Bacterial mediators of postnatal growth in preterm infants

摘要 众所周知，肠道微生物群在成人的营养和新陈代谢中发挥着不可或缺的作用，但 在我们对微生物群在生长和生长中的作用的理解上仍然存在很大的根本性差距 婴儿期的营养。极早产儿通常会出现生长不良和营养吸收不良的情况。 在出生后时期，这与不利的神经发育结果独立相关。之前 申请人的工作表明，出生后发育不良的极早产儿有 在整个NICU期间持续存在的微生物组发育的差异 随着宿主新陈代谢的改变。此外，申请人的K23项目的初步调查结果表明 极早产儿肠道微生物群落定植的新生灵知生菌小鼠 出生后生长不良的小鼠体重和身长增长比被微生物定植的新生小鼠低 来自具有适当出生后生长轨迹的婴儿的群落，表明微生物群是 与出生后的生长有因果关系。这项建议将建立在申请人目前的K23研究的基础上，以 确定这些影响的特定细菌介质，并测试它们增加出生后体重和 从出生起就与早产儿营养不良的微生物群聚在一起的诺生菌小鼠的长度增长 出生后的生长。连同K23的工作，拟议的实验将提供一个易于处理的模型和 强大的基础数据支持侧重于了解机制的竞争性R01应用程序 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 发现支持早产儿健康成长和营养的微生物组靶向新方法 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.