Editing Hygiene hypothesis (section)

== Evidence ==

There is a significant amount of evidence supporting the idea that microbial exposure is linked to allergies or other conditions,<ref name="StiemsmaReynolds2015"/><ref name="Daley2014">{{cite journal |last1=Daley |first1=Denise |title=The evolution of the hygiene hypothesis |journal=Current Opinion in Allergy and Clinical Immunology |date=October 2014 |volume=14 |issue=5 |pages=390–396 |doi=10.1097/ACI.0000000000000101 |pmid=25102107 |s2cid=45420527 }}</ref><ref name="VersiniJeandel2015">{{cite journal |last1=Versini |first1=Mathilde |last2=Jeandel |first2=Pierre-Yves |last3=Bashi |first3=Tomer |last4=Bizzaro |first4=Giorgia |last5=Blank |first5=Miri |last6=Shoenfeld |first6=Yehuda |title=Unraveling the Hygiene Hypothesis of helminthes and autoimmunity: origins, pathophysiology, and clinical applications |journal=BMC Medicine |date=13 April 2015 |volume=13 |issue=1 |pages=81 |doi=10.1186/s12916-015-0306-7 |pmid=25879741 |pmc=4396177 |doi-access=free }}</ref> although scientific disagreement still exists.<ref name="Silva2018"/><ref name="Bjorksten2009"/><ref name="Bernardes2017"/> Since hygiene is difficult to define or measure directly, surrogate markers are used such as socioeconomic status, income, and diet.<ref name="Leong2016"/>

Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.<ref name=Okada2010/> This is true for asthma and other chronic inflammatory disorders.<ref name=rook2013 /> The increase in allergy rates is primarily attributed to diet and reduced microbiome diversity, although the mechanistic reasons are unclear.<ref name="LambrechtHammad2017">{{cite journal |last1=Lambrecht |first1=Bart N |last2=Hammad |first2=Hamida |title=The immunology of the allergy epidemic and the hygiene hypothesis |journal=Nature Immunology |date=1 October 2017 |volume=18 |issue=10 |pages=1076–1083 |doi=10.1038/ni.3829 |pmid=28926539 |s2cid=6239349 }}</ref>

The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases,<ref>{{cite journal |last1=Marra |first1=Fawziah |last2=Lynd |first2=Larry |last3=Coombes |first3=Megan |last4=Richardson |first4=Kathryn |last5=Legal |first5=Michael |last6=FitzGerald |first6=J. Mark |last7=Marra |first7=Carlo A. |title=Does Antibiotic Exposure During Infancy Lead to Development of Asthma? |journal=Chest |date=March 2006 |volume=129 |issue=3 |pages=610–618 |doi=10.1378/chest.129.3.610 |pmid=16537858 }}</ref> and increased asthma rates are also associated with birth by [[Caesarean section]].<ref>{{cite journal |last1=Thavagnanam |first1=S. |last2=Fleming |first2=J. |last3=Bromley |first3=A. |last4=Shields |first4=M. D. |last5=Cardwell |first5=C. R. |title=A meta-analysis of the association between Caesarean section and childhood asthma |journal=Clinical & Experimental Allergy |date=April 2008 |volume=38 |issue=4 |pages=629–633 |doi=10.1111/j.1365-2222.2007.02780.x |pmid=18352976 |s2cid=23077809 }}</ref> However, at least one study suggests that personal hygienic practices may be unrelated to the incidence of asthma.<ref name="Bernardes2017"/> Antibiotic usage reduces the diversity of gut microbiota. Although several studies have shown associations between antibiotic use and later development of asthma or allergy, other studies suggest that the effect is due to more frequent antibiotic use in asthmatic children. Trends in vaccine use may also be relevant, but epidemiological studies provide no consistent support for a detrimental effect of vaccination/immunization on [[atopy]] rates.<ref name=stanwellsmith /> In support of the old friends hypothesis, the intestinal microbiome was found to differ between allergic and non-allergic Estonian and Swedish children (although this finding was not replicated in a larger cohort), and the biodiversity of the intestinal flora in patients with Crohn's disease was diminished.<ref name=Okada2010/>

===Limitations===

The hygiene hypothesis does not apply to all populations.<ref name="Bernardes2017"/><ref name="Leong2016"/> For example, in the case of [[inflammatory bowel disease]], it is primarily relevant when a person's level of affluence increases, either due to changes in society or by moving to a more affluent country, but not when affluence remains constant at a high level.<ref name="Leong2016">{{cite journal |last1=Leong |first1=Rupert W. |last2=Mitrev |first2=Nikola |last3=Ko |first3=Yanna |title=Hygiene Hypothesis: Is the Evidence the Same All Over the World? |journal=Digestive Diseases |date=2016 |volume=34 |issue=1–2 |pages=35–42 |doi=10.1159/000442922 |pmid=26982573 |s2cid=21373849 }}</ref>

The hygiene hypothesis has difficulty explaining why allergic diseases also occur in less affluent regions.<ref name="Bernardes2017"/> Additionally, exposure to some microbial species actually increases future susceptibility to disease instead, as in the case of infection with [[rhinovirus]] (the main source of the [[common cold]]) which increases the risk of asthma.<ref name="Silva2018"/><ref name="Haspeslagh2018">{{cite journal |last1=Haspeslagh |first1=Eline |last2=Heyndrickx |first2=Ines |last3=Hammad |first3=Hamida |last4=Lambrecht |first4=Bart N |title=The hygiene hypothesis: immunological mechanisms of airway tolerance |journal=Current Opinion in Immunology |date=October 2018 |volume=54 |pages=102–108 |doi=10.1016/j.coi.2018.06.007 |pmid=29986301 |pmc=6202673 |doi-access=free }}</ref>