For roughly one in every hundred people, food containing even the smallest amounts of gluten can cause severe digestive distress.
While the genetic roots of this condition are known, numerous contributing factors have made it difficult to pinpoint the exact cause of gluten intolerance.
Using transgenic mice, an international team led by scientists from McMaster University in Canada has identified a crucial role played by the cells lining the gut. This discovery marks a major step toward new therapies.
Celiac disease is an autoimmune disorder triggered by gluten, a group of structural proteins found in wheat, barley, and rye. Eating foods containing gluten can cause symptoms like bloating, pain, diarrhea, constipation, and sometimes reflux and vomiting in people with celiac disease. The only current treatment is a strict gluten-free diet, which experts agree is insufficient.
Approximately 90 percent of people with celiac disease have genes encoding the protein HLA-DQ2.5. Most of the remaining 10 percent have a similar protein called HLA-DQ8. These proteins display pieces of gluten peptide that are resistant to digestion, instructing T cells to attack.
However, not everyone with these genes develops celiac disease. The gluten peptides need to be transported across the gut wall by an enzyme, which binds and alters them, making them more recognizable to the immune system.
Cells in the intestinal wall release this enzyme and also express HLA-DQ2.5 and HLA-DQ8, regulated by inflammatory responses in the gut. What wasn’t clear was the role these cells played in the disease’s pathology.
The research team studied the expression of these immune proteins in the gut cells of people with treated and untreated celiac disease and in mice with the human HLA-DQ2.5 gene. They created functional gut models, called organoids, using mouse intestinal cells to study the immune proteins’ expression when exposed to inflammatory triggers and gluten.
“This allowed us to narrow down the specific cause and effect and prove exactly whether and how the reaction takes place,” says McMasters biomedical engineer Tohid Didar.
The study revealed that gut cells are not passive bystanders but active participants, presenting gluten fragments to immune cells. This discovery highlights new targets for future treatments, potentially allowing millions worldwide to enjoy gluten without discomfort.
