The intestinal microbiota in inflammatory bowel disease

ILAR Journal

Volumn 56, Issue 2, 2015, Pages 192-204

  Becker, Christoph ^a   Neurath, Markus F ^a   Wirtz, Stefan ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Animal models; Crohn's disease; Inflammatory bowel disease; Intestinal microbiota; Ulcerative colitis

Indexed keywords

ANIMAL; ANIMAL MODEL; CROHN DISEASE; GENETICS; HUMAN; IMMUNOLOGY; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; MICROBIOLOGY; PHYSIOLOGY; ULCERATIVE COLITIS;

ANIMALS; COLITIS, ULCERATIVE; CROHN DISEASE; GASTROINTESTINAL MICROBIOME; HUMANS; INFLAMMATORY BOWEL DISEASES; MODELS, ANIMAL;

EID: 84941774045     PISSN: 10842020     EISSN: 19306180     Source Type: Journal    
DOI: 10.1093/ilar/ilv030     Document Type: Article

References (141)

1. Abdelouhab K, Rafa H, Toumi R, Bouaziz S, Medjeber O, Touil-Boukoffa C. 2012. Mucosal intestinal alteration in experimental colitis correlates with nitric oxide production by peritoneal macrophages: effect of probiotics and prebiotics. Immunopharmacol Immunotoxicol 34:590-597.
2. Andoh A, Kuzuoka H, Tsujikawa T, Nakamura S, Hirai F, Suzuki Y, Matsui T, Fujiyama Y, Matsumoto T. 2012. Multicenter analysisoffecal microbiota profiles in Japanese patients with Crohn's disease. J Gastroenterol 47:1298-1307.
3. Angelberger S, Reinisch W, Makristathis A, Lichtenberger C, Dejaco C, Papay P, Novacek G, Trauner M, Loy A, Berry D. 2013. Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol 108:1620-1630.
4. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Dore J, Meta HITC, Antolin M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Merieux A, Melo Minardi R, M'Rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P. 2011. Enterotypes of the human gut microbiome. Nature 473:174-180.
5. Behnsen J, Jellbauer S, Wong CP, Edwards RA, George MD, Ouyang W, Raffatellu M. 2014. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity 40:262-273.
6. Belkaid Y, Bouladoux N, Hand TW. 2013. Effector and memory T cell responses to commensal bacteria. Trends Immunol 34:299-306.
7. Benjamin JL, Hedin CR, Koutsoumpas A, Ng SC, McCarthy NE, Hart AL, Kamm MA, Sanderson JD, Knight SC, Forbes A, Stagg AJ, Whelan K, Lindsay JO. 2011. Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease. Gut 60:923-929.
8. Berg D, Clemente JC, Colombel JF. 2015. Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome? Expert Review of Gastroenterology and Hepatology 9:781-795.
9. Bibiloni R, Mangold M, Madsen KL, Fedorak RN, Tannock GW. 2006. The bacteriology of biopsies differs between newly diagnosed, untreated, Crohn's disease and ulcerative colitis patients. J Med Microbiol 55:1141-1149.
10. Bien J, Palagani V, Bozko P. 2013. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease? Therapeutic Advances in Gastroenterology 6:53-68.
11. Bourreille A, Cadiot G, Le Dreau G, Laharie D, Beaugerie L, Dupas JL, Marteau P, Rampal P, Moyse D, Saleh A, Le Guern ME, Galmiche JP, F.S. Group. 2013. Saccharomyces boulardii does not prevent relapse of Crohn'sdisease. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association 11:982-987.
12. Bringiotti R, Ierardi E, Lovero R, Losurdo G, Di Leo A, Principi M. 2014. Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease? World Journal of Gastrointestinal Pathophysiology 5:550-559.
13. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS, Virgin HW 4th. 2008. A key role for autophagy and the autophagy gene Atg1611 in mouse and human intestinal Paneth cells. Nature 456:259-263.
14. Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, Head RD, Xavier R, Stappenbeck TS, Virgin HW. 2010. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141:1135-1145.
15. Cammarota G, Ianiro G, Gasbarrini A. 2014. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol 48:693-702.
16. Camuesco D, Peran L, Comalada M, Nieto A, Di Stasi LC, Rodriguez-Cabezas ME, Concha A, Zarzuelo A, Galvez J. 2005. Preventative effects of lactulose in the trinitrobenzenesulphonic acid model of rat colitis. Inflamm Bowel Dis 11:265-271.
17. Cario E. 2012. Commensal-innate immune miscommunication in IBD pathogenesis. Digestive Diseases 30:334-340.
18. Cerf-Bensussan N, Gaboriau-Routhiau V. 2010. The immune system and the gut microbiota: friends or foes? Nature reviews. Immunology 10:735-744.
19. Chow J, Mazmanian SK. 2010. A pathobiont of the microbiota balances host colonization and intestinal inflammation. Cell Host and Microbe 7:265-276.
20. Colman RJ, Rubin DT. 2014. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. Journal of Crohn's and Colitis 8:1569-1581.
21. Cui B, Feng Q, Wang H, Wang M, Peng Z, Li P, Huang G, Liu Z, Wu P, Fan Z, Ji G, Wang X, Wu K, Fan D, Zhang F. 2015. Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results. J Gastroenterol Hepatol 30:51-58.
22. Dalal SR, Chang EB. 2014. The microbial basis of inflammatory bowel diseases. J Clin Invest 124:4190-4196.
23. Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, Desreumaux P, Gambiez L, Joly B, Cortot A, Colombel JF. 1998. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn'sdisease. Gastroenterology 115:1405-1413.
24. Dave M, Higgins PD, Middha S, Rioux KP. 2012. The human gut microbiome: current knowledge, challenges, and future directions. Translational Research: The Journal of Laboratory and Clinical Medicine 160:246-257.
25. Dieleman LA, Arends A, Tonkonogy SL, Goerres MS, Craft DW, Grenther W, Sellon RK, Balish E, Sartor RB. 2000. Helicobacter hepaticus does not induce or potentiate colitis in interleukin-10-deficient mice. Infect Immun 68:5107-5113.
26. Dieleman LA, Goerres MS, Arends A, Sprengers D, Torrice C, Hoentjen F, Grenther WB, Sartor RB. 2003. Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment. Gut 52:370-376.
27. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 107:11971-11975.
28. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH. 2006. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461-1463.
29. Eberl G. 2010. A new vision of immunity: homeostasis of the superorganism. Mucosal Immunology 3:450-460.
30. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. 2005. Diversity of the human intestinal microbial flora. Science 308:1635-1638.
31. Elguezabal N, Chamorro S, Molina E, Garrido JM, Izeta A, Rodrigo L, Juste RA. 2012. Lactase persistence, NOD2 status and Mycobacterium avium subsp. paratuberculosis infection associations to inflammatory bowel disease. Gut Pathogens 4:6.
32. Ellinghaus D, Bethune J, Petersen BS, Franke A. 2015. The genetics of Crohn's disease and ulcerative colitis-status quo and beyond. Scand J Gastroenterol 50:13-23.
33. Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, Clemente JC, Knight R, Heath AC, Leibel RL, Rosenbaum M, Gordon JI. 2013. The long-term stability of the human gut microbiota. Science 341:1237439.
34. Ferwerda G, Girardin SE, Kullberg BJ, Le Bourhis L, de Jong DJ, Langenberg DM, van Crevel R, Adema GJ, OttenhoffTH, Van der Meer JW, Netea MG. 2005. NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog 1:279-285.
35. Ferwerda G, Kullberg BJ, de Jong DJ, Girardin SE, Langenberg DM, van Crevel R, OttenhoffTH, Van der Meer JW, Netea MG. 2007. Mycobacterium paratuberculosis is recognized by Toll-like receptors and NOD2. J Leukoc Biol 82:1011-1018.
36. Fisher SA, Tremelling M, Anderson CA, Gwilliam R, Bumpstead S, Prescott NJ, Nimmo ER, Massey D, Berzuini C, Johnson C, Barrett JC, Cummings FR, Drummond H, Lees CW, Onnie CM, Hanson CE, Blaszczyk K, Inouye M, Ewels P, Ravindrarajah R, Keniry A, Hunt S, Carter M, Watkins N, Ouwehand W, Lewis CM, Cardon L, C. Wellcome Trust Case Control, Lobo A, Forbes A, Sanderson J, Jewell DP, Mansfield JC, Deloukas P, Mathew CG, Parkes M, Satsangi J. 2008. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn'sdisease. Nat Genet 40:710-712.
37. Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, Pace NR, Li E. 2011. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 17:179-184.
38. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. 2007. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104:13780-13785.
39. Friswell M, Campbell B, Rhodes J. 2010. The role of bacteria in the pathogenesis of inflammatory bowel disease. Gut and Liver 4:295-306.
40. Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, Punit S, Karlsson M, Bry L, Glickman JN, Gordon JI, Onderdonk AB, Glimcher LH. 2010. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host and Microbe 8:292-300.
41. Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH. 2007. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131:33-45.
42. Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, Gonzalez A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ. 2014. The treatment-naive microbiome in new-onset Crohn'sdisease. CellHost and Microbe 15:382-392.
43. Ghouri YA, Richards DM, Rahimi EF, Krill JT, Jelinek KA, DuPont AW. 2014. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in in-flammatory bowel disease. Clinical and Experimental Gastroenterology 7:473-487.
44. Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, Vitali B, Poggioli G, Miglioli M, Campieri M. 2003. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 124:1202-1209.
45. Gionchetti P, Rizzello F, Venturi A, Brigidi P, Matteuzzi D, Bazzocchi G, Poggioli G, Miglioli M, Campieri M. 2000. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119:305-309.
46. Gkouskou KK, Deligianni C, Tsatsanis C, Eliopoulos AG. 2014. The gut microbiota in mouse models of inflammatory bowel disease. Frontiers in Cellular and Infection Microbiology 4:28.
47. Goto Y, Kiyono H. 2012. Epithelial barrier: an interface for the cross-communication between gut flora and immune system. Immunol Rev 245:147-163.
48. Gradel KO, Nielsen HL, Schonheyder HC, Ejlertsen T, Kristensen B, Nielsen H. 2009. Increased short- and long-term risk of in-flammatory bowel disease after salmonella or campylobacter gastroenteritis. Gastroenterology 137:495-501.
49. Gunther C, Martini E, Wittkopf N, Amann K, Weigmann B, Neumann H, Waldner MJ, Hedrick SM, Tenzer S, Neurath MF, Becker C. 2011. Caspase-8 regulates TNF-alpha-induced epithelial necroptosis and terminal ileitis. Nature 477:335-339.
50. Guslandi M, Mezzi G, Sorghi M, Testoni PA. 2000. Saccharomyces boulardii in maintenance treatment of Crohn'sdisease. Dig Dis Sci 45:1462-1464.
51. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753-766.
52. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht M, Mayr G, De La Vega FM, Briggs J, Gunther S, Prescott NJ, Onnie CM, Hasler R, SiposB, Folsch UR, Lengauer T, Platzer M, Mathew CG, Krawczak M, Schreiber S. 2007. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207-211.
53. Hannemann S, Gao B, Galan JE. 2013. Salmonella modulation of host cell gene expression promotes its intracellular growth. PLoS Pathog 9:e1003668.
54. Hansen R, Thomson JM, El-Omar EM, Hold GL. 2010. The role of infectioninthe aetiology ofinflammatory bowel disease. J Gastroenterol 45:266-276.
55. Hold GL, Smith M, Grange C, Watt ER, El-Omar EM, Mukhopadhya I. 2014. Role of the gut microbiota in inflamma-tory bowel disease pathogenesis: what have we learnt in the past 10 years? World J Gastroenterol 20:1192-1210.
56. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G. 2001. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599-603.
57. Huttenhower C, Kostic AD, Xavier RJ. 2014. Inflammatory bowel disease as a model for translating the microbiome. Immunity 40:843-854.
58. Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, Skaros S, Weber LR, Komorowski RA, Knox JF, Emmons J, Bajaj JS, Binion DG. 2007. Impact of Clostridium dif-ficile on inflammatory bowel disease. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association 5:345-351.
59. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, WeiD, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485-498.
60. Jonkers D, Penders J, Masclee A, Pierik M. 2012. Probiotics in the management of inflammatory bowel disease: a systematic review of intervention studies in adult patients. Drugs 72:803-823.
61. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, LouisE, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, I.B.D.G.C. International, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH. 2012. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119-124.
62. Juste RA, Elguezabal N, Garrido JM, Pavon A, Geijo MV, Sevilla I, Cabriada JL, Tejada A, Garcia-Campos F, Casado R, Ochotorena I, Izeta A, Greenstein RJ. 2008. On the prevalence of M. avium subspecies paratuberculosis DNA in the blood of healthy individuals and patients with inflammatory bowel disease. PloS one 3:e2537.
63. Kamada N, Seo SU, Chen GY, Nunez G. 2013. Role of the gut micro-biota in immunity and inflammatory disease. Nature Reviews Immunology 13:321-335.
64. Kang S, Denman SE, Morrison M, Yu Z, Dore J, Leclerc M, McSweeney CS. 2010. Dysbiosis of fecal microbiota in Crohn's disease patients as revealed by a custom phylogenetic micro-array. Inflamm Bowel Dis 16:2034-2042.
65. Kim H, Rhee SH, Pothoulakis C, Lamont JT. 2007. Inflammation and apoptosis in Clostridium difficile enteritis is mediated by PGE2 up-regulation of Fas ligand. Gastroenterology 133:875-886.
66. Kirkwood CD, Wagner J, Boniface K, Vaughan J, Michalski WP, Catto-Smith AG, Cameron DJ, Bishop RF. 2009. Mycobacterium avium subspecies paratuberculosis in children with early-onset Crohn's disease. Inflamm Bowel Dis 15:1643-1655.
67. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, Angenent LT, Ley RE. 2011. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci USA 108(Suppl 1):4578-4585.
68. Kostic AD, Xavier RJ, Gevers D. 2014. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146:1489-1499.
69. Kuhbacher T, Ott SJ, Helwig U, Mimura T, Rizzello F, Kleessen B, Gionchetti P, Blaut M, Campieri M, Folsch UR, Kamm MA, Schreiber S. 2006. Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis. Gut 55: 833-841.
70. Kullberg MC, Jankovic D, Gorelick PL, Caspar P, Letterio JJ, Cheever AW, Sher A. 2002. Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus-induced colitis. J Exp Med 196:505-515.
71. Kullberg MC, Ward JM, Gorelick PL, Caspar P, Hieny S, Cheever A, Jankovic D, Sher A. 1998. Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 (IL-10)-deficient mice through an IL-12-and gamma interferon-dependent mechanism. Infect Immun 66:5157-5166.
72. Kumar H, Salminen S, Verhagen H, Rowland I, Heimbach J, Banares S, Young T, Nomoto K, Lalonde M. 2014. Novel probiotics and prebiotics: road to the market. Curr Opin Biotechnol 32C:99-103.
73. Lara-Villoslada F, Debras E, Nieto A, Concha A, Galvez J, Lopez-Huertas E, Boza J, Obled C, Xaus J. 2006. Oligosaccharides isolated from goat milk reduce intestinal inflammation in a rat model of dextran sodium sulfate-induced colitis. Clin Nutr 25:477-488.
74. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jorgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, RasmussenS, Sunagawa S, TapJ, Tims S, Zoetendal EG, Brunak S, Clement K, Dore J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T, Meta HITc, Bork P, Wang J, Ehrlich SD, Pedersen O. 2013. Richness of human gut microbiome correlates with metabolic markers. Nature 500:541-546.
75. Lee YK, Mazmanian SK. 2014. Microbial learning lessons: SFB educate the immune system. Immunity 40:457-459.
76. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. 2006. Microbial ecology: human gut microbes associated with obesity. Nature 444:1022-1023.
77. Li E, Hamm CM, Gulati AS, Sartor RB, Chen H, WuX, Zhang T, Rohlf FJ, Zhu W, Gu C, Robertson CE, Pace NR, Boedeker EC, Harpaz N, Yuan J, Weinstock GM, Sodergren E, Frank DN. 2012. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition. PloS one 7:e26284.
78. Lindsay JO, Whelan K, Stagg AJ, Gobin P, Al-Hassi HO, Rayment N, Kamm MA, Knight SC, Forbes A. 2006. Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease. Gut 55:348-355.
79. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. 2012. Diversity, stability and resilience of the human gut microbiota. Nature 489:220-230.
80. Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN. 1999. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology 116:1107-1114.
81. Malchow HA. 1997. Crohn's disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn's disease? J Clin Gastroenterol 25:653-658.
82. Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J. 2006. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55:205-211.
83. Mann EA, Saeed SA. 2012. Gastrointestinal infection as a trigger for inflammatory bowel disease. Curr Opin Gastroenterol 28:24-29.
84. Martinez-Medina M, Aldeguer X, Lopez-Siles M, Gonzalez-Huix F, Lopez-Oliu C, Dahbi G, Blanco JE, Blanco J, Garcia-Gil LJ, Darfeuille-Michaud A. 2009. Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn's disease. Inflamm Bowel Dis 15:872-882.
85. Martinez I, Muller CE, Walter J. 2013. Long-term temporal analysis of the human fecal microbiota revealed a stable core of dominant bacterial species. PloS one 8:e69621.
86. Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, Nicholls RJ, Gionchetti P, Campieri M, Kamm MA. 2004. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 53:108-114.
87. Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. 2015. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology.
88. Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, Bousvaros A, Korzenik J, Sands BE, Xavier RJ, Huttenhower C. 2012. Dys-function of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13:R79.
89. Naser SA, Ghobrial G, Romero C, Valentine JF. 2004. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn's disease. Lancet 364:1039-1044.
90. Nataro JP, Kaper JB. 1998. Diarrheagenic Escherichia coli. Clin Microbiol Rev 11:142-201.
91. Navaneethan U, Venkatesh PG, Shen B. 2010. Clostridium difficile infection and inflammatory bowel disease: understanding the evolving relationship. World J Gastroenterol 16:4892-4904.
92. Nell S, Suerbaum S, Josenhans C. 2010. The impact of the micro-biota on the pathogenesis of IBD: lessons from mouse infection models. Nature Reviews. Microbiology 8:564-577.
93. Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Huth M, Nikolaev A, Neufert C, Madison B, Gumucio D, Neurath MF, Pasparakis M. 2007. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446:557-561.
94. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. 2012. Host-gut microbiota metabolic interactions. Science 336:1262-1267.
95. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, BrittonH, Moran T, KaraliuskasR, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH. 2001. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411:603-606.
96. Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G. 2001. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 276: 4812-4818.
97. Olsen I, Tollefsen S, Aagaard C, Reitan LJ, Bannantine JP, Andersen P, Sollid LM, Lundin KE. 2009. Isolation of Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn'sdisease patients. PloS One 4:e5641.
98. Ott SJ, Schreiber S. 2006. Reduced microbial diversity in inflammatory bowel diseases. Gut 55:1207.
99. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. 2007. Development of the human infant intestinal microbiota. PLoS Biol 5:e177.
100. Perez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, Neulinger SC, Daumer C, Heinsen FA, Latorre A, Barbas C, Seifert J, dos Santos VM, Ott SJ, Ferrer M, Moya A. 2013. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut 62:1591-1601.
101. Petnicki-Ocwieja T, Hrncir T, Liu YJ, Biswas A, Hudcovic T, Tlaskalova-Hogenova H, Kobayashi KS. 2009. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci USA 106:15813-15818.
102. Pierce ES. 2010. Ulcerative colitis and Crohn'sdisease:isMyco-bacterium avium subspecies paratuberculosis the common villain? Gut Pathogens 2:21.
103. Plein K, Hotz J. 1993. Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn's disease with special respect to chronic diarrhea - apilot study. Z Gastroenterol 31:129-134.
104. Podolsky DK. 2002. Inflammatory bowel disease. N Engl J Med 347:417-429.
105. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, H.I.T.C. Meta, Bork P, Ehrlich SD, Wang J. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59-65.
106. Rahimi R, Nikfar S, Rahimi F, Elahi B, Derakhshani S, Vafaie M, Abdollahi M. 2008. A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn's disease. Dig Dis Sci 53: 2524-2531.
107. Rath HC, Herfarth HH, Ikeda JS, Grenther WB, Hamm TE Jr., Balish E, Taurog JD, Hammer RE, Wilson KH, Sartor RB. 1996. Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats. J Clin Invest 98:945-953.
108. Rhee KJ, Wu S, Wu X, Huso DL, Karim B, Franco AA, Rabizadeh S, GolubJE, Mathews LE, Shin J, Sartor RB, GolenbockD, Hamad AR, Gan CM, Housseau F, Sears CL. 2009. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun 77:1708-1718.
109. Rosenstiel P, Sina C, Franke A, Schreiber S. 2009. Towards a molecular risk map-recent advances on the etiology of inflammatory bowel disease. Semin Immunol 21:334-345.
110. Rossen NG, Fuentes S, van der Spek MJ, Tijssen J, Hartman JH, Duflou A, Lowenberg M, van den Brink GR, Mathus Vliegen EM, de Vos WM, Zoetendal EG, D'Haens GR, Ponsioen CY. 2015. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149:110-118.
111. Rossen NG, MacDonald JK, de Vries EM, D'Haens GR, de Vos WM, Zoetendal EG, Ponsioen CY. 2015. Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. World J Gastroenterol 21:5359-5371.
112. 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.
113. Sanderson JD, Moss MT, Tizard ML, Hermon-Taylor J. 1992. Myco-bacterium paratuberculosis DNA in Crohn's disease tissue. Gut 33:890-896.
114. Sartor RB. 2004. Therapeutic manipulation of the enteric micro-flora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology 126:1620-1633.
115. Schnupf P, Gaboriau-Routhiau V, Gros M, Friedman R, Moya Nilges M, Nigro G, Cerf-Bensussan N, Sansonetti PJ. 2015. Growth and host interaction of mouse segmented filamentous bacteria in vitro. Nature.
116. Schultz M, Veltkamp C, Dieleman LA, Grenther WB, Wyrick PB, Tonkonogy SL, Sartor RB. 2002. Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflamm Bowel Dis 8:71-80.
117. Scott FI, Aberra F. 2011. VSL#3 for ulcerative colitis: growing evidence? Gastroenterology 140:1685-1686; discussion 1686-1687.
118. Scribano ML, Prantera C. 2013. Antibiotics and inflammatory bowel diseases. Digestive Diseases 31:379-384.
119. Selby W, Pavli P, Crotty B, Florin T, Radford-Smith G, Gibson P, Mitchell B, Connell W, Read R, Merrett M, Ee H, Hetzel D. 2007. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn'sdisease. Gastroenterology 132:2313-2319.
120. Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB. 1998. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 66:5224-5231.
121. Serino M, Chabo C, Burcelin R. 2012. Intestinal MicrobiOMICS to define health and disease in human and mice. Curr Pharm Biotechnol 13:746-758.
122. Sheil B, MacSharry J, O'Callaghan L, O'Riordan A, Waters A, Morgan J, Collins JK, O'Mahony L, Shanahan F. 2006. Role of interleukin (IL-10) in probiotic-mediated immune modulation: an assessment in wild-type and IL-10 knock-out mice. Clin Exp Immunol 144:273-280.
123. Simpson KW, Dogan B, Rishniw M, Goldstein RE, Klaessig S, McDonough PL, German AJ, Yates RM, Russell DG, Johnson SE, Berg DE, Harel J, Bruant G, McDonough SP, Schukken YH. 2006. Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs. Infect Immun 74:4778-4792.
124. Sood A, MidhaV, Makharia GK, AhujaV, Singal D, Goswami P, Tandon RK. 2009. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of The American Gastroenterological Association 7:1202-1209, 1209 e1201.
125. Stoll M, Corneliussen B, Costello CM, Waetzig GH, Mellgard B, Koch WA, Rosenstiel P, Albrecht M, Croucher PJ, Seegert D, Nikolaus S, Hampe J, Lengauer T, Pierrou S, Foelsch UR, Mathew CG, Lagerstrom-Fermer M, Schreiber S. 2004. Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 36:476-480.
126. Strober W, Fuss I, Mannon P. 2007. The fundamental basis of in-flammatory bowel disease. J Clin Invest 117:514-521.
127. Tamboli CP, Neut C, Desreumaux P, Colombel JF. 2004. Dysbiosis as a prerequisite for IBD. Gut 53:1057.
128. Tanabe T, Chamaillard M, Ogura Y, Zhu L, Qiu S, Masumoto J, Ghosh P, Moran A, Predergast MM, Tromp G, Williams CJ, Inohara N, Nunez G. 2004. Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. EMBO J 23:1587-1597.
129. Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, Balish E, Hammer RE. 1994. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 180:2359-2364.
130. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. 2009. A core gut microbiome in obese and lean twins. Nature 457:480-484.
131. Tursi A, Brandimarte G, Papa A, Giglio A, Elisei W, Giorgetti GM, Forti G, Morini S, Hassan C, Pistoia MA, Modeo ME, Rodino S, D'Amico T, Sebkova L, Sacca N, Di Giulio E, Luzza F, Imeneo M, Larussa T, Di Rosa S, Annese V, Danese S, Gasbarrini A. 2010. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 105:2218-2227.
132. Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M, Viale A, Socci ND, van den Brink MR, Kamboj M, Pamer EG. 2010. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstreaminvasioninhumans. JClinInvest 120:4332-4341.
133. Veltkamp C, Tonkonogy SL, De Jong YP, Albright C, Grenther WB, Balish E, Terhorst C, Sartor RB. 2001. Continuous stimulation by normal luminal bacteria is essential for the development and perpetuation of colitis in Tg(epsilon26) mice. Gastroenterology 120:900-913.
134. Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, BrostoffJ, 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 11:7.
135. Ward JM, Anver MR, Haines DC, Melhorn JM, Gorelick P, Yan L, Fox JG. 1996. Inflammatory large bowel disease in immunode-ficient mice naturally infected with Helicobacter hepaticus. Laboratory Animal Science 46:15-20.
136. Watanabe T, Kitani A, Murray PJ, Strober W. 2004. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 5:800-808.
137. Wehkamp J, Fellermann K, Stange EF. 2005. Human defensins in Crohn's disease. Chem Immunol Allergy 86:42-54.
138. Wehkamp J, Salzman NH, PorterE, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, LinzmeierR, Feathers RW, Chu H, Lima H Jr., Fellermann K, Ganz T, Stange EF, Bevins CL. 2005. Reduced Paneth cell alpha-defen-sins in ileal Crohn's disease. Proc Natl Acad Sci USA 102:18129-18134.
139. Wirtz S, Finotto S, Kanzler S, Lohse AW, Blessing M, Lehr HA, Galle PR, Neurath MF. 1999. Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF-plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens. J Immunol 162:1884-1888.
140. Wirtz S, Neurath MF. 2007. Mouse models of inflammatory bowel disease. Adv Drug Deliv Rev 59:1073-1083.
141. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. 2012. Human gut microbiome viewed across age and geography. Nature 486:222-227.