An interdisciplinary team of researchers from the fields of medicine and engineering has dedicated six years to unraveling a crucial aspect of finding a cure for celiac disease: identifying how and where the gluten response initiates.
Individuals diagnosed with celiac disease must carefully avoid gluten, a protein found in wheat, rye, and barley, as it can lead to painful symptoms in the digestive system, hinder nutrient absorption, and increase the likelihood of other serious long-term health issues.
This autoimmune disorder affects roughly 1% of the population, with its prevalence having approximately doubled over the last 25 years, yet no treatment currently exists.
A collaborative team of medical and engineering experts based at McMaster University in Canada, along with colleagues from the United States, Australia, and Argentina, has focused their efforts on understanding how and where the gluten response starts.
Previously, researchers believed that the inflammatory reaction to gluten took place solely within the gut wall and primarily involved immune cells. However, a new study published today in the journal Gastroenterology reveals a more complex scenario.
The team discovered that the innermost lining of the upper intestine, known as the “epithelium,” which consists of various cells not traditionally associated with the immune system, also plays a vital role in triggering the inflammatory response to gluten.
By utilizing microscopic biomaterials in their lab, the researchers developed a functioning biological model of the intestinal epithelium, enabling them to examine the effects of specific molecules in the epithelial cells of individuals with celiac disease in isolation.
This model allowed for the observation and analysis of reactions in a controlled environment, an opportunity that is unattainable in the highly complex gut conditions found in living organisms.
Through this model, researchers were able to see how molecules signal immune cells about the presence of gluten, leading to the definitive conclusion that the epithelium is pivotal in activating the immune response related to celiac disease.
Though such a mechanism was previously theorized, it had never been conclusively proven. Addressing this debated issue could significantly propel the development of novel medications.
“Currently, the only way to manage celiac disease is by completely removing gluten from one’s diet, which is a challenging task, and experts agree that a gluten-free diet alone is insufficient,” notes Elena Verdu, a corresponding author of the paper and a professor of gastroenterology, as well as the director of McMaster’s Farncombe Family Digestive Health Research Institute.
Pinpointing the precise trigger of the immune response could pave the way for research into drug delivery systems that target the newly discovered role of the epithelium, using medications already in clinical trials, Verdu states.
“This research has enabled us to clarify specific cause-and-effect relationships and establish exactly whether and how these reactions occur,” explains Tohid Didar, a co-corresponding author on the paper and an associate professor at McMaster’s School of Biomedical Engineering, who also holds the Canada Research Chair in Nano-biomaterials.
Another important finding from this study is that after identifying gluten, the epithelium amplifies signals to immune cells if pathogens are also present.
This suggests that in the future, it may be possible to detect pathogens in individuals at risk of developing the disease and disrupt the interactions between gluten and the gut epithelium to prevent the onset of the disease, according to Sara Rahmani, the paper’s lead author and a PhD candidate in the Verdu and Didar labs.
