Abstract
With birth, there is a dramatic increase in an infant’s T cell exposures to commensal and pathogenic bacteria. We hypothesized that populations of T cells and microbiota co-develop in the human neonate, and that disruption of their coordination would associate with respiratory morbidity in the first year of life. To test this hypothesis, we analyzed blood and microbiota samples from 133 pre- and 79 full-term infants (PT and FT, respectively), collected through the Prematurity, Respiratory, Immune System and Microbiome (PRISM) study through one year of age. T cell function and phenotype were repeatedly measured by flow cytometry over the first year of life and summarized into immune state types (ISTs). Intestinal and nasal microbiota were measured weekly prior to hospital discharge, monthly thereafter, and during symptomatic respiratory illnesses, and were summarized into community state types (CSTs). Our major findings were three-fold. First, PT and FT CSTs and ISTs varied at birth, but showed an organized progression by postmenstrual age, and convergence by one year. Second, temporal associations between CSTs and ISTs suggest a bidirectional relationship between the microbiome and T cell development. Third, respiratory morbidity is increased in the first year of life in infants displaying atypical acquisition and maturation of microbiota and immune cell populations. These results together suggest that microbiota and T cell maturation are coordinated during infant development. Most importantly, atypical or asynchronous microbiota and T cell maturation is a risk factor for respiratory morbidity in the first year of life.
Footnotes
One Sentence Summary: Synchronized patterns of development of the immune system and microbiome in pre- and full-term infants are disrupted as a marker of respiratory disease.