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.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
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.
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.
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.
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.
•• 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.
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.
Thorburn AN, Macia L, Mackay CR. Diet, metabolites, and ‘Western-lifestyle’ inflammatory diseases. Immunity. 2014;40:833–42.
Zeng H, Chi H. Metabolic control of regulatory T cell development and function. Trends Immunol. 2015;36:3–12.
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.
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.
Vanamala JK, Knight R, Spector TD. Can your microbiome tell you what to eat? Cell Metab. 2015;22:960–1.
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.
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.
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.
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.
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.
Kilpeläinen M, Terho EO, Helenius H, Koskenvuo M. Farm environment in childhood prevents the development of allergies. Clin Exp Allergy. 2000;30:201–8.
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.
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.
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.
Strachan DP. Hay fever, hygiene and household size. Br Med J. 1989;299:1259–60.
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.
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.
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.
Danese S, Sans M, Fiocchi C. Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev. 2004;3:394–400.
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.
•• 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.
Nowak D, Suppli Ulrik C, von Mutius E. Asthma and atopy: has peak prevalence been reached? Eur Resp I. 2004;23:359–60.
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.
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.
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
Warner JO. Worldwide variations in the prevalence of atopic symptoms: what does it all mean? Thorax. 1999;54(Suppl 2):546–51.
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.
Russell G, Helms PJ. Trends in occurrence of asthma among children and young adults. BMJ. 1997;315:1014–5.
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.
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.
Mallia P, Johnston SL. Respiratory viruses: do they protect from or induce asthma? Allergy. 2002;57:1118–29.
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.
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.
Sheikh A, Strachan DP. The hygiene theory: fact or fiction? Curr Opin Otolaryngol Head Neck Surg. 2004;12:232–6.
Umetsu DT. Flu strikes the hygiene hypothesis. Nat Med. 2004;10:232–4.
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.
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.
Liu AH. Something old, something new: indoor endotoxin, allergens and asthma. Paediatr Respir Rev. 2004;5(Suppl 1A):S65–71.
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.
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.
Rook GA, Stanford JL. Skin-test responses to mycobacteria in atopy and asthma. Allergy. 1999;54:285–6.
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.
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.
Prescott SL, Macaubas C, Smallacombe T, et al. Development of allergenspecific T-cell memory in atopic and normal children. Lancet. 1999;353:196–200.
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.
Baldini M, Vercelli D, Martinez FD. CD14: an example of gene by environment interaction in allergic disease. Allergy. 2002;57:188–92.
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.
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.
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.
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)
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Haby MM, Peat JK, Marks GB, Woolcock AJ, Leeder SR. Asthma in preschool children: prevalence and risk factors. Thorax. 2001;56:589–95.
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.
Strachan D. Socioeconomic factors and the development of allergy. Toxicol Lett. 1996;86:199–203.
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.
Strachan DP, Harkins LS, Golding J. Sibship size and self reported inhalant allergy among adult women. Clin Exp Allergy. 1997;27:151–5.
Bodner C, Godden D, Seaton A. Family size, childhood infections and atopic disease. Thorax. 1998;53:28–32.
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.
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.
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.
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.
Gassner-Bachman M, Wuthrich B. Farmers’ children suffer less from hay fever and asthma. Dtsch Med Wochenschr. 2000;125:924–31.
Maziak W. Asthma and farming. Lancet. 2002;359(9306):623–4.
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.
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.
Chang TW. Changing patterns of antigen exposure and their impact on the prevalence of allergy. Pediatr Allergy Immunol. 2014;25:733–9.
Rook GAW, Brunet LR. Microbes, immunoregulation, and the gut. Gut. 2005;54:317–20.
•• 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.
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)
Durham AL, Wiegman C, Adcock IM. Epigenetics of asthma. Biochim Biophys Acta. 1810;2011:1103–9.
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.
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.
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
Author information
Authors and Affiliations
Corresponding author
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
About this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40136-017-0158-0