Abnormal microbial pioneer colonization in prenatally stressed offspring may drive lung and intestinal immune dysregulation

Prenatal stress (PNS) is associated with deleterious effects on childhood health and wellbeing. Among these consequential health repercussions, PNS-exposed children are at increased risk for acquiring early-life infections, with respiratory infections frequently reported. Stress-induced perturbations in the maternal microbiome during pregnancy represent a key link between stress in utero and aberrant offspring development and can drive abnormal pioneer colonization of offspring microbiomes. Using a mouse model of PNS, we aimed to understand how these early-life microbial perturbations may contribute to changes in health with an eye towards respiratory infections. The intestinal microbiome alongside intestinal and lung tissue gene expression were assessed over the first five weeks of life in PNS-exposed offspring to characterize basal immune response differences in relation to microbial composition. In addition to significant changes in microbiome diversity and differential abundance, PNS offspring exhibited significant immune dysregulation in ileal and lung tissues characterized by overall increased interferon and proinflammatory gene signatures. PNS-associated microbiome changes also correlated to gene expression in both the ileum and lung.