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Effects of intestinal microflora and the environment on the development of asthma and allergy

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Abstract

The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.

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References

  1. Adlerberth I, Jalil F, Carlsson B, et al (1998) High turnover rate of Escherichia coli strains in the intestinal flora of infants in Pakistan. Epidemiol Infect 121:587

    Google Scholar 

  2. Alm JS, Lilja G, Pershagen G, Scheynius A (1997) Early BCG vaccination and development of atopy. Lancet 350:400

    Google Scholar 

  3. Anyo G, Brunekreef B, Meer G de, Aarts F, Janssen NA, Vliet P van (2002) Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children. Clin Exp Allergy 32:361

    Google Scholar 

  4. Azizi BH, Zulkifli HI, Kasim MS (1995) Protective and risk factors for acute respiratory infections in hospitalized urban Malaysian children: a case control study. Southeast Asian J Trop Med Public Health 26:280

    Google Scholar 

  5. Baldini M, Lohman I, Halonen M, Erickson R, Holt P, Martinez F (1999) A polymorphism in the 5’-flanking region of the CD14 gene is associated with circulating soluble CD14 levels with total serum IgE. Am J Respir Cell Mol Biol 20:976

    Google Scholar 

  6. Benn CS, Thorsen P, Jensen JS, et al (2002) Maternal vaginal microflora during pregnancy and the risk of asthma hospitalization and use of antiasthma medication in early childhood. J Allergy Clin Immunol 110:72

    Google Scholar 

  7. Björkstén B (1983) Does breast-feeding prevent the development of allergy? Immunol Today 4:215

    Google Scholar 

  8. Björkstén B (1999) Allergy priming early in life. Lancet 353:167

    Google Scholar 

  9. Björkstén 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

    Google Scholar 

  10. Björkstén B, Sepp E, Julge K, Voor T, Mikelsaar M (2001) Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 108:516

    Google Scholar 

  11. Borriello S, Hammes W, Holzapfel W, et al (2003) Safety of probiotics that contain lactobacilli or bifidobacteria. Clin Infect Dis 36:775

    Google Scholar 

  12. Böttcher MF, Nordin EK, Sandin A, Midtvedt T, Björkstén B (2000) Microflora-associated characteristics in faeces from allergic and nonallergic infants. Clin Exp Allergy 30:1590

    Google Scholar 

  13. Böttcher MF, Björkstén B, Gustafson S, Voor T, Jenmalm MC (2003) Endotoxin levels in Estonian and Swedish house dust and atopy in infancy. Clin Exp Allergy 33:295

    Google Scholar 

  14. Brandzaeg P (1996) Development of the mucosal immune system in humans. In: Bindels J, Goedhart A, Visser H (eds) Recent developments ininfant nutrition. Kluwer, London, p 349

  15. Bråbäck L (1998) Hedberg A. Perinatal risk factors for atopic disease in conscripts. Clin Exp Allergy 28:936

    Google Scholar 

  16. Bullen CL, Tearle PV, Stewart MG (1977) The effect of “humanised” milks and supplemented breast feeding on the faecal flora of infants. J Med Microbiol 10:403

    Google Scholar 

  17. Burr ML, Limb ES, Maguire MJ, et al (1993) Infant feeding, wheezing, and allergy: a prospective study. Arch Dis Child 68:724

    Google Scholar 

  18. Cook DG, Strachan DP (1997) Health effects of passive smoking. 3. Parental smoking and prevalence of respiratory symptoms and asthma in school age children. Thorax 52:1081

    Google Scholar 

  19. D’Souza AL, Rajkumar C, Cooke J, Bulpitt CJ (2002) Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 324:1361

    Google Scholar 

  20. Gereda JE, Leung DY, Liu AH (2000) Levels of environmental endotoxin and prevalence of atopic disease. JAMA 284:1652

    Google Scholar 

  21. Gerrard J, Geddes C, Reggin P, Gerrard C, Horne S (1976) Serum IgE levels in white and metis communities in Saskatchewan. Ann Allergy 37:91

    Google Scholar 

  22. Golding J, Emmett PM, Rogers IS (1997) Eczema, asthma and allergy. Early Hum Dev 49 Suppl:S121

  23. Golding J, Emmett PM, Rogers IS (1997) Gastroenteritis, diarrhoea and breast feeding. Early Hum Dev 49 Suppl:S83

  24. Gruber C, Nilsson L, Björkstén B (2001) Do early childhood immunizations influence the development of atopy and do they cause allergic reactions? Pediatr Allergy Immunol 12:296

    Google Scholar 

  25. Halmerbauer G, Gartner C, Schier M, et al (2002) Study on the prevention of allergy in children in Europe (SPACE): allergic sensitization in children at 1 year of age in a controlled trial of allergen avoidance from birth. Pediatr Allergy Immunol 13 Suppl 15:47

    Google Scholar 

  26. Hesselmar B, Åberg N, Åberg B, Eriksson B, Björkstén B (1999) Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy 29:611

    Google Scholar 

  27. Holt PG, Sly PD, Björkstén B (1997) Atopic versus infectious diseases in childhood: a question of balance? Pediatr Allergy Immunol 8:53

    Google Scholar 

  28. Holzapfel WH, Haberer P, Snel J, Schillinger U, Huis in’t Veld JH (1998) Overview of gut flora and probiotics. Int J Food Microbiol 41:85

    Google Scholar 

  29. Hooper L, Gordon J (2001) Commensal host-bacterial relationships in the gut. Science 292:1115

    Google Scholar 

  30. Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ (2002) Efficacy of probiotic use in acute diarrhea in children: a meta-analysis. Dig Dis Sci 47:2625

    Google Scholar 

  31. Illi S, von Mutius E, Lau S, et al (2001) Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. Br Med J 322:390

    Google Scholar 

  32. Isolauri E, Arvola T, Sutas Y, Moilanen E, Salminen S (2000) Probiotics in the management of atopic eczema. Clin Exp Allergy 30:1604

    Google Scholar 

  33. Julge K, Vasar M, Björkstén B (2001) Development of allergy and IgE antibodies during the first five years of life in Estonian children. Clin Exp Allergy 31:1854

    Google Scholar 

  34. Kalliomäki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E (2001) Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 107:129

    Google Scholar 

  35. Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E (2001) Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 357:1076

    Google Scholar 

  36. Kalliomäki M, Salminen S, Poussa T, Arvilommi H, Isolauri E (2003) Probiotics and prevention of atopic disease; 4-year follow-up of a randomised placebo-controlled trial. Lancet 361:1869

    Google Scholar 

  37. Kandler O (1984) Current taxonomy of lactobacilli. Developments in industrial microbiology, Proc. 40th Gen Meet.Soc.Insustrial Microbiol., Srasota, Florida

  38. Kirjavainen PV, Arvola T, Salminen SJ, Isolauri E (2002) Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Gut 51:51

    Google Scholar 

  39. Kirjavainen PV, Salminen SJ, Isolauri E (2003) Probiotic bacteria in the management of atopic disease: underscoring the importance of viability. J Pediatr Gastroenterol Nutr 36:223

    Google Scholar 

  40. Lau S, Illi S, Sommerfeld C, et al (2000) Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Multicentre Allergy Study Group. Lancet 356:1392

    Google Scholar 

  41. Leynaert B, Neukirch C, Jarvis D, Chinn S, Burney P, Neukirch F (2001) Does living on a farm during childhood protect against asthma, allergic rhinitis, and atopy in adulthood? Am J Respir Crit Care Med 164:1829

    Google Scholar 

  42. Majamaa H, Isolauri E (1997) Probiotics: a novel approach in the management of food allergy. J Allergy Clin Immunol 99:179

    Google Scholar 

  43. Matricardi PM, Rosmini F, Riondino S, et al (2000) Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study. Br Med J 320:412

    Google Scholar 

  44. 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

    Google Scholar 

  45. Matricardi P, Björkstén B, Bonini S, et al (2003) Microbial products in allergy prevention and therapy. Allergy 58:461

    Google Scholar 

  46. Mevissen-Verhage EA, Marcelis JH, Harmsen-Van Amerongen WC, Vos NM de, Verhoef J (1985) Effect of iron on neonatal gut flora during the first three months of life. Eur J Clin Microbiol 4:273

    Google Scholar 

  47. Mevissen-Verhage EA, Marcelis JH, Harmsen-van Amerongen WC, Vos NM de, Berkel J, Verhoef J (1985) Effect of iron on neonatal gut flora during the first week of life. Eur J Clin Microbiol 4:14

    Google Scholar 

  48. Mikelsaar M, Annuk H, Stsepetova J, Kullisaar T, Zilmer M, Björkstén B (2002) Intestinal lactoflora of Estonian and Swedish children. Microbiol Ecol Health Dis 14:75

    Google Scholar 

  49. Nafstad P, Magnus P, Jaakkola JJ (2000) Early respiratory infections and childhood asthma. Pediatrics 106:E38

    Google Scholar 

  50. Nagler-Anderson C (2001) Man the barrier! Strategic defences in the intestinal mucosa. Nat Rev Immunol 1:59

    Google Scholar 

  51. Nagler-Anderson C, Terhoust C, Bhan AK, Podolsky DK (2001) Mucosal antigen presentation and the control of tolerance and immunity. Trends Immunol 22:120

    Google Scholar 

  52. Neish AS (2002) The gut microflora and intestinal epithelial cells: a continuing dialogue. Microbes Infect 4:309

    Google Scholar 

  53. Nilsson L, Kjellman NI, Lofman O, Björkstén B (1997) Parity among atopic and non-atopic mothers. Pediatr Allergy Immunol 8:134

    Google Scholar 

  54. Ouwehand AC, Isolauri E, He F, Hashimoto H, Benno Y, Salminen S (2001) Differences in Bifidobacterium flora composition in allergic and healthy infants. J Allergy Clin Immunol 108:144

    Google Scholar 

  55. Ownby DR, Johnson CC, Peterson EL (2002) Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 288:963

    Google Scholar 

  56. Peat J, Björkstén B (1998) Primary and secondary prevention of allergic asthma. Eur Respir J Suppl 27:28s

    Google Scholar 

  57. Riedler J, Braun-Fahrländer C, Eder W, et al (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129

    Google Scholar 

  58. Rook GA, Stanford JL (1998) Give us this day our daily germs. Immunol Today 19:113

    Google Scholar 

  59. Roost HP, Kunzli N, Schindler C, et al (1999) Role of current and childhood exposure to cat and atopic sensitization. European Community Respiratory Health Survey. J Allergy Clin Immunol 104:941

    Google Scholar 

  60. Rosenfeldt V, Benfeldt E, Nielsen SD, et al (2003) Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol 111:389

    Google Scholar 

  61. Sepp E, Julge K, Vasar M, Naaber P, Björkstén B, Mikelsaar M (1997) Intestinal microflora of Estonian and Swedish infants. Acta Paediatr 86:956

    Google Scholar 

  62. Sepp E, Naaber P, Voor T, Mikelsaar M, Björkstén B (2000) Development of intestinal micro-flora during the first month of life in Estonian and Swedish infants. Microbiol Ecol Health Dis 12:22

    Google Scholar 

  63. Shirakawa T, Enomoto T, Shimazu S, Hopkin JM (1997) The inverse association between tuberculin responses and atopic disorder. Science 275:77

    Google Scholar 

  64. Sigurs N (2002) Clinical perspectives on the association between respiratory syncytial virus and reactive airway disease. Respir Res 3 Suppl 1:S8

  65. Stene LC, Nafstad P (2001) Relation between occurrence of type 1 diabetes and asthma. Lancet 357:607

    Google Scholar 

  66. Strachan D (1989) Hay fever, hygiene and household size. Br Med J 299:1259

    Google Scholar 

  67. Strachan D (2000) Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 55 Suppl 1:S2

  68. Strachan DP (2000) The role of environmental factors in asthma. Br Med Bull 56:865

    Google Scholar 

  69. Strachan DP, Cook DG (1997) Health effects of passive smoking. 1. Parental smoking and lower respiratory illness in infancy and early childhood. Thorax 52:905

    Google Scholar 

  70. Strachan DP, Cook DG (1998) Health effects of passive smoking. 6. Parental smoking and childhood asthma: longitudinal and case-control studies. Thorax 53:204

    Google Scholar 

  71. Strachan DP, Cook DG (1998) Health effects of passive smoking .5. Parental smoking and allergic sensitisation in children. Thorax 53:117

    Google Scholar 

  72. Strannegård IL, Larsson LO, Wennergren G, Strannegård Ö (1998) Prevalence of allergy in children in relation to prior BCG vaccination and infection with atypical mycobacteria. Allergy 53:249

    Google Scholar 

  73. 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

    Google Scholar 

  74. Svanes C, Jarvis D, Chinn S, Burney P (1999) Childhood environment and adult atopy: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol 103:415

    Google Scholar 

  75. Van Niel C, Feudtner C, Garrison M, Christakis D (2002) Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 109:678

    Google Scholar 

  76. Von Mutius E, Braun-Fahrländer C, Schierl R, et al (2000) Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy 30:1230

    Google Scholar 

  77. Wahn U, Lau S, Bergmann R, et al (1997) Indoor allergen exposure is a risk factor for sensitization during the first three years of life. J Allergy Clin Immunol 99:763

    Google Scholar 

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  1. Centre for Allergy Research and Department of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden

    Bengt Björkstén

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Björkstén, B. Effects of intestinal microflora and the environment on the development of asthma and allergy. Springer Semin Immun 25, 257–270 (2004). https://doi.org/10.1007/s00281-003-0142-2

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