficient micefed standard lowcholesterol diet. J Atheroscler Thromb 2010; 17: 796-804.
133. Guarner F, Bourdet-Sicard R, Brandtzaeg P, Gill HS, McGuirk P, van Eden W et al. Mechanismsof disease: thehygienehypothesisrevisited. Nat Clin Pract Gastroenterol Hepatol 2006; 3: 275-284.
134. Strachan DP. Hay fever, hygiene, and householdsize. BMJ1989; 299: 1259-1260.
135. von Mutius E. Gene-environment interactions in asthma. J Allergy Clin Immunol 2009; 123: 3-11; quiz 2-3.
136. Adlerberth I, Strachan DP, Matricardi PM, Ahrne S, Orfei L, Aberg N et al. Gut microbiota and development of atopic eczema in 3 European birth cohorts. J Allergy Clin Immunol 2007; 120: 343-350. (Pubitemid 47102389)
137. Lodinova-Zadnikova R, Cukrowska B, Tlaskalova-Hogenova H. Oral administration of probiotic Escherichia coli after birth reduces frequency of allergies and repeated infections later in life (after 10 and 20 years). Int Arch Allergy Immunol 2003; 131: 209-211. (Pubitemid 36921060)
138. Bjorksten B. Allergy prevention. Interventions during pregnancy and early infancy. Clin Rev Allergy Immunol 2004; 26: 129-138. (Pubitemid 38918080)
139. Isolauri E, Salminen S. Probiotics: use in allergic disorders: a Nutrition, Allergy, Mucosal Immunology, and Intestinal Microbiota (NAMI) Research Group Report. J Clin Gastroenterol 2008; 42(Suppl 2) S91-S96.
140. Lonnqvist A, Ostman S, Almqvist N, Hultkrantz S, Telemo E, Wold AE et al. Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy. Eur J Immunol 2009; 39: 447-456.
141. Repa A, Kozakova H, Hudcovic T, Stepankova R, Hrncir T, Tlaskalova-Hogenova H et al. Susceptibility to nasal and oral tolerance induction to the major birch pollen allergen Bet v 1 is not dependent on the presence of the microflora. Immunol Lett 2008; 117: 50-56.
142. de Martel C, Franceschi S. Infections and cancer: established associations and new hypotheses. Crit Rev Oncol Hematol 2009; 70: 183-194.
143. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454:436-444.
144. Schottelius AJ, Dinter H. Cytokines, NF-kappaB, microenvironment, intestinal inflammation and cancer. Cancer Treat Res 2006; 130: 67-87.
145. McConnell BB, Yang VW. The role of Inflammation in the pathogenesis of colorectal cancer. Curr Colorectal Cancer Rep 2009; 5: 69-74.
146. O'Keefe SJ, Ou J, Aufreiter S, O'Connor D, Sharma S, Sepulveda J et al. Products of the colonic microbiota mediate the effects of diet on colon cancer risk. J Nutr 2009; 139: 2044-2048.
147. Vannucci L, Stepankova R, Grobarova V, Kozakova H, Rossmann P, Klimesova K et al. Colorectal carcinoma: Importance of colonic environment for anti-cancer responseand systemic immunity. J Immunotoxicol 2009; 6: 217-226.
148. Wang CZ, Ma XQ, Yang DH, Guo ZR, Liu GR, Zhao GX et al. Production of enterodiol from defattedflaxseedsthrough biotransformation byhuman intestinal bacteria. BMcMicrobiol 2010; 10: 115.
149. Velentzis LS, Cantwell MM, Cardwell C, Keshtgar MR, Leathem AJ, Woodside JV. Lignans and breast cancer risk in pre-and post-menopausal women: meta-analyses of observational studies. Br J Cancer 2009; 100: 1492-1498.
150. Chung KT, Stevens SE Jr, Cerniglia CE. The reduction of azo dyes by the intestinal microflora. Crit Rev Microbiol 1992; 18: 175-190.
151. Babu SD, Jayanthi V, Devaraj N, Reis CA, Devaraj H. Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium. Mol Cancer 2006; 5: 10.
152. Fukata M, Abreu MT. Role of Toll-like receptors in gastrointestinal malignancies. Oncogene 2008; 27: 234-243.
153. Reddy BS, Narisawa T, Wright P, Vukusich D, Weisburger JH, Wynder EL. Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats. Cancer Res 1975;35:287-290.
154. Sacksteder MR. Occurrenceof spontaneous tumors in the germfree F344 rat. J Natl Cancer Inst 1976; 57: 1371-1373. (Pubitemid 8009103)
155. Vannucci L, Stepankova R, Kozakova H, Fiserova A, Rossmann P, Tlaskalova-Hogenova H. Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environmentsaffectthesystemic immunity. Int J Oncol 2008; 32: 609-617. (Pubitemid 351330467)
156. Oozeer R, Rescigno M, Ross RP, Knol J, Blaut M, Khlebnikov A et al. Gut health: predictive biomarkers for preventive medicine and development of functional foods. Br J Nutr 2010; 103: 1539-1544.
157. Cukrowska B, Lod Inova-Zadn Ikova R, Enders C, Sonnenborn U, Schulze J, Tlaskalova-Hogenova H. Specific proliferative and antibody responses of premature infants to intestinalcolonizationwithnonpathogenicprobiotic E. colistrain Nissle 1917. Scand J Immunol 2002; 55: 204-209. (Pubitemid 34304560)
158. Bleich A, Sundberg JP, Smoczek A, von Wasielewski R, de Buhr MF, Janus LM et al. Sensitivityto Escherichiacoli Nissle 1917 in mice is dependenton environment and genetic background. Int J Exp Pathol 2008; 89: 45-54.
159. Preidis GA, Versalovic J. Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. Gastroenterology 2009; 136: 2015-2031.
160. Trebichavsky I, Rada V, Splichalova A, Splichal I. Cross-talk of human gut with bifidobacteria. Nutr Rev 2009; 67: 77-82.
161. Hormannsperger G, Haller D. Molecular crosstalk of probiotic bacteria with the intestinal immune system: clinical relevance in the context of inflammatory bowel disease. Int J Med Microbiol 2010; 300: 63-73.
162. Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RJ et al. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol 2010; 298: G851-G859.
163. Wells JM, Rossi O, Meijerink M, van Baarlen P. Microbes and Health Sackler Colloquium: epithelial crosstalk at the microbiota-mucosal interface. Proc Natl Acad Sci USA 2010; in press.
164. Fric P. Probiotics in gastroenterology. Z Gastroenterol 2002; 40: 197-201. Czech.
165. Floch MH, Kim AS (eds.))Probiotics:A Clinical Guide. 1st ed. Thorofare: SLACK Inc; 2010.
166. Kalliomaki M, Antoine JM, Herz U, Rijkers GT, Wells JM, Mercenier A. Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics. J Nutr 2010; 140: 713S-721S.
167. Matsuzaki T, Takagi A, Ikemura H, Matsuguchi T, Yokokura T. Intestinal microflora: probiotics and autoimmunity. J Nutr 2007; 137: 798S-802S. (Pubitemid 46397521)
168. Maassen CB, Claassen E. Strain-dependent effects of probiotic lactobacilli on EAE autoimmunity. Vaccine 2008; 26: 2056-2057.
169. van Baarlen P, Troost FJ, van Hemert S, van der Meer C, deVos WM, deGroot PJ et al. Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proc Natl Acad Sci USA 2009; 106: 2371-2376.
170. Hanniffy S, Wiedermann U, Repa A, Mercenier A, Daniel C, Fioramonti J et al. Potential and opportunities for use of recombinant lactic acid bacteria in human health. Adv Appl Microbiol 2004; 56: 1-64. (Pubitemid 39574531)
171. Schwarzer M, Repa A, Daniel C, Schabussova I, Hrncir T, Pot B et al. Neonatal colonization of mice with Lactobacillus plantarum producing the aeroallergen Bet v 1 biasestowardsTh1 and T-regulatory responses uponsystemicsensitization. Allergy 2010; in press.