Q&A: Understanding the link between the vaginal microbiome, preterm birth

Key takeaways:

• The March of Dimes awarded a grant to study the link between the vaginal microbiome and spontaneous preterm birth.
• This research will help further development of a preterm birth risk test.

The March of Dimes awarded a grant to further research into profiling the vaginal microbiome and investigate its connection with spontaneous preterm birth, part of a larger effort to develop a test for preterm birth risk.

“This March of Dimes funding is amazing for us, and it allows us to do things that we wouldn’t have been able to do otherwise,” Tal Korem, PhD, assistant professor of systems biology and reproductive sciences at Columbia University Irving Medical Center, told Healio. “Our research relies on decades of federal funding. The samples that we’re using were collected by another NIH-funded clinical study that ran about a decade ago, the nuMoM2b study. This underlines the importance of federal funding for clinical research and of continuous involvement of physicians and patients in these types of research studies that allow us to, over time, have a sustained impact that allows us to drive this field forward.”

Healio spoke with Korem about how what can be learned from profiling the vaginal microbiome, the impact of environmental exposures, and how research might lead to developing a test to assess spontaneous preterm birth.

Healio: How is the vaginal microbiome associated with spontaneous preterm birth?

Korem: We know that a good number of spontaneous preterm births are caused by an ascending infection from the vaginal microbiome. That’s an obvious route of involvement. In recent years, we’ve also discovered that the vaginal microbiome might be related to a nonideal immune state and might be involved in the production of metabolites that might have some involvement in preterm birth. We’ve known about the direct route of the infection for a while, and we’re now becoming more aware of the possibility of nondirected involvement.

Healio: What previous research have you been involved in regarding the vaginal microbiome and preterm birth?

Korem: In previous research, our group has examined small molecules in the reproductive tracts. We found a good number of xenobiotics, which are molecules that, to our knowledge, are not produced by either microbes or by human cells. They’re the result of what we call environmental exposures, but this could also be household exposures. Some of these molecules were very strongly associated with preterm birth in that study. We don’t have definitive proof for this, but the common factor behind four of our top hits in that study was that they were all present in hygienic and cosmetic household products. We thought that this is an interesting direction for future studies. We also showed that you could predict preterm birth early in pregnancy using those metabolite measurements. A lot of past studies in the vaginal microbiome space look at the composition of microbes by genus and species. We conducted a study where we looked at the genetic diversity of microbes within the species. We found that the diversity of a specific vaginal species, Gardnerella vaginalis, was strongly associated with preterm birth. This showed that we need to look much more deeply at the genetic structure of this community to further understand the relationship between the microbiome and preterm birth.

In the past several years, we’ve been generating a very big data set with hundreds of pregnancies, profiling both the vaginal microbiome and the vaginal metabolome. This is the cohort that is the basis for this March of Dimes award. The support enables us to profile the local host immune system from those samples and add that access to our investigation.

Healio: What research do you plan to conduct with that access?

Korem: We’re going to get these host immune profile measurements. Somewhat uniquely to our studies is that we’re going to look at these immune factors locally in the vaginal ecosystem, rather than looking at blood samples. We’re going to do this for close to 1,000 pregnancies. We already have very deep profiling of the vaginal microbiome in this cohort, and we’re now generating the metabolomics so we could look at how host immunity is interacting with the vaginal microbiome, and how host immunity is interacting with the molecular milieu, or the metabolism, of that system. Then we could look at all these three factors with respect to spontaneous preterm birth.

Healio: Could you discuss the preterm birth risk test that you plan to develop based on what you may find?

Korem: In a lot of smaller-scale studies, we showed that the microbiome, the metabolome and host immune factors, when we sample them earlier in pregnancy, have the capability of serving as biomarkers for subsequent diagnoses with adverse pregnancy outcomes. A few months ago, we published preliminary results showing that the same host immune factors that we are going to measure with this grant, along with microbial measurements, can also predict severe preeclampsia, which is another important adverse pregnancy outcome that is a big risk factor for maternal mortality. Our hope is to have a future where you could take a vaginal swab early in pregnancy, perhaps even during the first trimester, and have some indication of risk for multiple adverse pregnancy outcomes, but primarily for preterm birth.

Healio: How could a test for preterm birth risk test improve pregnancy outcomes?

Korem: There aren’t a lot of good clinical interventions right now for adverse pregnancy outcomes. High-risk pregnancies for preterm birth do get a different clinical management than normal-risk pregnancies, and there are some interventions for preeclampsia, like low-dose aspirin. Part of the reason that we don’t have good interventions is because it’s very hard to identify risk. I think that if we could stratify risk, that would accelerate research and would allow us to identify interventions. But an immediate effect of such a test could be improving access to care. There’s a lot of people in this country and elsewhere around the world that don’t have good access to medical care. Knowing that you’re at high risk and that you need to get access to care or you need to go to a hospital with access to a NICU, for example, could have an immediate impact on clinical outcomes.

For more information:

Tal Korem, PhD, can be reached at tk2829@cumc.columbia.edu; Bluesky: @tkorem.bsky.social.