Clinical and host microbiome features in the development of acute otitis media

摘要

ABSTRACT This Mentored Career Development (K01) Award proposal will provide an outstanding educational environment, mentoring, and training for Dr. Jillian Hurst, a pediatric infectious diseases researcher whose overarching career goal is to integrate clinical and biological data to further our understanding of the role of the microbiome and related host factors in modifying susceptibility to common childhood infections Dr. Hurst originally trained in biochemistry and molecular biology and has worked in translational pediatric research for the past five years. This career development award will allow her to receive training in omics and advanced statistical analyses using large datasets, permitting her to lead multidisciplinary teams that use large clinical and omics datasets to evaluate factors underlying common pediatric infections. The proposed research studies center on the role of the upper respiratory microbiome in the development and recurrence of acute otitis media (AOM; middle ear infection), the most common infectious disease of childhood. Dr. Hurst will test the hypothesis that early life antibiotic exposures disrupt the development of the URT microbiome, predisposing children to AOM and other common respiratory infections. She will use over eight years of electronic health records data, banked longitudinal upper respiratory specimens collected from children from birth to age 2, and samples and data from a prospective cohort of children with recurrent AOM to accomplish the following specific aims: 1) Assess the impact of early life antibiotic exposures on recurrent AOM development.; 2) Delineate the effects of early life antibiotic exposures on URT microbiome development; and 3) Evaluate associations between antibiotic exposures and the URT microbiome in children with recurrent AOM. Findings from these studies will guide the development of new strategies to prevent and treat AOM and associated infections, including guidance for antibiotic use and identification of therapeutic targets within the URT microbiome that could be leveraged to restore URT microbiome function and improve respiratory health among young children. Mentorship will be provided by a group of three established investigators with complementary expertise: Dr. Christopher Woods, an infectious diseases physician and clinical epidemiologist with expertise in the evaluation of host responses to infectious agents; Dr. Matthew Kelly, a pediatric infectious diseases physician with expertise in the human microbiome and clinical omics analyses; and Dr. Benjamin Goldstein, a biostatistician with expertise in the use of electronic health records data for population health analyses. Additionally, Dr. Hurst will be advised by internal and external advisors with expertise in antimicrobial stewardship, pediatric otolaryngology, health informatics and omics analyses, and the treatment and pathophysiology of AOM. Completion of the proposed training and research activities will establish Dr. Hurst as an independent investigator who will lead an NIH-funded research program investigating host factors and exposures underlying common infections in children.