Bacterial mediators of postnatal growth in preterm infants

摘要 已知肠道微生物组在成人的人体营养和代谢中发挥不可或缺的作用，但 我们对微生物组在生长中的作用的理解仍然存在很大的根本性差距， 婴儿期的营养极早产儿通常会经历不良的生长和营养积累 在出生后时期，这是独立相关的不良神经发育结果。之前 申请人的工作表明，出生后生长不良的极早产儿 在整个NICU期间持续存在的微生物组发育差异， 改变了宿主的新陈代谢此外，申请人K23项目的初步调查结果表明， 极早产儿的肠道微生物群落定植的新生儿gnotobiotic小鼠 出生后生长不良的小鼠体重和身长增长低于微生物定植的新生小鼠， 来自具有适当产后生长轨迹的婴儿的微生物群落，这表明微生物组是 与出生后的生长有因果关系。该提案将基于申请人目前的K23研究， 鉴定这些作用的特定细菌介质，并测试它们增加出生后体重的潜力， 从出生起就被患有贫困的早产儿的微生物群落定殖的非细菌性小鼠的长度增加 出生后的成长与K23的工作一起，拟议的实验将提供一个易于处理的模型， 强大的基础数据，可支持竞争性R01应用程序，重点是了解机制 微生物对出生后生长和发育的影响。此外，这项工作有可能导致 发现新的微生物靶向方法，以支持早产儿的健康生长和营养 在一个关键的发展时期。

ABSTRACT The intestinal microbiome is known to play an integral role in human nutrition and metabolism in adults, but there remain large fundamental gaps in our understanding of the role of the microbiome in growth and nutrition during infancy. Extremely preterm infants commonly experience poor growth and nutrient accretion in the postnatal period, which is independently associated with adverse neurodevelopmental outcomes. Prior work from the applicant demonstrates that extremely preterm infants with poor postnatal growth have differences in the development of the microbiome that persist throughout the NICU period and are associated with altered host metabolism. Further, preliminary findings from the applicant’s K23 project demonstrate that neonatal gnotobiotic mice colonized by intestinal microbial communities from extremely preterm infants with poor postnatal growth have lower weight and length gain than neonatal mice colonized by microbial communities from infants with appropriate postnatal growth trajectories, suggesting that the microbiome is causally related to postnatal growth. This proposal will build upon the applicant’s current K23 research to identify specific bacterial mediators of these effects and test their potential to increase postnatal weight and length gain in gnotobiotic mice colonized from birth with the microbiomes of preterm infants with poor postnatal growth. Together with the K23 work, the proposed experiments will provide a tractable model and strong foundational data to support a competitive R01 application focused on understanding the mechanisms of microbial influences on postnatal growth and development. Further, this work has potential to lead to discovery of new microbiome-targeted approaches to support healthy growth and nutrition in preterm infants during a critical developmental period.