The microbiome’s murky role in pregnancy loss and complication

The same vaginal bacteria linked to promotion — and prevention — of various pregnancy complications, studies find
Pregnant woman's torso
The microbiome's role in pregnancy is not always clear. Researchers have recently found that the same vaginal bacteria can have opposite effects on different pregnancy complications, even among the same population of women. Stock photo by FeaturePics

It could take more than two to make a healthy baby — many, many more.

Researchers are beginning to better understand how the millions of bacteria that make up the vaginal microbiome help shape a normal pregnancy — as well as the devastating complications that may arise when that microbial community is off balance.

A study published recently by scientists at Temple University and Fred Hutchinson Cancer Research Center found that the very same bacteria can have entirely different effects on women’s risk of premature delivery or miscarriage. And that dichotomy — one bacteria causing help and harm — has researchers both baffled and intrigued.

It’s long been understood that the wrong mix of vaginal bacteria can increase the risk of premature delivery, when a baby is born earlier than 37 weeks gestation. More than 450,000 babies are born premature every year in the U.S., according to the Centers for Disease Control and Prevention. Preterm birth contributed to 35 percent of all infant deaths in 2010, more than any other single cause.

Photo of David Fredricks
Dr. David Fredricks

Normally, the vaginal environment is dominated by a few key bacterial species from the genus Lactobacillus, said Dr. David Fredricks, Fred Hutch’s resident vaginal microbiome expert. When that community is out of whack, bacterial vaginosis can result.

Bacterial vaginosis is a single condition, characterized by local irritation and a unique odor (although many women who have it don’t experience any symptoms), but it’s caused by any number of not-so-healthy bacterial mixtures.

“When somebody has bacterial vaginosis, they don’t have one set of bacteria,” Fredricks said while gesturing to portray the presence of different, invisible bacteria. “It could be this set of bacteria, or this set of bacteria, or this set of bacteria.”

It’s those variables that make the condition especially tricky to study.

Untangling the microbiome’s influence

Previous research has shown associations between bacterial vaginosis and increased risks of premature delivery and of miscarriage, Fredricks said.

But here’s one medical catch-22: Knocking out the risky bacteria with antibiotics during pregnancy doesn’t necessarily alleviate the risk. Fredricks and his colleagues think that could be because the condition is so diverse.

“Maybe those different bacterial communities impart different risks,” he said.

So they set out in the recent study to tease those communities apart.

Fredricks’ collaborator, Temple University obstetrics and public health researcher Dr. Deborah Nelson, leads a National Institutes of Health-funded study known as ProjectBABIES to examine the links between different vaginal bacteria and pregnancy outcomes. ProjectBABIES included nearly 1,900 pregnant women who visited obstetrics clinics in Philadelphia early in their pregnancies.

The women who enrolled collected samples of their own vaginal fluids in their first trimester of pregnancy. Fredricks and his team then looked for the presence of different bacteria in those samples and the researchers followed the women over the course of their pregnancies to see how they fared.

What they found was a puzzling mix of effects that they’re still working to untangle: Chiefly, how and why both good and bad effects — in the same population of women — are related to the same bacteria.

For example, in a paper published last year, the researchers described their findings that among 48 women with a prior history of premature delivery, there are three specific microbial types that seem to increase risk of another early delivery.

More recently, the team asked whether certain microbes present early in pregnancy affect the risk of miscarriage, or early pregnancy loss. This research turned up yet another apparent contradiction. They found two bacterial types that seemed to lower the risk of miscarriage. But both those bacterial groups — known as Leptotrichia and Megasphaera — increased risk of preterm delivery in the researchers’ previous study.

Fredricks, Nelson and their colleagues also found a third species, dubbed Mageeibacillus indolicus, that seemed to increase risk of miscarriage. Women with this bacterium present early in pregnancy were about twice as likely to miscarry as women without it. However, another research team found that M. indolicus actually decreases risk of premature birth — although that study did not look at miscarriage risk.

 The bottom line: the same bacterium could have opposite effects on what’s essentially the same issue — too-early delivery — depending on when during pregnancy it occurs.

“That was actually surprising to us,” Nelson said.

The researchers have some theories, though. It’s possible that different bacteria are able to climb from the vagina into the uterus at different stages of pregnancy, thus triggering potentially dangerous inflammation at different times, Fredricks said. But within that theory, more questions remain.

“We don’t know why it is that we’re seeing these kind of flipped results,” Fredricks said. “We don’t understand it.”

More mitigating factors

Still other mysteries remain to be cracked in the vaginal microbiome story.

The women in the Philadelphia study were primarily African-American, and women of different ethnicities host very different vaginal communities, Fredricks said. For example, one of the bacteria that increased risk of preterm birth in their study is far more common among black and Hispanic women than among white women.

Scientists don’t know whether these differences are genetic or cultural, Fredricks said, recommending such studies be repeated in different populations to determine whether their findings apply universally or not.

Another interesting twist to their study: Men also carry M. indolicus, the microbe associated with increased risk of miscarriage, and can pass it to their partners during sex.

“So it may be that … the health of the male sexual partner as well as the vaginal microbiota of the female sexual partner may be an interesting area to explore in trying to prevent miscarriage,” Nelson said.

Fredricks is leading an ongoing study to explore how men and women pass reproductive-tract microbes between each other.

What can women do?

It’s going to be tricky to continue to pick apart these results, Fredricks said.

But for him, the takeaway is that women with a history of certain pregnancy complications should talk to their doctors about bacterial vaginosis.

“My take is that if a woman has a history of preterm birth, then that’s where I would be concerned in particular about bacterial vaginosis in pregnancy and would consider frequent follow-up and screening and the potential for treatment in those women,” he said.

Antibiotics have not yet been developed to specifically address individual vaginal bacterial species. But some broad-spectrum antibiotics are effective at killing all bacterial-vaginosis-associated bugs.

On the miscarriage side of the equation, Nelson believes that a better understanding of a woman’s health before conception can help.

Because bacterial vaginosis tends to recur but often crops up without noticeable symptoms, she recommends women who’ve had the condition before get screened — and treated, if necessary — before trying to get pregnant.

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Rachel Tompa is a former staff writer at Fred Hutchinson Cancer Center. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Follow her on Twitter @Rachel_Tompa.

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