The contribution of antibiotic exposure in the prenatal, peripartum and infancy period to intestinal microbiome perturbations and association with early childhood obesity.

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The research program proposed herein is to support the development of Suchitra Hourigan, MD, into an independent investigator aiming to conduct novel and transformative research into the role of gut microbiome development in early childhood health and disease, with a focus on obesity. She seeks a K23 award in order to obtain the skill set, knowledge, formalized training and mentored research experience critical for her transition from an early career physician-scientist with a solid foundation in the basics of trial design, recruitment, epidemiology and microbiome analysis to an independent scientist who conducts trials designed to intervene on microbial communities that contribute to childhood disease. Two essential components of her transition into research independence are hands-on mentored training in 1) the conduct and design of trials and translational microbiome studies and 2) the interpretation of longitudinal microbiome analysis combined with rich epidemiological data. The proposed K23 Career Development plan will accomplish these goals. Obesity is a worldwide epidemic. There is a critical window in very early life that is conjectured to be predictive of later obesity risk, in part due to the establishment of the gut microbiome and metabolic programming that occur. Epidemiological studies have indicated that early exposure to antibiotics increases the risk of childhood obesity. It is hypothesized that early antibiotic exposure causes detrimental gut microbiota perturbations that ‘program’ the host to an obesity-prone metabolic phenotype which persists after discontinuation of antibiotics; however this has never been shown in humans. To test this hypothesis, prospective longitudinal studies with microbiome analysis are needed. The overall goal of this project is to determine the relative contributions of antibiotic exposure in the prenatal, peripartum and infancy period to intestinal microbiome perturbations and association with early childhood obesity. This will be achieved by leveraging the infrastructure of the unique established longitudinal cohort study at Inova (NIH-NICHD ECHO 4UH3OD023337-03). Dr. Hourigan will carry out this proposal in the rich research environment of the Inova Translational Medicine Institute with additional training at the Johns Hopkins School of Medicine where she remains a faculty member. Under the collaborative and supportive mentorship of her primary mentor Dr. John Niederhuber, MD (Executive Vice President of the Inova Health System and CEO of the Genomics and Bioinformatics Research Institute at Inova), co-mentor Dr. Cynthia Sears, MD (Professor of Medicine in the Division of Infectious Disease and Gastroenterology, Johns Hopkins) and advisors, she is well positioned to complete the proposed activities. In addition to leading this research, Dr. Hourigan will attend courses, workshops, scientific meetings and participate in weekly study activities with her mentors. This mentored training will enable Dr. Hourigan to grow into an independent researcher, with expertise in the design, conduct and analysis of longitudinal microbiome studies, focused on understanding role of the developing gut microbiome in childhood health outcomes.