Linking lifestyle with microbiota and risk of chronic inflammatory disorders

  • Fergus Shanahan
Part of the Progress in Inflammation Research book series (PIR)


The inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, are among several immune-mediated disorders that consistently increase in incidence and prevalence when a society undergoes transition from ‘developing’ to ‘developed’ status. The impact of a changing lifestyle and environment associated with modernisation is greatest during early life. The mechanism may involve an alteration in composition or metabolic activity of the commensal microbiota colonising the host during early life. Since the commensal microbiota influences immunologic maturation and shapes the function of the developing immune system, disturbances in microbial biodiversity may contribute to individual variations in immunologic behaviour during and after childhood. Thus, an environmental influence on the commensal microbiota may underpin much of the changing epidemiology common to several immune-mediated chronic inflammatory disorders.


Inflammatory Bowel Disease Ulcerative Colitis Crohn Disease Mycobacterium Avium Subspecies Paratuberculosis Chronic Inflammatory Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Skrabenek P (1999) Risk factor epidemiology: Science or non-science? In: False Premises False Promises. Taragon Press, Whithorn, 153–163Google Scholar
  2. 2.
    Bernstein CN, Shanahan F (2008) Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut 57: 1185–91CrossRefPubMedGoogle Scholar
  3. 3.
    Probert CS, Jayanthi V, Pinder D, Wicks AC, Mayberry JF (1992) Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire. Gut 33: 687–93CrossRefPubMedGoogle Scholar
  4. 4.
    Pinsk V, Lemberg DA, Grewal K, Barker CC, Schreiber RA, Jacobson K (2007) Inflammatory bowel disease in the South Asian pediatric population of British Columbia. Am J Gastroenterol 102: 1077–83CrossRefPubMedGoogle Scholar
  5. 5.
    Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347: 911–20CrossRefPubMedGoogle Scholar
  6. 6.
    Cho JH (2008) The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 8: 458–66CrossRefPubMedGoogle Scholar
  7. 7.
    Mathew CG (2008) New links to the pathogenesis of Crohn disease provided by genome-wide association scans. Nat Rev Genet 9: 9–14CrossRefPubMedGoogle Scholar
  8. 8.
    Marchesi J, Shanahan F (2007) The normal intestinal microbiota. Curr Opin Infect Dis 20: 508–13CrossRefPubMedGoogle Scholar
  9. 9.
    Kitano H, Oda K (2006) Robustness trade-offs and host-microbial symbiosis in the immune system. Molecular Systems Biology 2: 2006.0022CrossRefPubMedGoogle Scholar
  10. 10.
    Cebra JJ (1999) Influences of microbiota on intestinal immune system development. Am J Clin Nutr 69: 1046S–1051SPubMedGoogle Scholar
  11. 11.
    O’Hara AM, Shanahan F (2006) The gut flora as a forgotten organ. EMBO Rep 7: 688–93CrossRefPubMedGoogle Scholar
  12. 12.
    Artis D (2008) Epithelial cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nature Rev Immunol 8: 411–420CrossRefGoogle Scholar
  13. 13.
    Coombes JL, Powrie F (2008) Dendritic cells in intestinal immune regulation. Nature Rev Immunol 8: 435–446CrossRefGoogle Scholar
  14. 14.
    Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122: 107–18CrossRefPubMedGoogle Scholar
  15. 15.
    Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453: 620–625CrossRefPubMedGoogle Scholar
  16. 16.
    Bouskra D, Brézillon C, Bérard M, Werts C, Varona R, Boneca IG, Eberl G (2008) Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456: 507–510CrossRefPubMedGoogle Scholar
  17. 17.
    Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118: 229–41CrossRefPubMedGoogle Scholar
  18. 18.
    Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449: 818–826CrossRefGoogle Scholar
  19. 19.
    Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2: 361–367CrossRefPubMedGoogle Scholar
  20. 20.
    Macpherson AJ, Uhr T (2004) Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303: 1662–1665CrossRefPubMedGoogle Scholar
  21. 21.
    Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V, Rao AS, Madara JL (2000) Prokaryotic regulation of epithelial responses by inhibition of Ikappa B-alpha ubiquitination. Science 289: 1560–1563CrossRefPubMedGoogle Scholar
  22. 22.
    Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG, Pettersoon S, Conway S (2004) Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol 5: 104–112CrossRefPubMedGoogle Scholar
  23. 23.
    Petrof EO, Kojima K, Ropeleski MJ, Musch MW, Tao Y, De Simone C, Chang EB (2004) Probiotics inhibit nuclear factor-kappaB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition. Gastroenterology 127: 1474–1487CrossRefPubMedGoogle Scholar
  24. 24.
    Rimoldi M, Chieppa M, Salucci V, Avogadri F, Sonzogni A, Sampietro GM, Nespoli A, Viale G, Allavena P, Rescigno M (2005) Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 6: 507–514CrossRefPubMedGoogle Scholar
  25. 25.
    Zaph C, Troy AE, Taylor BC, Berman-Booty LD, Guild KJ, Du Y, Yost EA, Gruber AD, May MJ, Greten FR, Eckmann L, Karin M, Artis D (2007) Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis. Nature 446: 552–6CrossRefPubMedGoogle Scholar
  26. 26.
    Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Huth M, Nikolaev A, Neufert C, Madison B, Gumucio D, Neurath MF, Pasparakis M (2007) Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446: 557–61CrossRefPubMedGoogle Scholar
  27. 27.
    Hughes DT, Sperandio V (2008) Inter-kingdom signaling: communication between bacteria and their hosts. Nat Rev Microbiol 6: 111–120CrossRefPubMedGoogle Scholar
  28. 28.
    Ryu JH, Kim SH, Lee HY, Bai JY, Nam YD, Bae JW, Lee DG, Shin SC, Ha EM, Lee WJ (2008) Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319: 777–82CrossRefPubMedGoogle Scholar
  29. 29.
    Suzuki K, Meek B, Doi Y, Muramatsu M, Chiba T, Honjo T, Fagarasan S (2004) Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc Natl Acad Sci USA 101: 1981–6CrossRefPubMedGoogle Scholar
  30. 30.
    Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131: 33–45CrossRefPubMedGoogle Scholar
  31. 31.
    Sartor RB (2008) Microbial influences in inflammatory bowel diseases. Gastroenterology 134: 577–94CrossRefPubMedGoogle Scholar
  32. 32.
    Murch SH (2001) Toll of allergy reduced by probiotics. Lancet 357: 1057–1059CrossRefPubMedGoogle Scholar
  33. 33.
    Rhodes JM (2007) The role of Escherichia coli in inflammatory bowel disease. Gut 56: 610–2CrossRefPubMedGoogle Scholar
  34. 34.
    Feller M, Huwiler K, Stephan R, Altpeter E, Shang A, Furrer H, Pfyffer GE, Jemmi T, Baumgartner A, Egger M (2007) Mycobacterium avium subspecies paratuberculosis and Crohn’s disease: a systematic review and meta-analysis. Lancet Infect Dis 7: 607–13CrossRefPubMedGoogle Scholar
  35. 35.
    Peterson DA, Frank DN, Pace NR, Gordon JI (2008) Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe 3: 417–27CrossRefPubMedGoogle Scholar
  36. 36.
    Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G et al (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA 105: 16731–6CrossRefPubMedGoogle Scholar
  37. 37.
    Ivanov II, Frutos R de L, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, Finlay BB, Littman DR (2008) Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4: 337–49CrossRefPubMedGoogle Scholar
  38. 38.
    DiBaise JK, Zhang H, Crowell MD, Krajmalnik-Brown R, Decker GA, Rittmann BE (2008) Gut microbiota and its possible relationship with obesity. Mayo Clin Proc 83: 460–9CrossRefPubMedGoogle Scholar
  39. 39.
    Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV (2008) Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455: 1109–13CrossRefPubMedGoogle Scholar
  40. 40.
    Flint HJ, Duncan SH, Scott KP, Louis P (2007) Interactions and competition within the microbial community of the human colon: links between diet and health. Environ Microbiol 9: 1101–11CrossRefPubMedGoogle Scholar
  41. 41.
    Shoda R, Matsueda K, Yamato S, Umeda N (1996) Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 63: 741–5PubMedGoogle Scholar
  42. 42.
    Shanahan F, Kiely B (2007) The gut microbiota and disease — an inner repository for drug discovery. Drug Discov Today: Ther Strategies 4: 195–200CrossRefGoogle Scholar
  43. 43.
    Sartor RB (2008) Therapeutic correction of bacterial dysbiosis discovered by molecular techniques. Proc Natl Acad Sci USA 105: 16413–4CrossRefPubMedGoogle Scholar
  44. 44.
    Mitsuyama K, Sata M (2008) Gut microflora: a new target for therapeutic approaches in inflammatory bowel disease. Expert Opin Ther Targets 12: 301–12CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2009

Authors and Affiliations

  • Fergus Shanahan
    • 1
  1. 1.Department of Medicine, Alimentary Pharmabiotic Centre, University College CorkNational University of IrelandCorkIreland

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