The Microbiome and Metabolism in Postnatal Growth Failure

产后生长障碍中的微生物组和代谢

• 批准号: 9906899
• 负责人: Noelle Elizabeth Younge
• 金额: $ 18.74万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906899
• 关键词: Active Learning; Affect; Birth; Characteristics; Childhood; Clinical Research; Complex; Data; Development; Development Plans; Diet; Elderly; Energy Intake; Failure; Foundations; Future; Gene Expression Profiling; Germ-Free; Gestational Age; Gnotobiotic; Goals; Growth; Growth and Development function; Health; Hypertension; Infant; Intervention; Knowledge; Life; Lipolysis; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Metabolic Marker; Metabolic Pathway; Metabolism; Modeling; Modernization; Multiomic Data; Mus; Nature; Neurodevelopmental Impairment; Nutrient; Nutritional; Obesity; Outcome; Pathogenesis; Pathogenicity; Phenotype; Physicians; Physiology; Play; Premature Infant; Property; Records; Refractory; Regulation; Research; Research Methodology; Risk; Role; Scientist; Training; Translational Research; Transplantation; Vulnerable Populations; Weight Gain; Work; base; cardiometabolism; career; career development; critical developmental period; design; experience; fatty acid oxidation; gut microbiome; gut microbiota; high risk infant; improved; insight; intestinal maturation; metabolome; metabolomics; metatranscriptomics; microbial; microbial community; microbiome; microbiome research; microbiota; microbiota profiles; mouse model; novel; novel strategies; postnatal; postnatal development; preclinical study; prevent; programs; research and development; skills

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.

摘要 这个指导病人为导向的研究职业发展奖（K23）的目的是提供博士。 Noelle Yellow拥有成为独立研究员所需的指导，培训和研究经验 医学科学家，了解早产儿微生物组及其对早期生活的影响的领导者 成长失败为了帮助她过渡到独立，Yellow博士和她的导师制定了一个 全面的研究和职业发展计划，包括来自杰出团队的指导， 科学家在微生物调控方面具有成功的指导记录和广泛的专业知识， 宿主代谢和生理学;密集的教学培训;以及有目的地设计的研究计划 提供先进研究方法的经验学习，以研究微生物组和代谢组， 早产儿出生后生长障碍是一个普遍存在的问题，早产儿往往是难治性的 现代营养管理，并预示着不良的长期神经发育结果。小说 需要减少生命早期生长失败的负担的方法来改善健康， 早产儿的发育结果。Yellow博士和她的导师最近的工作表明， 患有出生后生长障碍的极早产儿破坏了肠道微生物群的成熟 和宿主代谢物组。在K23提案中概述的研究计划中，Yellow博士将对此进行扩展 通过1）确定微生物组的代谢功能来区分早产儿的生长 失败的早产儿与适当的产后生长，和2）调查的性质， 微生物菌群，代谢和生长之间的关系，在受控条件下，在一个gnotobiotic 小鼠模型这项工作将产生新的见解，早产儿出生后生长障碍的发病机制， 婴儿，并将作为基础，博士Yellow建立一个独立的研究计划，进行 旨在改善早产儿健康和发育的临床和临床前研究。在 完成这些目标，Yellow博士将开发一个独特的和专业的技能，在多个集成， 组学数据和转化研究，这将有助于她过渡到一个独立的研究生涯。