A new study has revealed advances in our understanding of celiac disease (gluten intolerance) that may one day help develop new drugs for the disease. The discovery was made by a multidisciplinary team of medical researchers and engineers led by McMaster University in Canada, with colleagues from the United States, Australia and Argentina, who have spent the past six years trying to solve a key piece of the puzzle in the search for a cure for the disease: how the response to gluten begins and where it begins.
Celiac disease
People with celiac disease must avoid gluten, a protein found in wheat and barley that can cause painful digestive symptoms, interfere with the absorption of nutrients, and increase the risk of serious long-term health problems.
This immune disorder affects about 1% of the population, and its incidence has nearly doubled over the past 25 years, but there is currently no cure available.
It was previously thought that the inflammatory response to gluten occurred within the gut wall and involved only immune cells, but in a new paper published in the journal Gastroenterology on August 9, the team shows that the story goes deeper than that.
New discovery
Researchers have discovered that the inner lining of the upper intestine, known as the epithelium—which is made up of a variety of cells not traditionally part of the immune system—also plays an active role in directing the inflammatory response to gluten.
Using microscopic biomaterials in the lab, the team created a biological model that functions as the intestinal epithelium, allowing the researchers to isolate the effects of specific molecules in the epithelial cells of people with celiac disease.
This model also allowed researchers to generate and monitor interactions under controlled conditions, an option not available in the highly complex intestinal environments of living organisms.
They were able to observe how the molecules inform immune cells of the presence of gluten, and came to the firm conclusion that the epithelium plays a crucial role in activating the immune system in celiac disease.
This mechanism has been postulated before, but the hypothesis has not been proven, and this discovery is expected to contribute to the development of new drugs.
Celiac disease treatment
“The only way we can cure celiac disease today is to completely eliminate gluten from the diet,” says Elena Verdue, co-author of the paper, professor of gastroenterology and director of the Farncombe Digestive Health Research Institute at McMaster University. “This is difficult, and experts agree that a gluten-free diet is not enough.”
“Identifying exactly where the immune response starts could spur research into delivering drugs to block this new role of the epithelium using experimental drugs already in human trials,” Verdue added, according to EurekAlert.
“This allowed us to narrow down the specific cause and effect and establish whether and how the interaction is actually happening,” says Tohid Didar, another co-author of the paper and an associate professor in the School of Bioengineering at McMaster University.
Another important finding from the study is that the epithelium sends stronger signals to immune cells when it detects gluten if harmful microbes are also present.
“In the future, it may be possible to detect the microbe in a person at risk of developing the disease, and block interactions with gluten and the intestinal epithelium to prevent disease,” says Sarah Rahmani, the paper’s lead author and a doctoral student in Verdue and Didar’s labs.