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Microbial regulation of allergic responses to food

Seminars in Immunopathology volume 34, pages 671–688 (2012)Cite this article

Abstract

The incidence of food allergy in developed countries is rising at a rate that cannot be attributed to genetic variation alone. In this review, we discuss the environmental factors that may contribute to the increasing prevalence of potentially fatal anaphylactic responses to food. Decreased exposure to enteric infections due to advances in vaccination and sanitation, along with the adoption of high-fat (Western) diets, antibiotic use, Cesarean birth, and formula feeding of infants, have all been implicated in altering the enteric microbiome away from its ancestral state. This collection of resident commensal microbes performs many important physiological functions and plays a central role in the development of the immune system. We hypothesize that alterations in the microbiome interfere with immune system maturation, resulting in impairment of IgA production, reduced abundance of regulatory T cells, and Th2-skewing of baseline immune responses which drive aberrant responses to innocuous (food) antigens.

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Fig. 1
Fig. 2

Abbreviations

TLR:

Toll-like receptor

Treg:

Regulatory T cells

SCFA:

Short-chain fatty acids

LP:

Lamina propria

GF:

Germ free

APC:

Antigen presenting cell

DC:

Dendritic cell

MLN:

Mesenteric lymph node

OVA:

Chicken egg ovalbumin

References

  1. Branum AM, Lukacs SL (2008) Food allergy among U.S. children: trends in prevalence and hospitalizations. National Center for Health Statistics Data Brief.

  2. Hong X, Tsai H-J, Wang X (2009) Genetics of food allergy. Curr Opin Pediatr 21(6):770–776

    PubMed  Article  Google Scholar 

  3. Vercelli D (2003) Genetic polymorphism in allergy and asthma. Curr Opin Immunol 15(6):609–613

    PubMed  CAS  Article  Google Scholar 

  4. Vercelli D (2008) Advances in asthma and allergy genetics in 2007. J Allergy Clin Immunol 122(2):267–271

    PubMed  CAS  Article  Google Scholar 

  5. Vercelli D (2004) Genetics, epigenetics, and the environment: switching, buffering, releasing. J Allergy Clin Immunol 113(3):381–386

    PubMed  CAS  Article  Google Scholar 

  6. Strachan DP (1989) Hay fever, hygiene, and household size. Brit Med J 299(6710):1259–1260

    PubMed  CAS  Article  Google Scholar 

  7. Alm JS et al (1999) Atopy in children of families with an anthroposophic lifestyle. Lancet 353(9163):1485–1488

    PubMed  CAS  Article  Google Scholar 

  8. Sepp E et al (1997) Intestinal microflora of Estonian and Swedish infants. Acta Pædiatrica 86(9):956–961

    PubMed  CAS  Article  Google Scholar 

  9. Graham-Rowe D (2011) Lifestyle: when allergies go west. Nature 479(7374):S2–S4

    Article  Google Scholar 

  10. Mutius EV et al (1992) Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison. Brit Med J 305(6866):1395–1399

    Article  Google Scholar 

  11. von Hertzen L et al (2006) Growing disparities in atopy between the Finns and the Russians: a comparison of 2 generations. J of Allergy Clin Immunol 117(1):151–157

    Article  Google Scholar 

  12. Addo-Yobo EOD et al (2007) Exercise-induced bronchospasm and atopy in Ghana: two surveys ten years apart. PLoS Med 4(2):e70

    PubMed  Article  Google Scholar 

  13. Riedler J et al (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358(9288):1129–1133

    PubMed  CAS  Article  Google Scholar 

  14. von Mutius E, Vercelli D (2010) Farm living: effects on childhood asthma and allergy. Nat Rev Immunol 10(12):861–868

    Article  CAS  Google Scholar 

  15. Braun-Fahrländer C et al (1999) Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution. Clin Exp Allergy 29(1):28–34

    PubMed  Article  Google Scholar 

  16. Riedler J et al (2000) Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clin Exp Allergy 30(2):194–200

    PubMed  CAS  Article  Google Scholar 

  17. Braun-Fahrlander C et al (2002) Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 347(12):869–877

    PubMed  Article  Google Scholar 

  18. Waser M et al (2005) Exposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children. Allergy 60(2):177–184

    PubMed  CAS  Article  Google Scholar 

  19. Brunekreef B et al (2012) Early life exposure to farm animals and symptoms of asthma, rhinoconjunctivitis and eczema: an ISAAC Phase Three Study. Int J Epidemiol 41(3):753–761

    PubMed  Article  Google Scholar 

  20. Lauener RP et al (2002) Expression of CD14 and Toll-like receptor 2 in farmers’ and nonfarmers’ children. Lancet 360(9331):465–466

    PubMed  CAS  Article  Google Scholar 

  21. Ege MJ et al (2006) Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J Allergy Clin Immunol 117(4):817–823

    PubMed  Article  Google Scholar 

  22. Stern DA, Riedler J, Nowak D, Braun-Fahrlander C, Swoboda I, Balic N, Chen KW, Vrtala S, Gronlund H, van Hage M et al (2007) Exposure to a farming environment has allergen-specific protective effects on TH2-dependent isotype switching in response to common inhalants. J Allergy Clin Immunol 119(2):351–358

    PubMed  CAS  Article  Google Scholar 

  23. Schaub B et al (2009) Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol 123(4):774–782, e775

    PubMed  CAS  Article  Google Scholar 

  24. Peters M et al (2006) Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness. Thorax 61(2):134–139

    PubMed  CAS  Article  Google Scholar 

  25. Debarry J et al (2007) Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties. J Allergy Clin Immunol 119(6):1514–1521

    PubMed  Article  Google Scholar 

  26. Platts-Mills T et al (2001) Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 357(9258):752–756

    PubMed  CAS  Article  Google Scholar 

  27. Smallwood J, Ownby D (2012) Exposure to dog allergens and subsequent allergic sensitization: an updated review. Curr Allergy Asthma Rep [Epub ahead of print]

  28. Gern JE et al (2004) Effects of dog ownership and genotype on immune development and atopy in infancy. J Allergy Clin Immunol 113(2):307–314

    PubMed  Article  Google Scholar 

  29. 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(8):963–972

    PubMed  Article  Google Scholar 

  30. Fujimura KE et al (2010) Man’s best friend? The effect of pet ownership on house dust microbial communities. J Allergy Clin Immunol 126(2):410–412

    PubMed  Article  Google Scholar 

  31. Havstad S et al (2011) Effect of prenatal indoor pet exposure on the trajectory of total IgE levels in early childhood. J Allergy Clin Immunol 128(4):880–885

    PubMed  CAS  Article  Google Scholar 

  32. Heederik D, von Mutius E (2012) Does diversity of environmental microbial exposure matter for the occurrence of allergy and asthma? J Allergy Clin Immunol 130(1):44–50

    PubMed  Article  Google Scholar 

  33. Litonjua AA et al (2002) A longitudinal analysis of wheezing in young children: the independent effects of early life exposure to house dust endotoxin, allergens, and pets. J Allergy Clin Immunol 110(5):736–742

    PubMed  Article  Google Scholar 

  34. Bufford JD et al (2008) Effects of dog ownership in early childhood on immune development and atopic diseases. Clin Exp Allergy 38(10):1635–1643

    PubMed  CAS  Article  Google Scholar 

  35. Wegienka G et al (2010) Indoor pet exposure and the outcomes of total IgE and sensitization at age 18 years. J Allergy Clin Immunol 126(2):274–279

    PubMed  Article  Google Scholar 

  36. Wills-Karp M, Santeliz J, Karp CL (2001) The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 1(1):69–75

    PubMed  CAS  Article  Google Scholar 

  37. Lee YK, Mazmanian SK (2010) Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330(6012):1768–1773

    PubMed  CAS  Article  Google Scholar 

  38. Eberl G (2010) A new vision of immunity: homeostasis of the superorganism. Mucosal Immunol 3(5):450–460

    PubMed  CAS  Article  Google Scholar 

  39. Noverr MC, Huffnagle GB (2005) The ‘microflora hypothesis’ of allergic diseases. Clin Exp Allergy 35(12):1511–1520

    PubMed  CAS  Article  Google Scholar 

  40. Prioult G, Nagler-Anderson C (2005) Mucosal immunity and allergic responses: lack of regulation and/or lack of microbial stimulation? Immunol Rev 206:204–218

    PubMed  CAS  Article  Google Scholar 

  41. Björkstén B et al (2001) Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 108(4):516–520

    PubMed  Article  Google Scholar 

  42. Björkstén B et al (1999) The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 29(3):342–346

    PubMed  Article  Google Scholar 

  43. Kalliomaki M et al (2001) Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 107(1):129–134

    PubMed  CAS  Article  Google Scholar 

  44. Böttcher MF et al (2000) Microflora-associated characteristics in faeces from allergic and nonallergic infants. Clin Exp Allergy 30(11):1591–1596

    Article  Google Scholar 

  45. Kirjavainen PV et al (2001) Characterizing the composition of intestinal microflora as a prospective treatment target in infant allergic disease. FEMS Immunol Med Microbiol 32(1):1–7

    PubMed  CAS  Article  Google Scholar 

  46. Cho I, Blaser MJ (2012) The human microbiome: at the interface of health and disease. Nat Rev Genet 13(4):260–270

    PubMed  CAS  Google Scholar 

  47. Ley RE et al (2008) Worlds within worlds: evolution of the vertebrate gut microbiota. Nat Rev Microbiol 6(10):776–788

    PubMed  CAS  Article  Google Scholar 

  48. Dominguez-Bello MG et al (2011) Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenteroloy 140(6):1713–1719

    CAS  Article  Google Scholar 

  49. Turnbaugh PJ, Gordon JI (2009) The core gut microbiome, energy balance and obesity. J Physiol 587(Pt 17):4153–4158

    PubMed  CAS  Article  Google Scholar 

  50. Dethlefsen L et al (2008) The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 6(11):e280

    PubMed  Article  CAS  Google Scholar 

  51. Turnbaugh PJ et al (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3(4):213–223

    PubMed  CAS  Article  Google Scholar 

  52. De Filippo C et al (2010) Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 107(33):14691–14696

    PubMed  Article  Google Scholar 

  53. Walk ST et al (2010) Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus. Inflamm Bowel Dis 16(11):1841–1849

    PubMed  Article  Google Scholar 

  54. Dominguez-Bello MG et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 107(26):11971–11975

    PubMed  Article  Google Scholar 

  55. Yatsunenko T et al (2012) Human gut microbiome viewed across age and geography. Nature 486(7402):222–227

    PubMed  CAS  Google Scholar 

  56. Antonopoulos DA et al (2009) Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect Immun 77(6):2367–2375

    PubMed  CAS  Article  Google Scholar 

  57. Hill DA et al (2010) Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol 3(2):148–158

    PubMed  CAS  Article  Google Scholar 

  58. Ubeda C et al (2010) Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest 120(12):4332–4341

    PubMed  CAS  Article  Google Scholar 

  59. Blaser M (2011) Antibiotic overuse: stop the killing of beneficial bacteria. Nature 476(7361):393–394

    PubMed  CAS  Article  Google Scholar 

  60. Turnbaugh PJ et al (2007) The human microbiome project. Nature 449(7164):804–810

    PubMed  CAS  Article  Google Scholar 

  61. Reikvam DH et al (2011) Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression. PLoS One 6(3):e17996

    PubMed  CAS  Article  Google Scholar 

  62. Dethlefsen L, Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Pro Natl Acad Sci USA 108(Suppl 1):4554–4561

    CAS  Article  Google Scholar 

  63. Jernberg C, Lofmark S, Edlund C, Jansson JK (2007) Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J 1(1):56–66

    PubMed  CAS  Article  Google Scholar 

  64. De La Cochetière MF et al (2005) Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J Clin Microbiol 43(11):5588–5592

    Article  CAS  Google Scholar 

  65. Jakobsson HE et al (2010) Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One 5(3):e9836

    PubMed  Article  CAS  Google Scholar 

  66. Johnson CC et al (2005) Antibiotic exposure in early infancy and risk for childhood atopy. J Allergy Clin Immunol 115(6):1218–1224

    PubMed  CAS  Article  Google Scholar 

  67. Droste JHJ et al (2000) Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease. Clin Exp Allergy 30(11):1547–1553

    PubMed  CAS  Article  Google Scholar 

  68. Kozyrskyj AL, Ernst P, Becker AB (2007) Increased risk of childhood asthma from antibiotic use in early life. Chest 131(6):1753–1759

    PubMed  Article  Google Scholar 

  69. Wickens K et al (1999) Antibiotic use in early childhood and the development of asthma. Clin Exp Allergy 29(6):766–771

    PubMed  CAS  Article  Google Scholar 

  70. Wjst MHB et al (2001) Early antibiotic treatment and later asthma. Eur J Med Res 6(6):263–271

    PubMed  CAS  Google Scholar 

  71. Marra F et al (2006) Does antibiotic exposure during infancy lead to development of asthma?: a systematic review and metaanalysis. Chest 129(3):610–618

    PubMed  CAS  Article  Google Scholar 

  72. Dom S et al (2010) Pre- and post-natal exposure to antibiotics and the development of eczema, recurrent wheezing and atopic sensitization in children up to the age of 4 years. Clin Exp Allergy 40(9):1378–1387

    PubMed  CAS  Article  Google Scholar 

  73. Bashir ME et al (2004) Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J Immunol 172(11):6978–6987

    PubMed  CAS  Google Scholar 

  74. Atarashi K et al (2011) Induction of colonic regulatory T Cells by indigenous Clostridium species. Science 331(6015):337–341

    PubMed  CAS  Article  Google Scholar 

  75. Russell SL et al (2012) Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep 13(5):440–447

    PubMed  CAS  Article  Google Scholar 

  76. Hill DA et al (2012) Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18(4):538–546

    PubMed  CAS  Article  Google Scholar 

  77. Maslowski KM, Mackay CR (2011) Diet, gut microbiota and immune responses. Nat Immunol 12(1):5–9

    PubMed  CAS  Article  Google Scholar 

  78. Peng L et al (2009) Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr 139(9):1619–1625

    PubMed  CAS  Article  Google Scholar 

  79. Lewis K et al (2010) Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate. Inflamm Bowel Dis 16(7):1138–1148

    PubMed  Google Scholar 

  80. Maslowski KM et al (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461(7268):1282–1286

    PubMed  CAS  Article  Google Scholar 

  81. Høverstad T, Midtvedt T (1986) Short-chain fatty acids in germfree mice and rats. J Nutr 116(9):1772–1776

    PubMed  Google Scholar 

  82. Paturi G et al (2010) Cecal and colonic responses in rats fed 5 or 30 % corn oil diets containing either 7.5 % broccoli dietary fiber or microcrystalline cellulose. J Agric Food Chem 58(10):6510–6515

    PubMed  CAS  Article  Google Scholar 

  83. Paturi G et al (2012) Influence of dietary blueberry and broccoli on cecal microbiota activity and colon morphology in mdr1a−/− mice, a model of inflammatory bowel diseases. Nutrition 28(3):324–330

    PubMed  CAS  Article  Google Scholar 

  84. Harig JM et al (1989) Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med 320(1):23–28

    PubMed  CAS  Article  Google Scholar 

  85. Vernia P et al (1995) Short-chain fatty acid topical treatment in distal ulcerative colitis. Aliment Pharmacol Ther 9(3):309–313

    PubMed  CAS  Article  Google Scholar 

  86. Ley RE et al (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102(31):11070–11075

    PubMed  CAS  Article  Google Scholar 

  87. Hildebrandt MA et al (2009) High fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137(5):1716–1724

    PubMed  CAS  Article  Google Scholar 

  88. Devkota S et al (2012) Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487(7405):104–108

    PubMed  CAS  Google Scholar 

  89. Kull I et al (2006) Fish consumption during the first year of life and development of allergic diseases during childhood. Allergy 61(8):1009–1015

    PubMed  CAS  Article  Google Scholar 

  90. Dunstan JA et al (2003) Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol 112(6):1178–1184

    PubMed  CAS  Article  Google Scholar 

  91. Manley BJ et al (2011) High-dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes. Pediatrics 128(1):e71–e77

    PubMed  Article  Google Scholar 

  92. Kankaanpaa P et al (2001) Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy. Allergy 56(7):633–638

    PubMed  CAS  Article  Google Scholar 

  93. Arumugam M et al (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180

    PubMed  CAS  Article  Google Scholar 

  94. Wu GD et al (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334(6052):105–108

    PubMed  CAS  Article  Google Scholar 

  95. Hewitson JP, Grainger JR, Maizels RM (2009) Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity. Mol Biochem Parasitol 167(1):1–11

    PubMed  CAS  Article  Google Scholar 

  96. van den Biggelaar AH, van Ree R, Rodrigues LC et al (2000) Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced IL-10. Lancet 356(9243):1723–1727

    PubMed  Article  Google Scholar 

  97. Yazdanbakhsh M, van den Biggelaar A, Maizels RM (2001) Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends Immunol 22(7):372–377

    PubMed  CAS  Article  Google Scholar 

  98. Flohr C et al (2010) Reduced helminth burden increases allergen skin sensitization but not clinical allergy:a randomized, double-blind, placebo-controlled trial in Vietnam. Clin Exp Allergy 40(1):131–142

    PubMed  CAS  Google Scholar 

  99. Lynch NR et al (1993) Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum. J Allergy Clin Immunol 92(3):404–411

    PubMed  CAS  Article  Google Scholar 

  100. Wilson MS et al (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 202(9):1199–1212

    PubMed  CAS  Article  Google Scholar 

  101. Mangan NE et al (2004) Helminth infection protects mice from anaphylaxis via IL-10-producing B cells. J Immunol 173(10):6346–6356

    PubMed  CAS  Google Scholar 

  102. Mangan NE et al (2006) Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness. J Immunol 176(1):138–147

    PubMed  CAS  Google Scholar 

  103. Kitagaki K et al (2006) Intestinal helminths protect in a murine model of asthma. J Immunol 177(3):1628–1635

    PubMed  CAS  Google Scholar 

  104. Cardoso LS et al (2010) Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation. Clin Exp Immunol 160(2):266–274

    PubMed  CAS  Article  Google Scholar 

  105. Wilson MS et al (2010) Helminth-induced CD19 + CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol 40(6):1682–1696

    PubMed  CAS  Article  Google Scholar 

  106. McSorley HJ et al (2012) Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus. Eur J Immunol [Epub ahead of print]

  107. Bashir ME et al (2002) An enteric helminth infection protects against an allergic response to dietary antigen. J Immunol 169(6):3284–3292

    PubMed  CAS  Google Scholar 

  108. Feary JR et al (2010) Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clin Exp Allergy 40(2):299–306

    PubMed  CAS  Article  Google Scholar 

  109. Bager P et al (2010) Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. J Allergy Clin Immunol 125(1):123–130, e123

    PubMed  Article  Google Scholar 

  110. Jouvin M-H, Kinet J-P (2012) Trichuris suis ova: testing a helminth-based therapy as an extension of the hygiene hypothesis. J Allergy Clin Immunol 130(1):3–10

    PubMed  Article  Google Scholar 

  111. Perry S et al (2010) Infection with Helicobacter pylori is associated with protection against tuberculosis. PLoS One 5(1):e8804

    PubMed  Article  CAS  Google Scholar 

  112. Chen Y, Blaser MJ (2008) Helicobacter pylori colonization is inversely associated with childhood asthma. J Infect Dis 198(4):553–560

    PubMed  Article  Google Scholar 

  113. Chen Y, Blaser MJ (2007) Inverse associations of Helicobacter pylori with asthma and allergy. Arch Intern Med 167(8):821–827

    PubMed  Article  Google Scholar 

  114. Reibman J et al (2008) Asthma is inversely associated with Helicobacter pylori status in an urban population. PLoS One 3(12):e4060

    PubMed  Article  CAS  Google Scholar 

  115. Arnold IC et al (2011) Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J Clin Invest 121(8):3088–3093

    PubMed  CAS  Article  Google Scholar 

  116. Lupp C et al (2007) Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe 2(3):204

    PubMed  CAS  Article  Google Scholar 

  117. Barman M et al (2008) Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract. Infect Immun 76(3):907–915

    PubMed  CAS  Article  Google Scholar 

  118. Grölund M-M et al (1999) Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr 28(1):19–25

    Article  Google Scholar 

  119. Savage DC, Dubos R, Schaedler RW (1968) The gastrointestinal epithelium and its autochthonous bacterial flora. J Exp Med 127(1):67–76

    PubMed  CAS  Article  Google Scholar 

  120. Martin R et al (2010) Early life: gut microbiota and immune development in infancy. Benef Microbes 1(4):367–382

    PubMed  CAS  Article  Google Scholar 

  121. Costello EK et al (2009) Bacterial community variation in human body habitats across space and time. Science 326(5960):1694–1697

    PubMed  CAS  Article  Google Scholar 

  122. Huurre A et al (2008) Mode of delivery—effects on gut microbiota and humoral immunity. Neonatology 93(4):236–240

    PubMed  Article  Google Scholar 

  123. van Nimwegen FA et al (2011) Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. J Allergy Clin Immunol 128(5):948–955

    PubMed  Article  Google Scholar 

  124. Björkstén B (2005) Genetic and environmental risk factors for the development of food allergy. Curr Opin Allergy Clin Immunol 5(3):249–253

    PubMed  Article  Google Scholar 

  125. Salminen S et al (2004) Influence of mode of delivery on gut microbiota composition in seven year old children. Gut 53(9):1388–1389

    PubMed  CAS  Article  Google Scholar 

  126. Eggesbø M et al (2003) Is delivery by cesarean section a risk factor for food allergy? J Allergy Clin Immunol 112(2):420–426

    PubMed  Article  Google Scholar 

  127. Kero J et al (2002) Mode of delivery and asthma—is there a connection? Pediatr Rev 52(1):6–11

    Google Scholar 

  128. Decker E, Hornef M, Stockinger S (2011) Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children. Gut Microbes 2(2):91–98

    PubMed  Article  Google Scholar 

  129. Kramer MS (2011) Breastfeeding and allergy: the evidence. Ann Nutr Metab 59(Suppl 1):20–26

    PubMed  CAS  Article  Google Scholar 

  130. Fagarasan S, Honjo T (2003) Intestinal IgA synthesis: regulation of front-line body defences. Nat Rev Immunol 3(1):63–72

    PubMed  CAS  Article  Google Scholar 

  131. Greer FR et al (2008) Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 121(1):183–191

    PubMed  Article  Google Scholar 

  132. von Berg A et al (2003) The effect of hydrolyzed cow’s milk formula for allergy prevention in the first year of life: the German infant nutritional intervention study, a randomized double-blind trial. J Allergy Clin Immunol 111(3):533–540

    Article  Google Scholar 

  133. Laubereau B et al (2004) Effect of breast-feeding on the development of atopic dermatitis during the first 3 years of life—results from the GINI-birth cohort study. J Pediatr 144(5):602–607

    PubMed  Article  Google Scholar 

  134. Yang YW, Tsai CL, Lu CY (2009) Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta-analysis of prospective cohort studies. Br J Dermatol 161(2):373–383

    PubMed  CAS  Article  Google Scholar 

  135. Hascoët J-M et al (2011) Effect of formula composition on the development of infant gut microbiota. J Pediatr Gastroenterol Nutr 52(6):756–762

    PubMed  Article  Google Scholar 

  136. Maga EA et al (2012) Consumption of lysozyme-rich milk can alter microbial fecal populations. Appl Environ Microbiol 78(17):6153–6160

    Google Scholar 

  137. Smith DW, Nagler-Anderson C (2005) Preventing intolerance: the induction of nonresponsiveness to dietary and microbial antigens in the intestinal mucosa. J Immunol 174(7):3851–3857

    PubMed  CAS  Google Scholar 

  138. Vickery BP et al (2011) Mechanisms of immune tolerance relevant to food allergy. J Allergy Clin Immunol 127(3):576–584

    PubMed  CAS  Article  Google Scholar 

  139. Kim JS, Sampson HA (2012) Food allergy: a glimpse into the inner workings of gut immunology. Curr Opin Gastroenterol 28(2):99–103

    PubMed  CAS  Article  Google Scholar 

  140. Wang J, Sampson HA (2011) Food allergy. J Clin Invest 121(3):827–835

    PubMed  CAS  Article  Google Scholar 

  141. Weiner HL et al (2011) Oral tolerance. Immunol Rev 241(1):241–259

    PubMed  CAS  Article  Google Scholar 

  142. Hadis U et al (2011) Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 34(2):237–246

    PubMed  CAS  Article  Google Scholar 

  143. Cassani B et al (2011) Gut-tropic T Cells that express integrin α4β7 and CCR9 are required for induction of oral immune tolerance in mice. Gastroenterology 141(6):2109–2118

    PubMed  CAS  Article  Google Scholar 

  144. Pabst O, Mowat AM (2012) Oral tolerance to food protein. Mucosal Immunol 5(3):232–239

    PubMed  CAS  Article  Google Scholar 

  145. Jaensson E et al (2008) Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 205(9):2139–2149

    PubMed  CAS  Article  Google Scholar 

  146. Schulz O et al (2009) Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J Exp Med 206(13):3101–3114

    PubMed  CAS  Article  Google Scholar 

  147. Sun C-M et al (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204(8):1775–1785

    PubMed  CAS  Article  Google Scholar 

  148. Murai M et al (2009) Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 10(11):1178–1184

    PubMed  CAS  Article  Google Scholar 

  149. Medina-Contreras O et al (2011) CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice. J Clin Invest 121(12):4787–4795

    PubMed  CAS  Article  Google Scholar 

  150. Crispe IN (2009) The liver as a lymphoid organ. Annu Rev Immunol 27:147–163

    PubMed  CAS  Article  Google Scholar 

  151. Goubier A et al (2008) Plasmacytoid dendritic cells mediate oral tolerance. Immunity 29(3):464–475

    PubMed  CAS  Article  Google Scholar 

  152. Dubois B et al (2009) Sequential role of plasmacytoid dendritic cells and regulatory T cells in oral tolerance. Gastroenterology 137(3):1019–1028

    PubMed  CAS  Article  Google Scholar 

  153. Bar-On L et al (2010) CX3CR1+ CD8alpha+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells. Pro Natl Acad Sci USA 107(33):14745–14750

    CAS  Article  Google Scholar 

  154. Smith K, McCoy KD, Macpherson AJ (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19(2):59–69

    PubMed  CAS  Article  Google Scholar 

  155. Hamada H et al (2002) Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol 168(1):57–64

    PubMed  CAS  Google Scholar 

  156. Gaboriau-Routhiau V et al (2009) The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31(4):677–688

    PubMed  CAS  Article  Google Scholar 

  157. Ivanov II et al (2008) Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4(4):337–349

    PubMed  CAS  Article  Google Scholar 

  158. Mazmanian SK et al (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122(1):107–118

    PubMed  CAS  Article  Google Scholar 

  159. McCoy KD et al (2006) Natural IgE production in the absence of MHC Class II cognate help. Immunity 24(3):329–339

    PubMed  CAS  Article  Google Scholar 

  160. Itoh K, Mitsuoka T (1985) Characterization of clostridia isolated from faeces of limited flora mice and their effect on caecal size when associated with germ-free mice. Lab Anim 19(2):111–118

    PubMed  CAS  Article  Google Scholar 

  161. Geuking MB et al (2011) Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34(5):794–806

    PubMed  CAS  Article  Google Scholar 

  162. Round JL, Mazmanian SK (2010) Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 107(27):12204–12209

    PubMed  CAS  Article  Google Scholar 

  163. Fagarasan S, Honjo T (2004) Regulation of IgA synthesis at mucosal surfaces. Curr Opin Immunol 16(3):277–283

    PubMed  CAS  Article  Google Scholar 

  164. Feng T et al (2011) Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol 186(11):6313–6318

    PubMed  CAS  Article  Google Scholar 

  165. Wu H-J et al (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815–827

    PubMed  CAS  Article  Google Scholar 

  166. Nagano Y, Itoh K, Honda K (2012) The induction of Treg cells by gut-indigenous Clostridium. Curr Opin Immunol 24(4):392–297

    Google Scholar 

  167. Umesaki Y et al (1999) Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immunol 67(7):3504–3511

    CAS  Google Scholar 

  168. Cong Y et al (2009) A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc Natl Acad Sci USA 106(46):19256–19261

    PubMed  CAS  Article  Google Scholar 

  169. Nava GM, Friedrichsen HJ, Stappenbeck TS (2011) Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J 5(4):627–638

    PubMed  CAS  Article  Google Scholar 

  170. Duck LW et al (2007) Isolation of flagellated bacteria implicated in Crohn’s disease. Inflamm Bowel Dis 13(10):1191–1201

    PubMed  Article  Google Scholar 

  171. Shen C et al (2008) Enhanced CBir1-specific innate and adaptive immune responses in Crohn’s disease. Inflamm Bowel Dis 14(12):1641–1651

    PubMed  Article  Google Scholar 

  172. Round JL et al (2011) The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332(6032):974–977

    PubMed  CAS  Article  Google Scholar 

  173. Di Giacinto C et al (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-β-bearing regulatory cells. J Immunol 174(6):3237–3246

    PubMed  Google Scholar 

  174. Karimi K et al (2009) Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med 179(3):186–193

    PubMed  CAS  Article  Google Scholar 

  175. Josefowicz SZ et al (2012) Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482(7385):395–399

    PubMed  CAS  Article  Google Scholar 

  176. Lathrop SK et al (2011) Peripheral education of the immune system by colonic commensal microbiota. Nature 478(7368):250–254

    PubMed  CAS  Article  Google Scholar 

  177. Olszak T (2012) Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336(6080):489–493

    PubMed  CAS  Article  Google Scholar 

  178. Noverr MC, Huffnagle GB (2004) Does the microbiota regulate immune responses outside the gut? Trends Microbiol 12(12):562–568

    PubMed  CAS  Article  Google Scholar 

  179. Willyard C (2011) Microbiome: gut reaction. Nature 479(7374):S5–S7

    Article  Google Scholar 

  180. Molin G (2001) Probiotics in foods not containing milk or milk constituents, with special reference to Lactobacillus plantarum 299v. Am J Clin Nutr 73(2 Suppl):380S–385S

    PubMed  CAS  Google Scholar 

  181. Clarke G et al (2012) Review article: probiotics for the treatment of irritable bowel syndrome—focus on lactic acid bacteria. Aliment Pharmacol Ther 35(4):403–413

    PubMed  CAS  Article  Google Scholar 

  182. Jonkers D et al (2012) Probiotics in the management of inflammatory bowel disease: a systematic review of intervention studies in adult patients. Drugs 72(6):803–823

    PubMed  Article  Google Scholar 

  183. Heineman J et al (2012) Fighting fire with fire: is it time to use probiotics to manage pathogenic bacterial diseases? Curr Gastroenterol Rep 14(4):343–348

    PubMed  Article  Google Scholar 

  184. Wickens K et al (2008) A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 122(4):788–794

    PubMed  Article  Google Scholar 

  185. Wickens K et al (2012) A protective effect of Lactobacillus rhamnosus HN001 against eczema in the first 2 years of life persists to age 4 years. Clin Exp Allergy 42(7):1071–1079

    PubMed  CAS  Article  Google Scholar 

  186. Kalliomaki N et al (2001) Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 357(9262):1076–1079

    PubMed  CAS  Article  Google Scholar 

  187. Kukkonen K et al (2007) Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 119(1):192–198

    PubMed  CAS  Article  Google Scholar 

  188. Johansson ML et al (1993) Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. Appl Environ Microbiol 59(1):15–20

    PubMed  CAS  Google Scholar 

  189. Goossens D (2003) The effect of Lactobacillus plantarum 299v on the bacterial composition and metabolic activity in faeces of healthy volunteers: a placebo-controlled study on the onset and duration of effects. Aliment Pharmacol Ther 18(5):495–505

    PubMed  CAS  Article  Google Scholar 

  190. Tannock GW et al (2000) Analysis of the fecal microflora of human subjects consuming a probiotic product containing Lactobacillus rhamnosus DR20. Appl Environ Microbiol 66(6):2578–2588

    PubMed  CAS  Article  Google Scholar 

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Acknowledgments

This work was supported by the Food Allergy Initiative. We thank Joanna Wroblewska for assistance with preparation of the figures and review of the manuscript.

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Affiliations

  1. Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL, USA

    Taylor Feehley, Andrew T. Stefka & Severine Cao

  2. Department of Pathology, The University of Chicago, Jules F. Knapp Medical Research Building, 924 East 57th Street, R120, Chicago, IL, 60637, USA

    Cathryn R. Nagler

Authors
  1. Taylor Feehley
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  2. Andrew T. Stefka
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  3. Severine Cao
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  4. Cathryn R. Nagler
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Correspondence to Cathryn R. Nagler.

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This article is published as part of the Special Issue on Food Allergy [34:6].

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Feehley, T., Stefka, A.T., Cao, S. et al. Microbial regulation of allergic responses to food. Semin Immunopathol 34, 671–688 (2012). https://doi.org/10.1007/s00281-012-0337-5

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Keywords

  • Microbiome
  • Hygiene hypothesis
  • Dysbiosis
  • Atopy
  • Bacteria