Microbiota in Reproductive Tract Linked to Preterm Birth

Laura Arenschield

May 02, 2019

Certain bacteria in a woman's reproductive tract can contribute to early labor and can be a key predictor of premature birth, researchers have determined after a decade of studies into vaginal and cervical microbiota.

"We're not claiming the vaginal microbiota is the reason for every single preterm birth that happens, but what we have found is that some microbes could be associated with a majorly elevated risk of preterm birth," said Jacques Ravel, PhD, from the University of Maryland School of Medicine in Baltimore.

In their study of 2000 pregnant women, Ravel and his colleagues found that seven bacterial taxa, including Lactobacillus iners, significantly contribute to preterm birth — before 37 weeks of gestation — and that the risk is even higher for black women (Nat Commun. 2019;10:1305).

However, they also found that women whose vaginal microbiota contained high levels of the peptide beta-defensin 2 seem to be protected from spontaneous preterm birth, Ravel told Medscape Medical News.

"Beta-defensin is among the panoply of our innate immune defense," he explained. It can compensate for the presence of microbes associated with an elevated risk for preterm birth.

However, it is still unclear how potential clinical interventions could keep pregnancies from ending in early labor. "That is what we are looking at now," he reported.

A Multifactorial Problem

One of the first studies into the connection between microbiota in the reproductive tract and preterm birth was led by David Relman, MD, from Stanford University in California.

Before that, researchers assumed that the microbiome was important for both maternal and fetal health, but were not clear on the role they played, Relman told Medscape Medical News.

"It stood to reason that a disruption of some kind or some insufficiency or failure in the normal evolution of the microbiome during pregnancy could be a contributing factor in premature labor," he said. "But we were also mindful that there was already a lot of literature on premature birth around the world and we had a pretty good hunch that it was almost certainly a multifactorial problem, meaning genetics and a whole host of environmental factors — everything from stress to environmental pollution. And our research has proven that to be the case."

Relman and his colleagues started by studying the microbiomes of pregnant women who lived near the Stanford campus and then branched out to a cohort in Birmingham, Alabama. They found that certain bacteria — especially Lactobacillus crispatus — appear to be an indicator that a woman will carry her pregnancy to term, but that L. iners do not offer the same protection.

Other research groups around the world confirmed those findings and added new data that showed that L. iners might in fact be a threat to a pregnancy.

As the body of research grew, larger questions arose. "We are trying to understand more about the microbiota as a community and not just as a collection of arbitrary strains and species," said Relman. "How do they interact? What are they doing to facilitate each other's presence and welfare? And can we take advantage of some of those interactions to manipulate the microbiota community and support a healthy pregnancy?"

The work of both Ravel's team and Relman's team will be discussed during the March of Dimes Annual Lecture at the American College of Obstetricians and Gynecologists 2019 Annual Meeting, in Nashville, Tennessee, on reproductive tract microbiota and preterm birth.

I don't want people to go out and start taking probiotics yet.

The March of Dimes, which has funded the research of both teams, is focusing on potential clinical interventions to make microbiota more supportive of keeping a pregnancy intact, said Kelle Moley, MD, chief science officer at the organization.

"Where we're moving toward, at least therapeutically, is looking at replacing microbiota in the vaginal space," Moley told Medscape Medical News. "One option might be a suppository you would put in your vagina, something that would supplement the existing microbiota with the good microbiota, the Lactobacillus crispatus.

"I don't want people to go out and start taking probiotics yet. I think there is a better approach we can take to this, a precise approach, with the right supplementation in the vagina, that is ultimately going to be most effective," she said. "But we have to wait and see as the studies go forward to determine what that best approach is."

The study by Revel's team was funded by the National Institute for Nursing Research of the National Institutes for Health. Revel and two of his colleagues are listed as inventors on a patent application that covers compositions and methods for predicting risk of preterm birth.

American College of Obstetricians and Gynecologists (ACOG) 2019 Annual Meeting. To be presented May 4, 2019.

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