Abstract
The role of the gut microbiota in inflammatory bowel disease (IBD), an early focus of microbiome science, is the topic of this chapter. Specifically, we investigate the evidence for the gut microbiota as an integral player in the development and maintenance of IBD, we outline the alterations in community composition (‘dysbiosis’) that have been reported in the literature and we also describe mechanisms that connect host genotype to a pro-inflammatory dysbiosis, completing a link between disease susceptibility, molecular genetics, microbiome alterations and the subsequent positive feedback cycle between inflammation and dysbiosis. The aim is to highlight how advances in molecular genetics and microbiome science may be brought together to improve our understanding of IBD, while providing a blueprint for developing the next generation of hypotheses, biomarkers, and therapies.
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References
The Human Microbiome Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486(7402):207–214. https://doi.org/10.1038/nature11234
Chu DM, Ma J, Prince AL et al (2017) Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med 23:314. https://doi.org/10.1038/nm.4272
Sousa T, Paterson R, Moore V et al (2008) The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm 363(1):1–25. https://doi.org/10.1016/j.ijpharm.2008.07.009
Turnbaugh PJ, Ley RE, Mahowald MA et al (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1031
Hill MJ (1997) Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 6(2):S43–S45
Ridlon JM, Kang DJ, Hylemon PB et al (2014) Bile acids and the gut microbiome. Curr Opin Gastroenterol 30(3):332–338. https://doi.org/10.1097/MOG.0000000000000057
Thaiss CA, Levy M, Korem T et al (2016) Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167(6):1495–1510.e1412. https://doi.org/10.1016/j.cell.2016.11.003
Ungaro R, Bernstein CN, Gearry R et al (2014) Antibiotics associated with increased risk of new-onset Crohn’s disease but not ulcerative colitis: a meta-analysis. Am J Gastroenterol 109:1728. https://doi.org/10.1038/ajg.2014.246
Li Y, Tian Y, Zhu W et al (2014) Cesarean delivery and risk of inflammatory bowel disease: a systematic review and meta-analysis. Scand J Gastroenterol 49(7):834–844. https://doi.org/10.3109/00365521.2014.910834
Sokol H, Pigneur B, Watterlot L et al (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 105(43):16731–16736. https://doi.org/10.1073/pnas.0804812105
Jeffery IB, O’Toole PW, Öhman L et al (2012) An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 61(7):997–1006. https://doi.org/10.1136/gutjnl-2011-301501
Yu J, Feng Q, Wong SH et al (2017) Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66(1):70–78. https://doi.org/10.1136/gutjnl-2015-309800
Scher JU, Sczesnak A, Longman RS et al (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2:e01202. https://doi.org/10.7554/eLife.01202
Sharon G, Sampson TR, Geschwind DH et al (2016) The central nervous system and the gut microbiome. Cell 167(4):915–932. https://doi.org/10.1016/j.cell.2016.10.027
Zitvogel L, Ma Y, Raoult D et al (2018) The microbiome in cancer immunotherapy: diagnostic tools and therapeutic strategies. Science 359(6382):1366–1370. https://doi.org/10.1126/science.aar6918
Zeevi D, Korem T, Zmora N et al (2015) Personalized nutrition by prediction of glycemic responses. Cell 163(5):1079–1094. https://doi.org/10.1016/j.cell.2015.11.001
Chassaing B, Koren O, Goodrich JK et al (2015) Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519:92. https://doi.org/10.1038/nature14232
Maier L, Pruteanu M, Kuhn M et al (2018) Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555:623. https://doi.org/10.1038/nature25979
Wirtz S, Neufert C, Weigmann B et al (2007) Chemically induced mouse models of intestinal inflammation. Nat Protoc 2:541. https://doi.org/10.1038/nprot.2007.41
Garrett WS, Lord GM, Punit S et al (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131(1):33–45. https://doi.org/10.1016/j.cell.2007.08.017
Vandeputte D, Kathagen G, D’Hoe K et al (2017) Quantitative microbiome profiling links gut community variation to microbial load. Nature 551(7681):507–511. https://doi.org/10.1038/nature24460
Shkoporov AN, Ryan FJ, Draper LA et al (2018) Reproducible protocols for metagenomic analysis of human faecal phageomes. Microbiome 6(1):68. https://doi.org/10.1186/s40168-018-0446-z
Ben-Amor K, Heilig H, Smidt H et al (2005) Genetic diversity of viable, injured, and dead fecal bacteria assessed by fluorescence-activated cell sorting and 16S rRNA gene analysis. Appl Environ Microbiol 71(8):4679–4689. https://doi.org/10.1128/aem.71.8.4679-4689.2005
Million M, Angelakis E, Maraninchi M et al (2013) Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int J Obes (2005) 37(11):1460–1466. https://doi.org/10.1038/ijo.2013.20
Guerin E, Shkoporov A, Stockdale SR et al (2018) Biology and taxonomy of crAss-like bacteriophages, the most abundant virus in the human gut. Cell Host & Microbe 24(5):653–664.e656. https://doi.org/10.1016/j.chom.2018.10.002
Scanlan PD, Marchesi JR (2008) Micro-eukaryotic diversity of the human distal gut microbiota: qualitative assessment using culture-dependent and -independent analysis of faeces. Isme J 2:1183. https://doi.org/10.1038/ismej.2008.76
Richard ML, Sokol H (2019) The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 16:331–345. https://doi.org/10.1038/s41575-019-0121-2
McSorley HJ, Hewitson JP, Maizels RM (2013) Immunomodulation by helminth parasites: defining mechanisms and mediators. Int J Parasitol 43(3):301–310. https://doi.org/10.1016/j.ijpara.2012.11.011
Tito RY, Chaffron S, Caenepeel C et al (2018) Population-level analysis of Blastocystis subtype prevalence and variation in the human gut microbiota. Gut. https://doi.org/10.1136/gutjnl-2018-316106
Lloyd-Price J, Mahurkar A, Rahnavard G et al (2017) Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 550:61. https://doi.org/10.1038/nature23889
Arumugam M, Raes J, Pelletier E et al (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180
Wu GD, Chen J, Hoffmann C et al (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334(6052):105–108. https://doi.org/10.1126/science.1208344
Costea PI, Hildebrand F, Arumugam M et al (2018) Enterotypes in the landscape of gut microbial community composition. Nat Microbiol 3(1):8–16. https://doi.org/10.1038/s41564-017-0072-8
Lathrop SK, Bloom SM, Rao SM et al (2011) Peripheral education of the immune system by colonic commensal microbiota. Nature 478:250. https://doi.org/10.1038/nature10434
Koenig JE, Spor A, Scalfone N et al (2010) Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.1000081107
Yassour M, Vatanen T, Siljander H et al (2016) Natural history of the infant gut microbiome and impact of antibiotic treatments on strain-level diversity and stability. Sci Transl Med 8(343):343ra381. https://doi.org/10.1126/scitranslmed.aad0917
Yatsunenko T, Rey FE, Manary MJ et al (2012) Human gut microbiome viewed across age and geography. Nature 486(7402):222–227. https://doi.org/10.1038/nature11053
Stewart CJ, Ajami NJ, O’Brien JL et al (2018) Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 562(7728):583–588. https://doi.org/10.1038/s41586-018-0617-x
Bokulich NA, Chung J, Battaglia T et al (2016) Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med 8(343):343ra382. https://doi.org/10.1126/scitranslmed.aad7121
Atarashi K, Tanoue T, Oshima K et al (2013) Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500(7461):232–236. https://doi.org/10.1038/nature12331
Korpela K, Salonen A, Virta LJ et al (2016) Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun 7:10410. https://doi.org/10.1038/ncomms10410
Scheer S, Medina TS, Murison A et al (2017) Early-life antibiotic treatment enhances the pathogenicity of CD4(+) T cells during intestinal inflammation. J Leukoc Biol 101(4):893–900. https://doi.org/10.1189/jlb.3MA0716-334RR
Azad MB, Konya T, Maughan H et al (2013) Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 185(5):385–394. https://doi.org/10.1503/cmaj.121189
Vatanen T, Kostic AD, d’Hennezel E et al (2016) Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165(4):842–853. https://doi.org/10.1016/j.cell.2016.04.007
Renz-Polster H, David MR, Buist AS et al (2005) Caesarean section delivery and the risk of allergic disorders in childhood. Clin Exp Allergy 35(11):1466–1472. https://doi.org/10.1111/j.1365-2222.2005.02356.x
Beaugerie L, Langholz E, Nyboe-Andersen N et al (2018) Differences in epidemiological features between ulcerative colitis and Crohn’s disease: the early life-programmed versus late dysbiosis hypothesis. Med Hypotheses 115:19–21. https://doi.org/10.1016/j.mehy.2018.03.009
Lee JC, Biasci D, Roberts R et al (2017) Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn’s disease. Nat Genet 49:262. https://doi.org/10.1038/ng.3755
Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T et al (2016) The maternal microbiota drives early postnatal innate immune development. Science 351(6279):1296–1302. https://doi.org/10.1126/science.aad2571
Wesemann DR, Portuguese AJ, Meyers RM et al (2013) Microbial colonization influences early B-lineage development in the gut lamina propria. Nature 501(7465):112–115. https://doi.org/10.1038/nature12496
Olszak T, An D, Zeissig S et al (2012) Microbial exposure during early life has persistent effects on natural killer T cell function. Science (New York, NY) 336(6080):489–493. https://doi.org/10.1126/science.1219328
Gaboriau-Routhiau V, Rakotobe S, Lécuyer E et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31(4):677–689. https://doi.org/10.1016/j.immuni.2009.08.020
Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620. https://doi.org/10.1038/nature07008
Chassaing B, Van de Wiele T, De Bodt J et al (2017) Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut 66(8):1414–1427. https://doi.org/10.1136/gutjnl-2016-313099
Ananthakrishnan AN, Khalili H, Konijeti GG et al (2013) A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology 145(5):970–977. https://doi.org/10.1053/j.gastro.2013.07.050
Ananthakrishnan AN, Khalili H, Konijeti GG et al (2014) Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease. Gut 63(5):776–784. https://doi.org/10.1136/gutjnl-2013-305304
Claesson MJ, Jeffery IB, Conde S et al (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488(7410):178–184. https://doi.org/10.1038/nature11319
Parkes GC, Whelan K, Lindsay JO (2014) Smoking in inflammatory bowel disease: impact on disease course and insights into the aetiology of its effect. J Crohn’s Colitis 8(8):717–725. https://doi.org/10.1016/j.crohns.2014.02.002
Cullen TW, Schofield WB, Barry NA et al (2015) Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science (New York, NY) 347(6218):170–175. https://doi.org/10.1126/science.1260580
Fadlallah J, El Kafsi H, Sterlin D et al (2018) Microbial ecology perturbation in human IgA deficiency. Sci Transl Med 10(439). https://doi.org/10.1126/scitranslmed.aan1217
Rothschild D, Weissbrod O, Barkan E et al (2018) Environment dominates over host genetics in shaping human gut microbiota. Nature 555:210. https://doi.org/10.1038/nature25973
Goodrich JK, Waters JL, Poole AC et al (2014) Human genetics shape the gut microbiome. Cell 159(4):789–799. https://doi.org/10.1016/j.cell.2014.09.053
Knights D, Silverberg MS, Weersma RK et al (2014) Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med 6(12):107. https://doi.org/10.1186/s13073-014-0107-1
Imhann F, Vich Vila A, Bonder MJ et al (2018) Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut 67(1):108–119. https://doi.org/10.1136/gutjnl-2016-312135
Li D, Achkar J-P, Haritunians T et al (2016) A pleiotropic missense variant in SLC39A8 is associated with Crohn’s disease and human gut microbiome composition. Gastroenterology 151(4):724–732. https://doi.org/10.1053/j.gastro.2016.06.051
Tong M, McHardy I, Ruegger P et al (2014) Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism. ISME J 8(11):2193–2206. https://doi.org/10.1038/ismej.2014.64
Schaubeck M, Clavel T, Calasan J et al (2015) Dysbiotic gut microbiota causes transmissible Crohn’s disease-like ileitis independent of failure in antimicrobial defence. Gut. https://doi.org/10.1136/gutjnl-2015-309333
Chassaing B, Ley RE, Gewirtz AT (2014) Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology 147(6):1363–1377.e1317. https://doi.org/10.1053/j.gastro.2014.08.033
Kang SS, Bloom SM, Norian LA et al (2008) An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Med 5(3):e41. https://doi.org/10.1371/journal.pmed.0050041
Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F et al (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118(2):229–241. https://doi.org/10.1016/j.cell.2004.07.002
Garrett WS, Gallini CA, Yatsunenko T et al (2010) Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8(3):292–300. https://doi.org/10.1016/j.chom.2010.08.004
Lamas B, Richard ML, Leducq V et al (2016) CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med 22(6):598–605. https://doi.org/10.1038/nm.4102
Malik A, Sharma D, Zhu Q et al (2016) IL-33 regulates the IgA-microbiota axis to restrain IL-1alpha-dependent colitis and tumorigenesis. J Clin Invest 126(12):4469–4481. https://doi.org/10.1172/jci88625
Couturier-Maillard A, Secher T, Rehman A et al (2013) NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest 123(2):700–711. https://doi.org/10.1172/jci62236
Keubler LM, Buettner M, Häger C et al (2015) A multihit model: colitis lessons from the interleukin-10–deficient mouse. Inflamm Bowel Dis 21(8):1967–1975. https://doi.org/10.1097/MIB.0000000000000468
Kim SC, Tonkonogy SL, Albright CA et al (2005) Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128(4):891–906
Steck N, Hoffmann M, Sava IG et al (2011) Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 141(3):959–971. https://doi.org/10.1053/j.gastro.2011.05.035
Devkota S, Wang Y, Musch MW et al (2012) Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487(7405):104–108. https://doi.org/10.1038/nature11225
Kashyap PC, Marcobal A, Ursell LK et al (2013) Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota. Proc Natl Acad Sci U S A 110(42):17059–17064. https://doi.org/10.1073/pnas.1306070110
Lamas B, Michel ML, Waldschmitt N et al (2018) Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence. Gut 67(10):1836–1844. https://doi.org/10.1136/gutjnl-2017-314195
Pizarro TT, Pastorelli L, Bamias G et al (2011) The SAMP1/YitFc mouse strain: a spontaneous model of Crohn’s disease-like ileitis. Inflamm Bowel Dis 17(12):2566–2584. https://doi.org/10.1002/ibd.21638
Adolph TE, Tomczak MF, Niederreiter L et al (2013) Paneth cells as a site of origin for intestinal inflammation. Nature 503:272. https://doi.org/10.1038/nature12599
Tschurtschenthaler M, Adolph TE, Ashcroft JW et al (2017) Defective ATG16L1-mediated removal of IRE1α drives Crohn’s disease–like ileitis. J Exp Med 214(2):401–422. https://doi.org/10.1084/jem.20160791
Palm NW, de Zoete MR, Cullen TW et al (2014) Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158(5):1000–1010. https://doi.org/10.1016/j.cell.2014.08.006
Jostins L, Ripke S, Weersma RK et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119–124.
Jacobs JP, Goudarzi M, Singh N et al (2016) A disease-associated microbial and metabolomics state in relatives of pediatric inflammatory bowel disease patients. Cell Mol Gastroenterol Hepatol 2(6):750–766. https://doi.org/10.1016/j.jcmgh.2016.06.004
Hedin CR, van der Gast CJ, Stagg AJ et al (2017) The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease. Gut Microbes 8(4):359–365. https://doi.org/10.1080/19490976.2017.1284733
Rietdijk ST, D’Haens GR (2013) Recent developments in the treatment of inflammatory bowel disease. J Dig Dis 14(6):282–287. https://doi.org/10.1111/1751-2980.12048
Rutgeerts P, Goboes K, Peeters M et al (1991) Effect of faecal stream diversion on recurrence of Crohn’s disease in the neoterminal ileum. Lancet 338(8770):771–774
Rivas MA, Beaudoin M, Gardet A et al (2011) Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet 43(11):1066–1073. https://doi.org/10.1038/ng.952
Gordon H, Trier Moller F, Andersen V et al (2015) Heritability in inflammatory bowel disease: from the first twin study to genome-wide association studies. Inflamm Bowel Dis 21(6):1428–1434. https://doi.org/10.1097/MIB.0000000000000393
Sonnenburg ED, Smits SA, Tikhonov M et al (2016) Diet-induced extinctions in the gut microbiota compound over generations. Nature 529:212. https://doi.org/10.1038/nature16504
Ng SC, Bernstein CN, Vatn MH et al (2013) Geographical variability and environmental risk factors in inflammatory bowel disease. Gut 62(4):630–649. https://doi.org/10.1136/gutjnl-2012-303661
Falony G, Joossens M, Vieira-Silva S et al (2016) Population-level analysis of gut microbiome variation. Science 352(6285):560–564. https://doi.org/10.1126/science.aad3503
Frank DN, Robertson CE, Hamm CM et al (2011) Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 17(1):179–184. https://doi.org/10.1002/ibd.21339
Rausch P, Rehman A, Künzel S et al (2011) Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc Natl Acad Sci 108(47):19030–19035. https://doi.org/10.1073/pnas.1106408108
Morgan XC, Tickle TL, Sokol H et al (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13(9):R79. https://doi.org/10.1186/gb-2012-13-9-r79
Darfeuille-Michaud A, Boudeau J, Bulois P et al (2004) High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology 127(2):412–421. https://doi.org/10.1053/j.gastro.2004.04.061
Lapaquette P, Glasser A-L, Huett A et al (2010) Crohn’s disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell Microbiol 12(1):99–113. https://doi.org/10.1111/j.1462-5822.2009.01381.x
Palmela C, Chevarin C, Xu Z et al (2018) Adherent-invasive Escherichia coli in inflammatory bowel disease. Gut 67(3):574–587. https://doi.org/10.1136/gutjnl-2017-314903
Darfeuille-Michaud A, Neut C, Barnich N et al (1998) Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn’s disease. Gastroenterology 115(6):1405–1413. https://doi.org/10.1016/S0016-5085(98)70019-8
Abubakar I, Myhill D, Aliyu SH et al (2008) Detection of Mycobacterium avium subspecies paratuberculosis from patients with Crohn’s disease using nucleic acid-based techniques: a systematic review and meta-analysis. Inflamm Bowel Dis 14(3):401–410. https://doi.org/10.1002/ibd.20276
Ricanek P, Lothe SM, Szpinda I et al (2010) Paucity of mycobacteria in mucosal bowel biopsies from adults and children with early inflammatory bowel disease. J Crohn’s Colitis 4(5):561–566. https://doi.org/10.1016/j.crohns.2010.05.003
McNees AL, Markesich D, Zayyani NR et al (2015) Mycobacterium paratuberculosis as a cause of Crohn’s disease. Expert Rev Gastroenterol Hepatol 9(12):1523–1534. https://doi.org/10.1586/17474124.2015.1093931
Graham DY, Hardi R, Welton T et al (2018) LB06 – Phase III randomized, double blind, placebo-controlled, multicenter, parallel group study to assess the efficacy and safety of add-on fixed-dose anti-mycobacterial therapy (RHB-104) in moderately to severely active Crohn’s disease (MAP US). uegw2018. http://www.professionalabstracts.com/ueg2018/iplanner/#/presentation/3534
Khanna S, Shin A, Kelly CP (2017) Management of Clostridium difficile infection in inflammatory bowel disease: expert review from the clinical practice updates committee of the AGA institute. Clin Gastroenterol Hepatol 15(2):166–174. https://doi.org/10.1016/j.cgh.2016.10.024
Magro F, Gionchetti P, Eliakim R et al (2017) Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohn’s Colitis 11(6):649–670. https://doi.org/10.1093/ecco-jcc/jjx008
Willing BP, Dicksved J, Halfvarson J et al (2010) A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 139(6):1844–1854.e1841. https://doi.org/10.1053/j.gastro.2010.08.049
Pascal V, Pozuelo M, Borruel N et al (2017) A microbial signature for Crohn’s disease. Gut 66(5):813–822. https://doi.org/10.1136/gutjnl-2016-313235
Halfvarson J, Brislawn CJ, Lamendella R et al (2017) Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol 2:17004–17004. https://doi.org/10.1038/nmicrobiol.2017.4
Quince C, Ijaz UZ, Loman N et al (2015) Extensive modulation of the fecal metagenome in children with Crohn’s disease during exclusive enteral nutrition. Am J Gastroenterol 110(12):1718–1729. https://doi.org/10.1038/ajg.2015.357; quiz 1730
Eun CS, Kwak MJ, Han DS et al (2016) Does the intestinal microbial community of Korean Crohn’s disease patients differ from that of western patients? BMC Gastroenterol 16:28. https://doi.org/10.1186/s12876-016-0437-0
Lewis JD, Chen EZ, Baldassano RN et al (2015) Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe 18(4):489–500. https://doi.org/10.1016/j.chom.2015.09.008
Kang S, Denman SE, Morrison M et al (2010) Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray. Inflamm Bowel Dis 16(12):2034–2042. https://doi.org/10.1002/ibd.21319
Swidsinski A, Weber J, Loening-Baucke V et al (2005) Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol 43(7):3380–3389. https://doi.org/10.1128/JCM.43.7.3380-3389.2005
Rehman A, Rausch P, Wang J et al (2016) Geographical patterns of the standing and active human gut microbiome in health and IBD. Gut 65(2):238–248. https://doi.org/10.1136/gutjnl-2014-308341
Fujimoto T, Imaeda H, Takahashi K et al (2013) Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn’s disease. J Gastroenterol Hepatol 28(4):613–619. https://doi.org/10.1111/jgh.12073
Gevers D, Kugathasan S, Denson LA et al (2014) The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15(3):382–392. https://doi.org/10.1016/j.chom.2014.02.005
Quévrain E, Maubert MA, Michon C et al (2016) Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut 65(3):415–425. https://doi.org/10.1136/gutjnl-2014-307649
Sarrabayrouse G, Bossard C, Chauvin J-M et al (2014) CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease. PLoS Biol 12(4):e1001833. https://doi.org/10.1371/journal.pbio.1001833
Sarrabayrouse G, Alameddine J, Altare F et al (2015) Microbiota-specific CD4CD8alphaalpha Tregs: role in intestinal immune homeostasis and implications for IBD. Front Immunol 6:522. https://doi.org/10.3389/fimmu.2015.00522
Godefroy E, Alameddine J, Montassier E et al (2018) Expression of CCR6 and CXCR6 by gut-derived CD4(+)/CD8alpha(+) T-regulatory cells, which are decreased in blood samples from patients with inflammatory bowel diseases. Gastroenterology 155(4):1205–1217. https://doi.org/10.1053/j.gastro.2018.06.078
Kaakoush NO, Day AS, Huinao KD et al (2012) Microbial dysbiosis in pediatric patients with Crohn’s disease. J Clin Microbiol 50(10):3258–3266. https://doi.org/10.1128/jcm.01396-12
Haberman Y, Tickle TL, Dexheimer PJ et al (2014) Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature. J Clin Invest 124(8):3617–3633. https://doi.org/10.1172/jci75436
Hall AB, Yassour M, Sauk J et al (2017) A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med 9(1):103. https://doi.org/10.1186/s13073-017-0490-5
Joossens M, Huys G, Cnockaert M et al (2011) Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60(5):631–637. https://doi.org/10.1136/gut.2010.223263
Png CW, Linden SK, Gilshenan KS et al (2010) Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol 105(11):2420–2428. https://doi.org/10.1038/ajg.2010.281
Li KY, Wang JL, Wei JP et al (2016) Fecal microbiota in pouchitis and ulcerative colitis. World J Gastroenterol 22(40):8929–8939. https://doi.org/10.3748/wjg.v22.i40.8929
Machiels K, Joossens M, Sabino J et al (2014) A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63(8):1275–1283. https://doi.org/10.1136/gutjnl-2013-304833
Shah R, Cope JL, Nagy-Szakal D et al (2016) Composition and function of the pediatric colonic mucosal microbiome in untreated patients with ulcerative colitis. Gut Microbes 7(5):384–396. https://doi.org/10.1080/19490976.2016.1190073
Rajilic-Stojanovic M, Shanahan F, Guarner F et al (2013) Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis 19(3):481–488. https://doi.org/10.1097/MIB.0b013e31827fec6d
Mar JS, LaMere BJ, Lin DL et al (2016) Disease severity and immune activity relate to distinct interkingdom gut microbiome states in ethnically distinct ulcerative colitis patients. mBio 7(4):e01072-16. https://doi.org/10.1128/mBio.01072-16
Frank DN, St. Amand AL, Feldman RA et al (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci 104(34):13780–13785. https://doi.org/10.1073/pnas.0706625104
Atarashi K, Suda W, Luo C et al (2017) Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science 358(6361):359–365. https://doi.org/10.1126/science.aan4526
Martinez C, Antolin M, Santos J et al (2008) Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol 103(3):643–648. https://doi.org/10.1111/j.1572-0241.2007.01592.x
Sinha R, Abu-Ali G, Vogtmann E et al (2017) Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium. Nat Biotechnol 35(11):1077–1086. https://doi.org/10.1038/nbt.3981
Li J, Jia H, Cai X et al (2014) An integrated catalog of reference genes in the human gut microbiome. Nat Biotechnol 32:834. https://doi.org/10.1038/nbt.2942
Schirmer M, Franzosa EA, Lloyd-Price J et al (2018) Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol. https://doi.org/10.1038/s41564-017-0089-z
Kelly CJ, Zheng L, Campbell EL et al (2015) Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17(5):662–671. https://doi.org/10.1016/j.chom.2015.03.005
Smith PM, Howitt MR, Panikov N et al (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341(6145):569–573. https://doi.org/10.1126/science.1241165
Park J, Kim M, Kang SG et al (2014) Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR–S6K pathway. Mucosal Immunol 8:80. https://doi.org/10.1038/mi.2014.44
Marchesi JR, Holmes E, Khan F et al (2007) Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J Proteome Res 6(2):546–551. https://doi.org/10.1021/pr060470d
Le Gall G, Noor SO, Ridgway K et al (2011) Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. J Proteome Res 10(9):4208–4218. https://doi.org/10.1021/pr2003598
Maslowski KM, Vieira AT, Ng A et al (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282. https://doi.org/10.1038/nature08530
Singh N, Gurav A, Sivaprakasam S et al (2014) Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40(1):128–139. https://doi.org/10.1016/j.immuni.2013.12.007
Koh A, De Vadder F, Kovatcheva-Datchary P et al (2016) From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165(6):1332–1345. https://doi.org/10.1016/j.cell.2016.05.041
Duboc H, Rajca S, Rainteau D et al (2013) Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 62(4):531–539. https://doi.org/10.1136/gutjnl-2012-302578
Zelante T, Iannitti Rossana G, Cunha C et al (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39(2):372–385. https://doi.org/10.1016/j.immuni.2013.08.003
The Integrative Human Microbiome Project (2014) Dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 16(3):276–289. https://doi.org/10.1016/j.chom.2014.08.014
Sokol H, Leducq V, Aschard H et al (2017) Fungal microbiota dysbiosis in IBD. Gut 66(6):1039–1048. https://doi.org/10.1136/gutjnl-2015-310746
Sokol H, Conway KL, Zhang M et al (2013) Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology 145(3):591–601.e593. https://doi.org/10.1053/j.gastro.2013.05.047
Norman JM, Handley SA, Baldridge MT et al (2015) Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160(3):447–460. https://doi.org/10.1016/j.cell.2015.01.002
Cadwell K, Patel KK, Maloney NS et al (2010) Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell 141(7):1135–1145. https://doi.org/10.1016/j.cell.2010.05.009
Lupp C, Robertson ML, Wickham ME et al (2007) Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2(2):119–129. https://doi.org/10.1016/j.chom.2007.06.010
Vijay-Kumar M, Aitken JD, Carvalho FA et al (2010) Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science 328(5975):228–231. https://doi.org/10.1126/science.1179721
Carvalho FA, Koren O, Goodrich JK et al (2012) Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 12(2):139–152. https://doi.org/10.1016/j.chom.2012.07.004
Gill T, Asquith M, Brooks SR et al (2018) Effects of HLA–B27 on gut microbiota in experimental spondyloarthritis implicate an ecological model of dysbiosis. Arthritis Rheumatol 70(4):555–565. https://doi.org/10.1002/art.40405
Robertson SJ, Zhou JY, Geddes K et al (2013) Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis. Gut Microbes 4(3):222–231. https://doi.org/10.4161/gmic.24373
Stappenbeck TS, Virgin HW (2016) Accounting for reciprocal host–microbiome interactions in experimental science. Nature 534:191. https://doi.org/10.1038/nature18285
Zenewicz LA, Yin X, Wang G et al (2013) IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic. J Immunol 190(10):5306–5312. https://doi.org/10.4049/jimmunol.1300016
Monteleone I, Rizzo A, Sarra M et al (2011) Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. Gastroenterology 141(1):237–248.e231. https://doi.org/10.1053/j.gastro.2011.04.007
Kiss EA, Vonarbourg C, Kopfmann S et al (2011) Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334(6062):1561–1565. https://doi.org/10.1126/science.1214914
Mondot S, Lepage P, Seksik P et al (2015) Structural robustness of the gut mucosal microbiota is associated with Crohn’s disease remission after surgery. Gut. https://doi.org/10.1136/gutjnl-2015-309184
Wright EK, Kamm MA, Wagner J et al (2017) Microbial factors associated with postoperative Crohn’s disease recurrence. J Crohn’s Colitis 11(2):191–203. https://doi.org/10.1093/ecco-jcc/jjw136
Kolho KL, Korpela K, Jaakkola T et al (2015) Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am J Gastroenterol 110(6):921–930. https://doi.org/10.1038/ajg.2015.149
Zhou Y, Xu ZZ, He Y et al (2018) Gut microbiota offers universal biomarkers across ethnicity in inflammatory bowel disease diagnosis and infliximab response prediction. mSystems 3(1):e00188-00117. https://doi.org/10.1128/mSystems.00188-17
Rajca S, Grondin V, Louis E et al (2014) Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn’s disease. Inflamm Bowel Dis 20(6):978–986. https://doi.org/10.1097/MIB.0000000000000036
Ananthakrishnan AN, Luo C, Yajnik V et al (2017) Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases. Cell Host Microbe 21(5):603–610.e603. https://doi.org/10.1016/j.chom.2017.04.010
Moayyedi P, Surette MG, Kim PT et al (2015) Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149(1):102–109.e106. https://doi.org/10.1053/j.gastro.2015.04.001
Paramsothy S, Kamm MA, Kaakoush NO et al (2017) Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 389(10075):1218–1228. https://doi.org/10.1016/s0140-6736(17)30182-4
Rossen NG, Fuentes S, van der Spek MJ et al (2015) Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149(1):110–118.e114. https://doi.org/10.1053/j.gastro.2015.03.045
Buffie CG, Bucci V, Stein RR et al (2015) Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517(7533):205–208. https://doi.org/10.1038/nature13828
Papa E, Docktor M, Smillie C et al (2012) Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease. PLoS One 7(6):e39242. https://doi.org/10.1371/journal.pone.0039242
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Lavelle, A., Sokol, H. (2019). The Gut Microbiome in Inflammatory Bowel Disease. In: Hedin, C., Rioux, J., D'Amato, M. (eds) Molecular Genetics of Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-28703-0_16
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