The overall objective of Project 4 is to assess the relationship between exposure to pets, the infant home and gut microbiomes, and allergic asthma at 9 years of age, using an ethnically diverse, population-based general risk birth cohort (the WHEALS cohort). A premise with growing evidence is that lack of exposure to particular patterns of microbial stimuli during early infancy results in a heightened T-helper (Th) 2 response in the maturing immune system, likely due to a suboptimal regulatory capacity, which in turn is associated in childhood with increased immunoglobulin(lg)E, allergy, and clinical allergic conditions such as asthma. Epidemiological studies have revealed that atopic conditions have increased over the latter half of the twentieth century. Humans in earlier centuries had lifestyles associated with closer direct contact with soil, animals and other humans, suggesting exposure to environments with richer and more diverse microbiological burdens. We hypothesize that evolutionary adaptation to such microbial exposures with respect to immune recognition and regulation may result in untoward consequences when humans are presented with the different, and probably more limited, patterns of microbial exposures found in modern Westernized societies. Our theory is that in many settings, pets, as well as farm animals in close proximity, render the home microbiome, or bacterial community composition (BCC,) to be more similar to early 20th century environments with respect to an increased bacterial richness, diversity and a more even distribution of taxa. This home microbiome impacts directly through effects on the infant gastrointestinal tract BCC the immunogenesis of the infant and subsequently the development of clinically important outcomes such as childhood atopic asthma. Using a new technology (the G3 PhyloChipj, capable of cost-effectively identifying, to a great depth, bacteria in environmental and biological samples, our collaborative team has preliminary data suggesting that the presence of dogs and cats is associated with distinct home and infant gut microbiomes characterized by dramatic increases in bacterial diversity, richness and evenness. Using newly measured outcome variables measured by questionnaire and clinical examinations in the WHEALS cohort, in conjunction with PhyloChip analyses of stored infant stool and dust samples, we will test whether distinct patterns of pet exposure, home microbiome and infant gut microbiome are associated with current allergic asthma at age 9 years.

Public Health Relevance

We hypothesize that in many settings, household pets render the home microbial ecology to be more similar to pre-20th century environments, which may account for their protective effect on risk for childhood asthma. If certain parts of the environment are found to decrease the risk for asthma, public health interventions could be developed, such as safe medications for infants, that mimic these environmental exposure patterns.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI089473-03
Application #
8843147
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Type
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Durack, Juliana; Boushey, Homer A; Huang, Yvonne J (2018) Incorporating the airway microbiome into asthma phenotyping: Moving toward personalized medicine for noneosinophilic asthma. J Allergy Clin Immunol 141:82-83
Wegienka, Ganesa; Sitarik, Alexandra; Bassirpour, Gillian et al. (2018) The associations between eczema and food and inhalant allergen-specific IgE vary between black and white children. J Allergy Clin Immunol Pract 6:292-294.e2
Sitarik, Alexandra Rene; Kasmikha, Nena Sabri; Kim, Haejin et al. (2018) Breast-feeding and delivery mode modify the association between maternal atopy and childhood allergic outcomes. J Allergy Clin Immunol 142:2002-2004.e2
Cassidy-Bushrow, A E; Burmeister, C; Havstad, S et al. (2018) Prenatal antimicrobial use and early-childhood body mass index. Int J Obes (Lond) 42:1-7
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Sitarik, Alexandra R; Bobbitt, Kevin R; Havstad, Suzanne L et al. (2017) Breast Milk Transforming Growth Factor ? Is Associated With Neonatal Gut Microbial Composition. J Pediatr Gastroenterol Nutr 65:e60-e67
Johnson, Christine C; Ownby, Dennis R (2017) The infant gut bacterial microbiota and risk of pediatric asthma and allergic diseases. Transl Res 179:60-70
Havstad, Suzanne; Sitarik, Alexandra R; Johnson, Christine Cole et al. (2017) Allergic sensitization in American children of Middle Eastern ethnicity at age 2. Ann Allergy Asthma Immunol 119:464-466
Fonseca, W; Lucey, K; Jang, S et al. (2017) Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation. Mucosal Immunol 10:1569-1580
Cassidy-Bushrow, Andrea E; Sitarik, Alexandra R; Havstad, Suzanne et al. (2017) Burden of higher lead exposure in African-Americans starts in utero and persists into childhood. Environ Int 108:221-227

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