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Cited by 1,778Gut microbiota and healthInflammatory Bowel DiseaseOral microbiology and periodontitis research

Gut microbiota and IBD: causation or correlation?

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Ni, Josephine, Wu, Gary D., Albenberg, Lindsey, Tomov, Vesselin T.·2017·Nature Reviews Gastroenterology & Hepatology
DOI 10.1038/nrgastro.2017.88PMC PMC5880536
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Abstract

A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host-microbial relationships relevant to human disease and amenable to therapeutic interventions.

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  • Abnormal diversity (dysbiosis) in the gut has been proven to be associated with human diseases such as obesity, inflammatory bowel disease, and cancer.

    “Abnormal diversity (dysbiosis) in the gut has been proven to be associated with human diseases, such as obesity, inflammatory bowel disease, cancer, etc. 20,21,33,34”

    From The Diversity of Gut Microbiome is Associated With Favorable Responses to Anti–Programmed Death 1 Immunotherapy in Chinese Patients With NSCLC (2019) · cites this paper as [34]

    The ‘Microbiota composition and IBD’ section documents differences in gut microbial diversity and composition between people with IBD and healthy individuals, supporting the claimed association with IBD. Our copy does not establish the corresponding associations with obesity or cancer; the cancer-related reference alone does not substantiate that broader claim. The paper also cautions that association does not prove causation, although the citing sentence claims association rather than causation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Alterations in microbiota may contribute to disease progression in some conditions, including inflammatory bowel diseases.

    “It is very likely that this may contribute to disease progression in some conditions, including inflammatory bowel diseases 22,23 ,”

    From Human microbiome myths and misconceptions (2023) · cites this paper as [22]

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  1. [1]Dahlhamer JM Zammitti EP Ward BW Wheaton AG Croft JB Prevalence of inflammatory bowel disease among adults aged ≥18 Years — United States, 2015 MMWR Morb Mortal Wkly Rep 65 1166 1169 2016 27787492
  2. [2]Molodecky NA Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review Gastroenterology 142 46 54.e42 2012 22001864
  3. [3]Manichanh C Borruel N Casellas F Guarner F The gut microbiota in IBD Nat Rev Gastroenterol Hepatol 9 599 608 2012 22907164
  4. [5]Mosca A Leclerc M Hugot JP Gut microbiota diversity and human diseases: should we reintroduce key predators in our ecosystem? Front Microbiol 7 455 2016 27065999 PMC4815357
  5. [6]Ott SJ Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease Gut 53 685 693 2004 15082587 PMC1774050
  6. [7]Manichanh C Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach Gut 55 205 211 2006 16188921 PMC1856500
  7. [8]Khan KJ Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis Am J Gastroenterol 106 661 673 2011 21407187
  8. [9]Wang SL Wang ZR Yang CQ Meta-analysis of broad-spectrum antibiotic therapy in patients with active inflammatory bowel disease Exp Ther Med 4 1051 1056 2012 23226773 PMC3494118
  9. [10]Harper PH Lee EC Kettlewell MG Bennett MK Jewell DP Role of the faecal stream in the maintenance of Crohn's colitis Gut 26 279 284 1985 3972275 PMC1432617
  10. [11]Rutgeerts P Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum Lancet 338 771 774 1991 1681159
  11. [12]Janowitz HD Croen EC Sachar DB The role of the fecal stream in Crohn's disease: an historical and analytic review Inflamm Bowel Dis 4 29 39 1998 9552226
  12. [13]Kaplan GG Ng SC Understanding and preventing the global increase of inflammatory bowel disease Gastroenterology 152 313 321.e2 2017 27793607
  13. [15]Sokol H Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients Proc Natl Acad Sci USA 105 16731 16736 2008 18936492 PMC2575488
  14. [16]Van de Merwe JP Schroder AM Wensinck F Hazenberg MP The obligate anaerobic faecal flora of patients with Crohn's disease and their first-degree relatives Scand J Gastroenterol 23 1125 1131 1988 3247591
  15. [17]Walker AW 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 2011 21219646 PMC3032643
  16. [18]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 44 4136 4141 2006 16988016 PMC1698347
  17. [19]Frank DN Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases Proc Natl Acad Sci USA 104 13780 13785 2007 Culture-independent phylogenetic analysis to characterize the gut microbiotas of patients with IBD and non-IBD controls showed that a subset of Crohn's disease and ulcerative colitis samples contained abnormal gut microbiota, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes 17699621 PMC1959459
  18. [20]Martinez-Medina M Aldeguer X Gonzalez-Huix F Acero D Garcia-Gil LJ Abnormal microbiota composition in the ileocolonic mucosa of Crohn's disease patients as revealed by polymerase chain reaction-denaturing gradient gel electrophoresis Inflamm Bowel Dis 12 1136 1145 2006 17119388
  19. [21]Prescott NJ A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5 Gastroenterology 132 1665 1671 2007 17484864
  20. [22]Swidsinski A Loening-Baucke V Vaneechoutte M Doerffel Y Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora Inflamm Bowel Dis 14 147 161 2008 18050295
  21. [23]Rehman A Geographical patterns of the standing and active human gut microbiome in health and IBD Gut 65 238 248 2016 25567118
  22. [24]Halfvarson J Dynamics of the human gut microbiome in inflammatory bowel disease Nat Microbiol 2 17004 2017 28191884 PMC5319707
  23. [25]Hansen R Microbiota of de-novo pediatric IBD: increased Faecalibacterium prausnitzii and reduced bacterial diversity in Crohn's but not in ulcerative colitis Am J Gastroenterol 107 1913 1922 2012 23044767
  24. [26]Assa A Mucosa-associated ileal microbiota in new-onset pediatric crohn's disease Inflamm Bowel Dis 22 1533 1539 2016 27271491
  25. [27]Seksik P Alterations of the dominant faecal bacterial groups in patients with Crohn's disease of the colon Gut 52 237 242 2003 12524406 PMC1774977
  26. [28]Baumgart M 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 1 403 418 2007 18043660
  27. [29]Sartor RB Therapeutic correction of bacterial dysbiosis discovered by molecular techniques Proc Natl Acad Sci USA 105 16413 16414 2008 18948599 PMC2575433
  28. [30]Mangin I Molecular inventory of faecal microflora in patients with Crohn's disease FEMS Microbiol Ecol 50 25 36 2004 19712374
  29. [32]Willing BP A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes Gastroenterology 139 1844 1854.e1 2010 20816835
  30. [33]Lepage P Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis Gastroenterology 141 227 236 2011 21621540
  31. [34]Shah R Composition and function of the pediatric colonic mucosal microbiome in untreated patients with ulcerative colitis Gut Microbes 7 384 396 2016 27217061 PMC5046168
  32. [35]Kellermayer R Microbiota separation and C-reactive protein elevation in treatment-naive pediatric granulomatous Crohn disease J Pediatr Gastroenterol Nutr 55 243 250 2012 22699834 PMC3812911
  33. [36]Gevers D The treatment-naive microbiome in new-onset Crohn's disease Cell Host Microbe 15 382 392 2014 This paper analysed microbiomes from multiple gastrointestinal locations in new-onset Crohn's disease cases, identifying co-occurring and co-excluded Crohn's-disease-associated microorganism and finding that antibiotics amplify the dysbiosis associated with Crohn's disease 24629344 PMC4059512
  34. [37]Lewis JD Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn's disease Cell Host Microbe 18 489 500 2015 26468751 PMC4633303
  35. [38]Chow J Tang H Mazmanian SK Pathobionts of the gastrointestinal microbiota and inflammatory disease Curr Opin Immunol 23 473 480 2011 21856139 PMC3426444
  36. [39]Darfeuille-Michaud A Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease Gastroenterology 11 5 1405 1413 1998 9834268
  37. [40]Boudeau J Glasser AL Masseret E Joly B Darfeuille-Michaud A Invasive ability of an Escherichia coli strain isolated from the ileal mucosa of a patient with Crohn's disease Infect Immun 67 4499 4509 1999 10456892 PMC96770
  38. [41]Chiodini RJ Van Kruiningen HJ Thayer WR Merkal RS Coutu JA Possible role of mycobacteria in inflammatory bowel disease. I. An unclassified Mycobacterium species isolated from patients with Crohn's disease Dig Dis Sci 29 1073 1079 1984 6499624
  39. [43]Wagner J Mycobacterium avium subspecies paratuberculosis in children with early-onset Crohn's disease: a longitudinal follow-up study Inflamm Bowel Dis 17 1825 1826 2011 21744438
  40. [44]Timms VJ Daskalopoulos G Mitchell HM Neilan BA The association of Mycobacterium avium subsp paratuberculosis with inflammatory bowel disease PLoS ONE 11 e0148731 2016 26849125 PMC4746060
  41. [45]Selby W Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease Gastroenterology 132 2313 2319 2007 17570206
  42. [46]Liverani E Scaioli E Cardamone C Dal Monte P Belluzzi A Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn's disease, cause or epiphenomenon? World J Gastroenterol 20 13060 13070 2014 25278700 PMC4177485
  43. [47]Dharmani P Strauss J Ambrose C Allen-Vercoe E Chadee K Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha Infect Immun 79 2597 2607 2011 21536792 PMC3191979
  44. [49]Glover LE Lee JS Colgan SP Oxygen metabolism and barrier regulation in the intestinal mucosa J Clin Invest 126 3680 3688 2016 27500494 PMC5096807
  45. [50]Marteyn B Modulation of Shigella virulence in response to available oxygen in vivo Nature 465 355 358 2010 20436458 PMC3750455
  46. [51]Albenberg L Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota in humans and mice Gastroenterology 147 1055 1063.e8 2014 25046162 PMC4252572
  47. [53]Winter SE Lopez CA Baumler AJ The dynamics of gut-associated microbial communities during inflammation EMBO Rep 14 319 327 2013 23478337 PMC3615657
  48. [54]Breitbart M Metagenomic analyses of an uncultured viral community from human feces J Bacteriol 185 6220 6223 2003 14526037 PMC225035
  49. [55]Reyes A Viruses in the faecal microbiota of monozygotic twins and their mothers Nature 466 334 338 2010 20631792 PMC2919852
  50. [57]Wagner J Bacteriophages in gut samples from pediatric Crohn's disease patients: metagenomic analysis using 454 pyrosequencing Inflamm Bowel Dis 19 1598 1608 2013 23749273
  51. [59]Magin WS Van Kruiningen HJ Colombel JF Immunohistochemical search for viral and bacterial antigens in Crohn's disease J Crohns Colitis 7 161 166 2013 22537638
  52. [60]Main J Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease BMJ 297 1105 1106 1988 3143445 PMC1834894
  53. [61]Nilsson RH Taxonomic reliability of DNA sequences in public sequence databases: a fungal perspective PLoS ONE 1 e59 2006 17183689 PMC1762357
  54. [62]Underhill DM Iliev ID The mycobiota: interactions between commensal fungi and the host immune system Nat Rev Immunol 14 405 416 2014 24854590 PMC4332855
  55. [64]Sokol H Fungal microbiota dysbiosis in IBD Gut 66 1039 1048 2016 26843508 PMC5532459
  56. [65]Ott SJ Fungi and inflammatory bowel diseases: alterations of composition and diversity Scand J Gastroenterol 43 831 841 2008 18584522
  57. [66]Mukhopadhya I The fungal microbiota of de-novo paediatric inflammatory bowel disease Microbes Infect 17 304 310 2015 25522934 PMC4392392
  58. [67]Liguori G Fungal dysbiosis in mucosa-associated microbiota of Crohn's disease patients J Crohns Colitis 10 296 305 2016 26574491 PMC4957473
  59. [68]Richard ML Lamas B Liguori G Hoffmann TW Sokol H Gut fungal microbiota: the Yin and Yang of inflammatory bowel disease Inflamm Bowel Dis 21 656 665 2015 25545379
  60. [70]Lamas B CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands Nat Med 22 598 605 2016 27158904 PMC5087285
  61. [71]Chiaro TR A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice Sci Transl Med 9 eaaf9044 2017 28275154 PMC5994919
  62. [72]Wheeler ML Immunological consequences of intestinal fungal dysbiosis Cell Host Microbe 19 865 873 2016 27237365 PMC4900921
  63. [73]Wishart DS HMDB: the Human Metabolome Database Nucleic Acids Res 35 D521 D526 2007 17202168 PMC1899095
  64. [74]Morgan XC Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment Genome Biol 13 R79 2012 23013615 PMC3506950
  65. [76]Ogilvie LA Jones BV Dysbiosis modulates capacity for bile acid modification in the gut microbiomes of patients with inflammatory bowel disease: a mechanism and marker of disease? Gut 61 1642 1643 2012 22490526 PMC3463861
  66. [77]Duboc H Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases Gut 62 531 539 2013 22993202
  67. [78]Smith PM The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis Science 341 569 573 2013 23828891 PMC3807819
  68. [81]Omenetti S Pizarro TT The Treg/Th17 axis: a dynamic balance regulated by the gut microbiome Front Immunol 6 639 2015 26734006 PMC4681807
  69. [82]Rakoff-Nahoum S Paglino J Eslami-Varzaneh F Edberg S Medzhitov R Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis Cell 118 229 241 2004 15260992
  70. [84]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 105 2687 2692 2010 20940708
  71. [85]van Nood E Duodenal infusion of donor feces for recurrent Clostridium difficile N Engl J Med 368 407 415 2013 23323867
  72. [86]Rivas MA Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease Nat Genet 43 1066 1073 2011 21983784 PMC3378381
  73. [87]Barrett JC Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease Nat Genet 40 955 962 2008 18587394 PMC2574810
  74. [89]Almeida FF Belz GT Innate lymphoid cells:models of plasticity for immune homeostasis and rapid responsiveness in protection Mucosal Immunol 9 1103 1112 2016 27484190
  75. [90]Ignacio A Morales CI Camara NO Almeida RR Innate sensing of the gut microbiota: modulation of inflammatory and autoimmune diseases Front Immunol 7 54 2016 26925061 PMC4759259
  76. [91]Mohamed R Lord GM T-Bet as a key regulator of mucosal immunity Immunology 147 367 376 2016 26726991 PMC4799884
  77. [92]Kiesler P Fuss IJ Strober W Experimental models of inflammatory bowel diseases Cell Mol Gastroenterol Hepatol 1 154 170 2015 26000334 PMC4435576
  78. [93]Globig AM Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-gamma+ IL- 17+ coproducing CD4+ T cells in active inflammatory bowel disease Inflamm Bowel Dis 20 2321 2329 2014 25248005
  79. [94]Ramesh R Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids J Exp Med 211 89 104 2014 24395888 PMC3892977
  80. [95]Stepankova R Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells Inflamm Bowel Dis 13 1202 1211 2007 17607724
  81. [96]Jiang HQ Kushnir N Thurnheer MC Bos NA Cebra JJ Monoassociation of SCID mice with Helicobacter muridarum, but not four other enterics, provokes IBD upon receipt of T cells Gastroenterology 122 1346 1354 2002 11984521
  82. [97]Cahill RJ Inflammatory bowel disease: an immunity-mediated condition triggered by bacterial infection with Helicobacter hepaticus Infect Immun 65 3126 3131 1997 9234764 PMC175441
  83. [98]Mazmanian SK Round JL Kasper DL A microbial symbiosis factor prevents intestinal inflammatory disease Nature 453 620 625 2008 18509436
  84. [99]Round JL Mazmanian SK Inducible Foxp 3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota Proc Natl Acad Sci USA 107 12204 12209 2010 This study showed that Bacteroides fragilis capsular polysaccharide A (PSA) can alleviate inflammation in several colitis mouse models by promoting development of regulatory T cells 20566854 PMC2901479
  85. [100]Garrett WS Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis Cell Host Microbe 8 292 300 2010 20833380 PMC2952357
  86. [101]Garrett WS Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system Cell 131 33 45 2007 This study shows that T-bet deficiency in the innate immune system results in spontaneous and communicable ulcerative colitis, and T-bet−/−RAG−/− ulcerative colitis (TRUC) mice can transmit colitis even to wild-type animals 17923086 PMC2169385
  87. [103]Quintana FJ Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor Nature 453 65 71 2008 18362915
  88. [104]Alroqi FJ Chatila TA T regulatory cell biology in health and disease Curr Allergy Asthma Rep 16 27 2016 26922942 PMC5218767
  89. [105]Fantini MC Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression Gastroenterology 136 1308 1316.e1–e3 2009 19192480
  90. [106]Monteleone G Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease N Engl J Med 372 1104 1113 2015 25785968
  91. [107]Franke A Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci Nat Genet 42 1118 1125 2010 21102463 PMC3299551
  92. [108]Franke A Sequence variants in IL10. ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility Nat Genet 40 1319 1323 2008 18836448
  93. [109]Hoshi N MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice Nat Commun 3 1120 2012 23047678 PMC3521499
  94. [110]Rakoff-Nahoum S Hao L Medzhitov R Role of Toll-like receptors in spontaneous commensal-dependent colitis Immunity 25 319 329 2006 This study demonstrated a differential role of innate immune recognition by Toll-like receptors (TLRs) in the development of commensal-dependent colitis and a key pathogenic role of TLR signalling for chronic intestinal inflammation 16879997
  95. [111]Atarashi K Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota Nature 500 232 236 2013 23842501
  96. [112]Asquith M Powrie F An innately dangerous balancing act: intestinal homeostasis, inflammation, and colitis-associated cancer J Exp Med 207 1573 1577 2010 20679404 PMC2916138
  97. [113]De Jager PL The role of the Toll receptor pathway in susceptibility to inflammatory bowel disease Genes Immun 8 387 397 2007 17538633
  98. [114]Hugot JP Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease Nature 411 599 603 2001 11385576
  99. [115]Ogura Y A frameshit mutation in NOD2 associated with susceptibility to Crohn's disease Nature 411 603 606 2001 11385577
  100. [116]Pierek M Toll-like receptor-1, -2. and -6 polymorphisms influence disease extension in inflammatory bowel diseases Inflamm Bowel Dis 12 1 8 2006 16374251
  101. [117]Torok HP Crohn's disease is associated with Toll-like receptor-9 polymorphism Gastroenterology 127 365 366 2004 15236225
  102. [118]Villani AC Common variants in the NLRP3 region contribute to Crohn's disease susceptibility Nat Genet 41 71 76 2009 19098911 PMC2728932
  103. [120]Kim JY Kajino-Sakamoto R Omori E Jobin C Ninomiya-Tsuji J Intestinal epithelial-derived TAK1 signaling is essential for cytoprotection against chemical-induced colitis PLoS ONE 4 e4561 2009 19234607 PMC2642721
  104. [121]Malvin NP Seno H Stappenbeck TS Colonic epithelial response to injury requires Myd88 signaling in myeloid cells Mucosal Immunol 5 194 206 2012 22258450 PMC3791628
  105. [122]Podolsky DK Gerken G Eyking A Cario E Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency Gastroenterology 137 209 220 2009 19303021 PMC2812790
  106. [123]Pull SL Doherty JM Mills JC Gordon JI Stappenbeck TS Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury Proc Natl Acad Sci USA 102 99 104 2005 15615857 PMC544052
  107. [124]Zheng L Riehl TE Stenson W Regulation of colonic epithelial repair in mice by Toll-like receptors and hyaluronic acid Gastroenterology 137 2041 2051 2009 19732774 PMC2789856
  108. [125]Nenci A Epithelial NEMO links innate immunity to chronic intestinal inflammation Nature 446 557 561 2007 17361131
  109. [126]Allen IC The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer J Exp Med 207 1045 1056 2010 20385749 PMC2867287
  110. [127]Dupaul-Chicoine J Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases Immunity 32 367 378 2010 20226691
  111. [128]Zaki MH The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis Immunity 32 379 391 2010 20303296 PMC2982187
  112. [129]Takagi H Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice Scand J Gastroenterol 38 837 844 2003 12940437
  113. [130]Elinav E NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis Cell 145 745 757 2011 21565393 PMC3140910
  114. [131]Gibson DL MyD88 signalling plays a critical role in host defence by controlling pathogen burden and promoting epithelial cell homeostasis during Citrobacter rodentium-induced colitis Cell Microbiol 10 618 631 2008 17979981
  115. [132]Lebeis SL Bommarius B Parkos CA Sherman MA Kalman D TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium J Immunol 179 566 577 2007 17579078
  116. [133]Cadwell K Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis Nat Rev Immunol 16 661 675 2016 27694913 PMC5343289
  117. [134]Hampe J A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 Nat Genet 39 207 211 2007 17200669
  118. [135]Parkes M Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility Nat Genet 39 830 832 2007 17554261 PMC2628541
  119. [137]Cooney R NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation Nat Med 16 90 97 2010 19966812
  120. [138]Cadwell K A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells Nature 456 259 263 2008 18849966 PMC2695978
  121. [139]Salzman NH Enteric defensins are essential regulators of intestinal microbial ecology Nat Immunol 11 76 83 2010 19855381 PMC2795796
  122. [140]Wehkamp J Reduced Paneth cell alpha-defensins in ileal Crohn's disease Proc Natl Acad Sci USA 102 18129 18134 2005 16330776 PMC1306791
  123. [141]Cadwell K Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine Cell 141 1135 1145 2010 This study demonstrates that an interaction between a specific virus infection (murine norovirus) and a gene mutation induces Crohn's-disease-like intestinal pathologies in mice 20602997 PMC2908380
  124. [143]Kontoyiannis D Pasparakis M Pizarro TT Cominelli F Kollias G Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies Immunity 10 387 398 1999 10204494
  125. [145]Palm NW Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease Cell 158 1000 1010 2014 This paper shows that IgA coating of intestinal bacteria can distinguish colitogenic (IgA+) from commensal (IgA−) species, and IgA+ bacteria identified in this manner include known pathobionts (Prevotellaceae, Helicobacter and segmented filamentous bacteria) capable of mediating chemically induced colitis when transferred to specific pathogen-free mice 25171403 PMC4174347
  126. [146]Ludvigsson JF Neovius M Hammarstrom L Association between IgA deficiency and other autoimmune conditions: a population-based matched cohort study J Clin Immunol 34 444 451 2014 24584841
  127. [147]D'Haens GR Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum Gastroenterology 11 4 262 267 1998 9453485
  128. [148]Harig JM Soergel KH Komorowski RA Wood CM Treatment of diversion colitis with short-chain-fatty acid irrigation N Engl J Med 320 23 28 1989 2909876
  129. [150]Singh S Stroud AM Holubar SD Sandborn WJ Pardi DS Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis Cochrane Database Syst Rev 6 CD001176 2015 PMC4917283 26593456
  130. [151]Terao S Antibiotic combination therapy for steroid withdrawal in steroid-dependent ulcerative colitis Digestion 83 198 203 2011 21266816
  131. [152]Ohkusa T Newly developed antibioticcombination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial Am J Gastroenterol 105 1820 1829 2010 20216533
  132. [153]Uehara T Efficacy of antibiotic combinationtherapy in patients with active ulcerative colitis, including refractory or steroid-dependent cases J Gastroenterol Hepatol 25 Suppl. 1 S62 S66 2010 20586868
  133. [155]Lewis JD Abreu MT Diet as a trigger or therapy for inflammatory bowel diseases Gastroenterology 152 398 414.e6 2017 27793606
  134. [156]Sandhu BK Guidelines for the management of inflammatory bowel disease in children in the United Kingdom J Pediatr Gastroenterol Nutr 50 Suppl. 1 S1 S13 2010 20081543
  135. [157]Caprilli R European evidence based consensus on the diagnosis and management of Crohn's disease: special situations Gut 55 Suppl. 1 i36 i58 2006 16481630 PMC1859996
  136. [158]Fell JM Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease Aliment Pharmacol Ther 14 281 289 2000 10735920
  137. [159]Borrelli O Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial Clin Gastroenterol Hepatol 4 744 753 2006 16682258
  138. [160]Afzal NA Improvement in quality of life of children with acute Crohn's disease does not parallel mucosal healing after treatment with exclusive enteral nutrition Aliment Pharmacol Ther 20 167 172 2004 15233696
  139. [161]Froslie KF Jahnsen J Moum BA Vatn MH Group I Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort Gastroenterology 133 412 422 2007 17681162
  140. [162]Lionetti P Enteral nutrition and microflora in pediatric Crohn's disease JPEN J Parenter Enteral Nutr 29 4 Suppl. S173 S175 2005 15980280
  141. [163]Leach ST Mitchell HM Eng WR Zhang L Day AS Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn's disease Aliment Pharmacol Ther 28 724 733 2008 19145728
  142. [164]Tjellstrom B Effect of exclusive enteral nutrition on gut microflora function in children with Crohn's disease Scand J Gastroenterol 47 1454 1459 2012 23016828
  143. [165]Schwerd T Exclusive enteral nutrition in active pediatric Crohn disease: effects on intestinal microbiota and immune regulation J Allergy Clin Immunol 138 592 596 2016 26987574
  144. [166]Gerasimidis K Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn's disease during enteral nutrition Inflamm Bowel Dis 20 861 871 2014 24651582
  145. [167]Gough E Shaikh H Manges AR Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection Clin Infect Dis 53 994 1002 2011 22002980
  146. [170]Kunde S Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis J Pediatr Gastroenterol Nutr 56 597 601 2013 23542823
  147. [171]Suskind DL Singh N Nielson H Wahbeh G Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis J Pediatr Gastroenterol Nutr 60 27 29 2015 25162366
  148. [173]Moayyedi P Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial Gastroenterology 149 102 109.e6 2015 First randomized, placebo-controlled trial of faecal microbiota transplantation in ulcerative colitis showing potential benefit 25857665
  149. [175]US National Library of Medicine ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT03078803 2017 28792816
  150. [176]US National Library of Medicine ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT02097797 2016 28792816
  151. [177]Suskind DL Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease Inflamm Bowel Dis 21 556 563 2015 25647155 PMC4329080
  152. [178]Cui B Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results J Gastroenterol Hepatol 30 51 58 2015 25168749
  153. [179]Kolho KL Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation Am J Gastroenterol 110 921 930 2015 25986361
  154. [180]Hildebrand F Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice Genome Biol 14 R4 2013 23347395 PMC4053703
  155. [181]Turpin W Assoication of host genome with intestinal microbiota composition in a large healthy cohort Nat Genet 48 1413 1417 2016 27694960
  156. [182]Stein MM Innate immunity and asthma risk in Amish and Hutterite farm children N Engl J Med 375 411 42 1 2016 27518660 PMC5137793
  157. [183]Olszak T Microbial exposure during early life has persistent effects on natural killer T cell function Science 336 489 493 2012 22442383 PMC3437652
  158. [184]Cho I Antibiotics in early life alter the murine colonic microbiome and adiposity Nature 488 62 1 626 2012 PMC3553221 22914093

Cited by

Sorted by citations

Authors
Ni, J., Wu, G. D., Albenberg, L., & Tomov, V. T.
Affiliations
  • University of Pennsylvania (US)
  • Children's Hospital of Philadelphia (US)
Corresponding author
Tomov, Vesselin T.
ORCID
Venue
Nature Reviews Gastroenterology & Hepatology
Publisher
Springer Science and Business Media LLC
Published
2017-07-19
Volume
14
Issue
10
Pages
573-584
ISSN
  • 1759-5045 (ISSN-L)
  • 1759-5053
DOI
10.1038/nrgastro.2017.88
PMC
PMC5880536
OpenAlex
W2736839127
Cited by
1,778
References
25
Citations by year
2026: 185 · 2025: 248 · 2024: 245 · 2023: 247 · 2022: 255 · 2021: 234 · 2020: 176 · 2019: 117 · 2018: 62 · 2017: 8
FWCI
9.29
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Gastroenterology & Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (R24AI118629)
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007066, K23DK109136, K08DK097301, R01DK107565)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Keywords
gut microbiota, inflammatory bowel disease, Crohn's disease, ulcerative colitis, dysbiosis, correlation versus causation, animal models of colitis, host-microbe interactions, immune activation, chronic inflammation, microbiota-based therapy
MeSH terms
Gastrointestinal Microbiome, Animals, Humans, Inflammatory Bowel Diseases, Dysbiosis

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