Aberrant newborn T cell and microbiota developmental trajectories predict respiratory compromise during infancy

Neonatal immune-microbiota co-development is poorly understood, yet appropriate recognition of -- and response to -- pathogens and commensal microbiota is critical to health. In this longitudinal study of 148 pre- and 119 full-term infants from birth through one year of age we found that postmenstrual age, or weeks from conception, not post-natal age, is the dominant factor influencing T cell and mucosal microbiota development. Numerous features of the T cell and microbiota functional development remain unexplained, however, by either age metric and are instead shaped by discrete peri- and post-natal events. Most strikingly, we establish that prenatal antibiotics or infection disrupt the normal T cell population developmental trajectory, influencing subsequent respiratory microbial colonization and predicting respiratory morbidity. In this way, early exposures imprint the postnatal immune-microbiota axis and place an infant at significant risk for respiratory morbidity in early childhood.