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Microbial host interactions in IBD: Implications for pathogenesis and therapy

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Abstract

Crohn’s disease (CD), ulcerative colitis (UC), and pouchitis appear to be caused by pathogenic T-cell responses to discrete antigens from the complex luminal microbiota, with susceptibility conferred by genetic polymorphisms that regulate bacterial killing, mucosal barrier function, or immune responses. Environmental triggers initiate or reactivate inflammation and modulate genetic susceptibility. New pathogenesis concepts include defective bacterial killing by innate immune cells in CD, colonization of the ileum in CD with functionally abnormal Escherichia coli that adhere to and invade epithelial cells and resist bacterial killing, and alterations in enteric microbiota composition in CD, UC, and pouchitis detected by molecular probes. The considerable therapeutic potential of manipulating the enteric microbiota in inflammatory bowel disease patients has not been realized, probably due to failure to recognize heterogenic disease mechanisms that require individualized use of antibiotics, probiotics, prebiotics, combination therapies, and genetically engineered bacteria to restore mucosal homeostasis.

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References and Recommended Reading

  1. Eckburg PB, Relman DA: The role of microbes in Crohn’s disease. Clin Infect Dis 2007, 44:256–262.

    Article  PubMed  CAS  Google Scholar 

  2. Strober W, Fuss I, Mannon P: The fundamental basis of inflammatory bowel disease. J Clin Invest 2007, 117:514–521.

    Article  PubMed  CAS  Google Scholar 

  3. Sartor RB: Bacteria in Crohn’s disease: mechanisms of inflammation and therapeutic implications. J Clin Gastroenterol 2007, 41:S37–S43.

    Article  Google Scholar 

  4. Sartor RB: Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 2006, 3:390–407.

    Article  PubMed  CAS  Google Scholar 

  5. Frank DN, St Amand AL, Feldman RA, et al.: Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 2007, [In press].

  6. Eckburg PB, Bik EM, Bernstein CN, et al.: Diversity of the human intestinal microbial flora. Science 2005, 308:1635–1638.

    Article  PubMed  Google Scholar 

  7. Ley RE, Turnbaugh PJ, Klein S, Gordon JI: Microbial ecology: human gut microbes associated with obesity. Nature 2006, 444:1022–1023.

    Article  PubMed  CAS  Google Scholar 

  8. Swidsinski A, Weber J, Loening-Baucke V, et al.: Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol 2005, 43:3380–3389.

    Article  PubMed  Google Scholar 

  9. Mow WS, Vasiliauskas EA, Lin YC, et al.: Association of antibody responses to microbial antigens and complications of small bowel Crohn’s disease. Gastroenterology 2004, 126:414–424.

    Article  PubMed  CAS  Google Scholar 

  10. Dubinsky MC, Lin YC, Dutridge D, et al.: Serum immune responses predict rapid disease progression among children with Crohn’s disease: immune responses predict disease progression. Am J Gastroenterol 2006, 101:360–367.

    Article  PubMed  Google Scholar 

  11. Israeli E, Grotto I, Gilburd B, et al.: Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut 2005, 54:1232–1236.

    Article  PubMed  CAS  Google Scholar 

  12. Spivak J, Landers CJ, Vasiliauskas EA, et al.: Antibodies to I2 predict clinical response to fecal diversion in Crohn’s disease. Inflamm Bowel Dis 2006, 12:1122–1130.

    Article  PubMed  Google Scholar 

  13. Mow WS, Landers CJ, Steinhart AH, et al.: High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn’s disease: a pilot study. Dig Dis Sci 2004, 49:1280–1286.

    Article  PubMed  CAS  Google Scholar 

  14. Mei L, Targan SR, Landers CJ, et al.: Familial expression of anti-Escherichia coli outer membrane porin C in relatives of patients with Crohn’s disease. Gastroenterology 2006, 130:1078–1085.

    Article  PubMed  CAS  Google Scholar 

  15. Papadakis KA, Yang H, Ippoliti A, et al.: Anti-flagellin (CBir1) phenotypic and genetic Crohn’s disease associations. Inflamm Bowel Dis 2007, 13:524–530.

    Article  PubMed  Google Scholar 

  16. Devlin SM, Yang H, Ippoliti A, et al.: NOD2 variants and antibody response to microbial antigens in Crohn’s disease patients and their unaffected relatives. Gastroenterology 2007, 132:576–586.

    Article  PubMed  CAS  Google Scholar 

  17. Strober W, Murray PJ, Kitani A, Watanabe T: Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol 2006, 6:9–20.

    Article  PubMed  CAS  Google Scholar 

  18. Hampe J, Franke A, Rosenstiel P, et al.: A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn’s disease in ATG16L1. Nat Genet 2007, 39:207–211.

    Article  PubMed  CAS  Google Scholar 

  19. Rioux JD, Xavier RJ, Taylor KD, et al.: Genome-wide association study identifies new susceptibility loci for Crohn’s disease and implicates autophagy in disease pathogenesis. Nat Genet 2007, 39:596–604.

    Article  PubMed  CAS  Google Scholar 

  20. Lal S, Steinhart AH: Antibiotic therapy for Crohn’s disease: a review. Can J Gastroenterol 2006, 20:651–655.

    PubMed  Google Scholar 

  21. Bohm SK, Kruis W: Probiotics: do they help to control intestinal inflammation? Ann N Y Acad Sci 2006, 1072:339–350.

    Article  PubMed  CAS  Google Scholar 

  22. Sartor RB: Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics and prebiotics. Gastroenterology 2004, 126:1620–1633.

    Article  PubMed  Google Scholar 

  23. Bamias G, Okazawa A, Rivera-Nieves J, et al.: Commensal bacteria exacerbate intestinal inflammation but are not essential for the development of murine ileitis. J Immunol 2007, 178:1809–1818.

    PubMed  CAS  Google Scholar 

  24. Schultz M, Tonkonogy SL, Sellon RK, et al.: IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation. Am J Physiol 1999, 276:G1461–G1472.

    PubMed  CAS  Google Scholar 

  25. Kim SK, Tonkonogy SL, Karrasch T, et al.: Dual association of gnotobiotic IL-10-/-mice with two nonpathogenic commensal bacteria induces aggressive pancolitis. Inflamm Bowel Dis 2007, [In press].

  26. Kim SC, Tonkonogy SL, Albright CA, Sartor RB: Different host genetic backgrounds determine disease phenotypes induced by selective bacterial colonization [abstract]. Gastroenterology 2005, 128:A512.

    Google Scholar 

  27. Kim SC, Tonkonogy SL, Albright CA, et al.: Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 2005, 128:891–906.

    Article  PubMed  CAS  Google Scholar 

  28. Lodes MJ, Cong Y, Elson CO, et al.: Bacterial flagellin is a dominant antigen in Crohn’s disease. J Clin Invest 2004, 113:1296–1306.

    Article  PubMed  CAS  Google Scholar 

  29. Sartor RB: Probiotic therapy of intestinal inflammation and infections. Curr Opin Gastroenterol 2005, 21:44–50.

    PubMed  Google Scholar 

  30. Behr MA, Schurr E: Mycobacteria in Crohn’s disease: a persistent hypothesis. Inflamm Bowel Dis 2006, 12:1000–1004.

    Article  PubMed  Google Scholar 

  31. Sartor RB: Does Mycobacterium avium subspecies paratuberculosis cause Crohn’s disease? Gut 2005, 54:896–898.

    Article  PubMed  Google Scholar 

  32. Autschbach F, Eisold S, Hinz U, et al.: High prevalence of Mycobacterium avium subsp. paratuberculosis IS900 DNA in gut tissues from individuals with Crohn’s disease. Gut 2005, 54:944–999.

    Article  PubMed  CAS  Google Scholar 

  33. Sechi LA, Gazouli M, Sieswerda LE, et al.: Relationship between Crohn’s disease, infection with Mycobacterium avium subspecies paratuberculosis and SLC11A1 gene polymorphisms in Sardinian patients. World J Gastroenterol 2006, 12:7161–7164.

    PubMed  CAS  Google Scholar 

  34. Sartor RB, Blumberg RS, Braun J, et al.: CCFA microbial-host interactions workshop: highlights and key observations. Inflamm Bowel Dis 2007, 13:600–619.

    Article  PubMed  Google Scholar 

  35. Rumsey J, Valentine JF, Naser SA: Inhibition of phagosome maturation and survival of Mycobacterium avium subspecies paratuberculosis in polymorphonuclear leukocytes from Crohn’s disease patients. Med Sci Monit 2006, 12:BR130–BR139.

    PubMed  Google Scholar 

  36. Sechi LA, Gazouli M, Ikonomopoulos J, et al.: Mycobacterium avium subsp. paratuberculosis, genetic susceptibility to Crohn’s disease, and Sardinians: the way ahead. J Clin Microbiol 2005, 43:5275–5277.

    Article  PubMed  CAS  Google Scholar 

  37. Bernstein CN, Wang MH, Sargent M, et al.: Testing the interaction between NOD-2 status and serological response to Mycobacterium paratuberculosis in cases of inflammatory bowel disease. J Clin Microbiol 2007, 45:968–971.

    Article  PubMed  CAS  Google Scholar 

  38. Baumgart M, Dogan B, Rishniw M, et al.: Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. ISME J 2007, [In press].

  39. Abubakar I, Myhill DJ, Hart AR, et al.: A case-control study of drinking water and dairy products in Crohn’s disease—further investigation of the possible role of Mycobacterium avium paratuberculosis. Am J Epidemiol 2007, 165:776–783.

    Article  PubMed  Google Scholar 

  40. Selby W, Pavli P, Crotty B, et al.: Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 2007, 132:2313–2319.

    Article  PubMed  CAS  Google Scholar 

  41. Neut C, Bulois P, Desreumaux P, et al.: Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn’s disease. Am J Gastroenterol 2002, 97:939–946.

    Article  PubMed  Google Scholar 

  42. Darfeuille-Michaud A, Boudeau J, Bulois P, et al.: High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology 2004, 127:412–421.

    Article  PubMed  Google Scholar 

  43. Barnich N, Darfeuille-Michaud A: Adherent-invasive Escherichia coli and Crohn’s disease. Curr Opin Gastroenterol 2007, 23:16–20.

    Article  PubMed  Google Scholar 

  44. Barnich N, Carvalho FA, Glasser AL, et al.: CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Clin Invest 2007, 117:1566–1574.

    Article  PubMed  CAS  Google Scholar 

  45. Sasaki M, Sitaraman SV, Babbin BA, et al.: Invasive Escherichia coli are a feature of Crohn’s disease. Lab Invest 2007, [In press].

  46. Kotlowski R, Bernstein CN, Sepehri S, Krause DO: High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut 2007, 56:669–675.

    Article  PubMed  CAS  Google Scholar 

  47. Simpson KW, Dogan B, Rishniw M, et al.: Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs. Infect Immun 2006, 74:4778–4792.

    Article  PubMed  CAS  Google Scholar 

  48. Swidsinski A, Ladhoff A, Pernthaler A, et al.: Mucosal flora in inflammatory bowel disease. Gastroenterology 2002, 122:44–54.

    Article  PubMed  Google Scholar 

  49. Rolhion N, Carvalho FA, Darfeuille-Michaud A: OmpC and the sigma(E) regulatory pathway are involved in adhesion and invasion of the Crohn’s disease-associated Escherichia coli strain LF82. Mol Microbiol 2007, 63:1684–1700.

    Article  PubMed  CAS  Google Scholar 

  50. Conte MP, Schippa S, Zamboni I, et al.: Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. Gut 2006, 55:1760–1767.

    Article  PubMed  CAS  Google Scholar 

  51. Kleessen B, Kroesen AJ, Buhr HJ, Blaut M: Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls. Scand J Gastroenterol 2002, 37:1034–1041.

    Article  PubMed  CAS  Google Scholar 

  52. Mylonaki M, Rayment NB, Rampton DS, et al.: Molecular characterization of rectal mucosa-associated bacterial flora in inflammatory bowel disease. Inflamm Bowel Dis 2005, 11:481–487.

    Article  PubMed  Google Scholar 

  53. Martinez-Medina M, Aldeguer X, Acero D, et al.: Escherichia coli in the intestinal mucosa of Crohn’s disease patients: just a commensal bacterium? [abstract]. Gastroenterology 2007, 132:A705.

    Google Scholar 

  54. Ryan P, Kelly RG, Lee G, et al.: Bacterial DNA within granulomas of patients with Crohn’s disease—detection by laser capture microdissection and PCR. Am J Gastroenterol 2004, 99:1539–1543.

    Article  PubMed  CAS  Google Scholar 

  55. Matsuda H, Fujiyama Y, Andoh A, et al.: Characterization of antibody responses against rectal mucosa-associated bacterial flora in patients with ulcerative colitis. J Gastroenterol Hepatol 2000, 15:61–68.

    Article  PubMed  CAS  Google Scholar 

  56. Landers CJ, Cohavy O, Misra R, et al.: Selected loss of tolerance evidenced by Crohn’s disease-associated immune responses to auto-and microbial antigens. Gastroenterology 2002, 123:689–699.

    Article  PubMed  CAS  Google Scholar 

  57. Dichmann R, May E, Heike M, et al.: T cell specificity and cross reactivity towards Enterobacteria, Bacteroides, Bifidobacterium, and antigens from resident intestinal flora in humans. Gut 1999, 44:812–818.

    Article  Google Scholar 

  58. Yang PC, Liu T, Wang BQ, et al.: Rhinosinusitis derived Staphylococcal enterotoxin B possibly associates with pathogenesis of ulcerative colitis. BMC Gastroenterol 2005, 5:28.

    Article  PubMed  CAS  Google Scholar 

  59. Rhee K, Housseau F, Wu S, et al.: Enterotoxigenic Bacteroides fragilis induced colonic inflammation and epithelial hyperplasia in C57bl/6 mice [abstract]. Gastroenterology 2007, 137:A701.

    Google Scholar 

  60. Gophna U, Sommerfeld K, Gophna S, et al.: Differences between tissue-associated intestinal microfloras of patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol 2006, 44:4136–4141.

    Article  PubMed  CAS  Google Scholar 

  61. Bibiloni R, Mangold M, Madsen KL, et al.: The bacteriology of biopsies differs between newly diagnosed, untreated, Crohn’s disease and ulcerative colitis patients. J Med Microbiol 2006, 55:1141–1149.

    Article  PubMed  Google Scholar 

  62. Manichanh C, Rigottier-Gois L, Bonnaud E, et al.: Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 2006, 55:205–211.

    Article  PubMed  CAS  Google Scholar 

  63. Iwaya A, Iiai T, Okamoto H, et al.: Change in the bacterial flora of pouchitis. Hepatogastroenterology 2006, 53:55–59.

    PubMed  Google Scholar 

  64. Scanlan PD, Shanahan F, O’Mahony C, Marchesi JR: Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol 2006, 44:3980–3988.

    Article  PubMed  CAS  Google Scholar 

  65. Sokol H, Lepage P, Seksik P, et al.: Molecular comparison of dominant microbiota associated with injured versus healthy mucosa in ulcerative colitis. Gut 2007, 56:152–154.

    Article  PubMed  CAS  Google Scholar 

  66. Marchesi JR, Holmes E, Khan F, et al.: Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J Proteome Res 2007, 6:546–551.

    Article  PubMed  CAS  Google Scholar 

  67. Smith FM, Coffey JC, Kell MR, et al.: A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch. Colorectal Dis 2005, 7:563–570.

    Article  PubMed  CAS  Google Scholar 

  68. Korzenik JR: Is Crohn’s disease due to defective immunity? Gut 2007, 56:2–5.

    Article  PubMed  CAS  Google Scholar 

  69. Marks DJ, Harbord MW, MacAllister R, et al.: Defective acute inflammation in Crohn’s disease: a clinical investigation. Lancet 2006, 367:668–678.

    Article  PubMed  CAS  Google Scholar 

  70. Hisamatsu T, Suzuki M, Reinecker HC, et al.: CARD15/NOD2 functions as an anti-bacterial factor in human intestinal epithelial cells. Gastroenterology 2003, 124:993–1000.

    Article  PubMed  CAS  Google Scholar 

  71. Wehkamp J, Salzman NH, Porter E, et al.: Reduced Paneth cell alpha-defensins in ileal Crohn’s disease. Proc Natl Acad Sci U S A 2005, 102:18129–18134.

    Article  PubMed  CAS  Google Scholar 

  72. Watanabe T, Kitani A, Murray PJ, Strober W: NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 2004, 5:800–808.

    Article  PubMed  CAS  Google Scholar 

  73. Fellermann K, Stange DE, Schaeffeler E, et al.: A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn’s disease of the colon. Am J Hum Genet 2006, 79:439–448.

    Article  PubMed  CAS  Google Scholar 

  74. Nuding S, Fellermann K, Wehkamp J, Stange EF: Reduced mucosal antimicrobial activity in Crohn’s disease of the colon. Gut 2007, 56:1240–1247.

    Article  PubMed  Google Scholar 

  75. Rioux JD, Daly M, Silverberg M, et al.: Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn’s disease. Nat Genet 2001, 29:223–228.

    Article  PubMed  CAS  Google Scholar 

  76. Ho GT, Soranzo N, Nimmo ER, et al.: ABCB1/MDR1 gene determines susceptibility and phenotype in ulcerative colitis: discrimination of critical variants using a genewide haplotype tagging approach. Hum Mol Genet 2006, 15:797–805.

    Article  PubMed  CAS  Google Scholar 

  77. Panwala CM, Jones JC, Viney JL: A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, Mdr1a, spontaneously develop colitis. J Immunol 1998, 161:5733–5744.

    PubMed  CAS  Google Scholar 

  78. Olson TS, Reuter BK, Scott KG, et al.: The primary defect in experimental ileitis originates from a nonhematopoietic source. J Exp Med 2006, 203:541–552.

    Article  PubMed  CAS  Google Scholar 

  79. Clavel T, Haller D: Bacteria-and host-derived mechanisms to control intestinal epithelial cell homeostasis: implications for chronic inflammation. Inflamm Bowel Dis 2007, 13:1153–1164.

    Article  PubMed  Google Scholar 

  80. Coombes JL, Robinson NJ, Maloy KJ, et al.: Regulatory T cells and intestinal homeostasis. Immunol Rev 2005, 204:184–194.

    Article  PubMed  CAS  Google Scholar 

  81. Schreiter K, Hausmann M, Spoettl T, et al.: Glycoprotein (gp) 96 expression: induced during differentiation of intestinal macrophages but impaired in Crohn’s disease. Gut 2005, 54:935–943.

    Article  PubMed  CAS  Google Scholar 

  82. Duchmann R, Kaiser I, Hermann E, et al.: Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol 1995, 102:448–455.

    Article  PubMed  CAS  Google Scholar 

  83. Kraus TA, Cheifetz A, Toy L, et al.: Evidence for a genetic defect in oral tolerance induction in inflammatory bowel disease. Inflamm Bowel Dis 2006, 12:82–88.

    Article  PubMed  Google Scholar 

  84. Haller D: Intestinal epithelial cell signaling and host-derived negative regulators under chronic inflammation: to be or not to be activated determines the balance towards commensal bacteria. Neurogastroenterol Motil 2006, 18:184–199.

    Article  PubMed  CAS  Google Scholar 

  85. Sartor RB, Hoentjen F: Proinflammatory cytokines and signaling pathways in intestinal innate immune cells. In Mucosal Immunology. Edited by Mestecky J, Lamm ME, Strober W, et al. Boston: Elsevier Academic Press; 2005:681–701.

    Google Scholar 

  86. Kagnoff MF, Eckmann L: Epithelial cells as sensors for microbial infection. J Clin Invest 1997, 100:6–10.

    PubMed  CAS  Google Scholar 

  87. Kobayashi KS, Chamaillard M, Ogura Y, et al.: Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005, 307:731–734.

    Article  PubMed  CAS  Google Scholar 

  88. Sharma R, Tesfay S, Tomson FL, et al.: Balance of bacterial pro-and anti-inflammatory mediators dictates net effect of enteropathogenic Escherichia coli (EPEC) on intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2006, 290:G685–G694.

    Article  PubMed  CAS  Google Scholar 

  89. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al.: Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004, 118:229–241.

    Article  PubMed  CAS  Google Scholar 

  90. Schreiber S, Rosenstiel P, Albrecht M, et al.: Genetics of Crohn’s disease, an archetypal inflammatory barrier disease. Nat Rev Genet 2005, 6:376–388.

    Article  PubMed  CAS  Google Scholar 

  91. Ruiz PA, Shkoda A, Kim SC, et al.: IL-10 gene-deficient mice lack TGF beta/Smad signaling and fail to inhibit proinflammatory gene expression in intestinal epithelial cells after the colonization with colitogenic Enterococcus faecalis. J Immunol 2005, 174:2990–2999.

    PubMed  CAS  Google Scholar 

  92. Nenci A, Becker C, Wullaert A, et al.: Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 2007, 446:557–561.

    Article  PubMed  CAS  Google Scholar 

  93. Pierik M, Joossens S, Van Steen K, et al.: Toll-like receptor-1,-2, and-6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 2006, 12:1–8.

    Article  PubMed  Google Scholar 

  94. Griga T, Wilkens C, Schmiegel W, et al.: Association between the promoter polymorphism T/C at position-159 of the CD14 gene and anti-inflammatory therapy in patients with inflammatory bowel disease. Eur J Med Res 2005, 10:183–186.

    PubMed  CAS  Google Scholar 

  95. Lamhonwah AM, Ackerley C, Onizuka R, et al.: Epitope shared by functional variant of organic cation/carnitine transporter, OCTN1, Campylobacter jejuni and Mycobacterium paratuberculosis may underlie susceptibility to Crohn’s disease at 5q31. Biochem Biophys Res Commun 2005, 337:1165–1175.

    Article  PubMed  CAS  Google Scholar 

  96. Rahbar A, Bostrom L, Soderberg-Naucler C: Detection of cytotoxic CD13-specific autoantibodies in sera from patients with ulcerative colitis and Crohn’s disease. J Autoimmun 2006, 26:155–164.

    Article  PubMed  CAS  Google Scholar 

  97. Ebringer A, Rashid T, Tiwana H, Wilson C: A possible link between Crohn’s disease and ankylosing spondylitis via Klebsiella infections. Clin Rheumatol 2007, 26:289–297.

    Article  PubMed  Google Scholar 

  98. Polymeros D, Bogdanos DP, Day R, et al.: Does cross-reactivity between Mycobacterium avium paratuberculosis and human intestinal antigens characterize Crohn’s disease? Gastroenterology 2006, 131:85–96.

    Article  PubMed  CAS  Google Scholar 

  99. Rodemann JF, Dubberke ER, Reske KA, et al.: Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol 2007, 5:339–344.

    Article  PubMed  Google Scholar 

  100. Issa M, Vijayapal A, Graham MB, et al.: Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol 2007, 5:345–351.

    Article  PubMed  Google Scholar 

  101. Shen B, Goldblum JR, Hull TL, et al.: Clostridium difficile-associated pouchitis. Dig Dis Sci 2006, 51:2361–2364.

    Article  PubMed  Google Scholar 

  102. Kojima T, Watanabe T, Hata K, et al.: Cytomegalovirus infection in ulcerative colitis. Scand J Gastroenterol 2006, 41:706–711.

    Article  PubMed  Google Scholar 

  103. Matsuoka K, Iwao Y, Mori T, et al.: Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 2007, 102:331–337.

    Article  PubMed  Google Scholar 

  104. Rahimi R, Nikfar S, Rezaie A, Abdollahi M: A meta-analysis of broad-spectrum antibiotic therapy in patients with active Crohn’s disease. Clin Ther 2006, 28:1983–1988.

    Article  PubMed  CAS  Google Scholar 

  105. Perencevich M, Burakoff R: Use of antibiotics in the treatment of inflammatory bowel disease. Inflamm Bowel Dis 2006, 12:651–664.

    Article  PubMed  Google Scholar 

  106. Ewaschuk JB, Tejpar QZ, Soo I, et al.: The role of antibiotic and probiotic therapies in current and future management of inflammatory bowel disease. Curr Gastroenterol Rep 2006, 8:486–498.

    Article  PubMed  Google Scholar 

  107. Gionchetti P, Rizzello F, Lammers KM, et al.: Antibiotics and probiotics in treatment of inflammatory bowel disease. World J Gastroenterol 2006, 12:3306–3313.

    PubMed  CAS  Google Scholar 

  108. Rutgeerts P, Van Assche G, Vermeire S, et al.: Ornidazole for prophylaxis of postoperative Crohn’s disease recurrence: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2005, 128:856–861.

    Article  PubMed  CAS  Google Scholar 

  109. Shafran I, Johnson L: An open-label evaluation of rifaximin in the treatment of active Crohn’s disease. Curr Med Res Opin 2005, 21:1165–1169.

    Article  PubMed  CAS  Google Scholar 

  110. Prantera C, Lochs H, Campieri M, et al.: Antibiotic treatment of Crohn’s disease: results of a multicentre, double blind, randomized, placebo-controlled trial with rifaximin. Aliment Pharmacol Ther 2006, 23:1117–1125.

    Article  PubMed  CAS  Google Scholar 

  111. Ohkusa T, Nomura T, Terai T, et al.: Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up. Scand J Gastroenterol 2005, 40:1334–1342.

    Article  PubMed  CAS  Google Scholar 

  112. Rioux KP, Fedorak RN: Probiotics in the treatment of inflammatory bowel disease. J Clin Gastroenterol 2006, 40:260–263.

    Article  PubMed  Google Scholar 

  113. Hedin C, Whelan K, Lindsay JO: Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials. Proc Nutr Soc 2007, 66:307–315.

    Article  PubMed  Google Scholar 

  114. Floch MH, Madsen KK, Jenkins DJ, et al.: Recommendations for probiotic use. J Clin Gastroenterol 2006, 40:275–278.

    Article  PubMed  Google Scholar 

  115. Mach T: Clinical usefulness of probiotics in inflammatory bowel diseases. J Physiol Pharmacol 2006, 57:23–33.

    PubMed  Google Scholar 

  116. Sheil B, Shanahan F, O’Mahony L: Probiotic effects on inflammatory bowel disease. J Nutr 2007, 137:819S–824S.

    PubMed  CAS  Google Scholar 

  117. Bibiloni R, Fedorak R, Tannock GW, et al.: VSL#3 probiotic mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol 2005, 100:1539–1546.

    Article  PubMed  Google Scholar 

  118. Zocco MA, dal Verme LZ, Cremonini F, et al.: Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 2006, 23:1567–1574.

    Article  PubMed  CAS  Google Scholar 

  119. Bai AP, Ouyang Q, Xiao XR, Li SF: Probiotics modulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis. Int J Clin Pract 2006, 60:284–288.

    Article  PubMed  Google Scholar 

  120. Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F: Probiotics for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev 2006, (4):CD004826.

  121. Bousvaros A, Guandalini S, Baldassano RN, et al.: A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis 2005, 11:833–839.

    Article  PubMed  Google Scholar 

  122. Van Gossum A, Dewit O, Louis E, et al.: Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn’s disease after ileo-caecal resection. Inflamm Bowel Dis 2007, 13:135–142.

    Article  PubMed  Google Scholar 

  123. Marteau P, Lemann M, Seksik P, et al.: Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GETAID trial. Gut 2006, 55:842–847.

    Article  PubMed  CAS  Google Scholar 

  124. Carol M, Borruel N, Antolin M, et al.: Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn’s disease. J Leukoc Biol 2006, 79:917–922.

    Article  PubMed  CAS  Google Scholar 

  125. Cukovic-Cavka S, Likic R, Francetic I, et al.: Lactobacillus acidophilus as a cause of liver abscess in a NOD2/CARD15-positive patient with Crohn’s disease. Digestion 2006, 73:107–110.

    Article  PubMed  CAS  Google Scholar 

  126. Braat H, Rottiers P, Hommes DW, et al.: A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Clin Gastroenterol Hepatol 2006, 4:754–759.

    Article  PubMed  CAS  Google Scholar 

  127. Han W, Mercenier A, Ait-Belgnaoui A, et al.: Improvement of an experimental colitis in rats by lactic acid bacteria producing superoxide dismutase. Inflamm Bowel Dis 2006, 12:1044–1052.

    Article  PubMed  Google Scholar 

  128. Carroll IM, Andrus JM, Bruno-Barcena JM, et al.: Anti-inflammatory properties of Lactobacillus gasseri expressing managese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am J Physiol Gastrointest Liver Physiol 2007, 293:G729–G739.

    Article  PubMed  CAS  Google Scholar 

  129. Geier MS, Butler RN, Howarth GS: Inflammatory bowel disease: current insights into pathogenesis and new therapeutic options; probiotics, prebiotics and synbiotics. Int J Food Microbiol 2007, 115:1–11.

    Article  PubMed  CAS  Google Scholar 

  130. Casellas F, Borruel N, Torrejon A, et al.: Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin. Aliment Pharmacol Ther 2007, 25:1061–1067.

    Article  PubMed  CAS  Google Scholar 

  131. Furrie E, Macfarlane S, Cummings JH, Macfarlane GT: Systemic antibodies towards mucosal bacterial in ulcerative colitis and Crohn’s disease differentially activate the innate immune response. Gut 2004, 53:91–98.

    Article  PubMed  CAS  Google Scholar 

  132. Lewis S, Brazier J, Beard D, et al.: Effects of metronidazole and oligofructose on faecal concentrations of sulphate-reducing bacteria and their activity in human volunteers. Scand J Gastroenterol 2005, 40:1296–1303.

    Article  PubMed  CAS  Google Scholar 

  133. Suzuki A, Mitsuyama K, Koga H, et al.: Bifidogenic growth stimulator for the treatment of active ulcerative colitis: a pilot study. Nutrition 2006, 22:76–81.

    Article  PubMed  CAS  Google Scholar 

  134. Tai EK, Wu WK, Wong HP, et al.: A new role for cathelicidin in ulcerative colitis in mice. Exp Biol Med (Maywood) 2007, 232:799–808.

    CAS  Google Scholar 

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Balfour Sartor, R., Muehlbauer, M. Microbial host interactions in IBD: Implications for pathogenesis and therapy. Curr Gastroenterol Rep 9, 497–507 (2007). https://doi.org/10.1007/s11894-007-0066-4

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