1887

Abstract

Crohn disease (CD) is a chronic inflammatory condition primarily affecting the gastro-intestinal tract and is characterized by reduced bacterial diversity. The exact cause of disease is unknown; however, evidence suggests that several components, including microbiota, may contribute to the underlying pathology and disease development. Perturbation of the host–microbe commensal relationship is considered the main driving force of tissue destruction and pathological changes seen in CD. Several putative bacterial pathogens including species from Mycobacterium, Campylobacter and Helicobacter are postulated in the aetiology of CD. However, to date, no strong evidence supports a single bacterium contributing overall to CD pathogenesis. Alternatively, dysbiosis or bacterial imbalance is more widely accepted as a leading factor in the disrupted host–immune system cross-talk resulting in subsequent intestinal inflammation. Depletion of symbiont microbes including Firmicutes, Bifidobacterium and Clostridia, in conjunction with an increase in pathobiont microbes from Bacteroidetes and Enterobacteria, is a striking feature observed in CD. No single factor has been identified as driving this dysbiosis, although diet, antibiotic exposure and possible early life events in presence of underlying genetic susceptibility may contribute. The aim of this review is to highlight the current accumulating literature on the proposed role of bacteria in the pathogenesis of CD.

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2016-10-18
2019-09-15
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References

  1. Abraham C., Medzhitov R..( 2011;). Interactions between the host innate immune system and microbes in inflammatory bowel disease. . Gastroenterology 140: 1729–1737. [CrossRef] [PubMed]
    [Google Scholar]
  2. Alexander K. L., Targan S. R., Elson C. O..( 2014;). Microbiota activation and regulation of innate and adaptive immunity. . Immunol Rev 260: 206–220. [CrossRef] [PubMed]
    [Google Scholar]
  3. Alhagamhmad M. H., Day A. S., Lemberg D. A., Leach S. T..( 2012;). An update of the role of nutritional therapy in the management of Crohn's disease. . J Gastroenterol 47: 872–882. [CrossRef] [PubMed]
    [Google Scholar]
  4. Alhagamhmad M. H., Leach S. T., Lemberg D. A., Day A. S..( 2015;). Changing patterns in the epidemiology of Crohn disease. . J Gastroenterol Hepatol Res 4: 1805–1809.[CrossRef]
    [Google Scholar]
  5. Amre D. K., Mack D. R., Israel D., Krupoves A., Costea I., Lambrette P., Grimard G., Dong J., Levy E..( 2012;). NELL1, NCF4, and FAM92B genes are not major susceptibility genes for Crohn's disease in Canadian children and young adults. . Inflamm Bowel Dis 18: 529–535. [CrossRef] [PubMed]
    [Google Scholar]
  6. Atarashi K., Tanoue T., Oshima K., Suda W., Nagano Y., Nishikawa H., Fukuda S., Saito T., Narushima S. et al.( 2013;). Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. . Nature 500: 232–236. [CrossRef] [PubMed]
    [Google Scholar]
  7. Bartels L. E., Jepsen P., Christensen L. A., Gerdes L. U., Vilstrup H., Dahlerup J. F..( 2016;). Diagnosis of Helicobacter pylori infection is associated with lower prevalence and subsequent incidence of Crohn’s disease. . J Crohns Colitis 10: 443–448.[CrossRef]
    [Google Scholar]
  8. Bernstein C. N., Wang M. H., Sargent M., Brant S. R., Collins M. T..( 2007;). Testing the interaction between NOD-2 status and serological response to Mycobacterium paratuberculosis in cases of inflammatory bowel disease. . J Clin Microbiol 45: 968–971. [CrossRef] [PubMed]
    [Google Scholar]
  9. Biedermann L., Brülisauer K., Zeitz J., Frei P., Scharl M., Vavricka S. R., Fried M., Loessner M. J., Rogler G. et al.( 2014;). Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH. . Inflamm Bowel Dis 20: 1496–1501. [CrossRef] [PubMed]
    [Google Scholar]
  10. Brant S. R..( 2013;). Promises, delivery, and challenges of inflammatory bowel disease risk gene discovery. . Clin Gastroenterol Hepatol 11: 22–26. [CrossRef] [PubMed]
    [Google Scholar]
  11. Brazil J. C., Louis N. A., Parkos C. A..( 2013;). The role of polymorphonuclear leukocyte trafficking in the perpetuation of inflammation during inflammatory bowel disease. . Inflamm Bowel Dis 19: 1556–1565. [CrossRef] [PubMed]
    [Google Scholar]
  12. Brown K., DeCoffe D., Molcan E., Gibson D. L..( 2012;). Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. . Nutrients 4: 1095–1119. [CrossRef] [PubMed]
    [Google Scholar]
  13. Buttó L. F., Schaubeck M., Haller D..( 2015;). Mechanisms of microbe-host interaction in Crohn's disease: dysbiosis vs. pathobiont selection. . Front Immunol 6: 1–20. [CrossRef] [PubMed]
    [Google Scholar]
  14. Buttó L. F., Haller D..( 2016;). Dysbiosis in intestinal inflammation: cause or consequence. . Int J Med Microbiol 306: 302–309. [CrossRef] [PubMed]
    [Google Scholar]
  15. Cao A. T., Yao S., Gong B., Elson C. O., Cong Y..( 2012;). Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis. . J Immunol 189: 4666–4673. [CrossRef] [PubMed]
    [Google Scholar]
  16. Carbonero F., Zoetendal E. G., Ou J., O'Keefe S. J., Gaskins H. R..( 2012;). Traditional African and Western diets select distinct phylogenetic and functional colonic microbiota among different populations. . Gastroenterology 142: S641.[CrossRef]
    [Google Scholar]
  17. Casen C., Vebø H., Sekelja M., Hegge F., Karlsson M., Ciemniejewska E., Dzankovic S., Frøyland C., Nestestog R. et al.( 2015;). Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD. . Aliment Pharmacol Therap 42: 71–83. [CrossRef]
    [Google Scholar]
  18. Chamaillard M., Radulovic K..( 2016;). Defining dysbiosis threatens Koch's postulates and current dogma on the role of Paneth cells in Crohn's disease. . Gut 65: 190–191. [CrossRef] [PubMed]
    [Google Scholar]
  19. Chow J., Mazmanian S. K..( 2010;). A pathobiont of the microbiota balances host colonization and intestinal inflammation. . Cell Host Microbe 7: 265–276. [CrossRef] [PubMed]
    [Google Scholar]
  20. Christophi G. P., Rong R., Holtzapple P. G., Massa P. T., Landas S. K..( 2012;). Immune markers and differential signaling networks in ulcerative colitis and Crohn's disease. . Inflamm Bowel Dis 18: 2342–2356. [CrossRef] [PubMed]
    [Google Scholar]
  21. Chu H., Khosravi A., Kusumawardhani I. P., Kwon A. H., Vasconcelos A. C., Cunha L. D., Mayer A. E., Shen Y., Wu W. L. et al.( 2016;). Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. . Science 352: 1116–1120. [CrossRef] [PubMed]
    [Google Scholar]
  22. Chung H., Pamp S. J., Hill J. A., Surana N. K., Edelman S. M., Troy E. B., Reading N. C., Villablanca E. J., Wang S. et al.( 2012;). Gut immune maturation depends on colonization with a host- specific microbiota. . Cell 149: 1578–1593. [CrossRef] [PubMed]
    [Google Scholar]
  23. Claesson M. J., Jeffery I. B., Conde S., Power S. E., O'Connor E. M., Cusack S., Harris H. M., Coakley M., Lakshminarayanan B. et al.( 2012;). Gut microbiota composition correlates with diet and health in the elderly. . Nature 488: 178–184. [CrossRef] [PubMed]
    [Google Scholar]
  24. Clemente J. C., Ursell L. K., Parfrey L. W., Knight R..( 2012;). The impact of the gut microbiota on human health: an integrative view. . Cell 148: 1258–1270. [CrossRef] [PubMed]
    [Google Scholar]
  25. Cocolin L., Alessandria V., Dolci P., Gorra R., Rantsiou K..( 2013;). Culture independent methods to assess the diversity and dynamics of microbiota during food fermentation. . Int J Food Microbiol 167: 29–43. [CrossRef] [PubMed]
    [Google Scholar]
  26. Cuthbert A. P., Fisher S. A., Mirza M. M., King K., Hampe J., Croucher P. J., Mascheretti S., Sanderson J., Forbes A. et al.( 2002;). The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. . Gastroenterology 122: 867–874. [CrossRef] [PubMed]
    [Google Scholar]
  27. Dalton J. P., Desmond A., Shanahan F., Hill C..( 2014;). Detection of Mycobacterium avium subspecies paratuberculosis in patients with Crohn's disease is unrelated to the presence of single nucleotide polymorphisms rs2241880 (ATG16L1) and rs10045431 (IL12B). . Med Microbiol Immunol 203: 195–205. [CrossRef] [PubMed]
    [Google Scholar]
  28. Darfeuille-Michaud A., Boudeau J., Bulois P., Neut C., Glasser A. L., Barnich N., Bringer M. A., Swidsinski A., Beaugerie L. et al.( 2004;). High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. . Gastroenterology 127: 412–421. [CrossRef] [PubMed]
    [Google Scholar]
  29. De Cruz P., Kang S., Wagner J., Buckley M., Sim W. H., Prideaux L., Lockett T., McSweeney C., Morrison M. et al.( 2015;). Association between specific mucosa-associated microbiota in Crohn's disease at the time of resection and subsequent disease recurrence: a pilot study. . J Gastroenterol Hepatol 30: 268–278. [CrossRef] [PubMed]
    [Google Scholar]
  30. De Hertogh G., Aerssens J., Geboes K. P., Geboes K..( 2008;). Evidence for the involvement of infectious agents in the pathogenesis of Crohn's disease. . World J Gastroenterol 14: 845–852. [CrossRef] [PubMed]
    [Google Scholar]
  31. De Zoeten E. F., Fuss I. J..( 2013;). Cytokines and inflammatory bowel disease. . Pediatric Inflammatory Bowel Disease, pp. 25–33. Edited by Mamula P., Markowitz J. E., Baldassano R. N.. Springer:.[CrossRef]
    [Google Scholar]
  32. Dethlefsen L., Relman D. A..( 2011;). Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. . Proc Natl Acad Sci U S A 108: 4554–4561. [CrossRef] [PubMed]
    [Google Scholar]
  33. Devkota S., Chang E. B..( 2013;). Nutrition, microbiomes, and intestinal inflammation. . Curr Opin Gastroenterol 29: 603–607. [CrossRef] [PubMed]
    [Google Scholar]
  34. Dickson I..( 2016;). Crohn's disease: impaired bacterial clearance in IBD. . Nat Rev Gastroenterol Hepatol 13: 251. [CrossRef] [PubMed]
    [Google Scholar]
  35. Eckburg P. B., Bik E. M., Bernstein C. N., Purdom E., Dethlefsen L., Sargent M., Gill S. R., Nelson K. E., Relman D. A..( 2005;). Diversity of the human intestinal microbial flora. . Science 308: 1635–1638. [CrossRef] [PubMed]
    [Google Scholar]
  36. Ehsani L., Reddy S. C., Mosunjac M., Kraft C. S., Guarner J..( 2015;). Fatal aortic pseudoaneurysm from disseminated Mycobacterium kansasii infection: case report. . Hum Pathol 46: 467–470. [CrossRef] [PubMed]
    [Google Scholar]
  37. El Aidy S., van den Bogert B., Kleerebezem M..( 2015;). The small intestine microbiota, nutritional modulation and relevance for health. . Curr Opin Biotechnol 32: 14–20. [CrossRef] [PubMed]
    [Google Scholar]
  38. Fallani M., Young D., Scott J., Norin E., Amarri S., Adam R., Aguilera M., Khanna S., Gil A. et al.( 2010;). Intestinal microbiota of 6-week-old infants across Europe: geographic influence beyond delivery mode, breast-feeding, and antibiotics. . J Pediatr Gastroenterol Nutr 51: 77–84. [CrossRef] [PubMed]
    [Google Scholar]
  39. Fava F., Danese S..( 2011;). Intestinal microbiota in inflammatory bowel disease: friend of foe?. World J Gastroenterol 17: 557–566. [CrossRef] [PubMed]
    [Google Scholar]
  40. Favier C., Neut C., Mizon C., Cortot A., Colombel J. F., Mizon J..( 1997;). Fecal beta-D-galactosidase production and Bifidobacteria are decreased in Crohn's disease. . Dig Dis Sci 42: 817–822.[PubMed] [CrossRef]
    [Google Scholar]
  41. Fleming L. L., Floch M. H..( 1986;). Digestion and absorption of fiber carbohydrate in the colon. . Am J Gastroenterol 81: 507–511.[PubMed]
    [Google Scholar]
  42. Flint H. J., Scott K. P., Louis P., Duncan S. H..( 2012;). The role of the gut microbiota in nutrition and health. . Nat Rev Gastroenterol Hepatol 9: 577–589. [CrossRef] [PubMed]
    [Google Scholar]
  43. Fournier B. M., Parkos C. A..( 2012;). The role of neutrophils during intestinal inflammation. . Mucosal Immunol 5: 354–366. [CrossRef] [PubMed]
    [Google Scholar]
  44. Frank D. N., St Amand A. L., Feldman R. A., Boedeker E. C., Harpaz N., Pace N. R..( 2007;). Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. . Proc Natl Acad Sci U S A 104: 13780–13785. [CrossRef] [PubMed]
    [Google Scholar]
  45. Frank D. N., Robertson C. E., Hamm C. M., Kpadeh Z., Zhang T., Chen H., Zhu W., Sartor R. B., Boedeker E. C. et al.( 2011;). Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. . Inflamm Bowel Dis 17: 179–184. [CrossRef] [PubMed]
    [Google Scholar]
  46. Frosali S., Pagliari D., Gambassi G., Landolfi R., Pandolfi F., Cianci R..( 2015;). How the intricate interaction among toll-like receptors, microbiota, and intestinal immunity can influence gastrointestinal pathology. . J Immunol Res 2015: 1–12.[CrossRef]
    [Google Scholar]
  47. Fujimoto T., Imaeda H., Takahashi K., Kasumi E., Bamba S., Fujiyama Y., Andoh A..( 2013;). Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn's disease. . J Gastroenterol Hepatol 28: 613–619. [CrossRef] [PubMed]
    [Google Scholar]
  48. Golan L., Livneh-Kol A., Gonen E., Yagel S., Rosenshine I., Shpigel N. Y..( 2009;). Mycobacterium avium paratuberculosis invades human small-intestinal goblet cells and elicits inflammation. . J Infect Dis 199: 350–354. [CrossRef] [PubMed]
    [Google Scholar]
  49. Greenbloom S. L., Steinhart A. H., Greenberg G. R..( 1997;). Combination Ciprofloxacin and metronidazole for active Crohn’s disease. . Can J Gastroenterol 12: 53–56. [CrossRef]
    [Google Scholar]
  50. Greenstein R. J..( 2003;). Is Crohn's disease caused by a Mycobacterium. comparisons with leprosy, tuberculosis, and Johne's disease. . Lan Infect Dis 3: 507–514.[CrossRef]
    [Google Scholar]
  51. Griffith J. W., Sokol C. L., Luster A. D..( 2014;). Chemokines and chemokine receptors: positioning cells for host Defense and immunity. . Ann Rev Immunol 32: 659–702. [CrossRef]
    [Google Scholar]
  52. Harmsen H. J., Wildeboer-Veloo A. C., Raangs G. C., Wagendorp A. A., Klijn N., Bindels J. G., Welling G. W..( 2000;). Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. . J Pediatr Gastroenterol Nutr 30: 61–67. [CrossRef] [PubMed]
    [Google Scholar]
  53. Hashimoto T., Perlot T., Rehman A., Trichereau J., Ishiguro H., Paolino M., Sigl V., Hanada T., Hanada R. et al.( 2012;). ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. . Nature 487: 477–481. [CrossRef] [PubMed]
    [Google Scholar]
  54. Hiergeist A., Gläsner J., Reischl U., Gessner A..( 2015;). Analyses of intestinal microbiota: culture versus sequencing. . ILAR J 56: 228–240. [CrossRef] [PubMed]
    [Google Scholar]
  55. Hoffmann C., Dollive S., Grunberg S., Chen J., Li H., Wu G. D., Lewis J. D., Bushman F. D..( 2013;). Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. . PLoS One 8:,e66019. [CrossRef] [PubMed]
    [Google Scholar]
  56. Hold G. L., Smith M., Grange C., Watt E. R., El-Omar E. M., Mukhopadhya I..( 2014;). Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years?. World J Gastroenterol 20: 1192–1210. [CrossRef] [PubMed]
    [Google Scholar]
  57. Hooper L. V., Littman D. R., Macpherson A. J..( 2012;). Interactions between the microbiota and the immune system. . Science 336: 1268–1273. [CrossRef] [PubMed]
    [Google Scholar]
  58. Hruz P., Zinkernagel A. S., Jenikova G., Botwin G. J., Hugot J. P., Karin M., Nizet V., Eckmann L..( 2009;). NOD2 contributes to cutaneous defense against Staphylococcus aureus through α-toxin-dependent innate immune activation. . Proc Natl Acad Sci U S A 106: 12873–12878. [CrossRef] [PubMed]
    [Google Scholar]
  59. Ignacio A., Morales C. I., Câmara N. O., Almeida R. R..( 2016;). Innate sensing of the gut microbiota: modulation of inflammatory and autoimmune diseases. . Front Immunol 7: 1–11. [CrossRef] [PubMed]
    [Google Scholar]
  60. Igor’V M., Andreev D. N..( 2014;). Role of mutations in NOD2/CARD15, ATG16L1, and IRGM in the pathogenesis of Crohn's disease. . Int J Biomed 1: 7–10.
    [Google Scholar]
  61. Ivanov I. I., Atarashi K., Manel N., Brodie E. L., Shima T., Karaoz U., Wei D., Goldfarb K. C., Santee C. A. et al.( 2009;). Induction of intestinal Th17 cells by segmented filamentous bacteria. . Cell 139: 485–498. [CrossRef] [PubMed]
    [Google Scholar]
  62. Joossens M., Huys G., Cnockaert M., De Preter V., Verbeke K., Rutgeerts P., Vandamme P., Vermeire S..( 2011;). Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives. . Gut 60: 631–637. [CrossRef] [PubMed]
    [Google Scholar]
  63. Kamada N., Núñez G..( 2014;). Regulation of the immune system by the resident intestinal bacteria. . Gastroenterology 146: 1477–1488. [CrossRef] [PubMed]
    [Google Scholar]
  64. Kane A. V., Dinh D. M., Ward H. D..( 2014;). Childhood malnutrition and the intestinal microbiome. . Pediatr Res 77: 256–262. [CrossRef] [PubMed]
    [Google Scholar]
  65. Kayama H., Takeda K..( 2016;). Functions of innate immune cells and commensal bacteria in gut homeostasis. . J Biochem 159: 141–149. [CrossRef] [PubMed]
    [Google Scholar]
  66. Koboziev I., Reinoso Webb C., Furr K. L., Grisham M. B..( 2014;). Role of the enteric microbiota in intestinal homeostasis and inflammation. . Free Radic Biol Med 68: 122–133. [CrossRef] [PubMed]
    [Google Scholar]
  67. Koenig J. E., Spor A., Scalfone N., Fricker A. D., Stombaugh J., Knight R., Angenent L. T., Ley R. E..( 2011;). Succession of microbial consortia in the developing infant gut microbiome. . Proc Natl Acad Sci U S A 108: 4578–4585. [CrossRef] [PubMed]
    [Google Scholar]
  68. Koropatkin N. M., Cameron E. A., Martens E. C..( 2012;). How glycan metabolism shapes the human gut microbiota. . Nat Rev Microbiol 10: 323–335. [CrossRef] [PubMed]
    [Google Scholar]
  69. Kovach Z., Kaakoush N. O., Lamb S., Zhang L., Raftery M. J., Mitchell H..( 2011;). Immunoreactive proteins of Campylobacter concisus, an emergent intestinal pathogen. . FEMS Med Microbiol 63: 387–396. [CrossRef]
    [Google Scholar]
  70. Kullberg M. C., Jankovic D., Gorelick P. L., Caspar P., Letterio J. J., Cheever A. W., Sher A..( 2002;). Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus-induced colitis. . J Exp Med 196: 505–515.[PubMed] [CrossRef]
    [Google Scholar]
  71. Leach S. T., Day A. S..( 2006;). S100 proteins in the pathogenesis and diagnosis of inflammatory bowel disease. . Exp Rev Clin Immunol 2: 471–480.[CrossRef]
    [Google Scholar]
  72. Leone V., Chang E. B., Devkota S..( 2013;). Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases. . J Gastroenterol 48: 315–321. [CrossRef] [PubMed]
    [Google Scholar]
  73. Lepage P., Mondot S., Vasquez N..( 2009;). Bacterial recolonization after gut resection for Crohn’s disease: uniformity as an essential factor toward remission. . Gut 58: OPO 20.
    [Google Scholar]
  74. Lewis J. D., Chen E. Z., Baldassano R. N., Otley A. R., Griffiths A. M., Lee D., Bittinger K., Bailey A., Friedman E. S. et al.( 2015;). Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn's disease. . Cell Host Microbe 18: 489–500. [CrossRef] [PubMed]
    [Google Scholar]
  75. Ley R. E., Hamady M., Lozupone C., Turnbaugh P. J., Ramey R. R., Bircher J. S., Schlegel M. L., Tucker T. A., Schrenzel M. D. et al.( 2008;). Evolution of mammals and their gut microbes. . Science 320: 1647–1651. [CrossRef] [PubMed]
    [Google Scholar]
  76. Li J., Moran T., Swanson E., Julian C., Harris J., Bonen D. K., Hedl M., Nicolae D. L., Abraham C. et al.( 2004;). Regulation of IL-8 and IL-1β expression in Crohn's disease associated NOD2/CARD15 mutations. . Hum Mol Genet 13: 1715–1725. [CrossRef] [PubMed]
    [Google Scholar]
  77. Loh G., Blaut M..( 2012;). Role of commensal gut bacteria in inflammatory bowel diseases. . Gut Microbes 3: 544–555. [CrossRef] [PubMed]
    [Google Scholar]
  78. Lozupone C. A., Stombaugh J. I., Gordon J. I., Jansson J. K., Knight R..( 2012;). Diversity, stability and resilience of the human gut microbiota. . Nature 489: 220–230. [CrossRef] [PubMed]
    [Google Scholar]
  79. Lupp C., Robertson M. L., Wickham M. E., Sekirov I., Champion O. L., Gaynor E. C., Finlay B. B..( 2007;). Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. . Cell Host Microbe 2: 119–129. [CrossRef] [PubMed]
    [Google Scholar]
  80. Macfarlane G. T., Macfarlane S..( 2013;). Manipulating the indigenous microbiota in humans: prebiotics, probiotics, and synbiotics. The human microbiota. . In How Microbial Communities Affect Health and Disease, pp. 338–315. Edited by Fredrick D. N.. John Wiley & Son, Inc:.
    [Google Scholar]
  81. Mackie R. I., Sghir A., Gaskins H. R..( 1999;). Developmental microbial ecology of the neonatal gastrointestinal tract. . Am J Clin Nutr 69: 1035S–1045S.[PubMed]
    [Google Scholar]
  82. Mahida Y. R..( 2000;). The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. . Inflamm Bowel Dis 6: 21–33. [CrossRef] [PubMed]
    [Google Scholar]
  83. Man S. M., Zhang L., Day A. S., Leach S. T., Lemberg D. A., Mitchell H..( 2010;). Campylobacter concisus and other Campylobacter species in children with newly diagnosed Crohn's disease. . Inflamm Bowel Dis 16: 1008–1016. [CrossRef] [PubMed]
    [Google Scholar]
  84. Man S. M., Karki R., Kanneganti T.-D..( 2016;). DNA-sensing inflammasomes: regulation of bacterial host defense and the gut microbiota. . Pathog Dis 74: 1–9. [CrossRef]
    [Google Scholar]
  85. Manichanh C., Rigottier-Gois L., Bonnaud E., Gloux K., Pelletier E., Frangeul L., Nalin R., Jarrin C., Chardon P. et al.( 2006;). Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. . Gut 55: 205–211. [CrossRef] [PubMed]
    [Google Scholar]
  86. Marchesi J. R., Holmes E., Khan F., Kochhar S., Scanlan P., Shanahan F., Wilson I. D., Wang Y..( 2007;). Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. . J Proteome Res 6: 546–551. [CrossRef] [PubMed]
    [Google Scholar]
  87. Marchesi J. R., Adams D. H., Fava F., Hermes G. D., Hirschfield G. M., Hold G., Quraishi M. N., Kinross J., Smidt H. et al.( 2016;). The gut microbiota and host health: a new clinical frontier. . Gut 65: 330–339. [CrossRef] [PubMed]
    [Google Scholar]
  88. Martins dos Santos V., Müller M., de Vos W. M.. ( 2010;). Systems biology of the gut: the interplay of food, microbiota and host at the mucosal interface. . Curr Opin Biotechnol 21: 539–550. [CrossRef] [PubMed]
    [Google Scholar]
  89. Matricon J., Barnich N., Ardid D..( 2010;). Immunopathogenesis of inflammatory bowel disease. . Self Nonself 1: 299–309. [CrossRef] [PubMed]
    [Google Scholar]
  90. Martin H. M., Campbell B. J., Hart C. A., Mpofu C., Nayar M., Singh R., Englyst H., Williams H. F., Rhodes J. M..( 2004;). Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer. . Gastroenterology 127: 80–93.[PubMed] [CrossRef]
    [Google Scholar]
  91. McMullen L., Leach S. T., Lemberg D. A., Day A. S..( 2015;). Current roles of specific bacteria in the pathogenesis of inflammatory bowel disease. . Microbiol 1: 82–91.
    [Google Scholar]
  92. Metzker M. L..( 2005;). Emerging technologies in DNA sequencing. . Genome Res 15: 1767–1776. [CrossRef] [PubMed]
    [Google Scholar]
  93. Mukhopadhya I., Hansen R., El-Omar E. M., Hold G. L..( 2012;). IBD-what role do Proteobacteria play?. Nat Rev Gastroenterol Hepatol 9: 219–230. [CrossRef] [PubMed]
    [Google Scholar]
  94. Nagalingam N. A., Lynch S. V..( 2012;). Role of the microbiota in inflammatory bowel diseases. . Inflamm Bowel Dis 18: 968–984. [CrossRef] [PubMed]
    [Google Scholar]
  95. Ng S. C., Tang W., Ching J. Y., Wong M., Chow C. M., Hui A. J., Wong T. C., Leung V. K., Tsang S. W. Asia–Pacific Crohn's and Colitis Epidemiologic Study (ACCESS) Study Group et al.( 2013;). Incidence and phenotype of inflammatory bowel disease based on results from the Asia-Pacific Crohn's and colitis epidemiology study. . Gastroenterology 145: 158–165. [CrossRef] [PubMed]
    [Google Scholar]
  96. Nguyen H. T., Lapaquette P., Bringer M. A., Darfeuille-Michaud A..( 2013;). Autophagy and Crohn's disease. . J Innate Immun 5: 434–443. [CrossRef] [PubMed]
    [Google Scholar]
  97. Olsen G. J., Lane D. J., Giovannoni S. J., Pace N. R., Stahl D. A..( 1986;). Microbial ecology and evolution: a ribosomal RNA approach. . Ann Rev Microbiol 40: 337–365. [CrossRef]
    [Google Scholar]
  98. Pagliari D., Piccirillo C. A., Larbi A., Cianci R..( 2015;). The interactions between innate immunity and microbiota in gastrointestinal diseases. . J Immunol Res 2015: 1–3. [CrossRef]
    [Google Scholar]
  99. Palmer C., Bik E. M., DiGiulio D. B., Relman D. A., Brown P. O..( 2007;). Development of the human infant intestinal microbiota. . PLoS Biol 5: 1556–1573. [CrossRef]
    [Google Scholar]
  100. Palomino-Morales R. J., Oliver J., Gómez-García M., López-Nevot M. A., Rodrigo L., Nieto A., Alizadeh B. Z., Martín J..( 2009;). Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach. . Genes Immun 10: 356–364. [CrossRef] [PubMed]
    [Google Scholar]
  101. Pandey S., Kawai T., Akira S..( 2015;). Microbial sensing by toll-like receptors and intracellular nucleic acid sensors. . Cold Spring Harb Perspect Biol 7: 1–18. [CrossRef]
    [Google Scholar]
  102. Papamichael K., Konstantopoulos P., Mantzaris G. J..( 2014;). Helicobacter pylori infection and inflammatory bowel disease: is there a link?. World J Gastroenterol 20: 6374–6385. [CrossRef] [PubMed]
    [Google Scholar]
  103. Patel K. K., Stappenbeck T. S..( 2013;). Autophagy and intestinal homeostasis. . Annu Rev Physiol 75: 241–262. [CrossRef] [PubMed]
    [Google Scholar]
  104. Peterson L. W., Artis D..( 2014;). Intestinal epithelial cells: regulators of barrier function and immune homeostasis. . Nat Rev Immunol 14: 141–153. [CrossRef] [PubMed]
    [Google Scholar]
  105. Pokusaeva K., Fitzgerald G. F., van Sinderen D..( 2011;). Carbohydrate metabolism in Bifidobacteria. . Genes Nutr 6: 285–306. [CrossRef] [PubMed]
    [Google Scholar]
  106. Pérez-Cobas A. E., Gosalbes M. J., Friedrichs A., Knecht H., Artacho A., Eismann K., Otto W., Rojo D., Bargiela R. et al.( 2013;). Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. . Gut 62: 1591–1601. [CrossRef] [PubMed]
    [Google Scholar]
  107. Qin J., Li R., Raes J., Arumugam M., Burgdorf K. S., Manichanh C., Nielsen T., Pons N., Levenez F. et al.( 2010;). A human gut microbial gene catalogue established by metagenomic sequencing. . Nature 464: 59–65. [CrossRef] [PubMed]
    [Google Scholar]
  108. Quévrain E., Maubert M., Michon C., Chain F., Marquant R., Tailhades J., Miquel S., Carlier L., Bermúdez-Humarán L. et al.( 2015;). Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. . Gut 1: 1–11.
    [Google Scholar]
  109. Øyri S. F., Muzes G., Sipos F..( 2015;). Dysbiotic gut microbiome: a key element of Crohn's disease. . Comp Immunol Microbiol Infect Dis 43: 36–49. [CrossRef] [PubMed]
    [Google Scholar]
  110. Rajca S., Grondin V., Louis E., Vernier-Massouille G., Grimaud J. C., Bouhnik Y., Laharie D., Dupas J. L., Pillant H. et al.( 2014;). Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn's disease. . Inflamm Bowel Dis 20: 978–986. [CrossRef] [PubMed]
    [Google Scholar]
  111. Rakoff-Nahoum S., Paglino J., Eslami-Varzaneh F., Edberg S., Medzhitov R..( 2004;). Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. . Cell 118: 229–241. [CrossRef] [PubMed]
    [Google Scholar]
  112. Reaves T. A., Chin A. C., Parkos C. A..( 2005;). Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation. . Mem Inst Oswaldo Cruz 100: 191–198. [CrossRef] [PubMed]
    [Google Scholar]
  113. Rokkas T., Gisbert J., Niv Y., O’Morain C..( 2015;). The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis. . United European Gastroenterol J 3: 539–550. [CrossRef] [PubMed]
    [Google Scholar]
  114. Rutgeerts P., Goboes K., Peeters M., Hiele M., Penninckx F., Aerts R., Kerremans R., Vantrappen G..( 1991;). Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. . Lancet 338: 771–774. [CrossRef] [PubMed]
    [Google Scholar]
  115. Saez-Lara M. J., Gomez-Llorente C., Plaza-Diaz J., Gil A..( 2015;). The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: a systematic review of randomized human clinical trials. . BioMed Res Int 2015: 1–15.[CrossRef]
    [Google Scholar]
  116. Sartor R. B..( 2006;). Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. . Nat Clin Pract Gastroenterol Hepatol 3: 390–407. [CrossRef] [PubMed]
    [Google Scholar]
  117. Sartor R. B..( 2007;). Bacteria in Crohn's disease: mechanisms of inflammation and therapeutic implications. . J Clin Gastroenterol 41: S37–S43. [CrossRef] [PubMed]
    [Google Scholar]
  118. Scaldaferri F., Gerardi V., Lopetuso L. R., Del Zompo F., Mangiola F., Boškoski I., Bruno G., Petito V., Laterza L. et al.( 2013;). Gut microbial flora, prebiotics, and probiotics in IBD: their current usage and utility. . BioMed Research Int 2013: 1–9. [CrossRef]
    [Google Scholar]
  119. Schrezenmeir J., de Vrese M..( 2001;). Probiotics, prebiotics, and synbiotics – approaching a definition. . Am J Clin Nutr 73: 361s–364s.[PubMed]
    [Google Scholar]
  120. Scott K. P., Gratz S. W., Sheridan P. O., Flint H. J., Duncan S. H..( 2013;). The influence of diet on the gut microbiota. . Pharmacol Res 69: 52–60. [CrossRef] [PubMed]
    [Google Scholar]
  121. Segain J. P., Raingeard de la Blétière D., Bourreille A., Leray V., Gervois N., Rosales C., Ferrier L., Bonnet C., Blottière H. M. et al.( 2000;). Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. . Gut 47: 397–403. [CrossRef] [PubMed]
    [Google Scholar]
  122. Sekirov I., Russell S. L., Antunes L. C., Finlay B. B..( 2010;). Gut microbiota in health and disease. . Physiol Rev 90: 859–904. [CrossRef] [PubMed]
    [Google Scholar]
  123. Seksik P., Rigottier-Gois L., Gramet G., Sutren M., Pochart P., Marteau P., Jian R., Doré J..( 2003;). Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon. . Gut 52: 237–242. [CrossRef] [PubMed]
    [Google Scholar]
  124. Seksik P., Sokol H., Lepage P., Vasquez N., Manichanh C., Mangin I., Pochart P., Dore J., Marteau P..( 2006;). Review article: the role of bacteria in onset and perpetuation of inflammatory bowel disease. . Aliment Pharmacol Therap 24: 11–18.[CrossRef]
    [Google Scholar]
  125. Shang L., Fukata M., Thirunarayanan N., Martin A. P., Arnaboldi P., Maussang D., Berin C., Unkeless J. C., Mayer L. et al.( 2008;). Toll-like receptor signaling in small intestinal epithelium promotes B-cell recruitment and IgA production in lamina propria. . Gastroenterology 135: 529–538. [CrossRef] [PubMed]
    [Google Scholar]
  126. Shaw S. Y., Blanchard J. F., Bernstein C. N..( 2011;). Association between the use of antibiotics and new diagnoses of Crohn's disease and ulcerative colitis. . Am J Gastroenterol 106: 2133–2142. [CrossRef] [PubMed]
    [Google Scholar]
  127. Sheehan D., Moran C., Shanahan F..( 2015;). The microbiota in inflammatory bowel disease. . J Gastroenterol 50: 495–507. [CrossRef] [PubMed]
    [Google Scholar]
  128. Sokol H., Pigneur B., Watterlot L., Lakhdari O., Bermúdez-Humarán L. G., Gratadoux J. J., Blugeon S., Bridonneau C., Furet J. P. et al.( 2008;). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. . Proc Natl Acad Sci U S A 105: 16731–16736. [CrossRef] [PubMed]
    [Google Scholar]
  129. Sokol H., Seksik P., Furet J. P., Firmesse O., Nion-Larmurier I., Beaugerie L., Cosnes J., Corthier G., Marteau P. et al.( 2009;). Low counts of Faecalibacterium prausnitzii in colitis microbiota. . Inflamm Bowel Dis 15: 1183–1189. [CrossRef] [PubMed]
    [Google Scholar]
  130. Srinivas G., Möller S., Wang J., Künzel S., Zillikens D., Baines J. F., Ibrahim S. M..( 2013;). Genome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering. . Nat Commun 4: 1–7. [CrossRef]
    [Google Scholar]
  131. Sun L., Nava G. M., Stappenbeck T. S..( 2011;). Host genetic susceptibility, dysbiosis and viral triggers in IBD. . Curr Opin Gastroenterol 27: 321–327.[CrossRef]
    [Google Scholar]
  132. Swidsinski A., Loening-Baucke V., Vaneechoutte M., Doerffel Y..( 2008;). Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. . Inflamm Bowel Dis 14: 147–161. [CrossRef] [PubMed]
    [Google Scholar]
  133. Tamboli C. P., Neut C., Desreumaux P., Colombel J. F..( 2004;). Dysbiosis in inflammatory bowel disease. . Gut 53: 1–4. [CrossRef] [PubMed]
    [Google Scholar]
  134. Tanoue T., Atarashi K., Honda K..( 2016;). Development and maintenance of intestinal regulatory T cells. . Nat Rev Immunol 16: 295–309. [CrossRef] [PubMed]
    [Google Scholar]
  135. Tawfik A., Flanagan P. K., Campbell B. J..( 2014;). Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease. . World J Gastroenterol 20: 8751–8763. [CrossRef] [PubMed]
    [Google Scholar]
  136. Tlaskalová-Hogenová H., Stěpánková R., Kozáková H., Hudcovic T., Vannucci L., Tučková L., Rossmann P., Hrnčíř T., Kverka M. et al.( 2011;). 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. . Cell Mol Immunol 8: 110–120. [CrossRef] [PubMed]
    [Google Scholar]
  137. Turnbaugh P. J., Ley R. E., Hamady M., Fraser-Liggett C., Knight R., Gordon J. I.( 2007;). The human microbiome project: exploring the microbial part of ourselves in a changing world. . Nature 449: 804–810.[CrossRef]
    [Google Scholar]
  138. Turnbaugh P. J., Ridaura V. K., Faith J. J., Rey F. E., Knight R., Gordon J..( 2009;). The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. . Sci Trans Med 1: 614. [CrossRef]
    [Google Scholar]
  139. Ungaro R., Bernstein C. N., Gearry R., Hviid A., Kolho K. L., Kronman M. P., Shaw S., Van Kruiningen H., Colombel J. F., Atreja A..( 2014;). Antibiotics associated with increased risk of new-onset Crohn's disease but not ulcerative colitis: a meta-analysis. . Am J Gastroenterol 109: 1728–1738. [CrossRef] [PubMed]
    [Google Scholar]
  140. Vanhoutvin S. A., Troost F. J., Hamer H. M., Lindsey P. J., Koek G. H., Jonkers D. M., Kodde A., Venema K., Brummer R. J..( 2009;). Butyrate-induced transcriptional changes in human colonic mucosa. . PLoS One 4: 1–7. [CrossRef]
    [Google Scholar]
  141. Virta L., Auvinen A., Helenius H., Huovinen P., Kolho K. L..( 2012;). Association of repeated exposure to antibiotics with the development of pediatric Crohn's disease – a nationwide, register-based finnish case-control study. . Am J Epidemiol 175: 775–784. [CrossRef] [PubMed]
    [Google Scholar]
  142. Walker A. W., Sanderson J. D., Churcher C., Parkes G. C., Hudspith B. N., Rayment N., Brostoff J., Parkhill J., Dougan G., Petrovska L..( 2011;). High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. . BMC Microbiol 11: 1–12. [CrossRef] [PubMed]
    [Google Scholar]
  143. Wang M. H., Fiocchi C., Ripke S., Zhu X., Duerr R. H., Achkar J. P..( 2013;). A novel approach to detect cumulative genetic effects and genetic interactions in Crohn's disease. . Inflamm Bowel Dis 19: 1799–1808. [CrossRef] [PubMed]
    [Google Scholar]
  144. Weinstock G. M..( 2012;). Genomic approaches to studying the human microbiota. . Nature 489: 250–256. [CrossRef] [PubMed]
    [Google Scholar]
  145. Wright E. K., Kamm M. A., Teo S. M., Inouye M., Wagner J., Kirkwood C. D..( 2015;). Recent advances in characterizing the gastrointestinal microbiome in Crohn's disease: a systematic review. . Inflamm Bowel Dis 21: 1219–1228. [CrossRef] [PubMed]
    [Google Scholar]
  146. Young V. B., Schmidt T. M..( 2004;). Antibiotic-associated diarrhea accompanied by large-scale alterations in the composition of the fecal microbiota. . J Clin Microbiol 42: 1203–1206. [CrossRef] [PubMed]
    [Google Scholar]
  147. Zareie M., Singh P. K., Irvine E. J., Sherman P. M., McKay D. M., Perdue M. H..( 2001;). Monocyte/macrophage activation by normal bacteria and bacterial products: implications for altered epithelial function in Crohn's disease. . Am J Pathol 158: 1101–1109. [CrossRef] [PubMed]
    [Google Scholar]
  148. Zhang L., Lee H., Grimm M. C., Riordan S. M., Day A. S., Lemberg D. A..( 2014;). Campylobacter concisus and inflammatory bowel disease. . World J Gastroenterol 20: 1267.
    [Google Scholar]
  149. Zhang M., Liu B., Zhang Y., Wei H., Lei Y., Zhao L..( 2007;). Structural shifts of mucosa-associated lactobacilli and Clostridium leptum subgroup in patients with ulcerative colitis. . J Clin Microbiol 45: 496–500. [CrossRef] [PubMed]
    [Google Scholar]
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