$3.5M in NIH Grants to Help Unravel the Mysteries of the Gut

A pair of grants worth $3.5 million from the National Institutes of Health will help a research team led by a University of Maryland scientist track a few trillion of your body’s closest friends.

The grants will support groundbreaking work by Brantley Hall, an assistant professor of cell biology and molecular genetics with an appointment in the University of Maryland Institute for Advanced Computer Studies (UMIACS), to characterize microbial enzymes and develop wearable devices for monitoring the gut microbiome.

Science’s understanding of microorganisms has evolved dramatically, from viewing them primarily as pathogens to recognizing them as essential partners in health. Collectively known as the microbiome, these beneficial microorganisms—particularly abundant in our gut—form a symbiotic relationship with us: We provide nutrients and habitat, while they perform numerous functions crucial to our health. Each person's microbiome is unique, influenced by factors such as diet, environment and genetics. This combination of individuality and complexity leaves many aspects of the microbiome's role in human health yet to be fully understood.

One of the two grants, $1.9 million from the National Institute of General Medical Services, will support Hall and his research team in addressing this challenge, in part by systematically identifying and characterizing a class of microbial enzymes called ene-reductases. These enzymes play a pivotal role in the interactions between gut microbes and their human hosts.

“By discovering key gut microbial enzymes, we aim to uncover how gut microbial biotransformations influence overall human health,” Hall said.

A second grant for $1.6 million from the National Institute of Diabetes and Digestive and Kidney Diseases will provide three years of funding for Hall’s team to develop wearable devices that will enable the real-time monitoring of gut microbial activity. This project aims to translate laboratory findings into practical applications and has the potential to revolutionize the way gut health is measured and managed.

Gut microorganisms break down dietary fibers and carbohydrates that we can’t digest on our own while interacting with a range of organs and systems in our body.

For instance, the gut microbiome affects liver function through the gut-liver axis, a key focus of Hall’s research. In a recent study, he discovered that the microbes’ interactions with liver enzymes is what produces the distinct yellow color of urine.

While most gut microbes are beneficial, certain bacteria can contribute to health issues, including Inflammatory Bowel Disease (IBD), which afflicts millions globally. Certain gut bacteria can even produce compounds that elevate risk factors for heart disease, highlighting the broad impact of the microbiome on overall health.

Hall’s research offers significant insights into understanding gut-related disorders and advancing effective treatments, but the journey toward these breakthroughs has been marked by considerable technical hurdles.

For one, he said, “Gut microbes are really hard to grow.” Although his team uses an anerobic chamber, an environment in which conditions like temperature and oxygen concentration can be carefully controlled, cultivating these microorganisms is incredibly difficult. Additionally, identifying the correct enzyme among millions of genes is “like searching for a needle in a genomic haystack,” Hall said. He and his team use a complex mix of bioinformatics and biochemistry to identify which enzymes are involved in what reactions.

He is a member of the University of Maryland Center for Excellence in Microbiome Sciences, funded in part by a UMD Grand Challenge Impact Award, where he works with researchers from a diverse range of disciplines, including food safety and nutrition, computer science, bioengineering, civil and environmental engineering, and more.

UMIACS, which provides technical and administrative services and is home to the Center for Bioinformatics and Computational Biology, offers additional computational resources.

“I am deeply thankful to the NIH for their continued investment in microbiome research and to the centers and institutes at the University of Maryland that provide the resources and collaborative environment essential to the success of these projects,” Hall said.