Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

IBD across the age spectrum—is it the same disease?

Nature Reviews Gastroenterology & Hepatology volume 11, pages 88–98 (2014)Cite this article

Subjects

Key Points

  • Up to 25% of IBD cases develop during childhood or adolescence, whereas 10–15% of patients with IBD will receive their diagnosis >60 years of age

  • The Crohn's disease:ulcerative colitis ratio is higher in paediatric-onset than in adult-onset and elderly-onset age groups

  • Very-early-onset and elderly-onset Crohn's disease are characterized by the predominance of pure colonic disease, whereas in older children and adults, ileocolonic disease is more prevalent; in ulcerative colitis, an extensive location is more prevalent in early-onset than in later-onset disease

  • In Crohn's disease, disease extension occurs more frequently in paediatric-onset disease compared with adult and elderly age groups; complicated disease behaviour is more prevalent in early-onset than in late-onset Crohn's disease

  • Paediatric-onset ulcerative colitis is characterized by widespread location at diagnosis and a high rate of disease extension compared with late-onset disease

  • Disease heterogeneity, according to age of onset, points to differences in the respective contribution of biological networks in the aetiology, phenotype and natural history of IBD across the age spectrum

Abstract

IBD is a chronic disorder with disease onset ranging from early childhood to beyond the sixth decade of life. The factors that determine the age of onset currently remain unexplained. Is timing of occurrence a random event or is it indicative of different pathophysiological pathways leading to different phenotypes across the age spectrum? Over the past decade, several studies have suggested that the characteristics and natural history of IBD seem to be different according to age of onset. This heterogeneity suggests that the respective contributions of genetics, host immune system and environment to the aetiology and phenotype of Crohn's disease and ulcerative colitis are different across ages. Critical reviews that focus on differences characterizing IBD between age groups are scarce. Therefore, this Review updates the knowledge of the differences in epidemiology, clinical characteristics, and natural history of paediatric, adult and elderly-onset IBD. In addition, potential differences in host–gene–microbial interactions according to age are highlighted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Comparison of evolution of Crohn's disease behaviour between elderly-onset patients (n = 367) and paediatric-onset patients (n = 689) obtained from the EPIMAD registry.
Figure 2: Differences in the respective contribution of biological networks according to age of onset in IBD.

Similar content being viewed by others

References

  1. Virgin, H. W. & Todd, J. A. Metagenomics and personalized medicine. Cell 147, 44–56 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Gower-Rousseau, C. et al. Epidemiology of inflammatory bowel diseases: New insights from a French population-based registry (EPIMAD). Dig. Liv. Dis. 45, 89–94 (2013).

    Google Scholar 

  3. Charpentier, C. et al. Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study. Gut http://dx.doi.org/10.1136/gutjnl-2012-303864 (2013).

  4. Cosnes, J., Gower-Rousseau, C., Seksik, P. & Cortot, A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 140, 1785–1794 (2011).

    PubMed  Google Scholar 

  5. Molodecky, N. A. et al. Increasing incidence and prevalence of the inflammatory bowel disease with time, based on systematic review. Gastroenterology 142, 46–54 (2012).

    PubMed  Google Scholar 

  6. Kelsen, J. & Baldassano, R. N. Inflammatory bowel disease: the difference between children and adults. Inflamm. Bowel Dis. 14 (Suppl. 2), S9–S11 (2008).

    PubMed  Google Scholar 

  7. Travis, S. Is IBD different in the elderly? Inflamm. Bowel Dis. 14 (Suppl. 2), S12–S13 (2008).

    PubMed  Google Scholar 

  8. Bernstein, C. N. et al. The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am. J. Gastroenterol. 101, 1559–1568 (2006).

    PubMed  Google Scholar 

  9. Loftus, E. V. Jr et al. Crohn's disease in Olmsted County, Minnesota, 1940–1993: incidence, prevalence, and survival. Gastroenterology 114, 1161–1168 (1998).

    PubMed  Google Scholar 

  10. Loftus, E. V. Jr et al. Ulcerative colitis in Olmsted County, Minnesota, 1940–1993: incidence, prevalence, and survival. Gut 46, 336–343 (2000).

    PubMed  PubMed Central  Google Scholar 

  11. Van Limbergen, J. et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology 135, 1114–1122 (2008).

    PubMed  Google Scholar 

  12. Kariyawasam, V. C. et al. Natural history of elderly onset inflammatory bowel disease—Sydney IBD cohort (1942–2012). Gastroenterology 144 (Suppl. 1), Mo1314 (2013).

    Google Scholar 

  13. Mamula, P. et al. Inflammatory bowel disease in children 5 years of age and younger. Am. J. Gastroenterol. 97, 2005–2010 (2002).

    PubMed  Google Scholar 

  14. Gupta, N. et al. Gender differences in presentation and course of disease in pediatric patients with Crohn disease. Pediatrics 120, 1418–1425 (2007).

    Google Scholar 

  15. Shivananda, S. et al. Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). Gut 39, 690–697 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Auvin, S. et al. Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988–1999). J. Pediatr. Gastroenterol. Nutr. 41, 49–55 (2005).

    PubMed  Google Scholar 

  17. Ostman, J. et al. Gender differences and temporal variation in the incidence of type one diabetes: results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983–2002. J. Intern. Med. 263, 386–394 (2008).

    CAS  PubMed  Google Scholar 

  18. Guariso, G. et al. Inflammatory bowel disease developing in paediatric and adult age. J. Pediatr. Gastroenterol. Nutr. 51, 698–707 (2010).

    PubMed  Google Scholar 

  19. Turunen, P. et al. Incidence of inflammatory bowel disease in Finnish children, 1987–2003. Inflamm. Bowel Dis. 12, 677–683 (2006).

    PubMed  Google Scholar 

  20. Henderson, P. et al. Rising incidence of pediatric inflammatory bowel disease in Scotland. Inflamm. Bowel Dis. 18, 999–1005 (2012).

    PubMed  Google Scholar 

  21. Hope, B. et al. Rapid rise in incidence of Irish paediatric inflammatory bowel disease. Arch. Dis. Child. 97, 590–594 (2012).

    CAS  PubMed  Google Scholar 

  22. Jakobsen, C. et al. Pediatric inflammatory bowel disease: increasing incidence, decreasing surgery rate, and compromised nutritional status: a prospective population-based cohort study 2007–2009. Inflamm. Bowel Dis. 17, 2541–2550 (2011).

    PubMed  Google Scholar 

  23. Benchimol, E. I. et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm. Bowel Dis. 17, 423–439 (2011).

    PubMed  Google Scholar 

  24. Chouraki, V. et al. The changing pattern of Crohn's disease incidence in northern France: a continuing increase in the 10- to 19-year-old age bracket (1988–2007). Aliment. Pharmacol. Ther. 33, 1133–1142 (2011).

    CAS  PubMed  Google Scholar 

  25. Economou, M. et al. Crohn's disease incidence evolution in North-western Greece is not associated with alteration of NOD2/CARD15 variants. World J. Gastroenterol. 13, 5116–5120 (2007).

    PubMed  PubMed Central  Google Scholar 

  26. Molinié, F. et al. Opposite evolution in incidence of Crohn's disease and ulcerative colitis in Northern France (1988–1999). Gut 53, 843–848 (2004).

    PubMed  PubMed Central  Google Scholar 

  27. Vernier-Massouille, G. et al. Natural history of pediatric Crohn's disease: a population-based cohort study. Gastroenterology 135, 1106–1113 (2008).

    PubMed  Google Scholar 

  28. Benchimol, E. I. et al. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut 58, 1490–1497 (2009).

    CAS  PubMed  Google Scholar 

  29. Malaty, H. M., Fan, X., Opekun, A. R., Thibodeaux, C. & Ferry, G. D. Rising incidence of inflammatory bowel disease among children: a 12-year study. J. Pediatr. Gastroenterol. Nutr. 50, 27–31 (2010).

    PubMed  Google Scholar 

  30. Armitage, E., Drummond, H. E., Wilson, D. C. & Ghosh, S. Increasing incidence of both juvenile-onset Crohn's disease and ulcerative colitis in Scotland. Eur. J. Gastroenterol. Hepatol. 13, 1439–1447 (2001).

    CAS  PubMed  Google Scholar 

  31. Braegger, C. P. et al. Epidemiology of inflammatory bowel disease: is there a shift towards onset at a younger age? J. Pediatr. Gastroenterol. Nutr. 53, 141–144 (2011).

    PubMed  Google Scholar 

  32. Burisch, J. et al. East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort. Gut http://dx.doi.org/10.1136/gutjnl-2013-304636.

  33. Bernstein, C. N., Blanchard, J. F., Rawsthorne, P. & Wajda, A. Epidemiology of Crohn's disease and ulcerative colitis in a central Canadian province: a population-based study. Am. J. Epidemiol. 149, 916–924 (1999).

    CAS  PubMed  Google Scholar 

  34. Piront, P., Louis, E., Latour, P., Plomteux, O. & Belaiche, J. Epidemiology of inflammatory bowel diseases in the elderly in the province of Liège. Gastroenterol. Clin. Biol. 26, 157–161 (2002).

    PubMed  Google Scholar 

  35. Heresbach, D. et al. Crohn's disease in the over-60 age group: a population based study. Eur. J. Gastroenterol. Hepatol. 16, 657–664 (2004).

    PubMed  Google Scholar 

  36. Loftus, C. G. et al. Update on the incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota, 1940–2000. Inflamm. Bowel Dis. 13, 254–261 (2007).

    PubMed  Google Scholar 

  37. Heyman, M. B. et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J. Pediatr. 146, 35–40 (2005).

    PubMed  Google Scholar 

  38. Paul, T. et al. Distinct phenotype of early childhood inflammatory bowel disease. J. Clin. Gastroenterol. 40, 583–586 (2006).

    PubMed  Google Scholar 

  39. Langholz, E., Munkholm, P., Krasilnikoff, P. A. & Binder, V. Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort. Scand. J. Gastroenterol. 32, 139–147 (1997).

    CAS  PubMed  Google Scholar 

  40. Freeman, H. J. Comparison of longstanding pediatric-onset and adult-onset Crohn's disease. J. Pediatr. Gastroenterol. Nutr. 39, 183–186 (2004).

    PubMed  Google Scholar 

  41. Müller, K. E. et al. Incidence, Paris classification and follow-up in a nationwide, incident cohort of pediatric patients with inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr. 57, 576–582 (2013).

    PubMed  Google Scholar 

  42. Kugathasan, S. et al. Wisconsin Pediatric Inflammatory Bowel Disease Alliance. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J. Pediatr. 143, 525–531 (2003).

    PubMed  Google Scholar 

  43. Sauer, C. G. & Kugathasan, S. Pediatric inflammatory bowel disease: highlighting pediatric differences in IBD. Med. Clin. North Am. 94, 35–52 (2010).

    CAS  PubMed  Google Scholar 

  44. Juneja, M. et al. Geriatric inflammatory bowel disease: phenotypic presentation, treatment patterns, nutritional status, outcomes, and comorbidity. Dig. Dis. Sci. 57, 2408–2415 (2012).

    PubMed  Google Scholar 

  45. Lakatos, P. L. et al. IBD in the elderly population: results from a population-based study in Western Hungary, 1977–2008. J. Crohns Colitis 5, 5–13 (2011).

    PubMed  Google Scholar 

  46. Harper, P. C., McAuliffe, T. & Beeken, W. L. Crohn's disease in the elderly. A statistical comparison with younger patients matched for sex and duration of disease. Arch. Intern. Med. 146, 753–755 (1986).

    CAS  PubMed  Google Scholar 

  47. Riegler, G. et al. Age-related clinical severity at diagnosis in 1705 patients with ulcerative colitis: a study by GISC (Italian Colon-Rectum Study Group). Dig. Dis. Sci. 45, 462–465 (2000).

    CAS  PubMed  Google Scholar 

  48. Zimmerman, J., Gavish, D. & Rachmilewitz, D. Early and late onset ulcerative colitis: distinct clinical features. J. Clin. Gastroenterol. 7, 492–498 (1985).

    CAS  PubMed  Google Scholar 

  49. Levine, A. et al. Atypical disease phenotypes in pediatric ulcerative colitis: 5-year analyses of the EUROKIDS Registry. Inflamm. Bowel Dis. 19, 370–377 (2013).

    PubMed  Google Scholar 

  50. Griffiths, A. M., Nguyen, P., Smith, C., MacMillan, J. H. & Sherman, P. M. Growth and clinical course of children with Crohn's disease. Gut 34, 939–943 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Hildebrand, H., Karlberg, J. & Kristiansson, B. Longitudinal growth in children and adolescents with inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr. 18, 165–173 (1994).

    CAS  PubMed  Google Scholar 

  52. Markowitz, J., Grancher, K., Rosa, J., Aiges, H. & Daum, F. Growth failure in pediatric inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr. 16, 373–380 (1993).

    CAS  PubMed  Google Scholar 

  53. Pigneur, B. et al. Natural history of Crohn's disease: comparison between childhood- and adult-onset disease. Inflamm. Bowel Dis. 16, 953–961 (2010).

    PubMed  Google Scholar 

  54. Lee, J. J. et al. Final adult height of children with inflammatory bowel disease is predicted by parental height and patient minimum height Z-score. Inflamm. Bowel Dis. 16, 1669–1677 (2010).

    PubMed  Google Scholar 

  55. Wagtmans, M. J., Verspaget, H. W., Lamers, C. B. & van Hogezand, R. A. Crohn's disease in the elderly: a comparison with younger adults. J. Clin. Gastroenterol. 27, 129–133 (1998).

    CAS  PubMed  Google Scholar 

  56. Israeli, E., Ryan, J. D., Shafer, L. A. & Bernstein, C. N. Younger age at diagnosis is associated with panenteric, but not more aggressive, Crohn's disease. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/j.cgh.2013.06.027.

  57. Freeman, H. J. Long-term prognosis of early-onset Crohn's disease diagnosed in childhood or adolescence. Can. J. Gastroenterol. 18, 661–665 (2004).

    PubMed  Google Scholar 

  58. Cosnes, J. et al. Long-term evolution of disease behavior of Crohn's disease. Inflamm. Bowel Dis. 8, 244–250 (2002).

    PubMed  Google Scholar 

  59. Baldassano, R. N. et al. Pediatric Crohn's disease: risk factors for postoperative recurrence. Am. J. Gastroenterol. 96, 2169–2176 (2001).

    CAS  PubMed  Google Scholar 

  60. Besnard, M. et al. Postoperative outcome of Crohn's disease in 30 children. Gut 43, 634–638 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. El-Baba, M., Lin, C. H., Klein, M. & Tolia, V. Outcome after surgical intervention in children with chronic inflammatory bowel disease. Am. Surg. 62, 1014–1017 (1996).

    CAS  PubMed  Google Scholar 

  62. Griffiths, A. M., Wesson, D. E., Shandling, B., Corey, M. & Sherman, P. M. Factors influencing postoperative recurrence of Crohn's disease in childhood. Gut 32, 491–495 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Sedgwick, D. M., Barton, J. R., Hamer-Hodges, D. W., Nixon, S. J. & Ferguson, A. Population-based study of surgery in juvenile onset Crohn's disease. Br. J. Surg. 78, 171–175 (1991).

    CAS  PubMed  Google Scholar 

  64. Boualit, M. et al. Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: a population-based study. Inflamm. Bowel Dis. 19, 7–14 (2013).

    PubMed  Google Scholar 

  65. Gower-Rousseau, C. et al. The natural history of pediatric ulcerative colitis: a population-based cohort study. Am. J. Gastroenterol. 104, 2080–2088 (2009).

    PubMed  Google Scholar 

  66. Hyams, J. S. et al. Clinical outcome of ulcerative colitis in children. J. Pediatr. 129, 81–88 (1996).

    CAS  PubMed  Google Scholar 

  67. Malaty, H. M., Abraham, B. P., Mehta, S., Garnett, E. A. & Ferry, G. D. The natural history of ulcerative colitis in a pediatric population: a follow-up population-based cohort study. Clin. Exp. Gastroenterol. 6, 77–83 (2013).

    PubMed  PubMed Central  Google Scholar 

  68. Magro, F. et al. Review of the disease course among adult ulcerative colitis population-based longitudinal cohorts. Inflamm. Bowel Dis. 18, 573–583 (2012).

    PubMed  Google Scholar 

  69. Polito, J. M. et al. Crohn's disease: influence of age at diagnosis on site and clinical type of disease. Gastroenterology 111, 580–586 (1996).

    PubMed  Google Scholar 

  70. Carbonnel, F., Macaigne, G., Beaugerie, L., Gendre, J. P. & Cosnes, J. Crohn's disease severity in familial and sporadic cases. Gut 44, 91–95 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Jostins, L. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491, 119–124 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Brant, S. R. Promises, delivery, and challenges of inflammatory bowel disease risk gene discovery. Clin. Gastroenterol. Hepatol. 11, 22–26 (2013).

    PubMed  Google Scholar 

  73. Cho, J. H. & Brant, S. R. Recent insights into the genetics of inflammatory bowel disease. Gastroenterology 140, 1704–1712 (2011).

    CAS  PubMed  Google Scholar 

  74. Lesage, S. et al. CARD15/NOD2 mutational analysis and genotype–phenotype correlation in 612 patients with inflammatory bowel disease. Am. J. Hum. Genet. 70, 845–857 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Cho, J. H. Advances in the genetics of inflammatory bowel disease. Curr. Gastroenterol. Rep. 6, 467–473 (2004).

    PubMed  Google Scholar 

  76. Weiss, B. et al. NOD2/CARD15 mutation analysis and genotype–phenotype correlation in Jewish pediatric patients compared with adults with Crohn's disease. J. Pediatr. 145, 208–212 (2004).

    CAS  PubMed  Google Scholar 

  77. Kugathasan, S. et al. Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. Nat. Genet. 40, 1211–1215 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Imielinski, M. et al. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat. Genet. 41, 1335–1340 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. de Ridder, L. et al. Genetic susceptibility has a more important role in pediatric-onset Crohn's disease than in adult-onset Crohn's disease. Inflamm. Bowel Dis. 13, 1083–1092 (2007).

    PubMed  Google Scholar 

  80. Glocker, E. O. et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med. 361, 2033–2045 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Glocker, E. O. et al. Infant colitis—it's in the genes. Lancet 376, 1272 (2010).

    PubMed  Google Scholar 

  82. Worthey, E. A. et al. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet. Med. 13, 255–262 (2011).

    PubMed  Google Scholar 

  83. Blaydon, D. C. et al. Inflammatory skin and bowel disease linked to ADAM17 deletion. N. Engl. J. Med. 365, 1502–1508 (2011).

    CAS  PubMed  Google Scholar 

  84. Muise, A. M. et al. NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2. Gut 61, 1028–1035 (2012).

    CAS  PubMed  Google Scholar 

  85. Matute, J. D. et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood 114, 3309–3315 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Kotlarz, D. et al. Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy. Gastroenterology 143, 347–355 (2012).

    CAS  PubMed  Google Scholar 

  87. Moran, C. J. et al. IL-10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm. Bowel Dis. 19, 115–123 (2013).

    PubMed  Google Scholar 

  88. Odes, H. S. et al. Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis. Dig. Dis. Sci. 46, 1717–1721 (2001).

    CAS  PubMed  Google Scholar 

  89. Bjarnason, I. et al. Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans. Gastroenterology 93, 480–489 (1987).

    CAS  PubMed  Google Scholar 

  90. Radford-Smith, G. L. et al. Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn's disease. Gut 51, 808–813 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Soon, I. S. et al. The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis. BMC Gastroenterol. 12, 51 (2012).

    PubMed  PubMed Central  Google Scholar 

  92. Baron, S. et al. Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study. Gut 54, 357–363 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Molodecky, N. A. & Kaplan, G. G. Environnemental risk factors for inflammatory bowel disease. Gastroenterol. Hepatol. 6, 339–346 (2010).

    Google Scholar 

  94. Ananthakrishnan, A. N. Environmental risk factors for inflammatory bowel disease. Gastroenterol. Hepatol. 9, 367–374 (2013).

    Google Scholar 

  95. Cosnes, J., Beaugerie, L., Carbonnel, F. & Gendre, J. P. Smoking cessation and the course of Crohn's disease: an intervention study. Gastroenterology 120, 1093–1099 (2001).

    CAS  PubMed  Google Scholar 

  96. Boyko, E. J., Perera, D. R., Koepsell, T. D., Keane, E. M. & Inui, T. S. Effects of cigarette smoking on the clinical course of ulcerative colitis. Scand. J. Gastroenterol. 23, 1147–1152 (1988).

    CAS  PubMed  Google Scholar 

  97. Lakatos, P. L. Environmental factors affecting inflammatory bowel disease: have we made progress? Dig. Dis. 27, 215–225 (2009).

    PubMed  Google Scholar 

  98. Klement, E. et al. Childhood hygiene is associated with the risk for inflammatory bowel disease: a population-based study. Am. J. Gastroenterol. 103, 1775–1782 (2008).

    PubMed  Google Scholar 

  99. Koloski, N. A., Bret, L. & Radford-Smith, G. Hygiene hypothesis in inflammatory bowel disease: a critical review of the literature. World J. Gastroenterol. 14, 165–173 (2008).

    PubMed  PubMed Central  Google Scholar 

  100. López-Serrano, P. et al. Environmental risk factors in inflammatory bowel diseases. Investigating the hygiene hypothesis: a Spanish case-control study. Scand. J. Gastroenterol. 45, 1464–1471 (2010).

    PubMed  Google Scholar 

  101. Askling, J., Grahnquist, L., Ekbom, A. & Finkel, Y. Incidence of paediatric Crohn's disease in Stockholm, Sweden. Lancet 354, 1179 (1999).

    CAS  PubMed  Google Scholar 

  102. Yao, T., Matsui, T. & Hiwatashi, N. Crohn's disease in Japan: diagnostic criteria and epidemiology. Dis. Colon Rectum. 43 (Suppl. 10), S85–S93 (2000).

    CAS  PubMed  Google Scholar 

  103. Williams, M. E. et al. Leukocytes of patients with Schistosoma mansoni respond with a Th2 pattern of cytokine production to mitogen or egg antigens but with a Th0 pattern to worm antigens. J. Infect. Dis. 170, 946–954 (1994).

    CAS  PubMed  Google Scholar 

  104. Satoguina, J. et al. Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). Microbes Infect. 4, 1291–1300 (2002).

    CAS  PubMed  Google Scholar 

  105. King, C. L. et al. Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity. J. Immunol. 156, 4715–4721 (1996).

    CAS  PubMed  Google Scholar 

  106. 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. Crohns Colitis 6, 324–329 (2012).

    PubMed  Google Scholar 

  107. Hildebrand, H., Malmborg, P., Askling, J., Ekbom, A. & Montgomery, S. M. Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease. Scand. J. Gastroenterol. 43, 961–966 (2008).

    CAS  PubMed  Google Scholar 

  108. Shaw, S. Y., Blanchard, J. F. & Bernstein, C. N. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J. Gastroenterol. 105, 2687–2692 (2010).

    PubMed  Google Scholar 

  109. Shaw, S. Y., Blanchard, J. F. & Bernstein, C. N. Association between the use of antibiotics and new diagnoses of Crohn's disease and ulcerative colitis. Am. J. Gastroenterol. 106, 2133–2142 (2011).

    PubMed  Google Scholar 

  110. Virta, L., Auvinen, A., Helenius, H., Huovinen, P. & Kolho, K. L. 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. 175, 775–784 (2012).

    PubMed  Google Scholar 

  111. Cornish, J. A. et al. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am. J. Gastroenterol. 103, 2394–2400 (2008).

    PubMed  Google Scholar 

  112. Khalili, H. et al. Hormone therapy increases risk of ulcerative colitis but not Crohn's disease. Gastroenterology 143, 1199–1206 (2012).

    CAS  PubMed  Google Scholar 

  113. Chan, S. S. et al. Aspirin in the aetiology of Crohn's disease and ulcerative colitis: a European prospective cohort study. Aliment. Pharmacol. Ther. 34, 649–655 (2011).

    CAS  PubMed  Google Scholar 

  114. Ananthakrishnan, A. N. et al. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann. Intern. Med. 156, 350–359 (2012).

    PubMed  PubMed Central  Google Scholar 

  115. Sellon, R. K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224–5231 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Wild, G. E. The role of antibiotics in the management of Crohn's disease. Inflamm. Bowel Dis. 10, 321–323 (2004).

    PubMed  Google Scholar 

  117. Rutgeerts, P. et al. Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet 338, 771–774 (1991).

    CAS  PubMed  Google Scholar 

  118. Rautava, S., Luoto, R., Salminen, S. & Isolauri, E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat. Rev. Gastroenterol. Hepatol. 9, 565–576 (2012).

    CAS  PubMed  Google Scholar 

  119. Mackie, R. I., Sghir, A. & Gaskins, H. R. Developmental microbial ecology of the neonatal gastrointestinal tract. Am. J. Clin. Nutr. 69, 1035S–1045S (1999).

    CAS  PubMed  Google Scholar 

  120. Guérin-Danan, C. et al. Pattern of metabolism and composition of the fecal microflora in infants 10 to 18 months old from day care centers. J. Pediatr. Gastroenterol. Nutr. 25, 281–289 (1997).

    PubMed  Google Scholar 

  121. Faith, J. J. et al. The long-term stability of the human gut microbiota. Science 341, 1237439 (2013).

    PubMed  PubMed Central  Google Scholar 

  122. Mitsuoka, T. Intestinal flora and aging. Nutr. Rev. 50, 438–446 (1992).

    CAS  PubMed  Google Scholar 

  123. Mitsuoka, T. & Hayakawa, K. The fecal flora in man. I. Composition of the fecal flora of various age groups [German]. Zentralbl. Bakteriol. Orig. A. 223, 333–342 (1973).

    CAS  PubMed  Google Scholar 

  124. Hopkins, M. J., Sharp, R. & Macfarlane, G. T. Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut 48, 198–205 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Gavini, F. et al. Differences in distribution of bifidobacterial and enterobacterial species in human faecal microflora of three different (children, adults, elderly) age groups. Microb. Ecol. Health Dis. 13, 40–45 (2001).

    Google Scholar 

  126. Saunier, K. & Doré, J. Gastrointestinal tract and the elderly: functional foods, gut microflora and healthy ageing. Dig. Liver Dis. 34 (Suppl. 2), S19–S24 (2002).

    PubMed  Google Scholar 

  127. Tamboli, C. P., Neut, C., Desreumaux, P. & Colombel, J. F. Dysbiosis in inflammatory bowel disease. Gut 53, 1–4 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Sartor, R. D. Microbial influences in inflammatory bowel diseases. Gastroenterology 134, 577–594 (2008).

    CAS  PubMed  Google Scholar 

  129. Cucchiara, S., Iebba, V., Conte, M. P. & Schippa, S. The microbiota in inflammatory bowel disease in different age groups. Dig. Dis. 27, 252–258 (2009).

    PubMed  Google Scholar 

  130. Glasser, A. L. et al. 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 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Conte, M. P. et al. Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. Gut 55, 1760–1767 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. De Cruz, P. et al. Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. Inflamm. Bowel Dis. 18, 372–390 (2012).

    PubMed  Google Scholar 

  133. Kim, S. C. et al. Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128, 891–906 (2005).

    CAS  PubMed  Google Scholar 

  134. Wakabayashi, A., Utsuyama, M., Hosoda, T., Sato, K. & Hirokawa, K. Differential age effect of oral administration of an antigen on antibody response: an induction of tolerance in young mice but enhancement of immune response in old mice. Mech. Ageing Dev. 109, 191–201 (1999).

    CAS  PubMed  Google Scholar 

  135. Kato, H. et al. Lack of oral tolerance in aging is due to sequential loss of Peyer's patch cell interactions. Int. Immunol. 15, 145–158 (2003).

    CAS  PubMed  Google Scholar 

  136. de Faria, A. M. et al. Aging affects oral tolerance induction but not its maintenance in mice. Mech. Ageing Dev. 102, 67–80 (1998).

    CAS  PubMed  Google Scholar 

  137. Fujihashi, K. & Kiyono, H. Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol. 30, 334–343 (2009).

    CAS  PubMed  Google Scholar 

  138. Yung, R. L. & Julius, A. Epigenetics, aging, and autoimmunity. Autoimmunity 41, 329–335 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Pawelec, G. (1999). Immunosenescence: impact in the young as well as the old? Mech. Ageing Dev. 108, 1–7 (1999).

    CAS  PubMed  Google Scholar 

  140. Linton, P. J. & Dorshkind, K. Age-related changes in lymphocyte development and function. Nat. Immunol. 5, 133–139 (2004).

    CAS  PubMed  Google Scholar 

  141. Lynch, H. E. et al. Thymic involution and immune reconstitution. Trends Immunol. 30, 366–373 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Min, H., Montecino-Rodriguez, E. & Dorshkind, K. Effects of aging on the common lymphoid progenitor to pro-B cell transition. J. Immunol. 176, 1007–1012 (2006).

    CAS  PubMed  Google Scholar 

  143. Alter-Wolf, S., Blomberg, B. B. & Riley, R. L. Deviation of the B cell pathway in senescent mice is associated with reduced surrogate light chain expression and altered immature B cell phenotype, and light chain expression. J. Immunol. 182, 138–147 (2009).

    CAS  PubMed  Google Scholar 

  144. Sudo, K., Ema, H., Morita, Y. & Nakauchi, H. Age-associated characteristics of murine hematopoietic stem cells. J. Exp. Med. 192, 1273–1280 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Min, H., Montecino-Rodriguez, E. & Dorshkind, K. Effects of aging on early B- and T-cell development. Immunol. Rev. 205, 7–17 (2005).

    CAS  PubMed  Google Scholar 

  146. Rossi, D. J. et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc. Natl Acad. Sci. USA 102, 9194–9199 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Pang, W. W. et al. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc. Natl Acad. Sci. USA 108, 20012–20017 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Challen, G. A., Boles, N. C., Chambers, S. M. & Goodell, M. A. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-β1. Cell Stem Cell 6, 265–278 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Stephan, R. P., Reilly, C. R. & Witte, P. L. Impaired ability of bone marrow stromal cells to support B-lymphopoiesis with age. Blood 91, 75–88 (1998).

    CAS  PubMed  Google Scholar 

  150. Labrie, J. E. 3rd, Sah, A. P., Allman, D. M., Cancro, M. P. & Gerstein, R. M. Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice. J. Exp. Med. 200, 411–423 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Naveiras, O. et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 460, 259–263 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Chinn, I. K., Blackburn, C. C., Manley, N. R. & Sempowski, G. D. Changes in primary lymphoid organs with aging. Semin. Immunol. 24, 309–320 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Dixit, V. D. Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence. Semin. Immunol. 24, 321–330 (2012).

    CAS  PubMed  Google Scholar 

  154. Taub, D. D., Murphy, W. J. & Longo, D. L. Rejuvenation of the aging thymus: growth hormone- mediated and ghrelin-mediated signaling pathways. Curr. Opin. Pharmacol. 10, 408–424 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Dorshkind, K. & Horseman, N. D. The roles of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormones in lymphocyte development and function: insights from genetic models of hormone and hormone receptor deficiency. Endocr. Rev. 21, 292–312 (2000).

    CAS  PubMed  Google Scholar 

  156. Nikolich-Žugich, J., Li, G., Uhrlaub, J. L., Renkema, K. R. & Smithey, M. J. Age-related changes in CD8 T cell homeostasis and immunity to infection. Semin. Immunol. 24, 356–364 (2012).

    PubMed  PubMed Central  Google Scholar 

  157. Li, G. et al. Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat. Med. 18, 1518–1524 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Haynes, L. & Lefebvre, J. S. Age-related deficiencies in antigen-specific CD4 T cell responses: lessons from mouse models. Aging Dis. 2, 374–381 (2011).

    PubMed  PubMed Central  Google Scholar 

  159. Shi, Y. et al. Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J. Immunol. 175, 3262–3267 (2005).

    CAS  PubMed  Google Scholar 

  160. Frasca, D. & Blomberg, B. B. Effects of aging on B cell function. Curr. Opin. Immunol. 21, 425–430 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Montecino-Rodriguez, E., Berent-Maoz, B. & Dorshkind, K. Causes, consequences, and reversal of immune system aging. J. Clin. Invest. 123, 958–965 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Gibson, K. L. et al. B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell 8, 18–25 (2009).

    CAS  PubMed  Google Scholar 

  163. Agrawal, A. et al. Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J. Immunol. 178, 6912–6922 (2007).

    CAS  PubMed  Google Scholar 

  164. Della Bella, S. et al. Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin. Immunol. 122, 220–228 (2007).

    CAS  PubMed  Google Scholar 

  165. Jing, Y. et al. Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum. Immunol. 70, 777–784 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Lung, T. L., Saurwein-Teissl, M., Parson, W., Schönitzer, D. & Grubeck-Loebenstein, B. Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine 18, 1606–1612 (2000).

    CAS  PubMed  Google Scholar 

  167. Panda, A. et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J. Immunol. 184, 2518–2527 (2010).

    CAS  PubMed  Google Scholar 

  168. Park, S., Kang, S., Min, K. H., Woo Hwang, K. & Min, H. Age-associated changes in microRNA expression in bone marrow derived dendritic cells. Immunol. Invest. 42, 179–190 (2013).

    CAS  PubMed  Google Scholar 

  169. Plowden, J., Renshaw-Hoelscher, M., Engleman, C., Katz, J. & Sambhara, S. Innate immunity in aging: impact on macrophage function. Aging Cell 3, 161–167 (2004).

    CAS  PubMed  Google Scholar 

  170. Fülöp, T. Jr, Fóris, G., Wórum, I. & Leövey, A. Age-dependent alterations of Fc γ receptor-mediated effector functions of human polymorphonuclear leucocytes. Clin. Exp. Immunol. 61, 425–432 (1985).

    PubMed  PubMed Central  Google Scholar 

  171. Butcher, S. K. et al. Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J. Leukoc. Biol. 70, 881–886 (2001).

    CAS  PubMed  Google Scholar 

  172. Kawanishi, H. & Kiely, J. Immune-related alterations in aged gut-associated lymphoid tissues in mice. Dig. Dis. Sci. 34, 175–184 (1989).

    CAS  PubMed  Google Scholar 

  173. Koga, T. et al. Evidence for early aging in the mucosal immune system. J. Immunol. 165, 5352–5359 (2000).

    CAS  PubMed  Google Scholar 

  174. McDonald, K. G., Leach, M. R., Huang, C., Wang, C. & Newberry, R. D. Aging impacts isolated lymphoid follicle development and function. Immun. Ageing 8, 1 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Schmucker, D. L., Daniels, C. K., Wang, R. K. & Smith, K. Mucosal immune response to cholera toxin in ageing rats. I. Antibody and antibody-containing cell response. Immunology 64, 691–695 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Thoreux, K., Owen, R. L. & Schmucker, D. L. Intestinal lymphocyte number, migration and antibody secretion in young and old rats. Immunology 101, 161–167 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Van Kruiningen, H. J., West, A. B., Freda, B. J. & Holmes, K. A. Distribution of Peyer's patches in the distal ileum. Inflamm. Bowel Dis. 8, 180–185 (2002).

    PubMed  Google Scholar 

  178. Van Kruiningen, H. J., Ganley, L. M. & Freda, B. J. The role of Peyer's patches in the age-related incidence of Crohn's disease. J. Clin. Gastroenterol. 25, 470–475 (1997).

    CAS  PubMed  Google Scholar 

  179. Dukes, C. & Bussey, H. J. R. The number of lymphoid follicles in the human large intestine. J. Pathol. Bact. 29, 111–116 (1926).

    Google Scholar 

  180. Targan, S. R. et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease. Gastroenterology 128, 2020–2028 (2005).

    CAS  PubMed  Google Scholar 

  181. Ferrante, M. et al. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut 56, 1394–1403 (2007).

    PubMed  PubMed Central  Google Scholar 

  182. Markowitz, J. et al. Age of diagnosis influences serologic responses in children with Crohn's disease: a possible clue to etiology? Inflamm. Bowel Dis. 15, 714–719 (2009).

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors appreciate the skilful assistance of Dr D. Sachar in reviewing our manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1069, New York, 10029, NY, USA

    Joannie Ruel, Darren Ruane, Saurabh Mehandru & Jean-Frédéric Colombel

  2. Gastroenterology Unit, Lille University Nord de France, CHU Lille, 2 Avenue Oscar Lambret, Lille, 59 000, France

    Corinne Gower-Rousseau

Authors
  1. Joannie Ruel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Darren Ruane
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saurabh Mehandru
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Corinne Gower-Rousseau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Frédéric Colombel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J. Ruel, S. Mehandru, and J.-F. Colombel contributed to all aspects of this manuscript. D. Ruane researched data for the article, contributed to discussion of content and writing the article. C. Gower-Rousseau contributed to the discussion of content and reviewing/editing the manuscript before submission.

Corresponding author

Correspondence to Jean-Frédéric Colombel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruel, J., Ruane, D., Mehandru, S. et al. IBD across the age spectrum—is it the same disease?. Nat Rev Gastroenterol Hepatol 11, 88–98 (2014). https://doi.org/10.1038/nrgastro.2013.240

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2013.240

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing