Imagine sitting down to enjoy your favorite meal. With the help of your knife and fork, you slice and poke the contents on your plate and raise a bite to your lips to eat.

Much like the dinnertime utensils prepped your meal for consumption, the human body is equipped with legions of microscopic helpers that not only break down and process our food, but also support homeostasis, early life development, immune system function, and possibly much more.

This mighty ecosystem comprised of trillions of microorganisms living on our skin and inhabiting our mouths, gut, and reproductive tracts is the microbiome. While the microbiome is often associated with digestion (“the knife and fork of our genome”), scientific investigation continues into the entirety of the microbiome’s behavior and functions, and its influence on our overall health.

Why Does the Microbiome Matter?

For many years, microbes, or those little bugs living and working in our internal ecosystem, were associated with the development of disease. About 15 to 20 years ago, things changed.

With the advent of recent technologies to sequence the microbes outside of a Petri dish, scientists began to probe other microbiome functions, discovering that it has much more to do with supporting our overall well-being than previously thought.

“We realized that [microbes] have absolutely critical functions for life on Earth — especially for our own physiological functioning,” explains Dr. Eldin Jašarević, a Primary Investigator at Magee- Womens Research Institute (MWRI) and Assistant Professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences and the Department of Computational and Systems Biology at the University of Pittsburgh.

“We think they’re involved in things like food processing, and then our microbes transform these food components into tens of thousands of metabolites, vitamins, and nutrients. How is this incredible diversity and richness contributing to our health? These are unknowns, but we think they are essential for development, maturation of our immune system, and proper brain function.”

But the microbiome can also turn against us. Research conducted by Dr. Jašarević showed for the first time that childhood trauma or stress during pregnancy disrupted the ability of the mother’s microbiome to produce critical nutrients for the developing brain. These offspring were more sensitive to stress, displayed behavioral dysfunction, and showed lasting changes in the brain.

Dr. Jašarević’s research team is now tackling the most important questions that remain about the ways the microbiome works during pregnancy, and how its information could be used to improve clinical care. Could the microbiome tell us what therapeutic interventions should be offered during pregnancy? Can it help us in predicting offspring outcomes? Might it offer insights into ways to prevent health disparities from affecting future generations? These are the very questions Dr. Jašarević, and the “Maternal Microbes” research team are motivated and focused on better understanding.

Part of this research requires teasing out foundational comprehension of how the microbiome assists in pregnancy, so that therapeutic interventions are more precisely guided.

“We are currently facing a real global challenge: Less than 16% of studies on dietary and nutritional recommendations include pregnant individuals,” Dr. Jašarević says. “If we do not have a solid understanding of nutritional requirements in pregnancy, how are we going to know when that baseline goes into the pathological? Or how do we know if you veer into the pathological, how do we bring you back to a baseline?”

Tapping into the Local Ecosystem

This historical exclusion of pregnant people from clinical trials has produced significant gaps in
our understanding of proper dietary intake and nutrition recommendations during this critical
time — a concerning fact considering that medical nutrition therapies are the mainstay management in pregnancy and that diet is one of the most potent modifiers of microbial communities.

By combining forces with other researchers in the MWRI community, Dr. Jašarević hopes to explore these various branching points for expanding research that can have direct implications and applications for clinical care.

“When I started my research group one year ago, I saw an immense potential at MWRI to usher
in a new frontier of science that is focused on maternal and child health through the lens of the microbiome,” he says. “The world-renowned basic and translational research programs with the clinical integration at Magee-Womens Hospital provided the perfect setting to conduct this boundary- pushing research.”

One example of this symbiotic relationship is Dr. Jašarević’s collaboration with Dr. Maisa Feghali, a pioneer in identifying novel therapies for diabetes mellitus in pregnancy as a physician in maternal fetal medicine at UPMC Magee and Primary Investigator at MWRI.

This research team is exploring whether changes in the microbiome can predict the likelihood of a pregnant individual developing gestational diabetes and whether they will respond to a specific nutritional and pharmacological intervention. They hope this work will provide a more sensitive tool for predicting which patient will be at the greatest risk for adverse pregnancy outcomes, and how we can take better care of both mother and child.

He adds that collaborating with physician-scientists like Dr. Feghali offers key insights into the areas in need of improvement that come straight from patients.

“That’s been a beautiful marriage of someone who sees the patients and who knows what they’re going through and allowing that to drive our research questions so we can build better models and treatments,” he says.

Research that Benefits Communities

Serving the public through research isn’t just a priority to Dr. Jašarević, but it is a responsibility in reporting their findings that he and his team take seriously.

“One of the most profound experiences that has informed the way I think about our science was moving from Philadelphia to Baltimore City during my postdoctoral training. We were doing a lot of research on the lasting impacts of maternal stress and trauma on the offspring brain using mouse models. It was not until we started interacting with community members that it became profoundly clear that our research was not reaching them. In some ways, I realized that we are failing at our most fundamental role of being scientists, and that is to advocate for our local communities using our research,” Dr. Jašarević says. And it is this vision that brought Dr. Jašarević to Pittsburgh and MWRI.

As a first-generation refugee from Bosnia and Herzegovina, Dr. Jašarević draws inspiration from communities that can withstand, adapt to, heal from adversity and trauma, and flourish. Current studies taking place around the world hold great promise, showing that we can alleviate childhood malnutrition through microbiota-directed interventions and can develop better, culturally competent interventions in pregnancy.

As Dr. Jašarević lists projects and findings that could help us better understand our microbial ecosystem, he pauses to add: “For so long, I have thought about how our research can be a benefit locally and globally. I cannot help but feel sheer excitement being surrounded by students, trainees, and collaborators that share the same dedication and worldview.”

To learn more about Dr. Jašarević and his team’s work, visit maternalmicrobes.org