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

Andrew McDavid; Nathan Laniewski; Alex Grier; Ann L Gill; Haeja A Kessler; Heidie Huyck; Elizabeth Carbonell; Jeanne Holden-Wiltse; Sanjukta Bandyopadhyay; Jennifer Carnahan; Andrew M Dylag; David J Topham; Ann R Falsey; Mary T Caserta; Gloria S Pryhuber; Steven R Gill; Kristin M Scheible

doi:10.1016/j.isci.2022.104007

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

iScience. 2022 Mar 1;25(4):104007. doi: 10.1016/j.isci.2022.104007. eCollection 2022 Apr 15.

Authors

Andrew McDavid¹, Nathan Laniewski², Alex Grier³, Ann L Gill², Haeja A Kessler², Heidie Huyck⁴, Elizabeth Carbonell⁴, Jeanne Holden-Wiltse¹, Sanjukta Bandyopadhyay¹, Jennifer Carnahan⁴, Andrew M Dylag⁴, David J Topham², Ann R Falsey⁵, Mary T Caserta⁴, Gloria S Pryhuber⁴, Steven R Gill², Kristin M Scheible⁴

Affiliations

¹ Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA.
² Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
³ Genomics Research Center, University of Rochester, Rochester, NY, USA.
⁴ Department of Pediatrics, University of Rochester, Rochester, NY, USA.
⁵ Department of Medicine, University of Rochester, Rochester, NY, USA.

Abstract

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 preterm 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 perinatal and postnatal 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.

Keywords: Immunology; Microbiome.