Bacterial mediators of postnatal growth in preterm infants

摘要

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.