The Microbiome and Metabolism in Postnatal Growth Failure

摘要 这个以患者为导向的导师研究职业发展奖(K23)的目的是为Dr。 Noelle Young拥有成为独立企业所必需的导师、培训和研究经验 内科医生、科学家和了解早产儿微生物组及其对早期生活影响的领军人物 成长失败。为了促进她向独立的过渡，杨格博士和她的导师们开发了一种 全面的研究和职业发展计划，包括来自 拥有成功指导记录和在微生物调控方面具有丰富专业知识的科学家 宿主新陈代谢和生理学；强化教学训练；以及有目的地设计的研究计划 提供先进研究方法的体验式学习，研究微生物群和代谢组 早产儿。出生后发育迟缓是早产儿普遍存在的问题，通常是难治性的。 对现代营养管理的影响，并预示着不良的长期神经发育结果。小说 需要采取措施减轻早期生命发育失败的负担，以改善健康和 早产儿的发育结局。杨格博士和她的导师们最近的研究表明 患有出生后发育障碍的极早产儿扰乱了肠道微生物区系的成熟 和宿主代谢物。在这份K23提案中概述的研究计划中，杨格博士将对此进行详细阐述 通过1)确定区分早产儿和生长发育的微生物组的代谢功能 出生后发育正常的早产儿失败，以及2)调查 灵知生菌在受控条件下的微生物区系、代谢和生长之间的关系 老鼠模型。这项工作将对早产儿出生后发育障碍的发病机制提供新的见解。 并将作为杨格博士的基金会建立一个独立的研究项目进行 临床和临床前研究旨在改善早产儿的健康和发育。在……里面 为了实现这些目标，杨格博士将发展一套独特的专门技能，将多个 组学数据和翻译研究，这将促进她过渡到独立的研究生涯。

ABSTRACT 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.