Studying the microbiome in pregnancy, postpartum and preterm births

Researchers at Baylor College of Medicine and Texas Children’s Hospital have been studying the vaginal microbiome community throughout pregnancy and after delivery for nearly a decade. Their work included a subgroup of women starting in early pregnancy who later experienced a spontaneous preterm birth. They have now been able to track and decipher patterns of which beneficial bacteria tended to harmoniously co-occur and change patterns prior to preterm births. Their findings were published in Med.

“For well over 100 years, both physicians and scientists have understood that a healthy vagina has a community of bacteria, now known as the vaginal microbiome. In most women, this community has always thought to be dominated by the largely beneficial and health promoting species of Lactobacillus bacteria. However, if and how these communities of healthy bacteria normally change over a women’s lifespan and before and after pregnancy has only recently been understood,” said Dr. Kjersti Aagaard, professor of obstetrics and gynecology at Baylor and Texas Children’s and principal investigator of the study.

By tracking bacteria strains over time and trying to determine whether any certain strains and the genes they express were either predictive or protective against preterm birth, the researchers gained some key insights.

First, not all healthy women who were pregnant or recently pregnant had a vaginal microbiome that was overwhelmingly Lactobacillus bacteria. Second, they found that there were no strong associations between the early absolute presence or absence of any specific strain of vaginal bacteria with preterm birth. However, they did again observe clear patterns suggesting that once a Lactobacillus bacteria strain colonizes the vagina, it can exclude other more or less beneficial microbes from colonizing that same woman’s vaginal microbiome. Researchers noted that they considered social determinants of health when making these observations since different groups of people are more likely to have certain issues during pregnancy. For example, African American women are known to bear over twice the risk of preterm birth.  Third, these principles held true with several potential pathogenic or disease-causing bacteria, such as Group B streptococcus (GBS).

GBS is a Gram-positive alpha-hemolytic bacterium that can cause invasive GBS disease in the early newborn, usually less than 6 days old, characterized primarily by neonatal sepsis and pneumonia. For the last two decades, in an effort to eliminate neonatal mortality due to early invasive GBS disease, in the United States, obstetrical providers have tested all pregnant women about a month prior to delivery (or with preterm labor) by vaginal/rectal cultures for GBS.

In their current study, the researchers found that some of the beneficial Lactobacillus bacteria appeared to exclude co-occurrence of GBS in the vaginal microbiome of women during pregnancy.

According to Aagaard, a key to their findings relied on the advanced sequencing approaches and their analysis.

“In our hands, WGS metagenomic sequencing, although costlier and more computationally intensive, provides a more sensitive detection of the major and minor constituents of the vaginal microbiome, including Gardnerella vaginalis, Lactobacillus species, and Group B Streptococcus. In addition, WGS metagenomic sequencing enables strain-level differentiation, which may be of importance when attempting to understand the complex ecology of the vaginal niche,” she said. “When we let the data speak for itself, it is clear that getting down to the strain level of identifying bacteria is crucial to understand the governing principles of the vaginal microbiome. This led us to understand both during pregnancy and the post-partum period, the ecology of the vaginal microbiome is mainly driven by the abundance of four keystone species, and that more attention should be focused on the contribution of individual strains with respect to potential differences in health outcomes such as preterm birth and likely invasive GBS disease.”

This study is funded by of the NIH–NINR (R01 NR014792, K.M.A.), NIH-NICHD (R01 HD091731, K.M.A.), NIH National Children’s Study Formative Research (N01-HD-80020, K.M.A.), the Burroughs Wellcome Fund Preterm Birth Initiative (K.M.A.), the March of Dimes Preterm Birth Research Initiative (K.M.A.).

To see a full list of contributing authors, see the publication.