This revised Program Project Grant (PPG) application seeks an increased understanding of the relationships between dog or cat exposure during infancy and a lower risk of allergic asthma. We believe that this protective association is related to different patterns of microbial stimulation during immune development. Four synergistic Projects will examine our hypothesis that the presence of pets in a home results in a more diverse bacterial community composition (BCC) of the dust in the home which in turn influences the development of the gut BCC of a newborn infant living in the home. A more diverse gut BCC shifts the maturation of the infant's immune system such that later immune responses are less likely to produce IgE antibody responses and allergic asthma. Project 1 examines the relationships between the presence of a dog or cat in a home, the BCC of dust in the home, the BCC of stools of infants living in homes and allergic sensitization at 2 years of age. An innovative, culture-independent microarray (G3 PhyloChip) will be used to characterize the BCCs utilizing previously collected samples from the ongoing WHEALS birth cohort study. Changes in home BCC following introduction of a dog are also examined. To further examine relationships between dog exposure and immune development. Project 2 will recruit a new birth cohort of children either living with or without a dog, measure infant stool BCC, and follow the cohort with detailed studies of immune function until 18 months of age to determine the impact of dog exposure on immune maturation. Project 3 uses mouse models of allergic asthma to further examine the influence of house dust from homes with and without dogs on immune responses that result in lung inflammation. The use of mouse models allows more detailed studies of immune functions from multiple compartments of the body than are possible with human children. Project 4 again utilizes the existing WHEALS birth cohort to examine the relationships between dog or cat exposure during the first year of age, 6-month infant stool BCC, and the presence of allergic asthma at 9 years of age. The Projects are supported by five Cores which each provide essential services to all four Projects.
Allergic asthma is a common disease producing high levels of morbidity in children throughout the United States. An increase in the prevalence of childhood asthma since the 1960's suggests that one or more environmental changes are related to the increase. Our hope is to discover patterns of environmental and gut microbiota that are associated with a lower risk of developing allergic disorders which would suggest methods of primary prevention of these conditions.
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|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|
|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|
|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|
|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|
|Sitarik, Alexandra R; Bobbitt, Kevin R; Havstad, Suzanne L et al. (2017) Breast Milk TGF? is Associated with Neonatal Gut Microbial Composition. J Pediatr Gastroenterol Nutr :|
|Levin, Albert M; Sitarik, Alexandra R; Havstad, Suzanne L et al. (2016) Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity. Sci Rep 6:31775|
|Cassidy-Bushrow, Andrea E; Havstad, Suzanne; Basu, Niladri et al. (2016) Detectable Blood Lead Level and Body Size in Early Childhood. Biol Trace Elem Res 171:41-7|
|Lynch, Susan V; Boushey, Homer A (2016) The microbiome and development of allergic disease. Curr Opin Allergy Clin Immunol 16:165-71|
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