The Mechanisms of Celiac Disease: Study Reveals New Insights

A team of researchers from McMaster University in Canada, along with colleagues from the United States, Australia, and Argentina, have made a significant breakthrough in understanding celiac disease. Over six years of research, they have uncovered a crucial aspect of the gluten response, potentially paving the way for new treatments.

According to the study, in people with celiac disease, gluten can trigger painful gut symptoms, hinder nutrient absorption, and increase the risk of severe long-term health issues. Affecting about one percent of the population, the author’s explained that the incidence of celiac disease has nearly doubled in the past 25 years, yet no treatment exists beyond a strict gluten-free diet.

The study’s findings, published in the journal Gastroenterology, reveal that the inflammatory response to gluten begins not just within the gut wall and immune cells, but also involves the inner lining of the upper intestine, known as the epithelium. The authors explained that the epithelium, which consists of various cells traditionally not part of the immune system, plays a vital role in directing the inflammatory response to gluten. This discovery challenges the previous belief that the gut wall's immune cells solely orchestrated the response.

By creating a biologically functioning model of the intestinal epithelium using microscopic biomaterials in the lab, the researchers could isolate and observe the effects of specific molecules in epithelial cells from celiac patients under controlled conditions. The model allowed the team to generate and monitor reactions that would be impossible to study in the complex gut environments of living beings. They observed how epithelial molecules signal immune cells to the presence of gluten, proving the epithelium's crucial role in activating the immune response in celiac disease.

"The only way we can treat celiac disease today is by fully eliminating gluten from the diet. This is difficult to do, and experts agree that a gluten-free diet is insufficient," said Elena Verdu, MD, PhD, a corresponding author and professor of gastroenterology at McMaster University, who also directs the Farncombe Family Digestive Health Research Institute. She explained that precisely locating the immune response's origin could spur research into targeted drug delivery to inhibit the epithelium's newly discovered role, utilizing drugs already in clinical trials.

"This allowed us to narrow down the specific cause and effect and prove exactly whether and how the reaction takes place,” said Tohid Didar, PhD, another corresponding author and associate professor at McMaster's School of Biomedical Engineering.

Additionally, the study found that the epithelium sends stronger signals to immune cells if pathogens are present alongside gluten. The authors said this insight suggests future possibilities for detecting pathogens in individuals at risk of developing celiac disease and preventing the disease by inhibiting interactions between gluten and the gut epithelium.

The authors concluded that this study and one like it could revolutionize preventive strategies for at-risk populations and pave the way for innovative treatments for the millions already living with celiac disease.