Is it necessary to live in too clean environment ? using of various types of sensitizer, cleaning soaps? or just like that live  naturally without any fear of  that expectant opportunistic creatures that may invade our bodies with all their deleterious weapons!  Over use of such means may be simply two edges sword. This is the premise of the puzzle (hygiene hypothesis),our environment is too clean and our immune systems are no longer as heavily taxed with fighting off germs and bacteria. Increased rates of  allergies and other conditions like asthma partly attributed to deviation in immune response because of poor immune response towards the infectious agents might be caught by normal contact with them

Edrees Ahmed Shubber, Ebtehal

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                                         A flashlight on Hygiene Hypothesis             (Review Article) 
Ebtehal Edrees Ahmed Shubber  
Ph.D. Microbiology. Science Faculty/ Kufa University 
Introduction 
       Is it necessary to live in too clean environment ? using of various types of sensitizer, 
cleaning soaps? or just like that live  naturally without any fear of  that expectant opportunistic 
creatures that may invade our bodies with all their deleterious weapons!  Over use of such 
means may be simply two edges sword. This is the premise of the puzzle (hygiene 
hypothesis),our environment is too clean and our immune systems are no longer as heavily 
taxed with fighting off germs and bacteria. Increased rates of  allergies and other conditions 
like asthma partly attributed to deviation in immune response because of poor immune 
response towards the infectious agents might be caught by normal contact with them. 
       Living simply with natural micro living components of the environment leads to more 
activating of neutralizing potency immune system represented by all its types natural active 
and passive means.(Wander et al.,2012)    
      The decreased fighting ability of our immune system is also due to the emergence and 
overuse  of antibiotics and vaccines. The immune system is no longer as challenged and 
becomes dependent on these products to assist in fighting off even the most common bacterial 
infections. Antibiotics , particularly those with broad spectrum do not target invading 
microorganism only but also have deleterious effect on microbial commensals which badly 
affect future response to later on infections.(Bloomfield et al., 2006) 
      One of such immune overreactions is Eczema; a common skin disorder, Researchers 
recently reviewed 20 studies of first year of age and prenatals antibiotic use in connection with 
later skin problems. The results of these studies showed that risk for the disease was increased 
by up to 40% in children who had been exposed to antibiotics in their first year of life.  
The Early  Beginning : 
     This hypothesis was originally postulated by a lecturer in epidemiology. Where he used 
very big sample of population represented by British children born during the same week in 
1958 and followed them up to age 23 years their number was 17414 , he came out with three 
results he further investigated first: self reported "hay fever d during the past 12 months" 
at age 23; second: parental report of "hay fever or allergic rhinitis in the past 12 months" at age 
11; third: parental recall of "eczema in the first year of life" occurred when the child was at 7 
years old(Strachan,1989) . 
     The conclusion of that study was that the children in larger families had more exposure to 
pathogens than smaller families this will make them less possibility to get hay fever , asthma or 
other atopic diseases(Umetsu, 2012; Okada et al., 2012; Benn et al., 2004; Tulic et al., 2004) 
the association between the decreased exposure to microbial  agents during early infancy and 
increased allergic diseases later in life  has been expanded to include also increased 
autoimmune diseases such as  inflammatory diseases and type 1 diabetes mellitus.(Azad et 
al.,2013) 
 
 
Al-Kufa University Journal for Biology / VOL.10 / NO.2 / Year: 2018 
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Examples of tangible clues supporting the hygiene hypothesis: 
1-in Kilimanjaro increased delayed hypersensitivity to Candida is related with early life 
infection (Wander et al.,2012) 
 2-Variation of microflora of gut support healthy immune system lowering predisposing to 
autoimmune diseases including T1D, the HEV infection could suppress the genetically driven 
autoimmune disease by activating immune system(Azad et al., 2013) 
3-Using Eschericha coli in infecting mice led to decrease of  some parameters mediating the 
allergic response represented by allergic airway disease ( AAD)   (Pang et al., 2013) 
4- an inverse link between getting infected with Helicobacter pylori  and allergic asthma 
(Matsushima and Nagai, 2012)  
5-Hepatitis- A Virus was inversely linked with incidence of hay fever.(Umetsu,2012) 
6-Other relationship is based on the mild intracellular living pathogens like Mycobacteria  
mainly from soil and Salmonella , in other words those were ingested with food would protect 
from atopic diseases through the development of  immune response further(Matricardi,2010) 
7-The hygiene hypothesis is thought to be a significant supporter to the growing incidence of 
inflammatory bowel disease (IBD) around the world(Koloski et al., 2008) 
 
Immunological Mechanisms underlying the hygiene hypothesis : 
 
       All immature T-cells contain CD3 designated as CD3
+
 and after differentiation are 
subdivided into two subsets, first effector T-cells which are characterized by the presence of 
CD8 having cytotoxic functions and so the name cytotoxic T-cells. These cells are capable of 
killing tumor cells, allografts, and viral infected cells. Second subset are the regulator T-cells 
also named helper T-cells characterized by their possession of CD4 , which further subdivided 
into two types called the T helper-1 (T h-1), and T helper -2 (T h-2) cells. The first produce 
interleukin -2 (IL-2)which stimulate cytotoxic activity in the CD8
+
 cytotoxic T- cells , while 
production of  IL-2 and interferon -γ(IFN- γ) will stimulate delayed type hypersensitivity 
response by macrophage.(Th-2) cells produce IL-4, IL-5 that stimulate B- cells to be plasma 
cells antibody producing cells  
       The atopic diseases that hypothesized to be correlated with lowered exposure to microbes 
in early immune system development is caused by antibody mediated immunity whereas the 
immune response against pathogens  especially those in gastrointestinal tract is cellular 
mediated  immunity. (Levinson, 2004 ) 
The most famous elaboration was that the poor early exposure to infectious agents would lead 
to an immunological  deviation towards Th-2 mediated immune response away from the Th1- 
immune response. (Martinez and Holt,1999)  
       Other explanations focusing on that the invariant natural killer T-cells can directly respond 
to some of bacterial glycolipids  like that derived from H. pylori which leads to expand cell 
subset of suppressor iNKT-cells preventing the development of experimentally designed 
asthma in mice (Chang et al.,2011) 
other correlates the immune regulation by T-regulator cells by cytokines produced by other 
cells (Pang et al., 2013) 
in short the hypothesis needs for more researches that focusing on various aspects of the 
immunological disorders associated with the modern life style in order to modulate it in the 
way providing more protection against such disorders in the future. 
 
 
 
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References 
 
  Azad,M.B., Konya, T., Maughan, H., Guttman, D., Field, C., Sears, M., Becker, A.,  
Scott2, J., and Kozyrskyj, A.( 2013). Infant gut microbiota and the hygiene hypothesis 
of allergic disease: impact of household pets and siblings on microbiota composition 
and diversity. Allergy, Asthma & Clinical Immunology . 9:15 
  
Benn, C. S., Melbye, M., Wohlfahrt, J., Björkstén, B., & Aaby, P. (2004). Cohort study 
of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months 
of life. BMJ : British Medical Journal, 328(7450), 1223. 
  Bloomfield, S., Stanwell-Smith, R., Crevel, R., & Pickup, J. (2006). Too clean, or not 
too clean: the Hygiene Hypothesis and home hygiene. Clinical and Experimental 
Allergy , 36(4), 402–425.  
  Chang, Y.-J., Kim, H. Y., Albacker, L. A., Lee, H. H., Baumgarth, N., Akira, S., … 
Umetsu, D. T. (2011). Influenza infection in suckling mice expands an NKT cell subset 
that protects against airway hyperreactivity. The Journal of Clinical 
Investigation, 121(1), 57–69.  
   Koloski, N., Bret, L., and Radford-Smith G.(2008). Hygiene hypothesis in 
inflammatory bowel disease: A critical review of the literature. World J Gastroenterol . 
14(2): 165-173  
  Levinson,W.(2004). Review of Medical Microbiology and Immunology. 9
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Medical Books. 
  Martinez, F.D., and Holt, P.G. (1999) .Role of microbial burden in aetiology of allergy 
and asthma. Lancet 354: SII12–SII15 
  Matsushima, K., and  Nagai, S.(2012). Unraveling the mystery of the hygiene 
hypothesis 
through Helicobacter pylori infection. Clin Invest. 122(3):801–804. 
  Okada, H., Kuhn, C., Feilletand H., and Bach J.-F. (2010). The ‘hygiene hypothesis’ for 
autoimmune and allergic diseases: an update. British Society for Immunology, Clinical 
and Experimental Immunology, 160(1):1–9  
  Pang, W., Wang, H., Shi, L., Sun,Y., Wang, X., Wang, M., Li, J., Wang, H., and Shi, 
G.(2013). Immunomodulatory Effects of Escherichia coli ATCC 25922 on Allergic 
Airway Inflammation in a Mouse Model. PLOS ONE .8 (3): e59174 
  Strachan, D.,P.(1989). Hay fever, hygiene, and household size. Br. Med. J. 299:1259-
1260 
  Tulic, M.K., Fiset, P-O., Manoukian, J.J., et al.(2004). Role of toll-like receptor 4 in 
protection bacterial lipopolysaccharide in the nasal mucosa of atopic children but not 
adults. Lancet.363:1689–1697 
  Umetsu, D.(2012). Early exposure to germs and the Hygiene Hypothesis. Cell Research 
(2012) 22:1210-1211. 
   Wander, K., O’Connor, K., and Shell-Duncan, B.(2012). Expanding the Hygiene 
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Hypothesis: Early Exposure to Infectious Agents Predicts Delayed-Type 
Hypersensitivity to Candida among Children in Kilimanjaro. PLoS ONE. 7( 5) :e37406 
  
 


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