Tracy L. Bale, PhD
Director, Center for Epigenetic Research in Child Health & Brain Development; Professor, Departments of Pharmacology and Psychiatry, University of Maryland
Financial Disclosure: None
Infant mortality rates remain exceptionally high in the U.S., where babies born to African American (AA) women continue to die at 2.5-3 times the rate of babies born to non-Hispanic white women. Compounding determinants of maternal health, such as diet, infection, and lifetime trauma are known risk factors, and are especially important during pregnancy. Unfortunately, much is still needed to learn as to the biological basis for risk factors, including the role of maternal obesity, diabetes, and dysbiotic microbial communities. The mechanisms through which fetal antecedents contribute to infant morbidity and mortality are complex and compounding. For example, maternal obesity and diabetes are known risk factors for preterm birth and infant mortality, increasing prematurity and death by 40%. A second important interaction with the maternal microbiome occurs at birth when the maternal vaginal microbiome can serve as a key inoculant for the naïve newborn gut. A dysbiotic microbiome is positioned to produce ‘alarm’ to the newborn immune system, especially one primed from gestating in an unhealthy prenatal environment. Unlike the gut, a healthy vaginal microbiome consists of minimal diversity and a predictable microbial community, known as community state type (CST). Generally, state types I-III and V have low diversity and are dominated by Lactobacillus. CST IV, however, is characterized as having no dominant species, a higher diversity, and is more prevalent in AA women. In our studies examining the effects of a high-risk human cervicovaginal microbiota on brain development by exposing c-section delivered mice by oral gavage, we identified an unexpected increase in offspring mortality. This inoculation produced 60% mortality only when offspring had gestated in a high-risk in utero environment, and builds on our previous studies and premise that prenatal programming determines a response to the postnatal environment. We found that exposing newborn mice to a dysbiotic microbial community at birth precipitated immune-related responses and reduced survival.