The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model

Eldin Jašarević,Elizabeth M Hill,Lillian Folts,Jacques Ravel,Kylie D Rock,Tracy L Bale,Lindsay Rutt,Christopher D Howard,Kathleen E Morrison,Trevonn Gyles,Patrick J Kane

doi:10.1038/s41467-021-26634-9

Abstract

Newborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation.

Highlights

Newborns are colonized by maternal microbiota that is essential for offspring health and development
Strain-resolved analyses showed that maternal vaginal bacteria, including Lactobacillus crispatus, G. vaginalis, and A. vaginae, are among the earliest colonizers to persist within the infant intestinal tract during the first few days after birth[3]
Additional sample selection criteria for mouse transplantation experiments included: (1) sequencingbased and cultivation-dependent confirmation of community state types (CST) I or CST IV vaginal microbiota; (2) availability of samples between 36 and 39 weeks of pregnancy to capture the microbial communities with the greatest relevance toward what would be vertically transferred to newborns during birth; and (3) women remained in their respective CST throughout pregnancy

Summary

Introduction

Newborns are colonized by maternal microbiota that is essential for offspring health and development. We validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. Strain-resolved analyses showed that maternal vaginal bacteria, including Lactobacillus crispatus, G. vaginalis, and A. vaginae, are among the earliest colonizers to persist within the infant intestinal tract during the first few days after birth[3] While these members of CST I (L. crispatus) and CST IV (G. vaginalis, A. vaginae) exhibit distinct metabolic and immune properties in the female reproductive tract[12,27,28], the possible functional consequences of transferring these communities from mother to the newborn is not clear[3]. We used a separate mouse model to determine whether single or compounding prenatal risk factors—diet-induced obesity and the presence of G. vaginalis—impact prenatal endpoints and the postnatal response to the colonizing microbiota

Methods

Results

Conclusion