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Wise et al.

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Evidence for the hygiene hypothesis in the development of allergic rhinitis Study Year LOE Study design Study groups Clinical endpoint Conclusion Campbell et al. 647 2015 2a SR 29 studies (1999–2014): 26 cross sectional, 3 longitudinal. Meta analysis: 8 studies Association of farm exposure with sensitization in childhood or adulthood Protective effect of farm exposure in infancy on allergic disease in childhood and adulthood in majority of studies. Exposure during adulthood had no consistent relationship with sensitization. Karmaus & Botezan 645 2002 2a Meta-analysis 53 studies (1986–2000). Hay fever: 17 studies (n = 253,304); Sensitization: 16 studies (n = 46,758) Association of sensitization and AR with 3 or more siblings vs no siblings Higher number of siblings was associated with less atopy. Effect was not explained by hygiene factors. Fujimura et al. 645 2016 2b Longitudinal birth cohort study 298 children followed until age 4 years Association of sensitization and asthma at age 2 years with fecal microbiota in neonates targeted at age 1 month (n = 130) or 6 months (n = 168) Reduced colonization of Bifidobacteria, Lactobacillus, Faecalibacterium, Akkermansia , and Malassezia during the neonatal period may influence the risk of multisensitization predictive for asthma. House et al. 648 2016 2b Nested case control study Farmers and spouses: Cases: asthma (n = 1198); Controls: no asthma (n = 2031). Association of sensitization, rhinitis, eczema, and asthma with living on a farm when born and with being exposed to farm environment when mother was performing farm activities during pregnancy Early-life farm exposure associated with less atopy. No association with asthma. study

Reduced colonization of Faecalibacterium, Lachnospira, Veillonella , and Rothia during the first 3 months of life may increase the risk of atopic asthma.

Author Manuscript Author Manuscript Author Manuscript Author Manuscript TABLE VI.G.3.

Reduced fecal biodiversity and altered composition associated with more allergy. No association with asthma and eczema.

Protective effect of older and total number of siblings on self-reported AR. Effect was significantly stronger in affluent countries.

Exposure to more diverse bacterial flora associated with less sensitization.

Reduced bacterial diversity associated with higher risk of sensitization and AR in childhood.

Farm-children had less asthma and atopy. Indoor microbial exposure much higher and diverse in

farm homes. Microbial diversity related to asthma but not to atopy.

1879 adult subjects Association of seasonal allergy with fecal microbial biodiversity 319 children followed from birth until 5 years of age

Association of sensitization and wheezing at 1 year with fecal microbiota at age 3 months and 1 year

Association of hay fever with three or more siblings vs no siblings

Association of sensitization with mattress bacterial diversity

Association of sensitization and AR with high fecal microbial biodiversity

Association of sensitization with microbes in mattress (PARSIFAL) and in airborne dust (GABRIELA)

Children 6–7 years of age in 31 countries (n = 210,200); 13–14

years of age in 52 countries (n = 337,226)

GABRIELA study: 224 children, 6– 12 years

followed from birth to age 7 years

PARSIFAL study: 489 rural and suburban children; GABRIELA study: 444 rural children

nested case-control study study

stratified

population study

sectional studies

Hua et al. 664 2016 2b Cross-sectional

Arrieta et al. 663 2015 2b Longitudinal

Strachan et al. 646 2015 2b Cross-sectional

Valkonen et al. 661 2015 2b Cross-sectional

Bisgaard et al. 449 2011 2b Longitudinal study 253 high-asthma-risk children Ege et al. 659 2011 2b Two cross

Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.