Research News

A collaborative study between Inflammation & Immunity researchers in the lab of Thaddeus Stappenbeck, MD, PhD, and Jacob Kurowski, MD, pediatric gastroenterologist in Cleveland Clinic Children’s, has uncovered new information about how a common food microbe interacts with the immune system in Crohn’s disease (CD).

The results, published in mBio, build on the team’s previous research about Debaryomyces hansenii, a widely utilized food yeast they surprisingly found inside the intestinal ulcers of patients with CD.

Investigating an “exuberant” immune response

CD is a long-term condition that causes swelling and irritation in the digestive tract, which may result in ulcers that damage the intestinal barrier. That damage may allow food microbes that are normally harmless, like D. hansenii, to reach places those microbes shouldn’t. When that happens, the immune system reacts.

The research team, led by first author Kevin Newhall, PhD, a graduate student in the MD-PhD program at Case Western Reserve University who works in Dr. Stappenbeck’s lab, wondered why D. hansenii was provoking such a significant response.

“This yeast, which is often used in food production and commonly found in foods like cheese, isn’t necessarily acting like a pathogen that’s invading a person’s body and making them sick,” Newhall explains. “It’s more that there is an exuberant response occurring to something that should be tolerated.”

Exchanging feedback across bench and bedside

The Stappenbeck Lab has long collaborated on research with Dr. Kurowski and his colleagues. This particular project grew from the curiosity of Aditi Mittal, MD, a pediatric gastroenterology fellow in Cleveland Clinic Children’s who wanted to know whether D. hansenii was present in pediatric patients with CD. Newhall began working directly with Dr. Kurowski as part of his clinical training experience.

Through learning from each other and challenging assumptions, Newhall and Dr. Kurowski realized that analyzing samples from pediatric patients could help them learn more about D. hansenii and why the immune system was reacting to it.

“Working with a ‘treatment-naïve’ population was, in this case, ideal for extending our research on D. hansenii,” Newhall says. “These patients were newly diagnosed with CD, and since they had not yet been heavily treated or exposed to years of medication, their samples gave us a window into the early stages of the disease.”

Valuable cohort advances research

Researchers found D. hansenii microbes interacted with the immune system differently than expected based on the length of a specific protein produced by the HIL1 gene.

This protein sticks out from the surface of the yeast, like an antenna on a car. Strains of D. hansenii found in food are longer, stick to surfaces better and are easier for antibodies in a person’s immune system to see. By contrast, the strains researchers found in patient samples (tissue from ulcers) were shorter — which may mean the protein is harder for the immune system to detect. The researchers found that patient antibodies tended to bind more strongly to the food strains, which is the opposite of what they expected.

While the question of what is happening inside the body to shorten that protein will require further investigation, Dr. Kurowski notes that Newhall’s work in this project challenged him to think about CD on a cellular level.

“Kevin brought a basic science approach to these clinical cases and patient samples, and our discovery about D. hansenii characterizes CD as a complex condition with different phenotypes,” Dr. Kurowski says. “Pediatric patients with CD often present with a greater degree of malnutrition and growth failure than patients diagnosed at a later age, and I want to move the needle for this disease any way I can.”

For the Stappenbeck Lab, this research opens up even more avenues for exploration and discovery.

“This is a first step toward understanding how a common industrial food microbe can interact with the immune system of Crohn’s disease,” Dr. Stappenbeck says. “Kevin and Jacob’s collaborative investigation gave us a clearer view of this disease than we had before — and that may help us shape treatments in the future.”