Skip to main content
SpringerLink
Log in

Pathogenesis of IBD

  • Chapter
  • First Online:
Book cover Introduction to Gastrointestinal Diseases Vol. 1

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) are the main representatives of inflammatory bowel diseases (IBD). IBD are defined as a group of chronic, immune system-mediated inflammatory diseases of the gastrointestinal (GI) tract (Xavier and Podolsky in Nature 448:427–434, 2007 [1]). The pathogenesis of IBD is not fully understood; however, a similar cytokine activation profile is observed in psoriasis, rheumatoid arthritis and systemic lupus erythematosus, which are all associated with generalized immune imbalance (Mikhailov and Furner in World J Gastroenterol 15(3):270–279, 2009 [2]; Baumgart and Carding in Lancet 369(9573):1627–1640, 2007 [3]; Kaser et al. in Annu Rev Immunol 28:573–621, 2010 [4]). On the other hand, clinical symptoms differ among these diseases and may involve various organs. Importantly, environmental and infectious factors, together with genetic predisposition lead to elevated levels of pro-inflammatory cytokines and specific (abnormal) tissue responses during the course of IBD (Podolsky in N Engl J Med 347(6):417–429, 2002 [5]; Molodecky et al. in Gastroenterology 142(1):46–54, 2012 [6]). Recent studies suggest that the etiology of IBD involves environmental and genetic factors that cause dysfunction of the epithelial barrier with consequent deregulation of the mucosal immune system and responses to gut microbiota. In this chapter, an overview to IBD pathogenesis will be presented.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448(7152):427–434

    CAS  PubMed  Google Scholar 

  2. Mikhailov TA, Furner SE (2009) Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children. World J Gastroenterol 15(3):270–279

    PubMed  PubMed Central  Google Scholar 

  3. Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369(9573):1627–1640

    CAS  PubMed  Google Scholar 

  4. Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347(6):417–429

    CAS  PubMed  Google Scholar 

  6. Molodecky NA, Soon IS, Rabi DM et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142(1):46–54

    PubMed  Google Scholar 

  7. Antoni L, Nuding S, Wehkamp J, Stange EF (2014) Intestinal barrier in inflammatory bowel disease. World J Gastroenterol 20(5):1165–1179

    PubMed  PubMed Central  Google Scholar 

  8. Sankey EA, Dhillon AP, Anthony A et al (1993) Early mucosal changes in Crohn’s disease. Gut 34(3):375–381

    CAS  PubMed  PubMed Central  Google Scholar 

  9. “Cytokine” in John Lackie (2010) A dictionary of biomedicine. Oxford University Press. ISBN 9780199549351

    Google Scholar 

  10. Fransen L, Müller R, Marmenout A, Tavernier J, Van der Heyden J, Kawashima E, Chollet A, Tizard R, Van Heuverswyn H, Van Vliet A (1985) Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression. Nucleic Acids Res 13(12):4417–4429

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Kriegler M, Perez C, DeFay K, Albert I, Lu SD (1988) A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 53(1):45–53

    Google Scholar 

  12. Sherry B, Jue DM, Zentella A, Cerami A (1990) Characterization of high molecular weight glycosylated forms of murine tumor necrosis factor. Biochem Biophys Res Commun 173(3):1072–1078

    Google Scholar 

  13. Cobrin GM, Abreu MT (2005) Defects in mucosal immunity leading to Crohn’s disease. Immunol Rev 206:277–295

    CAS  PubMed  Google Scholar 

  14. Targan SR, Karp LC (2005) Defects in mucosal immunity leading to ulcerative colitis. Immunol Rev 206:296–305

    CAS  PubMed  Google Scholar 

  15. Hovhannisyan Z, Treatman J, Littman DR, Mayer L (2011) Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology 140(3):957–965. doi:10.1053/j.gastro.2010.12.002 Epub 2010 Dec 11

    Article  CAS  PubMed  Google Scholar 

  16. Włodarczyk M, Sobolewska A, Wójcik B, Loga K, Fichna J, Wiśniewska-Jarosińska M (2014) Correlations between skin lesions induced by anti-tumor necrosis factor-α and selected cytokines in Crohn’s disease patients. World J Gastroenterol 20(22):7019–7026

    PubMed  PubMed Central  Google Scholar 

  17. Van Limbergen J, Wilson DC, Satsangi J (2009) The genetics of Crohn’s disease. Annu Rev Genomics Hum Genet 10:89–116

    PubMed  Google Scholar 

  18. Liu JZ, Anderson CA (2014) Genetic studies of Crohn’s disease: past, present and future. Best Pract Res Clin Gastroenterol 28(3):373–386

    PubMed  PubMed Central  Google Scholar 

  19. Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D (2005) Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn’s disease. Hum Mol Genet 14:3499–3506

    CAS  PubMed  Google Scholar 

  20. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211

    CAS  PubMed  Google Scholar 

  21. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39:596–604

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Libioulle C, Louis E, Hansoul S, Sandor C, Farnir F, Franchimont D (2007) Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13. 1 and modulates expression of PTGER4. PLoS Genet 3:e58

    PubMed  PubMed Central  Google Scholar 

  24. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 39:830–832

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Franke A, Hampe J, Rosenstiel P, Becker C, Wagner F, Häsler R (2007) Systematic association mapping identifies NELL1 as a Novel IBD Disease Gene. PLoS ONE 2:e691

    PubMed  PubMed Central  Google Scholar 

  26. Raelson JV, Little RD, Ruether A, Fournier H, Paquin B, Van Eerdewegh P (2007) Genome-wide association study for Crohn’s disease in the Quebec founder population identifies multiple validated disease loci. Proc Natl Acad Sci USA 104:14747–14752

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Control Wellcome Trust Case (2007) C Genome-wide association study of 14,000 cases of seven common diseases and 3000 shared controls. Nature 447:661–678

    Google Scholar 

  28. Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ (1994) Molecular evidence for two forms of Crohn disease. Proc Natl Acad Sci USA 91(26):12721–12724

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas G (1996) Mapping of a susceptibility locus for Crohn’s disease on chromosome 16. Nature 379(6568):821–823

    CAS  PubMed  Google Scholar 

  30. Adler J, Rangwalla SC, Dwamena BA, Higgins PD (2011) The prognostic power of the NOD2 genotype for complicated Crohn’s disease: a meta-analysis. Am J Gastroenterol 106(4):699–712

    CAS  PubMed  Google Scholar 

  31. Fritz T, Niederreiter L, Adolph T, Blumberg RS, Kaser A (2011) Crohn’s disease: NOD2, autophagy and ER stress converge. Gut 60(11):1580–1588

    CAS  PubMed  Google Scholar 

  32. Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355

    Google Scholar 

  33. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Google Scholar 

  34. Archanioti P, Gazouli M, Theodoropoulos G, Vaiopoulou A, Nikiteas N (2011) Micro-RNAs as regulators and possible diagnostic bio-markers in inflammatory bowel disease. J Crohns Colitis 5(6):520–524

    PubMed  Google Scholar 

  35. Chapman CG, Pekow J (2015) The emerging role of miRNAs in inflammatory bowel disease: a review. Therap Adv Gastroenterol 8(1):4–22

    PubMed  PubMed Central  Google Scholar 

  36. Sartor RB (2006) Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 3(7):390–407

    CAS  PubMed  Google Scholar 

  37. Slattery E, Mitchell P, Mulcahy HE (2011) Cigarette smoking in Crohns disease: can we do more? J Crohns Colitis 5(5):505

    PubMed  Google Scholar 

  38. Graham C (2013) Understanding smoking and nicotine effects on the gastrointestinal tract. Gastrointest Nurs 11(1):44

    Google Scholar 

  39. To N, Ford AC, Gracie DJ (2016) Systematic review with meta-analysis: the effect of tobacco smoking on the natural history of ulcerative colitis. Aliment Pharmacol Ther 44(2):117–126

    CAS  PubMed  Google Scholar 

  40. Pfeffer-Gik T, Levine A (2014) Dietary clues to the pathogenesis of Crohn’s disease. Dig Dis 32(4):389–394

    PubMed  Google Scholar 

  41. Kawaguchi T, Mori M, Saito K et al (2014) Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice. J Gastroenterol 50(4):394–405

    PubMed  PubMed Central  Google Scholar 

  42. Ferguson LR (2012) Potential value of nutrigenomics in Crohn’s disease. Nat Rev Gastroenterol Hepatol 9(5):260–270

    CAS  PubMed  Google Scholar 

  43. Ruemmele FM (2016) Role of diet in inflammatory bowel disease. Ann Nutr Metab 68(Suppl 1):33–41

    PubMed  Google Scholar 

  44. Hansen R, Thomson JM, El-Omar EM, Hold GL (2010) The role of infection in the aetiology of inflammatory bowel disease. J Gastroenterol 45:266–276

    PubMed  PubMed Central  Google Scholar 

  45. Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, Desreumaux P, Gambiez L, Joly B, Cortot A, Colombel JF (1998) Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn’s disease. Gastroenterology 115:1405–1413

    CAS  PubMed  Google Scholar 

  46. O’Brien CL, Pavli P, Gordon DM, Allison GE (2014) Detection of bacterial DNA in lymph nodes of Crohn’s disease patients using high throughput sequencing. Gut 63:1596–1606

    PubMed  Google Scholar 

  47. Barnich N, Darfeuille-Michaud A (2007) Role of bacteria in the etiopathogenesis of inflammatory bowel disease. World J Gastroenterol 13:5571–5576

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Wine E, Ossa JC, Gray-Owen SD, Sherman PM (2010) Adherent-invasive Escherichia coli target the epithelial barrier. Gut Microbes 1:80–84

    PubMed  PubMed Central  Google Scholar 

  49. Glasser AL, Boudeau J, Barnich N, Perruchot MH, Colombel JF, Darfeuille-Michaud A (2001) Adherent invasive Escherichia coli strains from patients with Crohn’s disease survive and replicate within macrophages without inducing host cell death. Infect Immun 69:5529–5537

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Friswell M, Campbell B, Rhodes J (2010) The role of bacteria in the pathogenesis of inflammatory bowel disease. Gut Liver 4:295–306

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Lidar M, Langevitz P, Shoenfeld Y (2009) The role of infection in inflammatory bowel disease: initiation, exacerbation and protection. Isr Med Assoc J 11:558–563

    PubMed  Google Scholar 

  52. Hermon-Taylor J, Moss M, Tizard M, Malik Z, Sanderson J (1990) Molecular biology of Crohn’s disease mycobacteria. Baillieres Clin Gastroenterol 4(1):23–42

    CAS  PubMed  Google Scholar 

  53. Naser SA, Ghobrial G, Romero C, Valentine JF (2004) Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. Lancet 364:1039–1044

    PubMed  Google Scholar 

  54. Väre PO, Heikius B, Silvennoinen JA, Karttunen R, Niemelä SE, Lehtola JK, Karttunen TJ (2001) Seroprevalence of Helicobacter pylori infection in inflammatory bowel disease: is Helicobacter pylori infection a protective factor? Scand J Gastroenterol 36:1295–1300

    PubMed  Google Scholar 

  55. Luther J, Dave M, Higgins PD, Kao JY (2010) Association between Helicobacter pylori infection and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Inflamm Bowel Dis 16:1077–1084

    PubMed  Google Scholar 

  56. Luther J, Owyang SY, Takeuchi T, Cole TS, Zhang M, Liu M, Erb-Downward J, Rubenstein JH, Chen CC, Pierzchala AV et al (2011) Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis. Gut 60:1479–1486

    CAS  PubMed  Google Scholar 

  57. Papamichael K, Konstantopoulos P, Mantzaris GJ (2014) Helicobacter pylori infection and inflammatory bowel disease: is there a link? World J Gastroenterol 20:6374–6385

    PubMed  PubMed Central  Google Scholar 

  58. Ryan KJ, Ray CG (2004) Sherris medical microbiology, 4th edn. McGraw Hill, pp 322–324

    Google Scholar 

  59. Bien J, Palagani V, Bozko P (2013) The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease? Therap Adv Gastroenterol 6:53–68

    PubMed  PubMed Central  Google Scholar 

  60. Navaneethan U, Venkatesh PG, Shen B (2010) Clostridium difficile infection and inflammatory bowel disease: understanding the evolving relationship. World J Gastroenterol 16:4892–4904

    PubMed  PubMed Central  Google Scholar 

  61. Nitzan O, Elias M, Chazan B, Raz R, Saliba W (2013) Clostridium difficile and inflammatory bowel disease: role in pathogenesis and implications in treatment. World J Gastroenterol 19:7577–7585

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Feeney M, Ciegg A, Winwood P, Snook J (1997) A case-control study of measles vaccination and inflammatory bowel disease. Lancet 350:764–766 The East Dorset Gastroenterology Group

    CAS  PubMed  Google Scholar 

  63. D’Souza Y, Dionne S, Seidman EG, Bitton A, Ward BJ (2007) No evidence of persisting measles virus in the intestinal tissues of patients with inflammatory bowel disease. Gut 56:886–888

    PubMed  PubMed Central  Google Scholar 

  64. Linton MS, Kroeker K, Fedorak D, Dieleman L, Fedorak RN (2013) Prevalence of Epstein-Barr virus in a population of patients with inflammatory bowel disease: a prospective cohort study. Aliment Pharmacol Ther 38:1248–1254

    CAS  PubMed  Google Scholar 

  65. Iizuka M, Saito H, Yukawa M, Itou H, Shirasaka T, Chiba M, Fukushima T, Watanabe S (2001) No evidence of persistent mumps virus infection in inflammatory bowel disease. Gut 48:637–641

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Sipponen T, Turunen U, Lautenschlager I, Nieminen U, Arola J, Halme L (2011) Human herpesvirus 6 and cytomegalovirus in ileocolonic mucosa in inflammatory bowel disease. Scand J Gastroenterol 46:1324–1333

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by the National Science Center (2015/17/N/NZ5/00677 to ASW).

Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland

    Aleksandra Sobolewska-Włodarczyk & Marcin Włodarczyk

  2. Faculty of Military Medicine, Department of Gastroenterology, Medical University of Lodz, Lodz, Poland

    Aleksandra Sobolewska-Włodarczyk

  3. Faculty of Military Medicine, Department of General and Colorectal Surgery, Medical University of Lodz, Hallera Sq 1, Lodz, Poland

    Marcin Włodarczyk

Authors
  1. Aleksandra Sobolewska-Włodarczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcin Włodarczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Aleksandra Sobolewska-Włodarczyk or Marcin Włodarczyk .

Editor information

Editors and Affiliations

  1. Department of Biochemistry, Medical University of Lodz, Lodz, Poland

    Jakub Fichna

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Sobolewska-Włodarczyk, A., Włodarczyk, M. (2017). Pathogenesis of IBD. In: Fichna, J. (eds) Introduction to Gastrointestinal Diseases Vol. 1. Springer, Cham. https://doi.org/10.1007/978-3-319-49016-8_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-49016-8_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-49015-1

  • Online ISBN: 978-3-319-49016-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation