Eva Helmerhorst, a Henry M. Goldman School of Dental Medicine associate professor of molecular and cell biology, is investigating an enzyme in human saliva that may lead to a novel treatment for celiac disease. Photos by Dan Aguirre

This story was originally published on the BU Research website.

A diagnosis of celiac disease means a life without crusty bread, chewy bagels, or fluffy pancakes. When someone with celiac disease eats gluten—a protein found in wheat, rye, and barley—the immune system overreacts, damaging the small intestine. The damage can lead to serious long-term health effects, from skin rashes and anemia to autoimmune disorders like type 1 diabetes and multiple sclerosis.

About one in 100 people worldwide suffers from the disease, and currently the only treatment is to cut gluten from the diet completely; that means no more pizza, pasta, or birthday cake (at least the traditional varieties). And while going gluten-free has become a fad, sticking strictly to the diet can be difficult and expensive.

Now Eva Helmerhorst, a Goldman School of Dental Medicine associate professor of molecular and cell biology, is researching a new tool that may lead to a novel treatment for celiac disease: an enzyme in human saliva that helps break down gluten. In other words, the secret to surviving celiac disease may be in our spit.

The human mouth is a surprisingly diverse ecosystem, with more than 600 different types of bacteria living in the tiny spaces between your teeth, under your tongue, and in other nooks and crannies in your mouth. Most biochemists who study the proteins in saliva are interested in their relation to oral health—problems like gum disease and tooth decay. But the microbes in our mouth are up to much more than preventing (or causing) cavities. During her PhD work at Vrije University in the Netherlands, Helmerhorst became interested in this diverse salivary world, originally focusing on proteins that kill fungal pathogens.

After coming to BU, her research turned in a new direction. “I noticed that many of the salivary proteins are degraded very quickly into smaller pieces,” she says.

Helmerhorst uses buffers with a similar ion composition as human saliva. She has collected hundreds of samples of spit, seeking to isolate and purify an enzyme that helps to digest gluten.

She started to wonder about the process, and soon discovered an enzyme in saliva that partially digests gluten. Gluten is a tricky protein because it has an unusual molecular structure, so the digestive enzymes in our gut that break down most proteins can’t chop up gluten very well.

“Gluten proteins in general are difficult to digest, so that doesn’t differ between healthy people and celiac people,” says Helmerhorst. “There are fragments that survive, and they’re rather long.” In people with celiac disease, these fragments trigger an inappropriate immune response.

The enzyme Helmerhorst discovered, from a bacterium called Rothia, chops up harmful sections of gluten that are rich in an amino acid called glutamine. All people seem to have this enzyme in their mouths, whether or not they have celiac disease. But Helmerhorst wondered if a purified version of the enzyme might provide a treatment by eliminating the harmful immune response. “That’s what actually changed my research to look into that particular enzyme,” she says.

To study whether the enzyme might make a successful treatment, she needed samples. This meant collecting spit, and lots of it. She began a fruitful collaboration with the Museum of Science, Boston, which features a Living Laboratory in the Hall of Human Life, where museum visitors can participate in scientific research. For three hours every Thursday, Helmerhorst set up a table and asked people to spit into a 50-ml tube.

“It really took off,” she says. “The kids loved it.”

She planned to collect close to 900 samples by the time the project ended in August 2014. While the samples were given anonymously, the tubes were marked with the spitter’s age, race, and gender, so she could investigate whether some groups have higher levels of enzyme activity than others. She also collected samples and demographic information from patients at Beth Israel Deaconess Medical Center’s Celiac Center.

Helmerhorst’s next step will be to isolate the enzyme, a tricky task because human saliva contains very little of it, and she has to make sure that it isn’t damaged in the process. Eventually, she hopes that the purified enzyme can be made into a dietary supplement. She doesn’t think this one enzyme could cure celiac disease, but it could help people who eat gluten accidentally—mistaking orzo for rice, for instance, or unknowingly eating chowder thickened with flour.

“It is unlikely that with a dietary supplement, people can completely go for pizza and cookies and everything else, but we could help them manage their dietary restrictions,” she says. “I hope that we can ultimately make a difference in the lives of celiac patients.”

Barbara Moran can be reached at bmoran@bu.edu.