Project 1 Early Microbiota-Related Risk Factors and the Development of a Multi-Sensitized High Risk for Allergic Asthma Phenotype

儿童的健康状况对国家具有长期的社会和经济影响。哮喘

The health status of our children has long lasting social and economic ramifications for the nation. Asthma is the most common chronic condition in the U.S. pediatric age group. This disease often carries on into adulthood and is associated with lifelong deficits in lung function. The majority of these children are also allergic, and a sub-group have asthma that is difficult to control. Despite substantial research effort, the dramatic increase in asthma prevalence over the past decades has not been mitigated. New hope is centered on research investigating the influence and possible interventional opportunities afforded by study of the gut microbiota. This has become possible with the advent of culture-independent technology. Our initial P01 used our WHEALS birth cohort to demonstrate that numerous child and also maternal characteristics were associated with the infant's gut microbiota community composition. Infant gut microbiota characteristics, such as lower bacterial diversity and higher fungal diversity, were associated with a multi-allergen-sensitized (IgE) phenotype at age 2 years and asthma at age 4 yrs. Our new data reveals that this age 2yr phenotype is associated with a high risk of multi-sensitized allergic asthma at age 10 yrs, and the same gut microbiota characteristics are associated with this higher risk. Our new P01 murine data supports a maternal microbiota influence on the offspring's immune system. The WHEALS birth cohort was not initially designed to examine how the infant gut microbiota is related to allergy, or the maternal contributions to this association. Infant stool samples were obtained using limited institutional funds and therefore at only one or two points in time and relatively sporadically. This Project will capitalize on a new, large and diverse health system-based general risk birth cohort with the focus of studying the gut microbiota with the latest sample collection and analytic techniques and collection of stool specimens at earlier and more frequent infant time points and one in late pregnancy. We propose detailed studies of multiple variables likely to affect the maternal microbiota during pregnancy, how these effects are related to the child's risk of allergic sensitization, and how the maternal and infant gut microbiotas can mediate risk. Project 1 is designed to home in on maternal/infant exposures and gut microbiotas and how they associate with the child's risk of becoming highly multi-sensitized or not sensitized (resilient to sensitization) by the age of 2 yrs. Altogether, the coordinated Projects in this P01 are addressing hypotheses highly informative to future development of potential microbial-related preventive interventions through both behavioral/social or direct microbial means.