Presentation Abstract

Program#/Poster#: 380.13/JJJ40
Presentation Title: Of vaginas and guts: The microbiome as a novel mechanism for maternal stress reprogramming of the offspring brain
Location: Halls B-H
Presentation time: Monday, Nov 11, 2013, 8:00 AM - 9:00 AM
Topic: ++E.05.c. Early life experience
Authors: C. L. HOWERTON, C. D. HOWARD, *T. L. BALE;
Dept Animal Biol, Univ. Pennsylvania, PHILADELPHIA, PA
Abstract: Prenatal stress is associated with an increased risk for neurodevelopmental diseases. In our established mouse model of early prenatal stress (EPS), the long-term programming effects on offspring stress pathway neurodevelopment have been demonstrated. The process through which this fetal antecedent contributes to reprogramming of the developing brain is not clear. Current evidence points to a likely influence of maternal stress experience on the maternal vaginal microbiome. The host-microbe interaction between the enteric microbial ecology and the developing neonate is a novel and innovative mechanism with the potential to significantly affect neurodevelopment through early postnatal nutrient availability and endogenous signaling pathways in the offspring gut. As the neonate’s gut is initially populated by the maternal vaginal microbiome following passage through the birth canal, changes in the vaginal microbiome produced by maternal stress experience would then alter this initial microbe population. Using targeted approaches in mice, we have determined that EPS affects both the maternal and offspring levels of Lactobacillus, and further that there is a significant positive relationship between the maternal vaginal levels and that of her offspring’s gut. From these findings we hypothesize that the vaginal microbiome is modulated by stress through changes in the mucosal immunity, and that these changes in the vaginal microbiome alter the initial population of the offspring’s gut microbiome impacting neurodevelopment. To test these hypotheses, we took a multi-dimensional approach using deep sequencing, mass spectrometry and whole transcriptome analyses. Specifically, we monitored the microbial ecology of both the maternal vagina and the offspring gut, evaluated metabolic consequences in the offspring by measuring circulating nutrients and key metabolites, observed changes in early offspring hypothalamic gene expression and determined key changes in the maternal vaginal mucosal immunity. Together, data from these experiments have identified a novel mechanism by which maternal stress contributes to reprogramming of the developing brain and may predispose individuals to neurodevelopmental disorders.
Disclosures:  C.L. Howerton: None. C.D. Howard: None. T.L. Bale: None.
Keyword(s): PRENATAL
SEX DIFFERENCES
STRESS
Support: NIH Grant MH091258




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