Study finds bacteria linked to preterm birth

Researchers at North Carolina State University have found that multiple species of Gardnerella, bacteria sometimes associated with bacterial vaginosis (BV) and preterm labor, can coexist in the same vaginal microbiome. The findings, published in the journal mSystems, add to a growing understanding of the impact of Gardnerella on human health.

Gardnerella is a group of anaerobic bacteria that are commonly found in the vaginal microbiome. Elevated levels of these bacteria are a hallmark of BV and are associated with an increased risk of preterm birth, but they are also found in women with no evidence of the disease.

"We were trying to understand the diversity within Gardnerella," says Ben Callahan, an assistant professor of population health and pathobiology at North Carolina State University and a co-author of the paper.

"Scientists have only recently begun to study individual species of Gardnerella, so we don't yet know whether different species might have different health effects. Our main goal was to study the ecology of Gardnerella."

A unique challenge with sequencing the vaginal microbiome is that any samples are primarily composed of host DNA, making extracting microbial data more expensive and time-consuming. The research team's first task was to develop a methodology to identify different species of Gardnerella from the microbiome data.

"The current tools for studying the vaginal microbiome treat all Gardnerella as a single species," says Hannah Berman, a postdoctoral fellow at North Carolina State University and lead author of the paper. "To do this work, we had to build our own database of Gardnerella genomes and develop a method to identify different species of Gardnerella. Hopefully, this will also allow more researchers to study the diversity of Gardnerella."

The research team examined sequencing data from three cohorts: two random populations of pregnant women and one population with a history of preterm birth. They analyzed the Gardnerella metagenomic sequences from the samples to see if there was a link between a specific Gardnerella species and preterm birth.

While they didn't find the smoking gun, they did make two surprising discoveries.

First, they identified a potential 14th Gardnerella species among the samples — only 13 species had been identified before this work.

They also found that in most of the samples that had Gardnerella, multiple Gardnerella species coexisted in the same microbiome: anywhere from two to all 14 known Gardnerella species were found in individual samples.

"Typically, if a species of bacteria colonizes the environment, we expect it to exclude close relatives that would occupy the same ecological niche and consume the same resources," Callahan says. "I often say that with bacteria anything is possible, but this is still unusual. We also saw that when the overall microbial load is higher, Gardnerella makes up a large portion of that load.

"Evidence continues to mount that Gardnerella is associated with preterm birth, but the details of the relationship are complex. We didn't find one harmful species of Gardnerella in this work—it's possible they are all harmful. That's not the end of the story." p>

Researchers hope to further study issues of species coexistence and microbiome composition.

"The vaginal microbiome is underestimated," Callahan says. "For example, it is often dominated by one species of Lactobacillus, which creates an environment that excludes other bacteria. When it is not there, Gardnerella is there. So how do these bacteria interact?

"Answers to these questions could lead to more effective treatments for BV and ways to predict and prevent preterm birth. This work is an important step in that process."