Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

Gastroenterology

Volumn 152, Issue 2, 2017, Pages 327-339.e4

  Sartor, R Balfour ^a   Wu, Gary D ^b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Dysbiosis; Fecal Transplant; Personalized Therapy; Viruses

Indexed keywords

ANTIBIOTIC AGENT; PROBIOTIC AGENT;

ANTIBIOTIC THERAPY; ARTICLE; DISEASE COURSE; DYSBIOSIS; ENTERIC VIRUS; FECAL MICROBIOTA TRANSPLANTATION; FUNGUS; HUMAN; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; SPECIES COMPOSITION; ANIMAL; BACTERIUM; CROHN DISEASE; GENETICS; ILEITIS; METABOLISM; METABOLOME; METAGENOME; MICROBIOLOGY; ULCERATIVE COLITIS; VIRUS;

ANIMALS; BACTERIA; COLITIS, ULCERATIVE; CROHN DISEASE; DYSBIOSIS; FUNGI; GASTROINTESTINAL MICROBIOME; HUMANS; INFLAMMATORY BOWEL DISEASES; METABOLOME; METAGENOME; POUCHITIS; VIRUSES;

EID: 85007508333     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2016.10.012     Document Type: Article

References (172)

1. 1 Sartor, R.B., Microbial influences in inflammatory bowel diseases. Gastroenterology 134 (2008), 577–594.
2. 2 Sartor, R.B., Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 3 (2006), 390–407.
3. 3 Kostic, A.D., Xavier, R.J., Gevers, D., The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146 (2014), 1489–1499.
4. 4 Forbes, J.D., Van Domselaar, G., Bernstein, C.N., The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol, 7, 2016, 1081.
5. 5 Butto, L.F., Schaubeck, M., Haller, D., Mechanisms of microbe-host interaction in Crohn's disease: dysbiosis vs. pathobiont selection. Front Immunol, 6, 2015, 555.
6. 6 Shah, R., Cope, J.L., Nagy-Szakal, D., et al. Composition and function of the pediatric colonic mucosal microbiome in untreated patients with ulcerative colitis. Gut Microbes, 2016, 1–13.
7. 7 Baldassano, S.N., Bassett, D.S., Topological distortion and reorganized modular structure of gut microbial co-occurrence networks in inflammatory bowel disease. Sci Rep, 6, 2016, 26087.
8. 8 Bruner, S.D., Jobin, C., Intestinal microbiota in inflammatory bowel disease and carcinogenesis: implication for therapeutics. Clin Pharmacol Ther 99 (2016), 585–587.
9. 9 Raffals, L.E., Chang, E.B., Navigating the microbial basis of inflammatory bowel diseases: seeing the light at the end of the tunnel. Gut Liver 10 (2016), 502–508.
10. 10 Becker, C., Neurath, M.F., Wirtz, S., The intestinal microbiota in inflammatory bowel disease. ILAR J 56 (2015), 192–204.
11. 11 DeGruttola, A.K., Low, D., Mizoguchi, A., et al. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis 22 (2016), 1137–1150.
12. 12 Huttenhower, C., Kostic, A.D., Xavier, R.J., Inflammatory bowel disease as a model for translating the microbiome. Immunity 40 (2014), 843–854.
13. 13 Gilbert, J.A., Quinn, R.A., Debelius, J., et al. Microbiome-wide association studies link dynamic microbial consortia to disease. Nature 535 (2016), 94–103.
14. 14 Backhed, F., Fraser, C.M., Ringel, Y., et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe 12 (2012), 611–622.
15. 15 Arumugam, M., Raes, J., Pelletier, E., et al. Enterotypes of the human gut microbiome. Nature 473 (2011), 174–180.
16. 16 Wu, G.D., Chen, J., Hoffmann, C., et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334 (2011), 105–108.
17. 17 Zupancic, M.L., Cantarel, B.L., Liu, Z., et al. Analysis of the gut microbiota in the old order Amish and its relation to the metabolic syndrome. PLoS One, 7, 2012, e43052.
18. 18 Qin, J., Li, R., Raes, J., et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464 (2010), 59–65.
19. 19 Turnbaugh, P.J., Hamady, M., Yatsunenko, T., et al. A core gut microbiome in obese and lean twins. Nature 457 (2009), 480–484.
20. 20 Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486 (2012), 207–214.
21. 21 Koenig, J.E., Spor, A., Scalfone, N., et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A 108:Suppl 1 (2011), 4578–4585.
22. 22 Backhed, F., Roswall, J., Peng, Y., et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe, 17, 2015, 852.
23. 23 Dethlefsen, L., Relman, D.A., Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A 108:Suppl 1 (2011), 4554–4561.
24. 24 Li, H., Qi, Y., Jasper, H., Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan. Cell Host Microbe 19 (2016), 240–253.
25. 25 Flores, G.E., Caporaso, J.G., Henley, J.B., et al. Temporal variability is a personalized feature of the human microbiome. Genome Biol, 15, 2014, 531.
26. 26 Costello, E.K., Lauber, C.L., Hamady, M., et al. Bacterial community variation in human body habitats across space and time. Science 326 (2009), 1694–1697.
27. 27 David, L.A., Maurice, C.F., Carmody, R.N., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505 (2014), 559–563.
28. 28 Sonnenburg, J.L., Backhed, F., Diet-microbiota interactions as moderators of human metabolism. Nature 535 (2016), 56–64.
29. 29 Propheter, D.C., Hooper, L.V., Bacteria come into focus: new tools for visualizing the microbiota. Cell Host Microbe 18 (2015), 392–394.
30. 30 Earle, K.A., Billings, G., Sigal, M., et al. Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe 18 (2015), 478–488.
31. 31 Chu, H., Khosravi, A., Kusumawardhani, I.P., et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 352 (2016), 1116–1120.
32. 32 Goodrich, J.K., Davenport, E.R., Beaumont, M., et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19 (2016), 731–743.
33. 33 Goodrich, J.K., Waters, J.L., Poole, A.C., et al. Human genetics shape the gut microbiome. Cell 159 (2014), 789–799.
34. 34 Org, E., Parks, B.W., Joo, J.W., et al. Genetic and environmental control of host-gut microbiota interactions. Genome Res 25 (2015), 1558–1569.
35. 35 Lamas, B., Richard, M.L., Leducq, V., et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med 22 (2016), 598–605.
36. 36 Shanahan, M.T., Carroll, I.M., Grossniklaus, E., et al. Mouse Paneth cell antimicrobial function is independent of Nod2. Gut 63 (2014), 903–910.
37. 37 Li, E., Hamm, C.M., Gulati, A.S., et al. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition. PLoS One, 7, 2012, e26284.
38. 38 Knights, D., Silverberg, M.S., Weersma, R.K., et al. Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med, 6, 2014, 107.
39. 39 Fischbach, M.A., Segre, J.A., Signaling in host-associated microbial communities. Cell 164 (2016), 1288–1300.
40. 40 Schloissnig, S., Arumugam, M., Sunagawa, S., et al. Genomic variation landscape of the human gut microbiome. Nature 493 (2013), 45–50.
41. 41 Luo, C., Knight, R., Siljander, H., et al. ConStrains identifies microbial strains in metagenomic datasets. Nat Biotechnol 33 (2015), 1045–1052.
42. 42 Li, S.S., Zhu, A., Benes, V., et al. Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science 352 (2016), 586–589.
43. 43 Brito, I.L., Alm, E.J., Tracking strains in the microbiome: insights from metagenomics and models. Front Microbiol, 7, 2016, 712.
44. 44 Patwa, L.G., Fan, T.J., Tchaptchet, S., et al. Chronic intestinal inflammation induces stress-response genes in commensal Escherichia coli. Gastroenterology., 141, 2011, 1842–1851 e1–10.
45. 45 Underhill, D.M., Iliev, I.D., The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol 14 (2014), 405–416.
46. 46 Tang, J., Iliev, I.D., Brown, J., et al. Mycobiome: approaches to analysis of intestinal fungi. J Immunol Methods 421 (2015), 112–121.
47. 47 Soll, D.R., Galask, R., Schmid, J., et al. Genetic dissimilarity of commensal strains of Candida spp. carried in different anatomical locations of the same healthy women. J Clin Microbiol 29 (1991), 1702–1710.
48. 48 Huffnagle, G.B., Noverr, M.C., The emerging world of the fungal microbiome. Trends Microbiol 21 (2013), 334–341.
49. 49 Dollive, S., Chen, Y.Y., Grunberg, S., et al. Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment. PLoS One, 8, 2013, e71806.
50. 50 Hoffmann, C., Dollive, S., Grunberg, S., et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS One, 8, 2013, e66019.
51. 51 Noverr, M.C., Noggle, R.M., Toews, G.B., et al. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun 72 (2004), 4996–5003.
52. 52 Levitz, S.M., Innate recognition of fungal cell walls. PLoS Pathog, 6, 2010, e1000758.
53. 53 Hoffmann, K.H., Rodriguez-Brito, B., Breitbart, M., et al. Power law rank-abundance models for marine phage communities. FEMS Microbiol Lett 273 (2007), 224–228.
54. 54 Rodriguez-Brito, B., Li, L., Wegley, L., et al. Viral and microbial community dynamics in four aquatic environments. ISME J 4 (2010), 739–751.
55. 55 Reyes, A., Haynes, M., Hanson, N., et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466 (2010), 334–338.
56. 56 Minot, S., Bryson, A., Chehoud, C., et al. Rapid evolution of the human gut virome. Proc Natl Acad Sci U S A 110 (2013), 12450–12455.
57. 57 Minot, S., Sinha, R., Chen, J., et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res 21 (2011), 1616–1625.
58. 58 Sorek, R., Kunin, V., Hugenholtz, P., CRISPR—a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat Rev Microbiol 6 (2008), 181–186.
59. 59 Pires, D.P., Cleto, S., Sillankorva, S., et al. Genetically engineered phages: a review of advances over the last decade. Microbiol Mol Biol Rev 80 (2016), 523–543.
60. 60 Virgin, H.W., The virome in mammalian physiology and disease. Cell 157 (2014), 142–150.
61. 61 Lewis, J.D., Chen, E.Z., Baldassano, R.N., et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn's disease. Cell Host Microbe 18 (2015), 489–500.
62. 62 Pfeiffer, J.K., Virgin, H.W., Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine. Science, 2016, 351.
63. 63 Kernbauer, E., Ding, Y., Cadwell, K., An enteric virus can replace the beneficial function of commensal bacteria. Nature 516 (2014), 94–98.
64. 64 Kane, M., Case, L.K., Kopaskie, K., et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334 (2011), 245–249.
65. 65 Wilks, J., Lien, E., Jacobson, A.N., et al. Mammalian lipopolysaccharide receptors incorporated into the retroviral envelope augment virus transmission. Cell Host Microbe 18 (2015), 456–462.
66. 66 Dolan, K.T., Chang, E.B., Diet, gut microbes, and the pathogenesis of inflammatory bowel diseases. Mol Nutr Food Res, 2016 Jun 27 http://dx.doi.org/10.1002/mnfr.201600129 [Epub ahead of print].
67. 67 Miyoshi, J., Chang, E.B., The gut microbiota and inflammatory bowel diseases. Transl Res, 2016 Jun 14 pii: S1931–5244(16)30095-0 http://dx.doi.org/10.1016/j.trsl.2016.06.002 [Epub ahead of print].
68. 68 Wlodarska, M., Kostic, A.D., Xavier, R.J., An integrative view of microbiome-host interactions in inflammatory bowel diseases. Cell Host Microbe 17 (2015), 577–591.
69. 69 Gevers, D., Kugathasan, S., Denson, L.A., et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 15 (2014), 382–392.
70. 70 Forbes, J.D., Van Domselaar, G., Bernstein, C.N., microbiome survey of the inflamed and noninflamed gut at different compartments within the gastrointestinal tract of inflammatory bowel disease patients. Inflamm Bowel Dis 22 (2016), 817–825.
71. 71 Walters, W.A., Xu, Z., Knight, R., Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 588 (2014), 4223–4233.
72. 72 Frank, D.N., St Amand, A.L., Feldman, R.A., et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104 (2007), 13780–13785.
73. 73 Huttenhower, C., Knight, R., Brown, C.T., et al. Advancing the microbiome research community. Cell 159 (2014), 227–230.
74. 74 Buttò, L.F., Haller, D., Dysbiosis in intestinal inflammation: cause or consequence. Int J Med Microbiol 306 (2016), 302–309.
75. 75 Sartor, R.B., Genetics and environmental interactions shape the intestinal microbiome to promote inflammatory bowel disease versus mucosal homeostasis. Gastroenterology 139 (2010), 1816–1819.
76. 76 Elinav, E., Strowig, T., Kau, A.L., et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145 (2011), 745–757.
77. 77 Gionchetti, P., Rizzello, F., Venturi, A., et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119 (2000), 305–309.
78. 78 Eun, C.S., Mishima, Y., Wohlgemuth, S., et al. Induction of bacterial antigen-specific colitis by a simplified human microbiota consortium in gnotobiotic interleukin-10-/- mice. Infect Immun 82 (2014), 2239–2246.
79. 79 Schäffler, H., Herlemann, D.P., Alberts, C., et al. Mucosa-attached bacterial community in Crohn's Disease coheres with the Clinical Disease Activity Index. Environ Microbiol Rep, 2016 Apr 15 http://dx.doi.org/10.1111/1758-2229.12411 [Epub ahead of print].
80. 80 Laubitz, D., Harrison, C.A., Midura-Kiela, M.T., et al. Reduced epithelial Na+/H+ exchange drives gut microbial dysbiosis and promotes inflammatory response in T cell-mediated murine colitis. PLoS One, 11, 2016, e0152044.
81. 81 Berry, D., Kuzyk, O., Rauch, I., et al. Intestinal microbiota signatures associated with inflammation history in mice experiencing recurring colitis. Front Microbiol, 6, 2015, 1408.
82. 82 Albenberg, L., Esipova, T.V., Judge, C.P., et al. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota in humans and mice. Gastroenterology 147 (2014), 1055–1063.e8.
83. 83 Winter, S.E., Lopez, C.A., Baumler, A.J., The dynamics of gut-associated microbial communities during inflammation. EMBO Rep 14 (2013), 319–327.
84. 84 Tchaptchet, S., Fan, T.J., Goeser, L., et al. Inflammation-induced acid tolerance genes gadAB in luminal commensal Escherichia coli attenuate experimental colitis. Infect Immun 81 (2013), 3662–3671.
85. 85 Darfeuille-Michaud, A., Boudeau, J., Bulois, P., et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 127 (2004), 412–421.
86. 86 Liu, Y., van Kruiningen, H.J., West, A.B., et al. Immunocytochemical evidence of Listeria, Escherichia coli, and Streptococcus antigens in Crohn's disease. Gastroenterology 108 (1995), 1396–1404.
87. 87 Larmonier, C.B., Shehab, K.W., Ghishan, F.K., et al. T lymphocyte dynamics in inflammatory bowel diseases: role of the microbiome. Biomed Res Int, 2015, 2015, 504638.
88. 88 Gunther, C., Josenhans, C., Wehkamp, J., Crosstalk between microbiota, pathogens and the innate immune responses. Int J Med Microbiol 306 (2016), 257–265.
89. 89 Buela, K.A., Omenetti, S., Pizarro, T.T., Cross-talk between type 3 innate lymphoid cells and the gut microbiota in inflammatory bowel disease. Curr Opin Gastroenterol 31 (2015), 449–455.
90. 90 Planer, J.D., Peng, Y., Kau, A.L., et al. Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice. Nature 534 (2016), 263–266.
91. 91 Tanoue, T., Atarashi, K., Honda, K., Development and maintenance of intestinal regulatory T cells. Nat Rev Immunol 16 (2016), 295–309.
92. 92 Atarashi, K., Tanoue, T., Oshima, K., et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500 (2013), 232–236.
93. 93 Furusawa, Y., Obata, Y., Fukuda, S., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504 (2013), 446–450.
94. 94 Obata, Y., Furusawa, Y., Endo, T.A., et al. The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells. Nat Immunol 15 (2014), 571–579.
95. 95 Nishio, J., Baba, M., Atarashi, K., et al. Requirement of full TCR repertoire for regulatory T cells to maintain intestinal homeostasis. Proc Natl Acad Sci U S A 112 (2015), 12770–12775.
96. 96 Sokol, H., Pigneur, B., Watterlot, L., et al. 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 (2008), 16731–16736.
97. 97 Rossi, O., van Berkel, L.A., Chain, F., et al. Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses. Sci Rep, 6, 2016, 18507.
98. 98 Quevrain, E., Maubert, M.A., Michon, C., et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease. Gut 65 (2016), 415–425.
99. 99 Miquel, S., Leclerc, M., Martin, R., et al. Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii. MBio(2), 2015, 6.
100. 100 Sarrabayrouse, G., Alameddine, J., Altare, F., et al. Microbiota-specific CD4CD8alphaalpha Tregs: role in intestinal immune homeostasis and implications for IBD. Front Immunol, 6, 2015, 522.
101. 101 Mazmanian, S.K., Round, J.L., Kasper, D.L., A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453 (2008), 620–625.
102. 102 Round, J.L., Lee, S.M., Li, J., et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332 (2011), 974–977.
103. 103 Shen, Y., Giardino Torchia, M.L., Lawson, G.W., et al. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12 (2012), 509–520.
104. 104 Ahern, P.P., Faith, J.J., Gordon, J.I., Mining the human gut microbiota for effector strains that shape the immune system. Immunity 40 (2014), 815–823.
105. 105 Baumgart, M., Dogan, B., Rishniw, M., et al. Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum. ISME J 1 (2007), 403–418.
106. 106 Kim, S.C., Tonkonogy, S.L., Albright, C.A., et al. Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128 (2005), 891–906.
107. 107 Chassaing, B., Darfeuille-Michaud, A., The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology 140 (2011), 1720–1728.
108. 108 Agus, A., Massier, S., Darfeuille-Michaud, A., et al. Understanding host-adherent-invasive Escherichia coli interaction in Crohn's disease: opening up new therapeutic strategies. Biomed Res Int, 2014, 2014, 567929.
109. 109 Rolhion, N., Hofman, P., Darfeuille-Michaud, A., The endoplasmic reticulum stress response chaperone: Gp96, a host receptor for Crohn disease-associated adherent-invasive Escherichia coli. Gut Microbes 2 (2011), 115–119.
110. 110 Chassaing, B., Garenaux, E., Carriere, J., et al. Analysis of the sigmaE regulon in Crohn's disease-associated Escherichia coli revealed involvement of the waaWVL operon in biofilm formation. J Bacteriol 197 (2015), 1451–1465.
111. 111 Ellermann, M., Huh, E.Y., Liu, B., et al. Adherent-invasive Escherichia coli production of cellulose influences iron-induced bacterial aggregation, phagocytosis, and induction of colitis. Infect Immun 83 (2015), 4068–4080.
112. 112 Dreux, N., Denizot, J., Martinez-Medina, M., et al. Point mutations in FimH adhesin of Crohn's disease-associated adherent-invasive Escherichia coli enhance intestinal inflammatory response. PLoS Pathog, 9, 2013, e1003141.
113. 113 Gibold, L., Garenaux, E., Dalmasso, G., et al. The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn's disease-associated Escherichia coli. Cell Microbiol 18 (2016), 617–631.
114. 114 Lapaquette, P., Bringer, M.A., Darfeuille-Michaud, A., Defects in autophagy favour adherent-invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response. Cell Microbiol 14 (2012), 791–807.
115. 115 Nguyen, H.T., Dalmasso, G., Muller, S., et al. Crohn's disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy. Gastroenterology 146 (2014), 508–519.
116. 116 Yan, X., Sivignon, A., Yamakawa, N., et al. Glycopolymers as antiadhesives of E. coli strains inducing inflammatory bowel diseases. Biomacromolecules 16 (2015), 1827–1836.
117. 117 Dogan, B., Suzuki, H., Herlekar, D., et al. Inflammation-associated adherent-invasive Escherichia coli are enriched in pathways for use of propanediol and iron and M-cell translocation. Inflamm Bowel Dis 20 (2014), 1919–1932.
118. 118 O'Brien, C.L., Bringer, M.A., Holt, K.E., et al. Comparative genomics of Crohn's disease-associated adherent-invasive Escherichia coli. Gut, 2016 Apr 20 pii: gutjnl-2015–311059.
119. 119 Kim, S.C., Tonkonogy, S.L., Karrasch, T., et al. Dual-association of gnotobiotic IL-10-/- mice with 2 nonpathogenic commensal bacteria induces aggressive pancolitis. Inflamm Bowel Dis 13 (2007), 1457–1466.
120. 120 Steck, N., Hoffmann, M., Sava, I.G., et al. Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 141 (2011), 959–971.
121. 121 Maharshak, N., Huh, E.Y., Paiboonrungruang, C., et al. Enterococcus faecalis gelatinase mediates intestinal permeability via protease-activated receptor 2. Infect Immun 83 (2015), 2762–2770.
122. 122 Ocvirk, S., Sava, I.G., Lengfelder, I., et al. Surface-associated lipoproteins link enterococcus faecalis virulence to colitogenic activity in IL-10-deficient mice independent of their expression levels. PLoS Pathog, 11, 2015, e1004911.
123. 123 De Preter, V., Metabolomics in the clinical diagnosis of inflammatory bowel disease. Dig Dis 33:Suppl 1 (2015), 2–10.
124. 124 Smirnov, K.S., Maier, T.V., Walker, A., et al. Challenges of metabolomics in human gut microbiota research. Int J Med Microbiol 306 (2016), 266–279.
125. 125 Valles-Colomer, M., Darzi, Y., Vieira-Silva, S., et al. Meta-omics in inflammatory bowel disease research: applications, challenges, and guidelines. J Crohns Colitis 10 (2016), 735–746.
126. 126 Fiocchi, C., Integrating omics: the future of IBD?. Dig Dis 32:Suppl 1 (2014), 96–102.
127. 127 Patel, N., Alkhouri, N., Eng, K., et al. Metabolomic analysis of breath volatile organic compounds reveals unique breathprints in children with inflammatory bowel disease: a pilot study. Aliment Pharmacol Ther 40 (2014), 498–507.
128. 128 Ahmed, O., Nguyen, G.C., Therapeutic challenges of managing inflammatory bowel disease in the elderly patient. Expert Rev Gastroenterol Hepatol, 2016, 1–6.
129. 129 Sun, M., Wu, W., Liu, Z., et al. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J Gastroenterol, 2016 Jul 23 [Epub ahead of print].
130. 130 Machiels, K., Joossens, M., Sabino, J., et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63 (2014), 1275–1283.
131. 131 Brotherton, C.S., Martin, C.A., Long, M.D., et al. Avoidance of fiber is associated with greater risk of Crohn's disease flare in a 6-month period. Clin Gastroenterol Hepatol 14 (2016), 1130–1136.
132. 132 Wilson, A., Teft, W.A., Morse, B.L., et al. Trimethylamine-N-oxide: a novel biomarker for the identification of inflammatory bowel disease. Dig Dis Sci 60 (2015), 3620–3630.
133. 133 Duboc, H., Rajca, S., Rainteau, D., et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 62 (2013), 531–539.
134. 134 Devkota, S., Wang, Y., Musch, M.W., et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487 (2012), 104–108.
135. 135 Haberman, Y., Tickle, T.L., Dexheimer, P.J., et al. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J Clin Invest 124 (2014), 3617–3633.
136. 136 Richard, M.L., Lamas, B., Liguori, G., et al. Gut fungal microbiota: the Yin and Yang of inflammatory bowel disease. Inflamm Bowel Dis 21 (2015), 656–665.
137. 137 Iliev, I.D., Funari, V.A., Taylor, K.D., et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336 (2012), 1314–1317.
138. 138 Wheeler, M.L., Limon, J.J., Bar, A.S., et al. Immunological consequences of intestinal fungal dysbiosis. Cell Host Microbe 19 (2016), 865–873.
139. 139 Prideaux, L., De Cruz, P., Ng, S.C., et al. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis 18 (2012), 1340–1355.
140. 140 Chehoud, C., Albenberg, L.G., Judge, C., et al. Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 21 (2015), 1948–1956.
141. 141 Sokol, H., Leducq, V., Aschard, H., et al. Fungal microbiota dysbiosis in IBD. Gut, 2016 Feb 3 pii: gutjnl-2015–310746 http://dx.doi.org/10.1136/gutjnl-2015-310746 [Epub ahead of print].
142. 142 Zwolinska-Wcislo, M., Brzozowski, T., Budak, A., et al. Effect of Candida colonization on human ulcerative colitis and the healing of inflammatory changes of the colon in the experimental model of colitis ulcerosa. J Physiol Pharmacol 60 (2009), 107–118.
143. 143 Hoarau, G., Mukherjee, P.K., Gower-Rousseau, C., et al. Bacteriome and mycobiome interactions underscore microbial dysbiosis in familial Crohn's disease. MBio, 7, 2016 e01250–16.
144. 144 Norman, J.M., Handley, S.A., Baldridge, M.T., et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160 (2015), 447–460.
145. 145 Cadwell, K., Liu, J.Y., Brown, S.L., et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456 (2008), 259–263.
146. 146 Cadwell, K., Patel, K.K., Maloney, N.S., et al. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141 (2010), 1135–1145.
147. 147 De Vlaminck, I., Khush, K.K., Strehl, C., et al. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell 155 (2013), 1178–1187.
148. 148 Young, J.C., Chehoud, C., Bittinger, K., et al. Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients. Am J Transplant 15 (2015), 200–209.
149. 149 Hansen, J.J., Sartor, R.B., Therapeutic manipulation of the microbiome in IBD: current results and future approaches. Curr Treat Options Gastroenterol 13 (2015), 105–120.
150. 150 Bejaoui, M., Sokol, H., Marteau, P., Targeting the microbiome in inflammatory bowel disease: critical evaluation of current concepts and moving to new horizons. Dig Dis 33:Suppl 1 (2015), 105–112.
151. 151 Ohkusa, T., Kato, K., Terao, S., et al. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am J Gastroenterol 105 (2010), 1820–1829.
152. 152 Turner, D., Levine, A., Kolho, K.L., et al. Combination of oral antibiotics may be effective in severe pediatric ulcerative colitis: a preliminary report. J Crohns Colitis 8 (2014), 1464–1470.
153. 153 Chassaing, B., Tran, H., Gewirtz, A., O-007 colitis vaccine: flagellin-elicited immunity keeps motile bacteria in check and protects against intestinal inflammation. Inflamm Bowel Dis, 22(Suppl 1), 2016, S3.
154. 154 Ratner, M., Microbial cocktails join fecal transplants in IBD treatment trials. Nat Biotechnol 33 (2015), 787–788.
155. 155 Machiels, K., Sabino, J., Vandermosten, L., et al. Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC. Gut, 2015 Sep 30 pii: gutjnl-2015–309398.
156. 156 Shaw, K.A., Bertha, M., Hofmekler, T., et al. Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease. Genome Med, 8, 2016, 75.
157. 157 Rajca, S., Grondin, V., Louis, E., et al. Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn's disease. Inflamm Bowel Dis 20 (2014), 978–986.
158. 158 Zhang, F., Luo, W., Shi, Y., et al. Should we standardize the 1,700-year-old fecal microbiota transplantation?. Am J Gastroenterol, 107, 2012, 1755.
159. 159 Kassam, Z., Lee, C.H., Yuan, Y., et al. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 108 (2013), 500–508.
160. 160 Borody, T.J., Warren, E.F., Leis, S., et al. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol 37 (2003), 42–47.
161. 161 Vrieze, A., Van Nood, E., Holleman, F., et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143 (2012), 913–916 e7.
162. 162 Kelly, C.R., Kahn, S., Kashyap, P., et al. Update on fecal microbiota transplantation 2015: indications, methodologies, mechanisms, and outlook. Gastroenterology 149 (2015), 223–237.
163. 163 Colman, R.J., Rubin, D.T., Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis 8 (2014), 1569–1581.
164. 164 Moayyedi, P., Surette, M.G., Kim, P.T., et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149 (2015), 102–109 e6.
165. 165 Rossen, N.G., Fuentes, S., van der Spek, M.J., et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149 (2015), 110–118 e4.
166. 166 Grinspan, A.M., Kelly, C.R., Fecal microbiota transplantation for ulcerative colitis: not just yet. Gastroenterology 149 (2015), 15–18.
167. 167 Angelberger, S., Reinisch, W., Makristathis, A., et al. Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol 108 (2013), 1620–1630.
168. 168 De Leon, L.M., Watson, J.B., Kelly, C.R., Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol 11 (2013), 1036–1038.
169. 169 Kelly, C.R., Ziud, H., Kahn, S., New diagnosis of Crohn's colitis 6 weeks after fecal microbiota transplantation?. Inflamm Bowel Dis, 20, 2014, S21.
170. 170 Kelly, C.R., Ihunnah, C., Fischer, M., et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol 109 (2014), 1065–1071.
171. 171 Hecht, G.A., Blaser, M.J., Gordon, J., et al. What is the value of a food and drug administration investigational new drug for fecal microbiota transplantation in Clostridium difficile infection?. Clin Gastroenterol Hepatol 12 (2014), 289–291.
172. 172 Chehoud, C., Dryga, A., Hwang, Y., et al. Transfer of viral communities between human individuals during fecal microbiota transplantation. MBio, 7, 2016, e00322.