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Introduction: The changing microbial environment, Darwinian medicine and the hygiene hypothesis

  • Graham A. W. Rook
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Man has undergone rapid cultural and rechnological evolution, with little simultaneous geneticevolution. Thus our physiology is adapted to the microbial exposures that prevailed in the huntergatherer environment, rather than to the clean living conditions of the rich industrialised countries. There is increasing evidence that lack of exposure to organisms that were part of mammalian evolutionary history is leading to disordered regulation of the immune system, and hence to increases in several chronic inflammatory disorders. The concept began with the allergic disorders, but there are now good reasons for extending it to autoimmunity, inflammatory bowel disease, neuroinflammatory disorders, atherosclerosis, depression associated with raised inflammatory cytokines, and some cancers. We discuss these possibilities in the context of Darwinian medicine. This approach enables one to identify some of the organisms that are important for the ‘hygiene’ or ‘old friends’ hypothesis, and to point to their potential exploitation in novel prophylactics and treatments, with applications in several branches of medicine.

Keywords

Allergy Clin Immunol Intestinal Microbiota Allergic Disorder Chronic Inflammatory Disorder Hygiene Hypothesis 
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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References

  1. 1.
    Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347: 911–920PubMedCrossRefGoogle Scholar
  2. 2.
    Strachan DP (1989) Hay fever, hygiene, and household size. Brit Med J 299: 1259–1260.PubMedCrossRefGoogle Scholar
  3. 3.
    Strachan DP, Taylor EM, Carpenter RG (1996) Family structure, neonatal infection, and hay fever in adolescence. Arch Dis Child 74: 422–426PubMedCrossRefGoogle Scholar
  4. 4.
    Matricardi PM, Franzinelli F, Franco A, Caprio G, Murru F, Cioffi D, Ferrigno L, Palermo A, Ciccarelli N, Rosmini F (1998) Sibship size, birth order, and atopy in 11,371 Italian young men. J Allergy Clin Immunol 101: 439–444PubMedCrossRefGoogle Scholar
  5. 5.
    von Ehrenstein OS, von Mutius E, Illi S, Baumann L, Bohm O, von Kries R (2000) Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 30: 187–193CrossRefGoogle Scholar
  6. 6.
    Riedler J, Braun-Fahrlander C, Eder W, Schreuer M, Waser M, Maisch S, Carr D, Schierl R, Nowak D, von Mutius E (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358: 1129–1133PubMedCrossRefGoogle Scholar
  7. 7.
    Braun-Fahrlander C, Riedler J, Herz U, Eder W, Waser M, Grize L, Maisch S, Carr D, Gerlach F, Bufe A et al (2002) Environmental exposure to endotoxin and its relation to asthma in school-age children. N. Engl J Med 347: 869–877PubMedCrossRefGoogle Scholar
  8. 8.
    Yazdanbakhsh M, Kremsner PG, van Ree R (2002) Allergy, parasites, and the hygiene hypothesis. Science 296: 490–494PubMedCrossRefGoogle Scholar
  9. 9.
    Bjorksten B, Naaber P, Sepp E, Mikelsaar M (1999) The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 29: 342–346PubMedCrossRefGoogle Scholar
  10. 10.
    Shirakawa T, Enomoto T, Shimazu S, Hopkin JM (1996) The inverse association between tuberculin responses and atopic disorder. Science 275: 77–79CrossRefGoogle Scholar
  11. 11.
    Zuany-Amorim C, Swaicka E, Manlius C, Le Moine A, Brunet LR, Kemeny DM, Bowen G, Rook G, Walker C (2002) Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 8: 625–629PubMedCrossRefGoogle Scholar
  12. 12.
    Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122: 107–118PubMedCrossRefGoogle Scholar
  13. 13.
    Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA et al (2008) Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455: 1109–1113PubMedCrossRefGoogle Scholar
  14. 14.
    Matricardi PM, Rosmini F, Riondino S, Fortini M, Ferrigno L, Rapicetta M, Bonini S (2000) Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma; epidemiological study. Brit Med J 320: 412–417PubMedCrossRefGoogle Scholar
  15. 15.
    Matricardi PM, Rosmini F, Panetta V, Ferrigno L, Bonini S (2002) Hay fever and asthma in relation to markers of infection in the United States. J Allergy Clin Immunol 110: 381–387PubMedCrossRefGoogle Scholar
  16. 16.
    McIntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C, Cavalli-Sforza LL, Barsh GS, Hallmayer JF, Underhill PA, Risch NJ et al (2003) Immunology: hepatitis A virus link to atopic disease. Nature 425: 576PubMedCrossRefGoogle Scholar
  17. 17.
    Dobzhansky T (1964) Biology, molecular and organismic. American Zoologist 4: 443–452.PubMedGoogle Scholar
  18. 18.
    (Audiovisual presentations by multiple authors) edited by Nesse R (2007) Evolution and Medicine. Henry Stewart Talks http://www.hstalks.com/evomed/Google Scholar
  19. 19.
    Bowlby J (1971 (first published by Hogarth press in 1969)) Attachment and Loss, Volume 1: Attachment. Penguin, Harmondsworth, Middlesex, EnglandGoogle Scholar
  20. 20.
    Hawks J, Wang ET, Cochran GM, Harpending HC, Moyzis RK (2007) Recent acceleration of human adaptive evolution. Proc. Natl Acad Sci USA 104: 20753–20758PubMedCrossRefGoogle Scholar
  21. 21.
    Armelagos GJ, Harper KN (2005) Genomics at the origins of agriculture, Part Two; evolutionary anthropology. Evol Anthropol 14: 109–121CrossRefGoogle Scholar
  22. 22.
    Hoberg EP (2006) Phylogeny of Taenia: Species definitions and origins of human parasites. Parasitol Int 55 (Suppl): S23–30CrossRefGoogle Scholar
  23. 23.
    Wikoff WR, Anfora AT, Liu J, Schultz PG., Lesley SA, Peters EC, Siuzdak G (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 106: 3698–3703PubMedCrossRefGoogle Scholar
  24. 24.
    Chow J, Mazmanian SK (2009) Getting the bugs out of the immune system: do bacterial microbiota “fix” intestinal T cell responses? Cell Host Microbe, 5: 8–12PubMedCrossRefGoogle Scholar
  25. 25.
    Rook GA, Adams V, Hunt J, Palmer R, Martinelli R, Brunet LR (2004) Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. Springer Semin Immunopathol 25: 237–255PubMedCrossRefGoogle Scholar
  26. 26.
    de Mazancourt C, Loreau M, Dieckmann U (2005) Understanding mutualism when there is adaptation to the partner. J Ecology 93: 305–314CrossRefGoogle Scholar
  27. 27.
    Jeon KW (1972) Development of cellular dependence on infective organisms: micrurgical studies in amoebas. Science 176: 1122–1123PubMedCrossRefGoogle Scholar
  28. 28.
    Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453: 620–625PubMedCrossRefGoogle Scholar
  29. 29.
    Cochran GM, Ewald PW, Cochran KD (2000) Infectious causation of disease: an evolutionary perspective. Perspect Biol Med 43: 406–448PubMedGoogle Scholar
  30. 30.
    Duffy DL (2007) Genetic determinants of diabetes are similarly associated with other immune-mediated diseases. Curr Opin Allergy Clin Immunol 7: 468–474PubMedCrossRefGoogle Scholar
  31. 31.
    Hoymans VY, Bosmans JM, Ieven MM, Vrints CJ (2007) Chlamydia pneumoniae-based atherosclerosis: a smoking gun. Acta Cardiol 62: 565–571PubMedCrossRefGoogle Scholar
  32. 32.
    Behr MA, Kapur V (2008) The evidence for Mycobacterium paratuberculosis in Crohn’s disease. Curr Opin Gastroenterol 24: 17–21PubMedCrossRefGoogle Scholar
  33. 33.
    Posnett DN (2008) Herpesviruses and autommunity. Curr Opin Investig Drugs 9: 505–514PubMedGoogle Scholar
  34. 34.
    Honeyman M (2005) How robust is the evidence for viruses in the induction of type 1 diabetes? Curr Opin Immunol 17: 616–623PubMedCrossRefGoogle Scholar
  35. 35.
    Maya R, Gershwin ME, Shoenfeld Y (2008) Hepatitis B virus (HBV) and autoimmune disease. Clin Rev Allergy Immunol 34: 85–102PubMedCrossRefGoogle Scholar
  36. 36.
    Benn CS, Melbye M, Wohlfahrt J, Bjorksten B, Aaby P (2004) Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life. BMJ 328: 1223PubMedCrossRefGoogle Scholar
  37. 37.
    Dunder T, Tapiainen T, Pokka T, Uhari M (2007) Infections in child day care centers and later development of asthma, allergic rhinitis, and atopic dermatitis: prospective followup survey 12 years after controlled randomized hygiene intervention. Arch Pediatr Adolesc Med 161: 972–977PubMedCrossRefGoogle Scholar
  38. 38.
    Cardwell CR, Carson DJ, Yarnell J, Shields MD, Patterson CC (2008) Atopy, home environment and the risk of childhood-onset type 1 diabetes: a population-based case-control study. Pediatr Diabetes 9: 191–196PubMedCrossRefGoogle Scholar
  39. 39.
    Amre DK, Lambrette P, Law L, Krupoves A, Chotard V, Costea F, Grimard G, Israel D, Mack D, Seidman EG (2006) Investigating the hygiene hypothesis as a risk factor in pediatric onset Crohn’s disease: a case-control study. Am J Gastroenterol 101: 1005–1011PubMedCrossRefGoogle Scholar
  40. 40.
    Bernstein CN, Rawsthorne P, Cheang M, Blanchard JF (2006) A population-based case control study of potential risk factors for IBD. Am J Gastroenterol 101: 993–1002PubMedCrossRefGoogle Scholar
  41. 41.
    Koloski NA, Bret L, Radford-Smith G (2008) Hygiene hypothesis in inflammatory bowel disease: a critical review of the literature. World J Gastroenterol 14: 165–173PubMedCrossRefGoogle Scholar
  42. 42.
    Yazdanbakhsh M, Matricardi PM (2004) Parasites and the hygiene hypothesis: regulating the immune system? Clin Rev Allergy Immunol 26: 15–24PubMedCrossRefGoogle Scholar
  43. 43.
    Flohr C, Tuyen LN, Lewis S, Quinnell R, Minh TT, Liem HT, Campbell J, Pritchard D, Hien TT, Farrar J et al (2006) Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: A cross-sectional study. J Allergy Clin Immunol 118: 1305–1311PubMedCrossRefGoogle Scholar
  44. 44.
    Garcia-Marcos L, Suarez-Varela MM, Canflanca IM, Garrido JB, Quiros AB, Lopez-Silvarrey Varela A, Hernandez GG, Guillen-Grima F, Diaz CG, Gonzalez IH et al (2005) BCG immunization at birth and atopic diseases in a homogeneous population of Spanish schoolchildren. Int Arch Allergy Immunol 137: 303–309PubMedCrossRefGoogle Scholar
  45. 45.
    Linehan MF, Frank TL, Hazell ML, Francis HC, Morris JA, Baxter DN, Niven RM (2007) Is the prevalence of wheeze in children altered by neonatal BCG vaccination? J Allergy Clin Immunol 119: 1079–1085PubMedCrossRefGoogle Scholar
  46. 46.
    Miyake Y, Arakawa M, Tanaka K, Sasaki S, Ohya Y (2008) Tuberculin reactivity and allergic disorders in schoolchildren, Okinawa, Japan. Clin Exp Allergy 38: 486–492PubMedCrossRefGoogle Scholar
  47. 47.
    Obihara CC, Kimpen JL, Gie RP, Lill SW, Hoekstra MO, Marais BJ, Schaaf HS, Lawrence K, Potter PC, Bateman ED et al (2006) Mycobacterium tuberculosis infection may protect against allergy in a tuberculosis endemic area. Clin Exp Allergy 36: 70–76PubMedCrossRefGoogle Scholar
  48. 48.
    Zuany-Amorim C, Manlius C, Trifilieff A, Brunet LR, Rook G, Bowen G, Pay G, Walker C (2002) Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation. J Immunol 169: 1492PubMedGoogle Scholar
  49. 49.
    Debarry J, Garn H, Hanuszkiewicz A, Dickgreber N, Blumer N, von Mutius E, Bufe A, Gatermann S, Renz H, Holst O et al (2007) Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties. J Allergy Clin Immunol 119: 1514–1521PubMedCrossRefGoogle Scholar
  50. 50.
    Kohashi O, Kohashi Y, Takahashi T, Ozawa A, Shigematsu N (1985) Reverse effect of gram-positive bacteria vs. gram-negative bacteria on adjuvant-induced arthritis in germfree rats. Microbiol Immunol 29: 487–497PubMedGoogle Scholar
  51. 51.
    Calcinaro F, Dionisi S, Marinaro M, Candeloro P, Bonato V, Marzotti S, Corneli RB, Ferretti E, Gulino A, Grasso F et al (2005) Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia 48: 1565–1575PubMedCrossRefGoogle Scholar
  52. 52.
    Feleszko W, Jaworska J, Rha RD, Steinhausen S, Avagyan A, Jaudszus A, Ahrens B, Groneberg DA, Wahn U, Hamelmann E (2007) Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy 37: 498–505PubMedCrossRefGoogle Scholar
  53. 53.
    Sheil B, McCarthy J, O’Mahony L, Bennett MW, Ryan P, Fitzgibbon JJ, Kiely B, Collins JK, Shanahan F (2004) Is the mucosal route of administration essential for probiotic function? Subcutaneous administration is associated with attenuation of murine colitis and arthritis. Gut 53: 694–700PubMedCrossRefGoogle Scholar
  54. 54.
    Degauque N, Mariat C, Kenny J, Zhang D, Gao W, Vu MD, Alexopoulos S, Oukka M, Umetsu DT, Dekruyff RH et al (2007) Immunostimulatory Tim-1-specific antibody deprograms Tregs and prevents transplant tolerance in mice. J Clin Invest 84: S12–16Google Scholar
  55. 55.
    Kuchroo VK, Meyers JH, Umetsu DT, DeKruyff RH (2006) TIM family of genes in immunity and tolerance. Adv Immunol 91: 227–249PubMedCrossRefGoogle Scholar
  56. 56.
    Hunninghake GM, Soto-Quiros ME, Avila L, Ly NP, Liang C, Sylvia JS, Klanderman BJ, Silverman EK, Celedon JC (2007) Sensitization to Ascaris lumbricoides and severity of childhood asthma in Costa Rica. J Allergy Clin Immunol 119: 654–661PubMedCrossRefGoogle Scholar
  57. 57.
    Karadag B, Ege M, Bradley JE, Braun-Fahrlander C, Riedler J, Nowak D, von Mutius E (2006) The role of parasitic infections in atopic diseases in rural school children. Allergy 61: 996–1001PubMedCrossRefGoogle Scholar
  58. 58.
    Wang CC, Nolan TJ, Schad GA, Abraham D (2001) Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin. Clin Exp Allergy 31: 495–503PubMedCrossRefGoogle Scholar
  59. 59.
    Wilson MS, Taylor MD, Balic A, Finney CA, Lamb JR, Maizels RM (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 202: 1199–1212PubMedCrossRefGoogle Scholar
  60. 60.
    Kitagaki K, Businga TR, Racila D, Elliott DE, Weinstock JV, Kline JN (2006) Intestinal helminths protect in a murine model of asthma. J Immunol 177: 1628–1635PubMedGoogle Scholar
  61. 61.
    Yang J, Zhao J, Yang Y, Zhang L, Yang X, Zhu X, Ji M, Sun N, Su C (2007) Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma. Immunology 120: 8–18PubMedCrossRefGoogle Scholar
  62. 62.
    Saunders KA, Raine T, Cooke A, Lawrence CE (2007) Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun 75: 397–407PubMedCrossRefGoogle Scholar
  63. 63.
    Summers RW, Elliott DE, Urban JF, Jr., Thompson RA, Weinstock JV (2005) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128: 825–832PubMedCrossRefGoogle Scholar
  64. 64.
    Summers RW, Elliott DE, Urban JF, Jr., Thompson R, Weinstock JV (2005) Trichuris suis therapy in Crohn’s disease. Gut 54: 87–90PubMedCrossRefGoogle Scholar
  65. 65.
    Mortimer K, Brown A, Feary J, Jagger C, Lewis S, Antoniak M, Pritchard D, Britton J (2006) Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg 75: 914–920PubMedGoogle Scholar
  66. 66.
    Correale J, Farez M (2007) Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol 61: 97–108PubMedCrossRefGoogle Scholar
  67. 67.
    Rook GA, Hamelmann E, Rosa Brunet L (2007) Mycobacteria and allergies. Immunobiology 212: 461–473PubMedCrossRefGoogle Scholar
  68. 68.
    Obihara CC, Beyers N, Gie RP, Potter PC, Marais BJ, Lombard CJ, Enarson DA, Kimpen JL (2005) Inverse association between Mycobacterium tuberculosis infection and atopic rhinitis in children. Allergy 60: 1121–1125PubMedCrossRefGoogle Scholar
  69. 69.
    Demissie A, Abebe M, Aseffa A, Rook G, Fletcher H, Zumla A, Weldingh K, Brock I, Andersen P, Doherty TM (2004) Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2. J Immunol 172: 6938PubMedGoogle Scholar
  70. 70.
    Fletcher HA, Owiafe P, Jeffries D, Hill P, Rook GA, Zumla A, Doherty TM, Brookes RH (2004) Increased expression of mRNA encoding interleukin (IL)-4 and its splice variant IL-4delta2 in cells from contacts of Mycobacterium tuberculosis, in the absence of in vitro stimulation. Immunology 112: 669PubMedCrossRefGoogle Scholar
  71. 71.
    Rook GA (2007) Th2 cytokines in susceptibility to tuberculosis. Curr Mol Med 7: 327–337PubMedCrossRefGoogle Scholar
  72. 72.
    Ellertsen LK, Wiker HG, Egeberg NT, Hetland G (2005) Allergic sensitisation in tuberculosis and leprosy patients. Int Arch Allergy Immunol 138: 217–224PubMedCrossRefGoogle Scholar
  73. 73.
    Suzuki N, Kudo K, Sano Y, Ito K (2001) Can Mycobacterium tuberculosis infection prevent asthma and other allergic disorders? Int Arch Allergy Immunol 124: 113–116PubMedCrossRefGoogle Scholar
  74. 74.
    Alm JS, Lilja G, Pershagen G, Scheynius A (1998) BCG vaccination does not seem to prevent atopy in children with atopic heredity. Allergy 53: 537PubMedCrossRefGoogle Scholar
  75. 75.
    Aaby P, Shaheen SO, Heyes CB, Goudiaby A, Hall AJ, Shiell AW, Jensen H, Marchant A (2000) Early BCG vaccination and reduction in atopy in Guinea-Bissau. Clin Exp Allergy 30: 644–650PubMedCrossRefGoogle Scholar
  76. 76.
    Gruber C, Meinlschmidt G, Bergmann R, Wahn U, Stark K (2002) Is early BCG vaccination associated with less atopic disease? An epidemiological study in German preschool children with different ethnic backgrounds. Pediatr Allergy Immunol 13: 177–181PubMedCrossRefGoogle Scholar
  77. 77.
    Fine PE (1995) Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346: 1339–1345PubMedCrossRefGoogle Scholar
  78. 78.
    Herz U, Gerhold K, Gruber C, Braun A, Wahn U, Renz H, Paul K (1998) BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model. J Allergy Clin Immunol 102: 867–974PubMedCrossRefGoogle Scholar
  79. 79.
    Wang CC, Rook GAW (1998) Inhibition of an established allergic response to ovalbumin in Balb/c mice by killed Mycobacterium vaccae. Immunology 93: 307–313PubMedCrossRefGoogle Scholar
  80. 80.
    Hopfenspirger MT, Parr SK, Hopp RJ, Townley RG, Agrawal DK (2001) Mycobacterial antigens attenuate late phase response, airway hyperresponsiveness, and bronchoalveolar lavage eosinophilia in a mouse model of bronchial asthma. Int Immunopharmacol 1: 1743–1751PubMedCrossRefGoogle Scholar
  81. 81.
    Ozdemir C, Akkoc T, Bahceciler NN, Kucukercan D, Barlan IB, Basaran MM (2003) Impact of Mycobacterium vaccae immunization on lung histopathology in a murine model of chronic asthma. Clin Exp Allergy 33: 266–270PubMedCrossRefGoogle Scholar
  82. 82.
    Smit JJ, Van Loveren H, Hoekstra MO, Schijf MA, Folkerts G, Nijkamp FP (2003) Mycobacterium vaccae administration during allergen sensitization or challenge suppresses asthmatic features. Clin Exp Allergy 33: 1083–1089PubMedCrossRefGoogle Scholar
  83. 83.
    Arkwright PD, Fujisawa C, Tanaka A, Matsuda H (2005) Mycobacterium vaccae reduces scratching behavior but not the rash in NC mice with eczema: a randomized, blinded, placebo-controlled trial. J Invest Dermatol 124: 140–143PubMedCrossRefGoogle Scholar
  84. 84.
    Hunt JR, Martinelli R, Adams VC, Rook GAW, Rosa Brunet L (2005) Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model. Clin Exp Allergy 35: 685–690PubMedCrossRefGoogle Scholar
  85. 85.
    Ricklin-Gutzwiller ME, Reist M, Peel JE, Seewald W, Brunet LR, Roosje PJ (2007) Intradermal injection of heat-killed Mycobacterium vaccae in dogs with atopic dermatitis: a multicentre pilot study. Vet Dermatol 18: 87–93PubMedCrossRefGoogle Scholar
  86. 86.
    Sudo N, Sawamura S, Tanaka K, Aiba Y, Kubo C, Koga Y (1997) The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction. J Immunol 159: 1739–1754PubMedGoogle Scholar
  87. 87.
    Adlerberth I, Strachan DP, Matricardi PM, Ahrne S, Orfei L, Aberg N, Perkin MR, Tripodi, S, Hesselmar B, Saalman R et al (2007) Gut microbiota and development of atopic eczema in 3 European birth cohorts. J Allergy Clin Immunol 120: 343–350PubMedCrossRefGoogle Scholar
  88. 88.
    Ivanov, II, Frutos Rde 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: 337–349PubMedCrossRefGoogle Scholar
  89. 89.
    Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, Ishii N, Evans R, Honda K et al (2008) ATP drives lamina propria T(H) 17 cell differentiation. Nature 455: 808–812PubMedCrossRefGoogle Scholar
  90. 90.
    Zaph C, Du Y, Saenz SA, Nair MG, Perrigoue JG, Taylor BC, Troy AE, Kobuley DE, Kastelein RA, Cua DJ et al (2008) Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J Exp Med 205: 2191–2198PubMedCrossRefGoogle Scholar
  91. 91.
    Hall JA, Bouladoux N, Sun CM, Wohlfer EA, Blank RB, Zhu Q, Grigg ME, Berzofsky JA, Belkaid Y (2008) Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 29: 637–649PubMedCrossRefGoogle Scholar
  92. 92.
    Farooqi IS, Hopkin JM (1998) Early childhood infection and atopic disorder. Thorax 53: 927–932PubMedCrossRefGoogle Scholar
  93. 93.
    Dethlefsen L, Huse S, Sogin ML, Relman DA (2008) The pervasive effects of an antibi otic on the human gut microbiota, as revealed by Deep 16S rRNA Sequencingsequencing. PLoS Biol 6: e280PubMedCrossRefGoogle Scholar
  94. 94.
    Guarner F, Bourdet-Sicard R, Brandtzaeg P, Gill HS, McGuirk P, van Eden W, Versalovic J, Weinstock JV, Rook GA (2006) Mechanisms of disease: the hygiene hypothesis revisited. Nat Clin Pract Gastroenterol Hepatol 3: 275–284PubMedCrossRefGoogle Scholar
  95. 95.
    Rachmilewitz D, Katakura K, Karmeli F, Hayashi T, Reinus C, Rudensky B, Akira S, Takeda K, Lee J, Takabayashi K et al (2004) Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology 126: 520–528PubMedCrossRefGoogle Scholar
  96. 96.
    Forsythe P, Inman MD, Bienenstock J (2007) Oral treatment with live Lactobacillus reuteri inhibits the allergic airway response in mice. Am J Respir Crit Care Med 175: 561–569PubMedCrossRefGoogle Scholar
  97. 97.
    Ogawa T, Hashikawa S, Asai Y, Sakamoto H, Yasuda K, Makimura Y (2006) A new synbiotic, Lactobacillus casei subsp. casei together with dextran, reduces murine and human allergic reaction. FEMS Immunol Med Microbiol 46: 400–409PubMedCrossRefGoogle Scholar
  98. 98.
    Kim H, Kwack K, Kim DY, Ji GE (2005) Oral probiotic bacterial administration suppressed allergic responses in an ovalbumin-induced allergy mouse model. FEMS Immunol Med Microbiol 45: 259–267PubMedCrossRefGoogle Scholar
  99. 99.
    Kim H, Lee SY, Ji GE (2005) Timing of bifidobacterium administration influences the development of allergy to ovalbumin in mice. Biotechnol Lett 27: 1361–1367PubMedCrossRefGoogle Scholar
  100. 100.
    Kato I, Endo-Tanaka K, Yokokura T (1998) Suppressive effects of the oral administration of Lactobacillus casei on type II collagen-induced arthritis in DBA/1 mice. Life Sci 63: 635–644PubMedCrossRefGoogle Scholar
  101. 101.
    O’Mahony C, Scully P, O’Mahony D, Murphy S O’Brien F, Lyons A, Sherlock G, MacSharry J, Kiely B, Shanahan F et al (2008) Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog 4: e1000112PubMedCrossRefGoogle Scholar
  102. 102.
    Rook GA (2007) The hygiene hypothesis and the increasing prevalence of chronic inflammatory disorders. Trans R Soc Trop Med Hyg 101: 1072–1074PubMedCrossRefGoogle Scholar
  103. 103.
    Wernli KJ, Fitzgibbons ED, Ray RM, Gao DL, Li W, Seixas NS, Camp JE, Astrakianakis G, Feng Z, Thomas DB et al (2006) Occupational risk factors for esophageal and stomach cancers among female textile workers in Shanghai, China. Am J Epidemiol 163: 717–725PubMedCrossRefGoogle Scholar
  104. 104.
    Ray RM, Gao DL, Li W, Wernli KJ, Astrakianakis G, Seixas NS, Camp JE, Fitzgibbons ED, Feng Z, Thomas DB et al (2007) Occupational exposures and breast cancer among women textile workers in Shanghai. Epidemiology 18: 383–392PubMedCrossRefGoogle Scholar
  105. 105.
    Astrakianakis G, Seixas NS, Ray R, Camp JE, Gao DL, Feng Z, Li W, Wernli KJ, Fitzgibbons ED, Thomas DB et al (2007) Lung cancer risk among female textile workers exposed to endotoxin. J Natl Cancer Inst 99: 357–364PubMedCrossRefGoogle Scholar
  106. 106.
    Mastrangelo G, Grange JM, Fadda E, Fedeli U, Buja A, Lange JH (2005) Lung cancer risk: effect of dairy farming and the consequence of removing that occupational exposure. Am J Epidemiol 161: 1037–1046PubMedCrossRefGoogle Scholar
  107. 107.
    Hoover RN (1976) Bacillus Calmette-Guerin vaccination and cancer prevention: a critical review of the human experience. Cancer Res 36: 652–654PubMedGoogle Scholar
  108. 108.
    Krone B, Kolmel KF, Henz BM, Grange JM (2005) Protection against melanoma by vaccination with Bacille Calmette-Guerin (BCG) and/or vaccinia: an epidemiology-based hypothesis on the nature of a melanoma risk factor and its immunological control. Eur J Cancer 41: 104–117PubMedCrossRefGoogle Scholar
  109. 109.
    Krug N, Madden J, Redington AE, Lackie P, Djukanovic R, Schauer U, Holgate ST, Frew AJ, Howarth PH (1996) T-cell cytokine profile evaluated at the single cell level in BAL and blood in allergic asthma. Am J Respir Cell Mol Biol 14: 319–326PubMedGoogle Scholar
  110. 110.
    Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, Akdis CA (2003) A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apoptosis release IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gamma-inducible alpha-chemoattractant for T cell chemotaxis toward epidermis in atopic dermatitis. J Immunol 171: 1078–1084PubMedGoogle Scholar
  111. 111.
    Lammas DA, Casanova JL, Kumararatne DS (2000) Clinical consequences of defects in the IL-12-dependent interferon-gamma (IFN-gamma) pathway. Clin Exp Immunol 121: 417–425PubMedCrossRefGoogle Scholar
  112. 112.
    Hansen G, Berry G, DeKruyff RH, Umetsu DT (1999) Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J Clin Invest 103: 175–183PubMedCrossRefGoogle Scholar
  113. 113.
    Lawrence CE, Paterson JC, Higgins LM, MacDonald TT, Kennedy MW, Garside P (1998) IL-4-regulated enteropathy in an intestinal nematode infection. Eur J Immunol 28: 2672PubMedCrossRefGoogle Scholar
  114. 114.
    Van Kampen C, Gauldie J, Collins SM (2005) Proinflammatory properties of IL-4 in the intestinal microenvironment Am J Physiol Gastrointest Liver Physiol 288: G111–117PubMedCrossRefGoogle Scholar
  115. 115.
    Tiemessen MM, Jagger AL, Evans HG, van Herwijnen MJ, John S, Taams LS (2007) CD+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci USA 104: 19446–19451PubMedCrossRefGoogle Scholar
  116. 116.
    Rook GAW, Stanford JL (1998) Give us this day our daily germs. Immunol Today 19: 113–116PubMedCrossRefGoogle Scholar
  117. 117.
    Stene LC, Nafstad P (2001) Relation between occurrence of type 1 diabetes and asthma. Lancet 357: 607PubMedCrossRefGoogle Scholar
  118. 118.
    Tremlett HL, Evans J, Wiles CM, Luscombe DK (2002) Asthma and multiple sclerosis: an inverse association in a case-control general practice population. Qjm 95: 753–756PubMedCrossRefGoogle Scholar
  119. 119.
    Tirosh A, Mandel D, Mimouni FB, Zimlichman E, Shochat T, Kochba I (2006) Autoimmune diseases in asthma. Ann Intern Med 144: 877–883PubMedGoogle Scholar
  120. 120.
    Rook GA, Martinelli R, Brunet LR (2003) Innate immune responses to mycobacteria and the downregulation of atopic responses. Curr Opin Allergy Clin Immunol 3: 337–342PubMedCrossRefGoogle Scholar
  121. 121.
    Babu S, Blauvelt CP, Kumaraswami V, Nutman TB (2006) Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. J Immunol 176: 3248–3256PubMedGoogle Scholar
  122. 122.
    Wildin RS, Smyk-Pearson S, Filipovich AH (2002) Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J. Med Genet 39: 537–545PubMedCrossRefGoogle Scholar
  123. 123.
    Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Valenta R, Fiebig H et al (2004) Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T Regulatory 1 and T Helper 2 Cells. J Exp Med 199: 1567–1575PubMedCrossRefGoogle Scholar
  124. 124.
    Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199: 971–979PubMedCrossRefGoogle Scholar
  125. 125.
    Kriegel MA, Lohmann T, Gabler C, Blank N, Kalden JR, Lorenz HM (2004) Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med 199: 1285–1291PubMedCrossRefGoogle Scholar
  126. 126.
    Kraus TA, Toy L, Chan L, Childs J, Mayer L (2004) Failure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease. Gastroenterology 126: 1771–1778PubMedCrossRefGoogle Scholar
  127. 127.
    Powrie F, Read S, Mottet C, Uhlig H, Maloy K (2003) Control of immune pathology by regulatory T cells. Novartis Found Symp 252: 92–98PubMedCrossRefGoogle Scholar
  128. 128.
    van der Kleij D, Latz E, Brouwers JF, Kruize YC, Schmitz M, Kurt-Jones EA, Espevik T, de Jong EC, Kapsenberg ML, Golenbock DT et al (2002) A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J Biol Chem 277: 48122–48129PubMedCrossRefGoogle Scholar
  129. 129.
    Smits HH, Engering A, van der Kleij D, de Jong EC, Schipper K, van Capel TM, Zaat BA, Yazdanbakhsh M, Wierenga EA, van Kooyk Y et al (2005) Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 115: 1260–1267PubMedCrossRefGoogle Scholar
  130. 130.
    Zaccone P, Fehervari Z, Jones FM, Sidobre S, Kronenberg M, Dunne DW, Cooke A (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol 33: 1439–1449PubMedCrossRefGoogle Scholar
  131. 131.
    Rook GAW (2009) The broader implications of the hygiene hypothesis. Immunology 126: 3–11PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2009

Authors and Affiliations

  • Graham A. W. Rook
    • 1
  1. 1.Centre for Infectious Diseases and International Health, Windeyer Institute of Medical SciencesUniversity College LondonLondonUK

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