Data Sheet 1_Abnormal intestinal microbial colonization in prenatally stressed offspring is related to lung and intestinal cytokine expression.pdf

IntroductionPrenatal 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.
MethodsUsing a mouse model of PNS, we aimed to understand the extent to which these early-life intestinal microbial perturbations are related to intestinal and lung cytokine gene expression. 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 cytokine differences in relation to intestinal microbial composition.
ResultsIn addition to significant changes in microbiome diversity and differential abundance, PNS offspring exhibited significant differences in ileal and lung cytokines characterized by overall increased interferon and proinflammatory gene signatures. PNS-associated microbiome changes also correlated to gene expression in both the ileum and lung. Finally, PNS-associated cytokine differences were not observed in MyD88−/− offspring which lack the ability to initiate inflammatory responses through microbially-stimulated toll-like receptor signaling.
ConclusionThese findings suggest that PNS-mediated changes in the early-life microbiome are linked to respiratory and ileal immune development and the microbe-immune interactions are MyD88 pathway-dependent.