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

McDavid, A;Laniewski, N;Grier, A;Gill, A;Kessler, H;Huyck, H;Carbonell, E;Holden-Wiltse, J;Bandyopadhyay, S;Carnahan, J;Dylag, A;Topham, D;Falsey, A;Caserta, M;Pryhuber, G;Gill, S;Scheible, K;

Neonatal immune-microbiota co-development is poorly understood, yet age-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 is a central 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 predict the postnatal immune-microbiota axis trajectory, placing infants at later risk for respiratory morbidity in early childhood.