The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to provide Dr. Noelle Younge with the mentorship, training, and research experience necessary to become an independent physician-scientist and leader in understanding the preterm infant microbiome and its impact on early life growth failure. To facilitate her transition to independence, Dr. Younge and her mentors have developed a comprehensive research and career development plan that includes mentorship from an exceptional team of scientists with proven track records of successful mentorship and extensive expertise in microbial regulation of host metabolism and physiology; intensive didactic training; and a research plan that is purposefully designed to provide experiential learning in advanced research methods to study the microbiome and metabolome of preterm infants. Postnatal growth failure is a pervasive problem among preterm infants that is often refractory to modern nutritional management and portends poor long-term neurodevelopmental outcomes. Novel approaches to reduce the burden of early life growth failure are needed to improve the health and developmental outcomes of preterm infants. Recent work from Dr. Younge and her mentors demonstrates that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota and host metabolome. In the research plan outlined in this K23 proposal, Dr. Younge will expand upon this work by 1) identifying metabolic functions of the microbiome that differentiate preterm infants with growth failure from preterm infants with appropriate postnatal growth, and 2) investigating the nature of the relationships between the microbiota, metabolism, and growth under controlled conditions in a gnotobiotic mouse model. This work will produce novel insights into the pathogenesis of postnatal growth failure in preterm infants and will serve as the foundation for Dr. Younge to build an independent research program conducting clinical and preclinical studies directed toward improving the health and development of preterm infants. In completing these aims, Dr. Younge will develop a unique and specialized skill set in the integration of multi- omics data and translational research that will facilitate her transition to an independent research career.
Early life growth failure is a major global problem that disproportionately affects preterm infants and is associated with long-term neurodevelopmental sequelae and other adverse health outcomes. The proposed research will advance our understanding of how disruptions in the development of the intestinal microbiome in preterm infants impact postnatal growth and metabolism. The knowledge generated from this research is anticipated to aid in the development of microbial and metabolic markers of growth failure in preterm infants and novel approaches to reduce the long-term burden of postnatal growth failure in this vulnerable population.