Skip to main content
SpringerLink
Log in

IBD Genetics and the Gut Microbiome

  • Chapter
  • First Online:
Molecular Genetics of Inflammatory Bowel Disease

Abstract

The pathogenesis of inflammatory bowel disease (IBD) is determined by multiple genetic variants and by gut microbiota. The role of interactions between these two factors has emerged recently. In this chapter, we focus on the crosstalk of gut microbiota and IBD genetic risk factors and give a review on the current progress and perspective of this research field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lindberg E, Tysk C, Andersson K, Järnerot G (1988) Smoking and inflammatory bowel disease. A case control study. Gut 29(3):352–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Thompson NP, Driscoll R, Pounder RE, Wakefield AJ (1996) Genetics versus environment in inflammatory bowel disease: results of a British twin study. BMJ 312(7023):95–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Orholm M, Binder V, Sørensen T, Rasmussen L, Kyvik K (2000) Concordance of inflammatory bowel disease among Danish twins: results of a nationwide study. Scand J Gastroenterol 35(10):1075–1081

    Article  CAS  PubMed  Google Scholar 

  4. Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, Cardon L, Takazoe M, Tanaka T, Ichimori T (2005) Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn’s disease. Hum Mol Genet 14(22):3499–3506

    Article  CAS  PubMed  Google Scholar 

  5. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA (2012) Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. de Lange KM, Moutsianas L, Lee JC, Lamb CA, Luo Y, Kennedy NA, Jostins L, Rice DL, Gutierrez-Achury J, Ji S-G (2017) Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 49(2):256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. McGovern DP, Daly MJ (2018) P164 using exome sequencing to expand the genetic architecture of inflammatory bowel disease. Gastroenterology 154(1):S88

    Article  Google Scholar 

  8. Liu JZ, van Sommeren S, Huang H, Ng SC, Alberts R, Takahashi A, Ripke S, Lee JC, Jostins L, Shah T (2015) Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 47(9):979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Conlan S, Kong HH, Segre JA (2012) Species-level analysis of DNA sequence data from the NIH human microbiome project. PLoS One 7(10):e47075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glöckner FO (2012) The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 41(D1):D590–D596

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Eisen JA (2007) Environmental shotgun sequencing: its potential and challenges for studying the hidden world of microbes. PLoS Biol 5(3):e82

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Pryce T, Palladino S, Kay I, Coombs G (2003) Rapid identification of fungi by sequencing the ITS1 and ITS2 regions using an automated capillary electrophoresis system. Med Mycol 41(5):369–381

    Article  CAS  PubMed  Google Scholar 

  13. Shkoporov AN, Khokhlova EV, Fitzgerald CB, Stockdale SR, Draper LA, Ross RP, Hill C (2018) ΦCrAss001 represents the most abundant bacteriophage family in the human gut and infects Bacteroides intestinalis. Nat Commun 9(1):4781

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Sokol H, Leducq V, Aschard H, Pham H-P, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I (2017) Fungal microbiota dysbiosis in IBD. Gut 66(6):1039–1048

    Article  CAS  PubMed  Google Scholar 

  15. Norman JM, Handley SA, Baldridge MT, Droit L, Liu CY, Keller BC, Kambal A, Monaco CL, Zhao G, Fleshner P (2015) Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160(3):447–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Baumann-Dudenhoeffer AM, D’Souza AW, Tarr PI, Warner BB, Dantas G (2018) Infant diet and maternal gestational weight gain predict early metabolic maturation of gut microbiomes. Nat Med 24(12):1822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vatanen T, Franzosa EA, Schwager R, Tripathi S, Arthur TD, Vehik K, Lernmark Å, Hagopian WA, Rewers MJ, She J-X (2018) The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 562(7728):589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T, Mujagic Z, Vila AV, Falony G, Vieira-Silva S (2016) Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352(6285):565–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, Kurilshikov A, Bonder MJ, Valles-Colomer M, Vandeputte D (2016) Population-level analysis of gut microbiome variation. Science 352(6285):560–564

    Article  CAS  PubMed  Google Scholar 

  20. Cash HL, Whitham CV, Behrendt CL, Hooper LV (2006) Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313(5790):1126–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ (2000) Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 1(2):113

    Article  CAS  PubMed  Google Scholar 

  22. Birchler T, Seibl R, Büchner K, Loeliger S, Seger R, Hossle JP, Aguzzi A, Lauener RP (2001) Human toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein. Eur J Immunol 31(11):3131–3137

    Article  CAS  PubMed  Google Scholar 

  23. Maloy KJ, Powrie F (2011) Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474(7351):298

    Article  CAS  PubMed  Google Scholar 

  24. Dicksved J, Halfvarson J, Rosenquist M, Järnerot G, Tysk C, Apajalahti J, Engstrand L, Jansson JK (2008) Molecular analysis of the gut microbiota of identical twins with Crohn’s disease. ISME J 2(7):716

    Article  CAS  PubMed  Google Scholar 

  25. Frank DN, Amand ALS, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci 104(34):13780–13785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R, Orsi RH, Wiedmann M, McDonough P, Kim SG (2007) 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(5):403

    Article  CAS  PubMed  Google Scholar 

  27. Fujimoto T, Imaeda H, Takahashi K, Kasumi E, Bamba S, Fujiyama Y, Andoh A (2013) Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn’s disease. J Gastroenterol Hepatol 28(4):613–619

    Article  CAS  PubMed  Google Scholar 

  28. Erickson AR, Cantarel BL, Lamendella R, Darzi Y, Mongodin EF, Pan C, Shah M, Halfvarson J, Tysk C, Henrissat B (2012) Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn’s disease. PLoS One 7(11):e49138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schirmer M, Franzosa EA, Lloyd-Price J, McIver LJ, Schwager R, Poon TW, Ananthakrishnan AN, Andrews E, Barron G, Lake K (2018) Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol 3(3):337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55(2):205–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hedin CR, van der Gast CJ, Stagg AJ, Lindsay JO, Whelan K (2017) The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease. Gut Microbes 8(4):359–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci 105(39):15064–15069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tsuboi K, Nishitani M, Takakura A, Imai Y, Komatsu M, Kawashima H (2015) Autophagy protects against colitis by the maintenance of normal gut microflora and secretion of mucus. J Biol Chem 290(33):20511–20526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhu S, Ding S, Wang P, Wei Z, Pan W, Palm NW, Yang Y, Yu H, Li H-B, Wang G (2017) Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 546(7660):667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sarrabayrouse G, Bossard C, Chauvin J-M, Jarry A, Meurette G, Quévrain E, Bridonneau C, Preisser L, Asehnoune K, Labarrière N (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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Narushima S, Sugiura Y, Oshima K, Atarashi K, Hattori M, Suematsu M, Honda K (2014) Characterization of the 17 strains of regulatory T cell-inducing human-derived clostridia. Gut Microbes 5(3):333–339

    Article  PubMed  PubMed Central  Google Scholar 

  37. Reboldi A, Arnon TI, Rodda LB, Atakilit A, Sheppard D, Cyster JG (2016) IgA production requires B cell interaction with subepithelial dendritic cells in Peyer’s patches. Science 352(6287):aaf4822

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Nakajima A, Vogelzang A, Maruya M, Miyajima M, Murata M, Son A, Kuwahara T, Tsuruyama T, Yamada S, Matsuura M (2018) IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria. J Exp Med 215(8):2019–2034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sterlin D, Fieschi C, Malphettes M, Larsen M, Gorochov G, Fadlallah J (2018) Immune/microbial interface perturbation in human IgA deficiency. Gut Microbes 18:1–5

    Google Scholar 

  40. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461(7268):1282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA (2008) Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455(7216):1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Glavan TW, Gaulke CA, Rocha CS, Sankaran-Walters S, Hirao LA, Raffatellu M, Jiang G, Bäumler AJ, Goulart LR, Dandekar S (2016) Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection. Mucosal Immunol 9(3):677

    Article  CAS  PubMed  Google Scholar 

  43. Mondot S, Barreau F, Al Nabhani Z, Dussaillant M, Le Roux K, Doré J, Leclerc M, Hugot J-P, Lepage P (2012) Altered gut microbiota composition in immune-impaired Nod2−/− mice. Gut 61(4):634–635

    Article  PubMed  Google Scholar 

  44. Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L (2017) A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 23(1):107

    Article  CAS  PubMed  Google Scholar 

  45. Sethi V, Kurtom S, Tarique M, Lavania S, Malchiodi Z, Hellmund L, Zhang L, Sharma U, Giri B, Garg B (2018) Gut microbiota promotes tumor growth in mice by modulating immune response. Gastroenterology 155(1):33–37. e36

    Article  CAS  PubMed  Google Scholar 

  46. Goodrich JK, Davenport ER, Beaumont M, Jackson MA, Knight R, Ober C, Spector TD, Bell JT, Clark AG, Ley RE (2016) Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19(5):731–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Davenport ER, Mizrahi-Man O, Michelini K, Barreiro LB, Ober C, Gilad Y (2014) Seasonal variation in human gut microbiome composition. PLoS One 9(3):e90731

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Turpin W, Espin-Garcia O, Xu W, Silverberg MS, Kevans D, Smith MI, Guttman DS, Griffiths A, Panaccione R, Otley A (2016) Association of host genome with intestinal microbial composition in a large healthy cohort. Nat Genet 48(11):1413

    Article  CAS  PubMed  Google Scholar 

  49. Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, Zeevi D, Costea PI, Godneva A, Kalka IN, Bar N (2018) Environment dominates over host genetics in shaping human gut microbiota. Nature 555(7695):210

    Article  CAS  PubMed  Google Scholar 

  50. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307(5710):731–734

    Article  CAS  PubMed  Google Scholar 

  51. Magalhaes JG, Lee J, Geddes K, Rubino S, Philpott DJ, Girardin SE (2011) Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands. Eur J Immunol 41(5):1445–1455

    Article  CAS  PubMed  Google Scholar 

  52. Elinav E, Strowig T, Henao-Mejia J, Flavell RA (2011) Regulation of the antimicrobial response by NLR proteins. Immunity 34(5):665–679

    Article  CAS  PubMed  Google Scholar 

  53. Petnicki-Ocwieja T, Hrncir T, Liu Y-J, Biswas A, Hudcovic T, Tlaskalova-Hogenova H, Kobayashi KS (2009) Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci 106(37):15813–15818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rehman A, Sina C, Gavrilova O, Häsler R, Ott S, Baines JF, Schreiber S, Rosenstiel P (2011) Nod2 is essential for temporal development of intestinal microbial communities. Gut 60(10):1354–1362

    Article  CAS  PubMed  Google Scholar 

  55. Butera A, Di Paola M, Pavarini L, Strati F, Pindo M, Sanchez M, Cavalieri D, Boirivant M, De Filippo C (2018) Nod2 deficiency in mice is associated with microbiota variation favouring the expansion of mucosal CD4+ LAP+ regulatory cells. Sci Rep 8(1):14241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Haesler R, Huot L, Grandjean T, Bressenot A, Delanoye-Crespin A (2013) NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest 123(2):700–711

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Bloom SM, Bijanki VN, Nava GM, Sun L, Malvin NP, Donermeyer DL, Dunne WM Jr, Allen PM, Stappenbeck TS (2011) Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe 9(5):390–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Imhann F, Bonder MJ, Vila AV, Fu J, Mujagic Z, Vork L, Tigchelaar EF, Jankipersadsing SA, Cenit MC, Harmsen HJ (2016) Proton pump inhibitors affect the gut microbiome. Gut 65(5):740–748

    Article  CAS  PubMed  Google Scholar 

  59. Rodriguez-Nunez I, Caluag T, Kirby K, Rudick CN, Dziarski R, Gupta D (2017) Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction. Sci Rep 7(1):548

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Ramanan D, San Tang M, Bowcutt R, Cadwell K (2014) Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus. Immunity 41(2):311–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Knights D, Silverberg MS, Weersma RK, Gevers D, Dijkstra G, Huang H, Tyler AD, Van Sommeren S, Imhann F, Stempak JM (2014) Complex host genetics influence the microbiome in inflammatory bowel disease. Genome Med 6(12):107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40(8):955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Tomlinson IP, Webb E, Carvajal-Carmona L, Broderick P, Howarth K, Pittman AM, Spain S, Lubbe S, Walther A, Sullivan K (2008) A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23. 3. Nat Genet 40(5):623

    Article  CAS  PubMed  Google Scholar 

  64. Cummings FJ, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, Geremia A, Hancock L, Guo C, Ahmad T (2007) Confirmation of the role of ATG16L1 as a Crohn’s disease susceptibility gene. Inflamm Bowel Dis 13(8):941–946

    Article  PubMed  Google Scholar 

  65. Kabat AM, Harrison OJ, Riffelmacher T, Moghaddam AE, Pearson CF, Laing A, Abeler-Doerner L, Forman SP, Grencis RK, Sattentau Q (2016) The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation. elife 5:e12444

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Homer CR, Richmond AL, Rebert NA, Achkar JP, McDonald C (2010) ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn’s disease pathogenesis. Gastroenterology 139(5):1630–1641. e1632

    Article  CAS  PubMed  Google Scholar 

  67. Plantinga TS, Crisan TO, Oosting M, van de Veerdonk FL, de Jong DJ, Philpott DJ, van der Meer JW, Girardin SE, Joosten LA, Netea MG (2011) Crohn’s disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2. Gut 60(9):1229–1235

    Article  CAS  PubMed  Google Scholar 

  68. Lassen KG, Kuballa P, Conway KL, Patel KK, Becker CE, Peloquin JM, Villablanca EJ, Norman JM, Liu T-C, Heath RJ (2014) Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense. Proc Natl Acad Sci 111(21):7741–7746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sadabad MS, Regeling A, de Goffau MC, Blokzijl T, Weersma RK, Penders J, Faber KN, Harmsen HJ, Dijkstra G (2015) The ATG16L1–T300A allele impairs clearance of pathosymbionts in the inflamed ileal mucosa of Crohn’s disease patients. Gut 64(10):1546–1552

    Article  CAS  Google Scholar 

  70. McGovern DP, Jones MR, Taylor KD, Marciante K, Yan X, Dubinsky M, Ippoliti A, Vasiliauskas E, Berel D, Derkowski C (2010) Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn’s disease. Hum Mol Genet 19(17):3468–3476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Johansson ME, Jakobsson HE, Holmén-Larsson J, Schütte A, Ermund A, Rodríguez-Piñeiro AM, Arike L, Wising C, Svensson F, Bäckhed F (2015) Normalization of host intestinal mucus layers requires long-term microbial colonization. Cell Host Microbe 18(5):582–592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Tong M, McHardy I, Ruegger P, Goudarzi M, Kashyap PC, Haritunians T, Li X, Graeber TG, Schwager E, Huttenhower C (2014) Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism. ISME J 8(11):2193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Rausch P, Rehman A, Künzel S, Häsler R, Ott SJ, Schreiber S, Rosenstiel P, Franke A, Baines JF (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wacklin P, Tuimala J, Nikkilä J, Tims S, Mäkivuokko H, Alakulppi N, Laine P, Rajilic-Stojanovic M, Paulin L, de Vos WM (2014) Faecal microbiota composition in adults is associated with the FUT2 gene determining the secretor status. PLoS One 9(4):e94863

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Pacheco AR, Curtis MM, Ritchie JM, Munera D, Waldor MK, Moreira CG, Sperandio V (2012) Fucose sensing regulates bacterial intestinal colonization. Nature 492(7427):113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Zhernakova DV, Le TH, Kurilshikov A, Atanasovska B, Bonder MJ, Sanna S, Claringbould A, Võsa U, Deelen P, Franke L (2018) Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome. Nat Genet 50(11):1524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhernakova A, Festen EM, Franke L, Trynka G, van Diemen CC, Monsuur AJ, Bevova M, Nijmeijer RM, van’t Slot R, Heijmans R (2008) Genetic analysis of innate immunity in Crohn’s disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP. Am J Hum Genet 82(5):1202–1210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sokol H, Conway KL, Zhang M, Choi M, Morin B, Cao Z, Villablanca EJ, Li C, Wijmenga C, Yun SH (2013) Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology 145(3):591–601. e593

    Article  CAS  PubMed  Google Scholar 

  79. Lamas B, Michel M-L, Waldschmitt N, Pham H-P, Zacharioudaki V, Dupraz L, Delacre M, Natividad JM, Da Costa G, Planchais J (2018) Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence. Gut 67(10):1836–1844

    Article  CAS  PubMed  Google Scholar 

  80. Ward MA, Pierre JF, Leal RF, Huang Y, Shogan B, Dalal SR, Weber CR, Leone VA, Musch MW, An GC (2016) Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility. Am J Physiol Gastrointest Liver Physiol 310(11):G973–G988

    Article  PubMed  PubMed Central  Google Scholar 

  81. Bonder MJ, Kurilshikov A, Tigchelaar EF, Mujagic Z, Imhann F, Vila AV, Deelen P, Vatanen T, Schirmer M, Smeekens SP (2016) The effect of host genetics on the gut microbiome. Nat Genet 48(11):1407

    Article  CAS  PubMed  Google Scholar 

  82. Bohn E, Bechtold O, Zahir N, Frick JS, Reimann J, Jilge B, Autenrieth IB (2006) Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains: common patterns and bacteria strain specific signatures. Inflamm Bowel Dis 12(9):853–862

    Article  PubMed  Google Scholar 

  83. Blekhman R, Goodrich JK, Huang K, Sun Q, Bukowski R, Bell JT, Spector TD, Keinan A, Ley RE, Gevers D (2015) Host genetic variation impacts microbiome composition across human body sites. Genome Biol 16(1):191

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Wang J, Thingholm LB, Skiecevičienė J, Rausch P, Kummen M, Hov JR, Degenhardt F, Heinsen F-A, Rühlemann MC, Szymczak S (2016) Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat Genet 48(11):1396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Pohjanen V-M, Koivurova O-P, Niemelä SE, Karttunen RA, Karttunen TJ (2016) Role of Helicobacter pylori and interleukin 6-174 gene polymorphism in dyslipidemia: a case–control study. BMJ Open 6(1):e009987

    Article  PubMed  PubMed Central  Google Scholar 

  86. Nakagome S, Chinen H, Iraha A, Hokama A, Takeyama Y, Sakisaka S, Matsui T, Kidd JR, Kidd KK, Said HS (2017) Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands. Hum Genet 136(4):387–397

    Article  CAS  PubMed  Google Scholar 

  87. Chen L, Wilson JE, Koenigsknecht MJ, Chou W-C, Montgomery SA, Truax AD, Brickey WJ, Packey CD, Maharshak N, Matsushima GK (2017) NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth. Nat Immunol 18(5):541

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Li D, Achkar J-P, Haritunians T, Jacobs JP, Hui KY, D’Amato M, Brand S, Radford-Smith G, Halfvarson J, Niess J-H (2016) A pleiotropic missense variant in SLC39A8 is associated with Crohn’s disease and human gut microbiome composition. Gastroenterology 151(4):724–732

    Article  CAS  PubMed  Google Scholar 

  89. Magyari L, Kovesdi E, Sarlos P, Javorhazy A, Sumegi K, Melegh B (2014) Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility. World J Gastroenterol: WJG 20(12):3208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kurilshikov A, Wijmenga C, Fu J, Zhernakova A (2017) Host genetics and gut microbiome: challenges and perspectives. Trends Immunol 38(9):633–647

    Article  CAS  PubMed  Google Scholar 

  91. Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, Creasy HH, Earl AM, FitzGerald MG, Fulton RS (2012) Structure, function and diversity of the healthy human microbiome. Nature 486(7402):207

    Article  CAS  Google Scholar 

  92. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci 110(22):9066–9071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kehrl JH (2004) G-protein-coupled receptor signaling, RGS proteins, and lymphocyte function. Crit Rev Immunol 24(6):409–423

    Article  CAS  PubMed  Google Scholar 

  94. Drobits B, Holcmann M, Amberg N, Swiecki M, Grundtner R, Hammer M, Colonna M, Sibilia M (2012) Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells. J Clin Invest 122(2):575–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kawano Y, Nakae J, Watanabe N, Kikuchi T, Tateya S, Tamori Y, Kaneko M, Abe T, Onodera M, Itoh H (2016) Colonic pro-inflammatory macrophages cause insulin resistance in an intestinal Ccl2/Ccr2-dependent manner. Cell Metab 24(2):295–310

    Article  CAS  PubMed  Google Scholar 

  96. Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, Kambayashi T, LaRosa DF, Renner ED, Orange JS (2012) Commensal bacteria–derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18(4):538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Yahiro K, Tsutsuki H, Ogura K, Nagasawa S, Moss J, Noda M (2014) DAP1, a negative regulator of autophagy, controls SubAB-mediated apoptosis and autophagy. Infect Immun 82(11):4899–4908

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Di Meglio P, Di Cesare A, Laggner U, Chu C-C, Napolitano L, Villanova F, Tosi I, Capon F, Trembath RC, Peris K (2011) The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. PLoS One 6(2):e17160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Drummond RA, Saijo S, Iwakura Y, Brown GD (2011) The role of Syk/CARD9 coupled C-type lectins in antifungal immunity. Eur J Immunol 41(2):276–281

    Article  CAS  PubMed  Google Scholar 

  100. Schreibelt G, Klinkenberg LJ, Cruz LJ, Tacken PJ, Tel J, Kreutz M, Adema GJ, Brown GD, Figdor CG, de Vries IJM (2012) The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-) presentation by human blood BDCA3+ myeloid dendritic cells. Blood 119(10):2284–2292

    Article  CAS  PubMed  Google Scholar 

  101. Zanet J, Benrabah E, Li T, Pelissier-Monier A, Chanut-Delalande H, Ronsin B, Bellen H, Payre F, Plaza S (2015) Pri sORF peptides induce selective proteasome-mediated protein processing. Science 349(6254):1356–1358

    Article  CAS  PubMed  Google Scholar 

  102. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311(5768):1770–1773

    Article  CAS  PubMed  Google Scholar 

  103. Zammit SC, Ellul P, Girardin G, Valpiani D, Nielsen KR, Olsen J, Goldis A, Lazar D, Shonová O, Nováková M (2018) Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study. Eur J Gastroenterol Hepatol 30(11):1297–1303

    Article  CAS  Google Scholar 

  104. Jin D, Wu S, Zhang Y-G, Lu R, Xia Y, Dong H, Sun J (2015) Lack of vitamin D receptor causes dysbiosis and changes the functions of the murine intestinal microbiome. Clin Ther 37(5):996–1009. e1007

    Article  CAS  PubMed  Google Scholar 

  105. Wang J, Kurilshikov A, Radjabzadeh D, Turpin W, Croitoru K, Bonder MJ, Jackson MA, Medina-Gomez C, Frost F, Homuth G et al (2018) Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative. Microbiome 6(1):101

    Article  PubMed  PubMed Central  Google Scholar 

  106. Imhann F, Vila AV, Bonder MJ, Fu J, Gevers D, Visschedijk MC, Spekhorst LM, Alberts R, Franke L, Van Dullemen HM (2018) Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut 67(1):108–119

    Article  CAS  PubMed  Google Scholar 

  107. Vila AV, Imhann F, Collij V, Jankipersadsing SA, Gurry T, Mujagic Z, Kurilshikov A, Bonder MJ, Jiang X, Tigchelaar EF (2018) Gut microbiota composition and functional changes in inflammatory bowel disease and irritable bowel syndrome. Sci Transl Med 10(472):eaap8914

    Article  CAS  Google Scholar 

  108. Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, Andersen V, Andrews JM, Annese V, Brand S (2016) Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet 387(10014):156–167

    Article  PubMed  PubMed Central  Google Scholar 

  109. Halfvarson J, Brislawn CJ, Lamendella R, Vázquez-Baeza Y, Walters WA, Bramer LM, D’Amato M, Bonfiglio F, McDonald D, Gonzalez A (2017) Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol 2(5):17004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands

    Shixian Hu & Rinse Weersma

  2. Department of Genetics, University of Groningen and University Medical Centre Groningen, Groningen, The Netherlands

    Alexander Kurilshikov & Alexandra Zhernakova

Authors
  1. Shixian Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander Kurilshikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexandra Zhernakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rinse Weersma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rinse Weersma .

Editor information

Editors and Affiliations

  1. Gastroenterology unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden

    Charlotte Hedin

  2. Montreal Heart Institute and Université de Montréal, Montréal, QC, Canada

    John D. Rioux

  3. School of Biological Sciences, Monash University, Clayton, VIC, Australia

    Mauro D'Amato

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hu, S., Kurilshikov, A., Zhernakova, A., Weersma, R. (2019). IBD Genetics and the Gut Microbiome. 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_11

Download citation

Publish with us

Policies and ethics

Search

Navigation