Skip to main content

Advertisement

Log in

Hygiene Hypothesis: What Is the Current Thinking?

  • Special Topics In Otorhinolaryngology: Otolaryngic Allergy (E Toskala, Section Editor)
  • Published:
Current Otorhinolaryngology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Our aim was to discuss the hygiene hypothesis and current thinking about it.

Recent Findings

Hygiene hypothesis suggests that an underlying reason for the recent prominent rise in allergic diseases may be linked with the diminution of the incidence of early childhood infections, which can be transmitted by means of contact with older siblings. Hygiene hypothesis suggests that contact with microbes in the environment in early life through pets, unpasteurized food, and nonsterilized water may protect from atopic diseases. Exposure to microbial pathogens and animals in infancy prevents atopy by Th1-like cytokine responses or by modifying Th2-like immune responses. Chronic infection and inflammation may protect against atopic disease. Alteration of exposure to microorganisms and access to clean water as well as issues related with food, sanitation, medical and obstetric practices, and urban lifestyle may have significant roles. Decreased exposure to bacteria in the early infancy period may shift the immune system to a predominantly Th2 state which is detected in atopic cases. Environmental exposure may lead to epigenetic changes which causes a shift of immune reactions against microorganisms.

Summary

The hygiene hypothesis implies that modern living conditions can be responsible for the rise in the incidences of allergic disease and asthma. Protective effect of food-borne microbes on allergic diseases is another remarkable issue.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Smith V. Chapter 3. Greek hygiene. In: Smith V, editor. Clean: a history of personal hygiene and purity. Oxford: Oxford University Press; 2007. p. 74–83.

    Google Scholar 

  2. Deckers IA, McLean S, Linssen S, Mommers M, van Schayck CP, Sheikh A. Investigating international time trends in the incidence and prevalence of atopic eczema 1990–2010: a systematic review of epidemiological studies. PLoS One. 2012;7(7):e39803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Asher MI, Montefort S, Björkstén B, Lai CK, Strachan DP, Weiland SK et al.; ISAAC Phase Three Study Group. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006; 368(9537): 733–743.

  4. Prescott SL, Pawankar R, Allen KJ, Campbell DE, Sinn JK, Fiocchi A, et al. A global survey of changing patterns of food allergy burden in children. World Allergy Organ Journal. 2013;6:21.

    Article  Google Scholar 

  5. •• Bloomfield SF, Rook GA, Scott EA, Shanahan F, Stanwell-Smith R, Turner P. Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene. Perspect Public Health. 2016;136(4):213–24. doi:10.1177/1757913916650225. Hygiene hypothesis and allergic diseases and the importance of human microbiome.

    Article  PubMed  PubMed Central  Google Scholar 

  6. McFall-Ngai M, Hadfield MG, Bosch TC, Carey HV, Domazet-Lošo T, Douglas AE, et al. Animals in a bacterial world, a new imperative for the life sciences. Proceedings of the National Academy of Sciences U S A. 2013;110:3229–36.

    Article  CAS  Google Scholar 

  7. Thorburn AN, Macia L, Mackay CR. Diet, metabolites, and ‘Western-lifestyle’ inflammatory diseases. Immunity. 2014;40:833–42.

    Article  CAS  PubMed  Google Scholar 

  8. Zeng H, Chi H. Metabolic control of regulatory T cell development and function. Trends Immunol. 2015;36:3–12.

    Article  CAS  PubMed  Google Scholar 

  9. Martín-Peláez S, Mosele JI, Pizarro N, Farràs M, de la Torre R, Subirana I et al. Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota. Eur J Nutr. 2015; doı: 10.1007/s00394-015-1063-2.

  10. Cuervo A, Hevia A, López P, Suárez A, Diaz C, Sánchez B, et al. Phenolic compounds from red wine and coffee are associated with specific intestinal microorganisms in allergic subjects. Food Funct. 2016;7:104–9.

    Article  CAS  PubMed  Google Scholar 

  11. Vanamala JK, Knight R, Spector TD. Can your microbiome tell you what to eat? Cell Metab. 2015;22:960–1.

    Article  CAS  PubMed  Google Scholar 

  12. Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, Sonnenburg JL. Diet-induced extinctions in the gut microbiota compound over generations. Nature. 2016;529:212–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Benn CS, Melbye M, Wohlfahrt J, Bjorksten B, Aaby P. Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life. Br Med J. 2004;328:1223–8.

    Article  Google Scholar 

  14. Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani PD, Backhed F. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 2015;22:658–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kaliannan K, Wang B, Li XY, Kim KJ, Kang JX. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep. 2015;5:11276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. von Hertzen L, Haahtela T. Disconnection of man and the soil: reason for the asthma and atopy epidemic? J Allergy Clin Immunol. 2006;117:334–44.

    Article  Google Scholar 

  17. Kilpeläinen M, Terho EO, Helenius H, Koskenvuo M. Farm environment in childhood prevents the development of allergies. Clin Exp Allergy. 2000;30:201–8.

    Article  PubMed  Google Scholar 

  18. Daley D. The evolution of the hygiene hypothesis: the role of early-life exposures to viruses and microbes and their relationship to asthma and allergic diseases. Curr Opin Allergy Clin Immunol. 2014;14:390–6.

    Article  CAS  PubMed  Google Scholar 

  19. Yeşil Ş, Kan A, Abdulmajed O, Bakirtaş A, Sultan N, Demirsoy MS. Role of hygienic factors in the etiology of allergic disorders in children. Turk J Med Sci. 2017;47(2):627–32. doi:10.3906/sag-1603-22.

    PubMed  Google Scholar 

  20. Bloomfield SF, Stanwell-Smith R, Crevel RW, Pickup J. Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy. 2006;36(4):402–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Strachan DP. Hay fever, hygiene and household size. Br Med J. 1989;299:1259–60.

    Article  CAS  Google Scholar 

  22. Marshall AL, Chetwynd A, Morris JA, et al. Type 1 diabetes mellitus in childhood: a matched case control study in Lancashire and Cumbria, UK. Diabet Med. 2004;21:1035–40.

    Article  CAS  PubMed  Google Scholar 

  23. Sheikh A, Smeeth L, Hubbard R. There is no evidence of an inverse relationship between TH2-mediated atopy and TH1-mediated autoimmune disorders: lack of support for the hygiene hypothesis. J Allergy Clin Immunol. 2003;111:131–5.

    Article  CAS  PubMed  Google Scholar 

  24. Sotgiu S, Pugliatti M, Sotgiu A, et al. Does the ‘hygiene hypothesis’ provide an explanation for the high prevalence of multiple sclerosis in Sardinia? Autoimmunity. 2003;36:257–60.

    Article  PubMed  Google Scholar 

  25. Danese S, Sans M, Fiocchi C. Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev. 2004;3:394–400.

    Article  CAS  PubMed  Google Scholar 

  26. Johnson RJ, Hurtado A, Merszei J, et al. Hypothesis: dysregulation of immunologic balance resulting from hygiene and socioeconomic factors may influence the epidemiology and cause of glomerulonephritis worldwide. Am J Kidney Dis. 2003;42:575–81.

    Article  PubMed  Google Scholar 

  27. •• Patel S, Gruchalla R. Can we be too clean for our own good? The hygiene hypothesis reviewed. Tex Med. 2017;113(2):54–9. Update for hygiene hypothesis, a review paper.

    PubMed  Google Scholar 

  28. Nowak D, Suppli Ulrik C, von Mutius E. Asthma and atopy: has peak prevalence been reached? Eur Resp I. 2004;23:359–60.

    Article  CAS  Google Scholar 

  29. Chang TW, Wu PC, Hsu CL, Hung AF. Anti-IgE antibodies for the treatment of IgE-mediated allergic diseases. Adv Immunol. 2007;93:63–119.

    Article  CAS  PubMed  Google Scholar 

  30. Versini M, Jeandel P-Y, Bashi T, Bizarro G, Blank M, Shoenfeld Y. Unraveling the hygiene hypothesis of helminthes and autoimmunity: origins, pathophysiology and clinical applications. BMC Med. 2015;13:81–96.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Allaerts W, Chang TW. Skewed exposure to environmental antigens complements hygiene hypothesis in explaining the rise of allergy. Acta Biotheor. 2017;65(2):117–34. doi:10.1007/s10441-017-9306-7. Epub 2017 Mar 24

    Article  PubMed  PubMed Central  Google Scholar 

  32. Warner JO. Worldwide variations in the prevalence of atopic symptoms: what does it all mean? Thorax. 1999;54(Suppl 2):546–51.

    Google Scholar 

  33. Platts-Mills TAE, Carter MC, Heymann PW. Specific and nonspecific obstructive lung disease in childhood: causes of changes in the prevalence of asthma. Environ Health Persp. 2000;108(Suppl 4):725–31.

    Article  Google Scholar 

  34. Russell G, Helms PJ. Trends in occurrence of asthma among children and young adults. BMJ. 1997;315:1014–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Upton MN, McConnachie A, McSharry C, et al. Intergenerational 20 year trends in the prevalence of asthma and hay fever in adults: the Midspan family study surveys of parents and offspring. BMJ. 2000;321:88–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bloomfield SF, Stanwell-Smithw R, Crevelz RWR, Pickup J. Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy. 36:402–25.

  37. Mallia P, Johnston SL. Respiratory viruses: do they protect from or induce asthma? Allergy. 2002;57:1118–29.

    Article  CAS  PubMed  Google Scholar 

  38. Bresciani M, Parisi C, Menghi G, Bonini S. The hygiene hypothesis: does it function worldwide? Curr Opin Allergy Clin Immunol. 2005;5(2):147–51.

    Article  PubMed  Google Scholar 

  39. Whary MT, Fox JG. Th1-mediated pathology in mouse models of human disease is ameliorated by concurrent Th2 responses to parasite antigens. Curr Op Med Chem. 2004;4:531–8.

    Article  CAS  Google Scholar 

  40. Sheikh A, Strachan DP. The hygiene theory: fact or fiction? Curr Opin Otolaryngol Head Neck Surg. 2004;12:232–6.

    Article  PubMed  Google Scholar 

  41. Umetsu DT. Flu strikes the hygiene hypothesis. Nat Med. 2004;10:232–4.

    Article  CAS  PubMed  Google Scholar 

  42. Dahl ME, Dabbagh K, Liggitt D, et al. Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells. Nat Immunol. 2004;5:337–43.

    Article  CAS  PubMed  Google Scholar 

  43. Linneberg A, Ostergaard C, Tvede M, et al. IgG antibodies against microorganisms and atopic disease in Danish adults: the Copenhagen Allergy Study. J Allergy Clin Immunol. 2003;111:847–53.

    Article  CAS  PubMed  Google Scholar 

  44. Liu AH. Something old, something new: indoor endotoxin, allergens and asthma. Paediatr Respir Rev. 2004;5(Suppl 1A):S65–71.

    Article  PubMed  Google Scholar 

  45. Heaton T, Mallon D, Venaille T, Holt P. Staphylococcal enterotoxin induced IL-5 stimulation as a cofactor in the pathogenesis of atopic disease: the hygiene hypothesis in reverse? Allergy. 2003;58:252–6.

    Article  CAS  PubMed  Google Scholar 

  46. Riedler J, Braun-Fahrlander C, Eder W, et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet. 2001;358:1129–33.

    Article  CAS  PubMed  Google Scholar 

  47. Rook GA, Stanford JL. Skin-test responses to mycobacteria in atopy and asthma. Allergy. 1999;54:285–6.

    Article  CAS  PubMed  Google Scholar 

  48. Von Ehrenstein OS, Von Mutius E, Illi S, et al. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy. 2000;30:187–93.

    Article  Google Scholar 

  49. Prescott SL, Macaubas C, Holt BJ, et al. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol. 1998;160:4730–7.

    CAS  PubMed  Google Scholar 

  50. Prescott SL, Macaubas C, Smallacombe T, et al. Development of allergenspecific T-cell memory in atopic and normal children. Lancet. 1999;353:196–200.

    Article  CAS  PubMed  Google Scholar 

  51. Baldini M, Lohman IC, Halonen M, et al. A polymorphism_ in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol. 1999;20:976–83.

    Article  CAS  PubMed  Google Scholar 

  52. Baldini M, Vercelli D, Martinez FD. CD14: an example of gene by environment interaction in allergic disease. Allergy. 2002;57:188–92.

    Article  CAS  PubMed  Google Scholar 

  53. Caliskan M, Bochkov YA, Kreiner-Moller E, et al. Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N Engl J Med. 2013;368:1398–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cox DW, Bizzintino J, Ferrari G, et al. Human rhinovirus species C infection in young children with acute wheeze is associated with increased acute respiratory hospital admissions. Am J Respir Crit Care Med. 2013;188:1358–64.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Elazab N, Mendy A, Gasana J, et al. Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics. 2013;132:e666–76.

    Article  PubMed  Google Scholar 

  56. Bisgaard H, Li N, Bonnelykke K, et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J Allergy Clin Immunol. 2011;128:646–52. (e1-5)

    Article  PubMed  Google Scholar 

  57. Abrahamsson TR, Jakobsson HE, Andersson AF, et al. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy. 2014;44:842–50.

    Article  CAS  PubMed  Google Scholar 

  58. Santiago HC, Nutman TB. Human helminths and allergic disease: the hygiene hypothesis and beyond. Am J Trop Med Hyg. 2016;95(4):746–53. Epub 2016 Aug 29

    Article  PubMed  Google Scholar 

  59. vanden Biggelaar AH, van Ree R, Rodrigues LC, Lell B, Deelder AM, Kremsner PG, et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet. 2000;356:1723–7. doi:10.1016/S0140-6736 (00)03206-2.

    Article  PubMed  Google Scholar 

  60. Cooper PJ, Chico ME, Rodrigues LC, Ordonez M, Strachan D, Griffin GE, et al. Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol. 2003;111:995–1000. doi:10.1067/mai.2003.1348.

    Article  PubMed  Google Scholar 

  61. Rodrigues LC, Newcombe PJ, Cunha SS, Alcantara-Neves NM, Genser B, Cruz AA, et al. Early infection with Trichuristrichiura and allergen skin test reactivity in later childhood. Clin Exp Allergy. 2008;38:1769–77. doi:10.1111/j.1365-2222.2008.03027.x.

    CAS  PubMed  Google Scholar 

  62. Leonardi-Bee J, Pritchard D, Britton J. Asthma and current intestinal parasite infection: systematic review and meta-analysis. Am J Respir Crit Care Med. 2006;174:514–23. doi:10.1164/rccm.200603-331OC.

    Article  PubMed  Google Scholar 

  63. Scrivener S, Yemaneberhan H, Zebenigus M, Tilahun D, Girma S, Ali S, et al. Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Lancet. 2001;358:1493–9. doi:10.1016/S0140-6736(01)06579-5.

    Article  CAS  PubMed  Google Scholar 

  64. Flohr C, Tuyen LN, Quinnell RJ, Lewis S, Minh TT, Campbell J, et al. Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam. Clin Exp Allergy. 2010;40:131–42. doi:10.1111/j.1365-2222.2009.03346.x.

    CAS  PubMed  Google Scholar 

  65. Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, et al. Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clin Exp Allergy. 2010;40:299–306. doi:10.1111/j.1365-2222.2009.03433.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mc Sorley HJ, Maizels RM. Helminth infections and host immune regulation. Clin Microbiol Rev. 2012;25(4):585–608. doi:10.1128/CMR.05040-11.

    Article  CAS  Google Scholar 

  67. Fitzsimmons CM, Falcone FH, Dunne DW. Helminth allergens, parasite-specific IgE, and its protective role in human immunity. Front Immunol. 2014 Feb 14;5:61. doi:10.3389/fimmu.2014.00061.eCollection 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Strachan DP, Harkins LS, Johnston IDA, Anderson HR. Clinical aspects of allergic disease. Childhood antecedents of allergic sensitisation in young British adults. J Allergy Clin Immunol. 1997;99:6–12.

    CAS  PubMed  Google Scholar 

  69. von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Roell G, Thiemann HH. Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med. 1994;49:358–64.

    Article  Google Scholar 

  70. Jarvis D, Chinn S, Luczynska C, Burney P. The association of family size with atopy and atopic disease. Clin Exp Allergy. 1997;27:240–5.

    Article  CAS  PubMed  Google Scholar 

  71. Haby MM, Peat JK, Marks GB, Woolcock AJ, Leeder SR. Asthma in preschool children: prevalence and risk factors. Thorax. 2001;56:589–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Infante-Rivard C, Amre D, Gautrin D, Malo JL. Family size, daycare attendance and breastfeeding in relation to the risk of childhood asthma. Am J Epidemiol. 2001;153:653–8.

    Article  CAS  PubMed  Google Scholar 

  73. Strachan D. Socioeconomic factors and the development of allergy. Toxicol Lett. 1996;86:199–203.

    Article  CAS  PubMed  Google Scholar 

  74. Svanes C, Jarvis D, Chinn S, Burney P. Childhood environment and adult atopy: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol. 1999;103:415–20.

    Article  CAS  PubMed  Google Scholar 

  75. Strachan DP, Harkins LS, Golding J. Sibship size and self reported inhalant allergy among adult women. Clin Exp Allergy. 1997;27:151–5.

    Article  CAS  PubMed  Google Scholar 

  76. Bodner C, Godden D, Seaton A. Family size, childhood infections and atopic disease. Thorax. 1998;53:28–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Karmaus W, Arshad H, Mattes J. Does the sibling effect have its origin in utero? Investigating birth order, cord serum immunoglobulin E concentration and allergic sensitisation at age 4 years. Am J Epidemiol. 2001;154:909–15.

    Article  CAS  PubMed  Google Scholar 

  78. Karmaus W, Arshad H, Sadeghnejad A, Twistleton R. Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance. Clin Exp Allergy. 2004;34:853–9.

    Article  CAS  PubMed  Google Scholar 

  79. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance and the risk of asthma and wheezing during childhood. N Engl J Med. 2000;343:538–43.

    Article  CAS  PubMed  Google Scholar 

  80. Braun-Fahrlander C, Gassner M, Grize L, et al. Prevalence of hay fever and allergic sensitisation in farmers’ children and their peers living in the same rural community. Clin Exp Allergy. 1999;29:28–34.

    Article  CAS  PubMed  Google Scholar 

  81. Gassner-Bachman M, Wuthrich B. Farmers’ children suffer less from hay fever and asthma. Dtsch Med Wochenschr. 2000;125:924–31.

    Article  Google Scholar 

  82. Maziak W. Asthma and farming. Lancet. 2002;359(9306):623–4.

  83. Lynch NR, Hagel IA, Palenque ME, Di Prisco MC, Escudero JE, Corao LA, et al. Relationship between helminthic infection and IgE response in atopic and nonatopic children in a tropical environment. J Allergy Clin Immunol. 1998;101:217–21.

    Article  CAS  PubMed  Google Scholar 

  84. Hamid F, Wiria AE, Wammes LJ, Kaisar MM, Djuardi Y, Versteeg SA, et al. Risk factors associated with the development of atopic sensitization in Indonesia. PLoS One. 2013;8(6):e67064. doi:10.1371/journal.pone.Print 2013.

  85. Chang TW. Changing patterns of antigen exposure and their impact on the prevalence of allergy. Pediatr Allergy Immunol. 2014;25:733–9.

    Article  PubMed  Google Scholar 

  86. Rook GAW, Brunet LR. Microbes, immunoregulation, and the gut. Gut. 2005;54:317–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. •• Clark A, Mach N. Role of vitamin D in the hygiene hypothesis: the interplay between vitamin D, vitamin D receptors, gut microbiota, and immune response. Front Immunol. 2016;7:627. doi:10.3389/fimmu.2016.00627.eCollection 2016. Vitamin D and hygiene hypothesis.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Abrahamsson TR, Jakobsson HE, Andersson AF, et al. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol. 2012;129:434–40. (40 e1-2)

    Article  PubMed  Google Scholar 

  89. Durham AL, Wiegman C, Adcock IM. Epigenetics of asthma. Biochim Biophys Acta. 1810;2011:1103–9.

    Google Scholar 

  90. Daley D, Park JE, He JQ, et al. Associations and interactions of genetic polymorphisms in innate immunity genes with early viral infections and susceptibility to asthma and asthma-related phenotypes. J Allergy Clin Immunol. 2012;130:1284–93.

    Article  CAS  PubMed  Google Scholar 

  91. Ali S, Hirschfeld AF, Mayer ML, et al. Functional genetic variation in NFKBIA and susceptibility to childhood asthma, bronchiolitis, and bronchopulmonary dysplasia. J Immunol. 2013;190:3949–58.

    Article  CAS  PubMed  Google Scholar 

  92. Leong RW, Mitrev N, Ko Y. Hygiene hypothesis: is the evidence the same all over the world? Dig Dis. 2016;34:35–42. doi:10.1159/000442922. Epub 2016 Mar 16

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cemal Cingi.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Special Topics In Otorhinolaryngology: Otolaryngic Allergy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cingi, C., Muluk, N.B. Hygiene Hypothesis: What Is the Current Thinking?. Curr Otorhinolaryngol Rep 5, 175–180 (2017). https://doi.org/10.1007/s40136-017-0158-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40136-017-0158-0

Keywords

Navigation