Environmental Triggers for IBD

  • Aoibhlinn O’Toole
  • Joshua KorzenikEmail author
Inflammatory Bowel Disease (S Hanauer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Inflammatory Bowel Disease


The fundamental elucidation of how environmental influences provoke the initiation of disease as well as flares of inflammatory bowel disease (IBD) remains incomplete. The current understanding of these diseases suggests that ulcerative colitis (UC) and Crohn’s disease (CD) result from poorly defined interactions between genetic and environmental factors which culminate in the pathologic effects and clinical manifestations of these diseases. The genetic variant appears not sufficient itself to lead to the development of the clinical disease, but likely must combine with the environmental factors. The intestinal microbiome is pivotal to IBD development. A greater understanding of the contribution of these factors to dysbiosis is critical, and we aspire to restoring a healthy microbiome to treat flares and ideally prevent the development of IBD and its complications. This article aims to place the environmental influences in the context of their potential contribution to the development of the pathophysiology of IBD.


Inflammatory bowel disease Crohn’s Ulcerative colitis Microbiome Environment Triggers Pathophysiology Dysbiosis 


Compliance with Ethics Guidelines

Conflict of Interest

Aoibhliin O’Toole declares no conflict of interest. Joshua Korzenik has served as an IBD consultant for Abbvie, Empiramed, Pfizer, Vithera, Prometheus, and Janssen; he has received research/grant support from Abbvie, and Warner-Chilcott and has served as a member of the Data Safety Monitoring Board for Roche.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. 1.
    Kabi A et al. Digesting the genetics of inflammatory bowel disease: insights from studies of autophagy risk genes. Inflamm Bowel Dis. 2012;18(4):782–92.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573–621.PubMedCrossRefGoogle Scholar
  3. 3.
    Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369(9573):1627–40.PubMedCrossRefGoogle Scholar
  4. 4.
    Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427–34.PubMedCrossRefGoogle Scholar
  5. 5.
    Jostins L et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119–24.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Arimura Y, et al Characteristics of Japanese inflammatory bowel disease susceptibility loci. J Gastroenterol. 2013. doi: 10.1007/s00535-013-0866-2.
  7. 7.
    Mahurkar S et al. Common variants in NOD2 and IL23R are not associated with inflammatory bowel disease in Indians. J Gastroenterol Hepatol. 2011;26(4):694–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299(6710):1259–60.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Forbes A, Kalantzis T. Crohn’s disease: the cold chain hypothesis. Int J Color Dis. 2006;21(5):399–401.CrossRefGoogle Scholar
  10. 10.
    Funkhouser LJ, Bordenstein SR. Mom knows best: the universality of maternal microbial transmission. PLoS Biol. 2013;11(8):e1001631.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Dominguez-Bello MG et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971–5.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Bager P et al. Cesarean section and offspring’s risk of inflammatory bowel disease: a national cohort study. Inflamm Bowel Dis. 2012;18(5):857–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Sonntag B et al. Preterm birth but not mode of delivery is associated with an increased risk of developing inflammatory bowel disease later in life. Inflamm Bowel Dis. 2007;13(11):1385–90.PubMedCrossRefGoogle Scholar
  14. 14.
    Cabrera-Rubio R et al. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012;96(3):544–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Khalili H et al. Early life factors and risk of inflammatory bowel disease in adulthood. Inflamm Bowel Dis. 2013;19(3):542–7.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Spooren CE et al. Review article: the association of diet with onset and relapse in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38(10):1172–87.PubMedCrossRefGoogle Scholar
  17. 17.
    Castiglione F et al. Risk factors for inflammatory bowel diseases according to the “hygiene hypothesis”: a case-control, multi-centre, prospective study in Southern Italy. J Crohn’s Colitis. 2012;6(3):324–9.CrossRefGoogle Scholar
  18. 18.
    Roberts CL et al. Translocation of Crohn’s disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers. Gut. 2010;59(10):1331–9.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Maslowski KM, Mackay CR. Diet, gut microbiota and immune responses. Nat Immunol. 2011;12(1):5–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Jakobsen C et al. Environmental factors and risk of developing paediatric inflammatory bowel disease—a population based study 2007–2009. J Crohn’s Colitis. 2013;7(1):79–88.CrossRefGoogle Scholar
  21. 21.
    Ananthakrishnan AN et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology. 2013;145(5):970–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Tsiountsioura M, et al Detailed assessment of nutritional status and eating patterns in children with gastrointestinal diseases attending an outpatients clinic and contemporary healthy controls. Eur J Clin Nutr. 2014;68(6):700–6.Google Scholar
  23. 23.
    Burisch J, et al Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe—an ECCO-EpiCom study. J Crohns Colitis. 2014;8(7):607–16.Google Scholar
  24. 24.
    Palmblad J, Gyllenhammar H. Effect of dietary lipids on immunity and inflammation. Review article. APMIS. 1988;96(7):571–83.PubMedCrossRefGoogle Scholar
  25. 25.
    Costea I et al. Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn’s disease. Gastroenterology. 2014;146(4):929–31.PubMedCrossRefGoogle Scholar
  26. 26.
    Laing B, Han DY, Ferguson LR. Candidate genes involved in beneficial or adverse responses to commonly eaten brassica vegetables in a New Zealand Crohn’s disease cohort. Nutrient. 2013;5(12):5046–64.CrossRefGoogle Scholar
  27. 27.
    Vind I et al. Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003–2005: a population-based study from the Danish Crohn colitis database. Am J Gastroenterol. 2006;101(6):1274–82.PubMedCrossRefGoogle Scholar
  28. 28.
    Benchimol EI et al. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut. 2009;58(11):1490–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Khalili H et al. Geographical variation and incidence of inflammatory bowel disease among US women. Gut. 2012;61(12):1686–92.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Wang TT et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010;285(4):2227–31.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Ooi JH et al. Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced colitis. J Nutr. 2013;143(10):1679–86.PubMedCrossRefGoogle Scholar
  32. 32.
    Baumgart M et al. Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. ISME J. 2007;1(5):403–18.PubMedCrossRefGoogle Scholar
  33. 33.
    Barnich N et al. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Clin Invest. 2007;117(6):1566–74.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Martinez-Medina M et al. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut. 2014;63(1):116–24.PubMedCrossRefGoogle Scholar
  35. 35.
    Leigh RJ, Turnberg LA. BCG vaccination and Crohn’s disease. Dig Dis Sci. 1980;25(12):972.PubMedCrossRefGoogle Scholar
  36. 36.
    Gilat T et al. Childhood factors in ulcerative colitis and Crohn’s disease. An international cooperative study. Scand J Gastroenterol. 1987;22(8):1009–24.PubMedCrossRefGoogle Scholar
  37. 37.
    Baron S et al. Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study. Gut. 2005;54(3):357–63.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Hansen TS et al. Environmental factors in inflammatory bowel disease: a case-control study based on a Danish inception cohort. J Crohn’s Colitis. 2011;5(6):577–84.CrossRefGoogle Scholar
  39. 39.
    Virta L et al. Association of repeated exposure to antibiotics with the development of pediatric Crohn’s disease—a nationwide, register-based Finnish case–control study. Am J Epidemiol. 2012;175(8):775–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Marchant A et al. Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guerin vaccination. J Immunol. 1999;163(4):2249–55.PubMedGoogle Scholar
  41. 41.
    Ennis FA et al. Primary induction of human CD8+ cytotoxic T lymphocytes and interferon-gamma-producing T cells after smallpox vaccination. J Infect Dis. 2002;185(11):1657–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Villumsen M et al. Risk of inflammatory bowel disease following Bacille Calmette-Guerin and smallpox vaccination: a population-based Danish case-cohort study. Inflamm Bowel Dis. 2013;19(8):1717–24.PubMedGoogle Scholar
  43. 43.
    Ng SC et al. Role of genetic and environmental factors in British twins with inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(4):725–36.PubMedCrossRefGoogle Scholar
  44. 44.
    Van Kruiningen HJ, Freda BJ. A clustering of Crohn’s disease in Mankato, Minnesota. Inflamm Bowel Dis. 2001;7(1):27–33.PubMedCrossRefGoogle Scholar
  45. 45.
    Pierce ES, Borowitz SM, Naser SA. The Broad Street pump revisited: dairy farms and an ongoing outbreak of inflammatory bowel disease in Forest, Virginia. Gut Pathog. 2011;3(1):20.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Pierce ES. Free-ranging Rocky Mountain bighorn sheep and an outbreak of inflammatory bowel disease along the Clark Fork River in Plains, Montana. Virulence. 2012;3(6):546–50.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Masclee GM et al. Is Clostridium difficile associated with relapse of inflammatory bowel disease? Results from a retrospective and prospective cohort study in the Netherlands. Inflamm Bowel Dis. 2013;19(10):2125–31.PubMedCrossRefGoogle Scholar
  48. 48.
    Ananthakrishnan AN et al. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann Intern Med. 2012;156(5):350–9.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Musumba C, Pritchard DM, Pirmohamed M. Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers. Aliment Pharmacol Ther. 2009;30(6):517–31.PubMedCrossRefGoogle Scholar
  50. 50.
    Jenkins AP et al. Do non-steroidal anti-inflammatory drugs increase colonic permeability? Gut. 1991;32(1):66–9.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Etminan M et al. Isotretinoin and risk for inflammatory bowel disease: a nested case-control study and meta-analysis of published and unpublished data. JAMA Dermatol. 2013;149(2):216–20.PubMedCrossRefGoogle Scholar
  52. 52.
    Looijer-van Langen M et al. Estrogen receptor-beta signaling modulates epithelial barrier function. Am J Physiol Gastrointest Liver Physiol. 2011;300(4):G621–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Khalili H et al. Hormone therapy increases risk of ulcerative colitis but not Crohn’s disease. Gastroenterology. 2012;143(5):1199–206.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Khalili H et al. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut. 2013;62(8):1153–9.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Higuchi LM et al. A prospective study of cigarette smoking and the risk of inflammatory bowel disease in women. Am J Gastroenterol. 2012;107(9):1399–406.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Biedermann L et al. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PLoS One. 2013;8(3):e59260.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Verschuere S et al. Cigarette smoke and the terminal ileum: increased autophagy in murine follicle-associated epithelium and Peyer’s patches. Histochem Cell Biol. 2012;137(3):293–301.PubMedCrossRefGoogle Scholar
  58. 58.
    He C et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 2012;481(7382):511–5.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Khalili H et al. Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses’ Health Study cohorts. BMJ. 2013;347:f6633.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Lange T, Dimitrov S, Born J. Effects of sleep and circadian rhythm on the human immune system. Ann N Y Acad Sci. 2010;1193:48–59.PubMedCrossRefGoogle Scholar
  61. 61.
    Uthgenannt D et al. Effects of sleep on the production of cytokines in humans. Psychosom Med. 1995;57(2):97–104.PubMedCrossRefGoogle Scholar
  62. 62.
    Swanson GR, Burgess HJ, Keshavarzian A. Sleep disturbances and inflammatory bowel disease: a potential trigger for disease flare? Expert Rev Clin Immunol. 2011;7(1):29–36.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Ranjbaran Z et al. The relevance of sleep abnormalities to chronic inflammatory conditions. Inflamm Res. 2007;56(2):51–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Opp MR. Cytokines and sleep. Sleep Med Rev. 2005;9(5):355–64.PubMedCrossRefGoogle Scholar
  65. 65.
    Ananthakrishnan AN et al. Sleep disturbance and risk of active disease in patients with Crohn’s disease and ulcerative colitis. Clin Gastroenterol Hepatol. 2013;11(8):965–71.PubMedCrossRefGoogle Scholar
  66. 66.
    Ali T et al. Assessment of the relationship between quality of sleep and disease activity in inflammatory bowel disease patients. Inflamm Bowel Dis. 2013;19(11):2440–3.PubMedCrossRefGoogle Scholar
  67. 67.
    Mawdsley JE, Rampton DS. The role of psychological stress in inflammatory bowel disease. Neuroimmunomodulation. 2006;13(5–6):327–36.PubMedCrossRefGoogle Scholar
  68. 68.
    Rampton DS. The influence of stress on the development and severity of immune-mediated diseases. J Rheumatol Suppl. 2011;88:43–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Ananthakrishnan AN et al. Association between depressive symptoms and incidence of Crohn’s disease and ulcerative colitis: results from the Nurses’ Health Study. Clin Gastroenterol Hepatol. 2013;11(1):57–62.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Langhorst J et al. Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study. Inflamm Bowel Dis. 2013;19(11):2380–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Vanuytsel T, et al Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut. 2014;63(8):1293–9.Google Scholar
  72. 72.
    Martin Sanchez F, et al, Exposome informatics: considerations for the design of future biomedical research information systems. J Am Med Inform Assoc. 2014;21(3):386–90.Google Scholar
  73. 73.
    Tringe SG, Rubin EM. Metagenomics: DNA sequencing of environmental samples. Nat Rev Genet. 2005;6(11):805–14.PubMedCrossRefGoogle Scholar
  74. 74.
    Gerber GK, Onderdonk AB, Bry L. Inferring dynamic signatures of microbes in complex host ecosystems. PLoS Comput Biol. 2012;8(8):e1002624.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Nes AA, et al Web-based, self-management enhancing interventions with e-diaries and personalized feedback for persons with chronic illness: a tale of three studies. Patient Educ Couns. 2013;93(3):451–8.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.BWH Crohn’s and Colitis CenterBrigham and Women’s HospitalBostonUSA

Personalised recommendations