NIH Trailblazer Award for Engineering Smarter Gut Metabolites to Affect Human Health

Researchers at the College of Engineering have won a Trailblazer Award from the National Institutes of Health’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) for their interdisciplinary work to cure or improve diseases by modulating microbial metabolism in the gut. The funding provides $628,000 for the team’s research over three years.

Benjamin Woolston, assistant professor, chemical engineering, is the principal investigator on the project, which seeks to engineer “smarter” gut microbes that can dynamically respond to the environment inside the human body.

“Scientists have had some initial successes utilizing microbes in our guts as potential therapies against diseases, but there are also some challenges,” says Woolston. “First, the way in which microbes behave in a test tube is different than in the complex environment of the human gut. Second, the microbes developed so far tend to be pre-programmed for a specific behavior (e.g. reducing the concentration of a toxic metabolite, or producing a therapeutic one) regardless of what is actually going on in the gut.”

The team’s research aims to tackle both issues by figuring out what factors exist in the complex gut that engineers need to consider, as well as developing microbes that can proactively react to the environment in the gut microbiome in a more intelligent way.

“The engineered microbe would have a decision-making process through which they could turn on or turn off metabolic pathways to maintain the proper levels of a particular metabolite — much like a thermostat does for the temperature in your house,” says Woolston.

For this project, Woolston and his team are concentrating on microbially produced hydrogen sulfide (H2S), which has been linked to health issues such as ulcerative colitis and Crohn’s disease. Existing research suggests that low levels of H2S have anti-inflammatory properties and support a healthy epithelium (or gut lining), whereas high concentrations are genotoxic, inhibit mitochondrial function and butyrate oxidation, and potentially weaken the mucosal barrier.

Woolston’s collaborators are also chemical engineering faculty; two of them — Abigail N. Koppes, associate professor, and Ryan Koppes, assistant professor —are developing gut-on-a-chip devices that allow the team to see what’s happening at the interface between human and bacterial biologies. With this technology, they can introduce the microbes Woolston is building in his lab onto those chips to simulate the gut environment and compare the performance to that of microbes analyzed in test tubes.

Another collaborator is Rebecca L. Carrier, professor and associate chair of research, chemical engineering. Carrier is also working on a gut-on-a-chip system, but hers focuses more on the mucosal barrier that lines the organ. H2S might interfere with the structure of this layer, so the team is interested in what happens if it breaks down and whether this might change the ability for microbes to cross through the barrier to the tissue underneath.

Several PhD students who are co-advised by members of the research team are also involved in the project.

For Woolston, one of the best things about the Trailblazer Award is that it’s earmarked specifically for junior investigators who are new to the NIH.

“All of my PhD and post-doctoral research was in microbial engineering, but more around biofuels and sustainability,” says Woolston. “This is the first funding I’ve received to delve into the microbiome space, and my first funding from the NIH. I appreciate the award as a great mechanism to get new researchers started in new directions.”

Woolston and his team hope that the lessons learned from this research developing the H2S-controlling microbes can be used in the future for different metabolites involved in other diseases, as well as provide some valuable basic science about the gut microbiome and how it behaves.

Related Faculty: Benjamin Woolston, Ryan Koppes, Abigail N. Koppes, Rebecca L. Carrier

Related Departments:Chemical Engineering