Immune Netw.  2017 Feb;17(1):1-12. 10.4110/in.2017.17.1.1.

Host-microbial Cross-talk in Inflammatory Bowel Disease

• Nagao-Kitamoto H
• Kamada N

• KMID: 2368971
• DOI: http://doi.org/10.4110/in.2017.17.1.1

Abstract

A vast community of commensal microorganisms, commonly referred to as the gut microbiota, colonizes the gastrointestinal tract (GI). The involvement of the gut microbiota in the maintenance of the gut ecosystem is two-fold: it educates host immune cells and protects the host from pathogens. However, when healthy microbial composition and function are disrupted (dysbiosis), the dysbiotic gut microbiota can trigger the initiation and development of various GI diseases, including inflammatory bowel disease (IBD). IBD, primarily includes ulcerative colitis (UC) and Crohn's disease (CD), is a major global public health problem affecting over 1 million patients in the United States alone. Accumulating evidence suggests that various environmental and genetic factors contribute to the pathogenesis of IBD. In particular, the gut microbiota is a key factor associated with the triggering and presentation of disease. Gut dysbiosis in patients with IBD is defined as a reduction of beneficial commensal bacteria and an enrichment of potentially harmful commensal bacteria (pathobionts). However, as of now it is largely unknown whether gut dysbiosis is a cause or a consequence of IBD. Recent technological advances have made it possible to address this question and investigate the functional impact of dysbiotic microbiota on IBD. In this review, we will discuss the recent advances in the field, focusing on host-microbial cross-talk in IBD.

Keyword

Gut microbiota; Dysbiosis; Pathobiont; Inflammatory bowel disease

MeSH Terms

Bacteria
Colitis, Ulcerative
Colon
Crohn Disease
Dysbiosis
Ecosystem
Gastrointestinal Microbiome
Gastrointestinal Tract
Humans
Inflammatory Bowel Diseases*
Microbiota
Public Health
United States

Reference

1. Kamada N, Nunez G. Regulation of the immune system by the resident intestinal bacteria. Gastroenterology. 2014; 146:1477–1488. PMID: 24503128.

2. Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature. 2016; 535:75–84. PMID: 27383982.

3. Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016; 535:65–74. PMID: 27383981.

4. Kamada N, Chen GY, Inohara N, Nunez G. Control of pathogens and pathobionts by the gut microbiota. Nat Immunol. 2013; 14:685–690. PMID: 23778796.

5. Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013; 13:321–335. PMID: 23618829.

6. Nagao-Kitamoto H, Kitamoto S, Kuffa P, Kamada N. Pathogenic role of the gut microbiota in gastrointestinal diseases. Intest Res. 2016; 14:127–138. PMID: 27175113.

7. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016; 16:341–352. PMID: 27231050.

8. Sonnenburg JL, Backhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016; 535:56–64. PMID: 27383980.

9. Lee WJ, Hase K. Gut microbiota-generated metabolites in animal health and disease. Nat Chem Biol. 2014; 10:416–424. PMID: 24838170.

10. Manichanh C, Borruel N, Casellas F, Guarner F. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol. 2012; 9:599–608. PMID: 22907164.

11. Nell S, Suerbaum S, Josenhans C. The impact of the microbiota on the pathogenesis of IBD: lessons from mouse infection models. Nat Rev Microbiol. 2010; 8:564–577. PMID: 20622892.

12. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007; 104:13780–13785. PMID: 17699621.

13. Gophna U, Sommerfeld K, Gophna S, Doolittle WF, Veldhuyzen van Zanten SJ. Differences between tissue-associated intestinal microfloras of patients with Crohn's disease and ulcerative colitis. J Clin Microbiol. 2006; 44:4136–4141. PMID: 16988016.

14. Kang S, Denman SE, Morrison M, Yu Z, Dore J, Leclerc M, McSweeney CS. Dysbiosis of fecal microbiota in Crohn's disease patients as revealed by a custom phylogenetic microarray. Inflamm Bowel Dis. 2010; 16:2034–2042. PMID: 20848492.

15. Joossens M, Huys G, Cnockaert M, De P. V, Verbeke K, Rutgeerts P, Vandamme P, Vermeire S. Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives. Gut. 2011; 60:631–637. PMID: 21209126.

16. Sokol H, Seksik P, Rigottier-Gois L, Lay C, Lepage P, Podglajen I, Marteau P, Dore J. Specificities of the fecal microbiota in inflammatory bowel disease. Inflamm Bowel Dis. 2006; 12:106–111. PMID: 16432374.

17. Vigsnaes LK, van den AP, Sulek K, Frandsen HL, Steenholdt C, Brynskov J, Vermeiren J, van de WT, Licht TR. Microbiotas from UC patients display altered metabolism and reduced ability of LAB to colonize mucus. Sci Rep. 2013; 3:1110. PMID: 23346367.

18. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottiere HM, Dore J, Marteau P, Seksik P, Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008; 105:16731–16736. PMID: 18936492.

19. Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Dore J. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009; 15:1183–1189. PMID: 19235886.

20. 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. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012; 13:R79. PMID: 23013615.

21. Machiels K, Joossens M, Sabino J, De P. V, Arijs I, Eeckhaut V, Ballet V, Claes K, Van IF, Verbeke K, Ferrante M, Verhaegen J, Rutgeerts P, Vermeire S. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014; 63:1275–1283. PMID: 24021287.

22. Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint HJ. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000; 66:1654–1661. PMID: 10742256.

23. Lopez-Siles M, Khan TM, Duncan SH, Harmsen HJ, Garcia-Gil LJ, Flint HJ. Cultured representatives of two major phylogroups of human colonic Faecalibacterium prausnitzii can utilize pectin, uronic acids, and host-derived substrates for growth. Appl Environ Microbiol. 2012; 78:420–428. PMID: 22101049.

24. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013; 504:446–450. PMID: 24226770.

25. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly Y, Glickman JN, Garrett WS. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013; 341:569–573. PMID: 23828891.

26. Zhang M, Zhou Q, Dorfman RG, Huang X, Fan T, Zhang H, Zhang J, Yu C. Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats. BMC Gastroenterol. 2016; 16:84. PMID: 27473867.

27. Downes J, Munson M, Wade WG. Dialister invisus sp. nov., isolated from the human oral cavity. Int J Syst Evol Microbiol. 2003; 53:1937–1940. PMID: 14657126.

28. Miller TL, Wolin MJ. Bioconversion of cellulose to acetate with pure cultures of Ruminococcus albus and a hydrogen-using acetogen. Appl Environ Microbiol. 1995; 61:3832–3835. PMID: 16535158.

29. Duncan SH, Barcenilla A, Stewart CS, Pryde SE, Flint HJ. Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol. 2002; 68:5186–5190. PMID: 12324374.

30. Flint HJ, Bayer EA, Rincon MT, Lamed R, White BA. Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat Rev Microbiol. 2008; 6:121–131. PMID: 18180751.

31. Leitch EC, Walker AW, Duncan SH, Holtrop G, Flint HJ. Selective colonization of insoluble substrates by human faecal bacteria. Environ Microbiol. 2007; 9:667–679. PMID: 17298367.

32. Mukherjee PK, Sendid B, Hoarau G, Colombel JF, Poulain D, Ghannoum MA. Mycobiota in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol. 2015; 12:77–87. PMID: 25385227.

33. Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol. 2012; 9:565–576. PMID: 22890113.

34. Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J Gastroenterol. 2010; 105:2687–2692. PMID: 20940708.

35. Kronman MP, Zaoutis TE, Haynes K, Feng R, Coffin SE. Antibiotic exposure and IBD development among children: a population-based cohort study. Pediatrics. 2012; 130:e794–e803. PMID: 23008454.

36. Pompei A, Cordisco L, Amaretti A, Zanoni S, Matteuzzi D, Rossi M. Folate production by bifidobacteria as a potential probiotic property. Appl Environ Microbiol. 2007; 73:179–185. PMID: 17071792.

37. Biasco G, Zannoni U, Paganelli GM, Santucci R, Gionchetti P, Rivolta G, Miniero R, Pironi L, Calabrese C, Di FG, Miglioli M. Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis. Cancer Epidemiol Biomarkers Prev. 1997; 6:469–471. PMID: 9184782.

38. Kinoshita M, Kayama H, Kusu T, Yamaguchi T, Kunisawa J, Kiyono H, Sakaguchi S, Takeda K. Dietary folic acid promotes survival of Foxp3⁺ regulatory T cells in the colon. J Immunol. 2012; 189:2869–2878. PMID: 22869901.

39. Wexler HM. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev. 2007; 20:593–621. PMID: 17934076.

40. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009; 9:313–323. PMID: 19343057.

41. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008; 453:620–625. PMID: 18509436.

42. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005; 122:107–118. PMID: 16009137.

43. Waidmann M, Bechtold O, Frick JS, Lehr HA, Schubert S, Dobrindt U, Loeffler J, Bohn E, Autenrieth IB. Bacteroides vulgatus protects against Escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice. Gastroenterology. 2003; 125:162–177. PMID: 12851881.

44. Rehman A, Lepage P, Nolte A, Hellmig S, Schreiber S, Ott SJ. Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients. J Med Microbiol. 2010; 59:1114–1122. PMID: 20522625.

45. Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R, Orsi RH, Wiedmann M, McDonough P, Kim SG, Berg D, Schukken Y, Scherl E, Simpson KW. 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; 1:403–418. PMID: 18043660.

46. Lapaquette P, Glasser AL, Huett A, Xavier RJ, rfeuille-Michaud A. Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell Microbiol. 2010; 12:99–113. PMID: 19747213.

47. Mukhopadhya I, Hansen R, El-Omar EM, Hold GL. IBD-what role do Proteobacteria play? Nat Rev Gastroenterol Hepatol. 2012; 9:219–230. PMID: 22349170.

48. Boudeau J, Glasser AL, Masseret E, Joly B, rfeuille-Michaud A. Invasive ability of an Escherichia coli strain isolated from the ileal mucosa of a patient with Crohn's disease. Infect Immun. 1999; 67:4499–4509. PMID: 10456892.

49. Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N, Bringer MA, Swidsinski A, Beaugerie L, Colombel JF. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology. 2004; 127:412–421. PMID: 15300573.

50. Barnich N, Carvalho FA, Glasser AL, Darcha C, Jantscheff P, Allez M, Peeters H, Bommelaer G, Desreumaux P, Colombel JF, rfeuille-Michaud A. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Clin Invest. 2007; 117:1566–1574. PMID: 17525800.

51. Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, Rhodes JM, Stintzi A, Simpson KW, Hansen JJ, Keku TO, Fodor AA, Jobin C. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012; 338:120–123. PMID: 22903521.

52. Nougayrede JP, Homburg S, Taieb F, Boury M, Brzuszkiewicz E, Gottschalk G, Buchrieser C, Hacker J, Dobrindt U, Oswald E. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science. 2006; 313:848–851. PMID: 16902142.

53. Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrede JP. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A. 2010; 107:11537–11542. PMID: 20534522.

54. Itzkowitz SH, Present DH. Consensus conference: Colorectal cancer screening and surveillance in inflammatory bowel disease. Inflamm Bowel Dis. 2005; 11:314–321. PMID: 15735438.

55. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010; 105:501–523. PMID: 20068560.

56. Horing E, Gopfert D, Schroter G, von GU. Frequency and spectrum of microorganisms isolated from biopsy specimens in chronic colitis. Endoscopy. 1991; 23:325–327. PMID: 1778136.

57. Plessier A, Cosnes J, Gendre JP, Beaugerie L. Intercurrent Klebsiella oxytoca colitis in a patient with Crohn's disease. Gastroenterol Clin Biol. 2002; 26:799–800. PMID: 12434087.

58. Wagner J, Short K, Catto-Smith AG, Cameron DJ, Bishop RF, Kirkwood CD. Identification and characterisation of Pseudomonas 16S ribosomal DNA from ileal biopsies of children with Crohn's disease. PLoS One. 2008; 3:e3578. PMID: 18974839.

59. 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. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe. 2010; 8:292–300. PMID: 20833380.

60. Deng Q, Barbieri JT. Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxins. Annu Rev Microbiol. 2008; 62:271–288. PMID: 18785839.

61. Ruby T, McLaughlin L, Gopinath S, Monack D. Salmonella's long-term relationship with its host. FEMS Microbiol Rev. 2012; 36:600–615. PMID: 22335190.

62. Geddes K, Rubino S, Streutker C, Cho JH, Magalhaes JG, Le BL, Selvanantham T, Girardin SE, Philpott DJ. Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model. Infect Immun. 2010; 78:5107–5115. PMID: 20921147.

63. 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. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001; 411:599–603. PMID: 11385576.

64. Verma R, Verma AK, Ahuja V, Paul J. Real-time analysis of mucosal flora in patients with inflammatory bowel disease in India. J Clin Microbiol. 2010; 48:4279–4282. PMID: 20861337.

65. Duffy M, O'Mahony L, Coffey JC, Collins JK, Shanahan F, Redmond HP, Kirwan WO. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis. Dis Colon Rectum. 2002; 45:384–388. PMID: 12068199.

66. Pitcher MC, Cummings JH. Hydrogen sulphide: a bacterial toxin in ulcerative colitis? Gut. 1996; 39:1–4. PMID: 8881797.

67. Loubinoux J, Bronowicki JP, Pereira IA, Mougenel JL, Faou AE. Sulfate-reducing bacteria in human feces and their association with inflammatory bowel diseases. FEMS Microbiol Ecol. 2002; 40:107–112. PMID: 19709217.

68. Muyzer G, Stams AJ. The ecology and biotechnology of sulphate-reducing bacteria. Nat Rev Microbiol. 2008; 6:441–454. PMID: 18461075.

69. Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature. 2012; 487:104–108. PMID: 22722865.

70. Rowan F, Docherty NG, Murphy M, Murphy B, Calvin CJ, O'Connell PR. Desulfovibrio bacterial species are increased in ulcerative colitis. Dis Colon Rectum. 2010; 53:1530–1536. PMID: 20940602.

71. Man SM, Kaakoush NO, Leach ST, Nahidi L, Lu HK, Norman J, Day AS, Zhang L, Mitchell HM. Host attachment, invasion, and stimulation of proinflammatory cytokines by Campylobacter concisus and other non-Campylobacter jejuni Campylobacter species. J Infect Dis. 2010; 202:1855–1865. PMID: 21050118.

72. Man SM, Zhang L, Day AS, Leach ST, Lemberg DA, Mitchell H. Campylobacter concisus and other Campylobacter species in children with newly diagnosed Crohn's disease. Inflamm Bowel Dis. 2010; 16:1008–1016. PMID: 19885905.

73. Mahendran V, Riordan SM, Grimm MC, Tran TA, Major J, Kaakoush NO, Mitchell H, Zhang L. Prevalence of Campylobacter species in adult Crohn's disease and the preferential colonization sites of Campylobacter species in the human intestine. PLoS One. 2011; 6:e25417. PMID: 21966525.

74. Gradel KO, Nielsen HL, Schonheyder HC, Ejlertsen T, Kristensen B, Nielsen H. Increased short- and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis. Gastroenterology. 2009; 137:495–501. PMID: 19361507.

75. Kaakoush NO, Deshpande NP, Wilkins MR, Tan CG, Burgos-Portugal JA, Raftery MJ, Day AS, Lemberg DA, Mitchell H. The pathogenic potential of Campylobacter concisus strains associated with chronic intestinal diseases. PLoS One. 2011; 6:e29045. PMID: 22194985.

76. Siegesmund AM, Konkel ME, Klena JD, Mixter PF. Campylobacter jejuni infection of differentiated THP-1 macrophages results in interleukin 1 beta release and caspase-1-independent apoptosis. Microbiology. 2004; 150:561–569. PMID: 14993305.

77. Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev. 2009; 22:349–369. PMID: 19366918.

78. Prindiville TP, Sheikh RA, Cohen SH, Tang YJ, Cantrell MC, Silva J Jr. Bacteroides fragilis enterotoxin gene sequences in patients with inflammatory bowel disease. Emerg Infect Dis. 2000; 6:171–174. PMID: 10756151.

79. Rabizadeh S, Rhee KJ, Wu S, Huso D, Gan CM, Golub JE, Wu X, Zhang M, Sears CL. Enterotoxigenic bacteroides fragilis: a potential instigator of colitis. Inflamm Bowel Dis. 2007; 13:1475–1483. PMID: 17886290.

80. Mottawea W, Chiang CK, Muhlbauer M, Starr AE, Butcher J, Abujamel T, Deeke SA, Brandel A, Zhou H, Shokralla S, Hajibabaei M, Singleton R, Benchimol EI, Jobin C, Mack DR, Figeys D, Stintzi A. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's disease. Nat Commun. 2016; 7:13419. PMID: 27876802.

81. Linden DR, Levitt MD, Farrugia G, Szurszewski JH. Endogenous production of H2S in the gastrointestinal tract: still in search of a physiologic function. Antioxid Redox Signal. 2010; 12:1135–1146. PMID: 19769466.

82. Cho I, Yamanishi S, Cox L, Methe BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I, Li H, Alekseyenko AV, Blaser MJ. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012; 488:621–626. PMID: 22914093.

83. Theriot CM, Koenigsknecht MJ, Carlson PE Jr, Hatton GE, Nelson AM, Li B, Huffnagle GB, Li Z, Young VB. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun. 2014; 5:3114. PMID: 24445449.

84. Sorg JA, Sonenshein AL. Bile salts and glycine as cogerminants for Clostridium difficile spores. J Bacteriol. 2008; 190:2505–2512. PMID: 18245298.

85. Buffie CG, Bucci V, Stein RR, McKenney PT, Ling L, Gobourne A, No D, Liu H, Kinnebrew M, Viale A, Littmann E, van den Brink MR, Jenq RR, Taur Y, Sander C, Cross JR, Toussaint NC, Xavier JB, Pamer EG. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2015; 517:205–208. PMID: 25337874.

86. Hoffmann TW, Pham HP, Bridonneau C, Aubry C, Lamas B, Martin-Gallausiaux C, Moroldo M, Rainteau D, Lapaque N, Six A, Richard ML, Fargier E, Le Guern ME, Langella P, Sokol H. Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice. ISME J. 2016; 10:460–477. PMID: 26218241.

87. Eun CS, Mishima Y, Wohlgemuth S, Liu B, Bower M, Carroll IM, Sartor RB. Induction of bacterial antigen-specific colitis by a simplified human microbiota consortium in gnotobiotic interleukin-10^–/– mice. Infect Immun. 2014; 82:2239–2246. PMID: 24643531.

88. Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, Ruggiero E, Cho JH, Goodman AL, Flavell RA. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell. 2014; 158:1000–1010. PMID: 25171403.

89. Okai S, Usui F, Yokota S, Hori I, Hasegawa M, Nakamura T, Kurosawa M, Okada S, Yamamoto K, Nishiyama E, Mori H, Yamada T, Kurokawa K, Matsumoto S, Nanno M, Naito T, Watanabe Y, Kato T, Miyauchi E, Ohno H, Shinkura R. High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice. Nat Microbiol. 2016; 1:16103. PMID: 27562257.

90. Nagao-Kitamoto H, Shreiner AB, Gillilland MG III, Kitamoto S, Ishii C, Hirayama A, Kuffa P, El-Zaatari M, Grasberger H, Seekatz AM, Higgins PD, Young VB, Fukuda S, Kao JY, Kamada N. Functional Characterization of Inflammatory Bowel Disease-Associated Gut Dysbiosis in Gnotobiotic Mice. Cell Mol Gastroenterol Hepatol. 2016; 2:468–481. PMID: 27795980.

91. Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2011; 9:88–96. PMID: 22183182.

92. Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016; 13:508–516. PMID: 27329806.

93. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013; 368:407–415. PMID: 23323867.

94. Hourigan SK, Chen LA, Grigoryan Z, Laroche G, Weidner M, Sears CL, Oliva-Hemker M. Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease. Aliment Pharmacol Ther. 2015; 42:741–752. PMID: 26198180.

95. Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, Lowenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D'Haens GR, Ponsioen CY. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology. 2015; 149:110–118. PMID: 25836986.

96. Voitk AJ, Echave V, Feller JH, Brown RA, Gurd FN. Experience with elemental diet in the treatment of inflammatory bowel disease. Is this primary therapy? Arch Surg. 1973; 107:329–333. PMID: 4198183.

97. Akobeng AK, Thomas AG. Enteral nutrition for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2007; 18:CD005984.

98. Halmos EP, Christophersen CT, Bird AR, Shepherd SJ, Gibson PR, Muir JG. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015; 64:93–100. PMID: 25016597.

99. Croagh C, Shepherd SJ, Berryman M, Muir JG, Gibson PR. Pilot study on the effect of reducing dietary FODMAP intake on bowel function in patients without a colon. Inflamm Bowel Dis. 2007; 13:1522–1528. PMID: 17828776.