Research & Discovery

Discovery Will Aid Gut-Microbiome Research Efforts

January 4, 2023 • By Russ Bahorsky, rsb5x@virginia.edu Russ Bahorsky, rsb5x@virginia.edu

Illustration including colorful circles over a person's stomache

(Photo illustration by Emily Faith Morgan, University Communications)

Bacteria can make you ill, but if all bacteria were bad for you, you’d be in big trouble.

Our bodies contain about as many microorganisms as human cells. We know that these microbes play an important role in our health and survival, but little is known about how they interact with the body to help maintain the healthy functioning of everything from our immune systems to our behavior.

However, a team of researchers at the University of Virginia, led by chemist Marcos Pires, published a paper in December in the journal Cell Chemical Biology describing a discovery that could provide medical science with a window into the complex relationship between our bodies and the community of microbes known as our microbiome. It could also lead to new treatments for a variety of diseases.

The most common way to study the interaction of the body and its microbiome has been to study that relationship in laboratory mice. But until now, it has only been possible to directly image those interactions in specimens that are no longer alive, which gives researchers little more than a snapshot of a highly dynamic ecosystem.

Despite the power of modern medical imaging, which allows scientists to observe the behavior of molecules in humans or animals and their impacts on groups of cells, there was no method for doing so with gut commensal bacteria. Those microorganisms, found in the digestive system, can serve as a first line of defense against a variety of harmful pathogens.

Before now, said Pires, a research chemist and associate professor of chemistry in UVA’s College and Graduate School of Arts & Sciences, there were no dyes available that could be used to tag microbial cells in such a way that they are visible through living tissue. The problem left researchers with limited ability to observe how the bacteria are affected by the foods their subjects eat, sleep or environmental conditions, how they respond to commonly prescribed pharmaceuticals like antibiotics, and whether taking those drugs to cure bacterial infections may have unwanted consequences.

“The power of biomedical imaging is immense,” Pires said. “It’s a very mature field with humans, and it’s equally powerful with animal models to the point where you can track the impact that a small molecule will have on a community of cells. But it was surprising to us that no such modality has been shown for gut commensal bacteria.”

At the same time, Pires said, he knew the material necessary to tag or label microbial cells for observation already existed.

With his research team, Pires studies the cell wall that surrounds individual bacteria cells, in particular a specific element known as peptidoglycan. The element consists of sugars and amino acids that form a rigid, mesh-like layer around most bacterial cells. In the lab, he has been able to develop molecules similar to peptidoglycan that attach to the walls of microbial cells. He can tag those cells with a light-emitting dye that can be observed with a high level of precision using a fluorescence microscope.

The non-invasive and non-harmful process will make it possible for researchers to see how these bacteria are moving and interacting with living cells in real time, a technological breakthrough that will significantly accelerate the pace of discovery for researchers studying the role of the microbiome.

According to Pires, it’s too early to say what benefit the discovery will have for human health, but it is a first step toward allowing scientists to observe the same processes in human subjects.

Given the number of microbes in the body, Pires said, science is beginning to think of the microbiome as another organ. That’s especially true in the digestive system, which represents the biggest population of microbes in the body.

“Our understanding of the links between bacterial cells is increasing dramatically,” Pires said. “It could impact immunology, diseases like diabetes and even our mental health. We think there are molecules being released by these cells that could actually impact neuro receptors.”

To help understand the implications of his work for medical science, Pires has partnered with Melanie Rutkowski, an associate professor of microbiology, immunology and cancer biology with UVA’s School of Medicine. Rutkowski’s research has established a strong connection between gut bacteria, the progression of breast cancer and the body’s ability to fight tumors.

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“Across a multitude of disease contexts, it’s becoming more and more evident that the gut microbiota have a profound effect on both health and disease,” Rutkowski said. “With this technology, there are a whole range of questions that we’ll now be able to answer.

“There is a lot of interest now in the oncobiome, a collection of microorganisms within tumors that have been shown to affect cancer outcomes and therapy response,” she added. “We’d like to use this technology to understand how the microorganisms arrive into the tumors and to define how the cells they’re interacting with are functionally affected. These questions remain unanswered because until now, there has not been a good way to visualize microbial translocation into tumors in real time. Ultimately, I’m really excited about the potential of the work Marcos is doing to understand the microbiome.”

“The collaboration between Drs. Pires and Rutkowski underscores the value of bringing together investigators from disparate fields to address important questions about health and disease,” said Amy Bouton, interim chair of the School of Medicine’s Department of Microbiology, Immunology, and Cancer Biology.

“By using the tools developed by Dr. Pires, Dr. Rutkowski is poised to visualize direct interactions between bacteria present within the microbiome and cells within and surrounding tumor tissues,” Bouton said. “These studies will lead to important discoveries on how the microbiota can influence tumor growth and progression and could help advance the efforts of other researchers studying a variety of devastating diseases.”