Tuesday, July 29, 2014

How do mom's microbes affect pregnancy outcomes? UAB research aims to find out

As a baby slides out of the birth canal, on the way to its first breath, its body becomes coated in its mother’s microbes. This first interaction with outside organisms could be key to shaping the development of the baby’s immune system.

Our microbes, collectively called the microbiome, most often live in harmony with our bodies. They support the immune system, help to digest food and keep the metabolism on track, and fight off disease-causing bacteria. But researchers suspect that mom’s microbiome could play a role in when her children are born, and what happens to them as they grow.

“Most people know about the microbes that colonize the gut,” says Rodney Edwards, M.D., an associate professor in UAB’s Department of Obstetrics and Gynecology. “But there are bugs in and on us in many other sites—our skin, our mouths, our noses, our genitalia.”

During pregnancy, it turns out, the new needs and demands of a woman’s body change the numbers and types of these microbes. Alterations in how the body divvies up nutrients, stores fat, and produces hormones shift the properties of the microbes’ environments. But exactly how the microbiome changes over this nine-month period varies between pregnancies. And these variations, researchers are discovering, could impact not only the well being of a pregnant women herself, but the likelihood of pregnancy complications and the long-term health of a baby.

Rodney Edwards has launched a
research program to probe how the
microbiome of an expectant mother shapes
maternal and fetal health. 
Edwards has launched a research program in the UAB School of Medicine to probe how the microbiome of an expectant mother—especially the flora that inhabit the genital tract—shape maternal and fetal health. He wants to know if the microbiome’s composition could make a woman go into labor early, or influence a baby’s chance of developing asthma or allergies, among other questions.

“If we could find a few organisms that—when present in the microbiome—were associated with a particular pregnancy or childhood outcome,” Edwards says, “we could use it as a targeted test for high-risk pregnancies and test putative interventions in that group.”

Investing in the Microbiome

Over the past decade, scientists around the world—armed with the new ability to take a genetic snapshot of the microbiome in any person at any given time—have been probing how changes to the microbe populations in a person’s gut can make them sick, weaken their immune system, or even change their risk of cancer or heart disease.

A few years ago, when the National Institute of Health’s Human Microbiome Project was announcing its early results, Casey Morrow, Ph.D., a professor in the UAB Department of Cell, Developmental and Integrative Biology, became excited about the possibilities of microbiome research and the potential to improve human health.

Morrow’s microbiology laboratory teamed up with UAB’s Heflin Center for Genomic Science—with its next-generation DNA sequencing capabilities—and bioinformaticians in the UAB Center for Clinical Translational Science to establish the necessary components at UAB to do microbiome analysis. With early seed support from the UAB Cancer Center and later from the UAB Center for AIDS Research and School of Medicine, they were able to launch a shared facility supporting microbiome research.

Today, barely two years later, the UAB Microbiome Resource is flourishing, says Morrow. “Any UAB researcher who wants to analyze a microbiome can submit a sample to the facility and from the microbiome analysis pipeline established at UAB can determine what microbes are present,” he says.

Casey Morrow says the UAB Microbiome
Resource gives researchers a strong
foundation to link basic science
and clinical science.
“Armed with that analysis, researchers can start figuring out the differences between different samples and what those differences might say about disease states,” says Morrow. “This is really giving us a strong foundation to link basic science and clinical science when it comes to the microbiome.”

UAB researchers are already studying how the gut microbiome could influence colon, breast, stomach, pancreatic, and brain cancer; how chronic infections in the digestive system can be cured by restoring microbial populations; and how chemotherapy and diet change the microbiome. (Learn more about research on cancer and the microbiome in the latest issue of the UAB Comprehensive Cancer Center magazine.)

Beginning with Bacterial Infections

Edwards’ interest in the microbiome began not with basic science, but with a clinical question: Why does bacterial vaginosis (BV) during pregnancy increase the risk of preterm births and low birth weight babies? BV is not an infection but rather a condition in which the normal flora of the vagina, dominated by Lactobacilli, is replaced by a mix of bacteria dominated by anaerobes and Gram-negative aerobic bacteria. BV increases the risk of going into labor before 39 weeks of gestation. But when clinicians aggressively screen for and treat BV in populations of pregnant women, they don’t see changes in preterm birth rates.

Researchers began to understand that BV is what is known as a heterogeneous problem, says Edwards. In other words, “BV in one woman isn’t the same as BV in another.”

The UAB Microbiome Resource offers researchers
many ways to analyze samples, including "heatmaps"
depicting levels of various microbes.
But classic methods of diagnosing BV didn’t give detailed information about what microbes take over the vagina during an infection—it’s typically diagnosed by measuring the acidity of the vagina (a high pH suggests BV) and looking at a smear from the vagina under a microscope to confirm the presence of bacteria. Edwards, though, wants to get a better sense of the exact species of bacteria normally present in the vagina, how that balance could change in different ways in women with BV, and which variants of BV are most dangerous to pregnant women.

In a pilot study, UAB researchers collected samples from 19 pregnant women diagnosed with BV. In collaboration with the UAB Microbiome Resource, they were able to detect the identity of the microbes present in each sample.

“What we’ve already found is that the organisms we used to think were predominant in BV may not actually be predominant,” Edwards says. “At least not in all cases.”

Now, with the knowledge that microbiome analysis can give more detailed information on a case of BV than classic, microscopy-based approaches, Edwards is moving toward understanding the link with preterm births. To that end, he’s working to establish, within the existing Center for Women’s Reproductive Health, a new UAB Prematurity Prevention and Research Related to the Microbiome (PREPARE-M) Clinic.

His first project within the new clinic: prospectively following women throughout pregnancy to track changes to their microbiomes. The women he plans to initially follow are those who have previously had a preterm birth, putting them at high risk of repeating that outcome. He’s received a grant from the General Endowment Fund of the UA Health Sciences Foundation to get the study off the ground.

If he can find specific subsets of BV that increase a woman’s chance of preterm birth, Edwards believes clinicians will be well on their way to determine how to best treat these women to decrease those odds.

Microbes Linger Long-Term

Simply preventing preterm births—at least those associated with infections—is a leap toward improving infant health, as babies born preterm are prone to health problems. But Edwards thinks that a mother’s microbiome does far more than affect her chances of an early delivery.

"There could be something we should be doing immediately after childbirth to make sure a baby's microbiome is shaped properly," Edwards says. "And this could have long-term childhood effects."
In the PREPARE-M Clinic, Edwards has launched a long-term study on how the transfer of microbes from mother to baby—which some researchers have found happens even in the womb—could alter a child’s health for years down the road. Initially, he’s going to follow mothers and children only through their first post-partum doctor’s visit, six weeks after birth. But eventually, he’d like to follow children through their fifth birthday.

“There could be something we should be doing immediately after childbirth to make sure a baby’s microbiome is shaped properly,” Edwards says. “And this could have long-term childhood effects.”
Of course, there are also plentiful basic questions about the genital microbiome: how it’s shaped by the microbes of the gut or skin, how it interacts with the immune system, and how it changes over a person’s lifetime. “Scientists have been studying the gut microbiome for 15 years now,” Edwards says, “But the applications to the vagina and obstetrics are even newer. So we have more basic questions left to answer.”

One day, microbiome analysis could become commonplace—not only during pregnancy, but at doctor’s visits throughout a person’s life, Morrow says. “Just as your doctor takes a blood sample today, taking samples of your microbiome to make sure your microbes are all in balance will become routine. We anticipate that 'microbiome management' will be an important component of a personalized medicine plan to monitor and improve human health.”

—Written by Sarah C.P. Williams

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