Conserved Covarying Gut Microbial Network in Preterm Infants and Childhood Growth During the First 5 Years of Life: A Prospective Cohort Study

Abstract

BackgroundLongitudinally conserved microbe-microbe interactions may provide insights to understand the complex dynamic system of early-life gut microbiota among preterm infants. ObjectivesWe aimed to profile the covarying network of gut microbiota among preterm infants and investigate its potential influence on host growth (2–5 y). MethodsWe collected time-series stool samples (n = 717 from children and n = 116 from mothers) among 51 preterm and 51 full-term infants from birth up to 5 y of age and among 53 mothers. The included infants underwent time-series measurements of early-life gut microbiota (0–5 y) and growth (2–5 y) from June 2014 to April 2017. The covarying taxa that exhibited consistent covariation from day 1 to year 5 were defined as conserved features in the development of gut microbiota. Childrens’ height-for-age z score (HAZ) and weight-for-age z score were calculated according to World Health Organization Child Growth Standards. ResultsWe observed distinct dynamic patterns of both microbial alpha and beta diversity comparing preterm infants with full-term controls during the very early stage (<3 mo). Moreover, we identified a covarying network containing 10 taxa as a conserved gut microbial feature of these preterm infants from birth to 5 y old. This covarying network was distinctive between preterm and full-term infants before 3 mo of age (P < 0.001) and tended to be similar as the infants grew up. Several covarying taxa of the network during early life (<3 mo) were associated with childhood growth (2–5 y) (eg, Clostridium_sensu_stricto_1 with HAZ, β = -0.32, q < 0.01), and the human milk feeding duration was a main modulating factor. ConclusionsPreterm born children possess conserved and distinct covarying microbiota during very early life, which may have a profound influence on their growth later in life.This trial was registered at clinicaltrials.gov as NCT03373721.