The Home Mycobiome and Childhood Asthma

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PROJECT ABSTRACT Early life exposures are known to alter the risk of asthma, a chronic disease of the airways that affects 6 million children in the U.S. Environmental microbes may contain taxa that “prime” the immune system to decrease asthma susceptibility, while other taxa may instead enhance allergic disease response. Environmental microbiome studies have developed in parallel to those of the human microbiome, with a spotlight on bacteria, and little to no emphasis on fungi. Research into the role of environmental fungal communities (the “mycobiome”) in allergic disease development represents an untapped domain with high potential knowledge gains, given that fungal communities are rich sources of innate immune stimuli, allergens and biologically active metabolites, the potency of which vary significantly by taxa. We hypothesize that the relationship between early life exposure to the home fungal mycobiome and allergic disease risk depends upon the specific taxonomic composition of the fungal community, its capability to produce particular types of immune-stimulatory cell wall components, and its production of secondary metabolites. For this study, we will use home environmental samples (house dust) and longitudinal allergic disease outcome data from the The Epidemiology of Home Allergens and Asthma Study (EHAAS) cohort. In specific aim 1, we will perform targeted (ITS) sequencing to identify home fungal communities and their specific taxonomic members associated with pediatric airway and allergic disease risk. In specific aim 2, we will relate gene signatures of biologically active fungal cell wall components and fungal secondary metabolites to respiratory and allergic disease outcomes. In specific aim 3, we will test “protective” fungal taxa, protective metabolites and house dust extracts enriched for multiple protective components in an immune cell in vitro model.