Alterations in the vaginal microbiome by maternal stress are associated with metabolic reprogramming of the offspring gut and brain

Abstract

The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primarysource for normal gutcolonization, hostimmune maturation, and metabolism. Theseearly interactions between the host and microbiota occur during a critical window of neuro development, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neuro developmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, toexamine the hypothesis that changesinthe vaginal micro biome are associated with effects on the off spring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that in fluence offspring microbiota composition and metabolic processes essential for normal neuro development. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the develop ingbrain. Takentogether, theseresults identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neuro developmental disorders.