For years, scientists have known that gluten—the protein found in wheat, barley, and rye—can cause painful and damaging immune responses in people with celiac disease. What they couldn’t pinpoint was where in the body this process actually begins.
Now, researchers from McMaster University in Canada have finally found the starting point. Their study, published in Gastroenterology, shows that the cells lining the gut wall are active participants in celiac disease, setting off the chain reaction that leads to inflammation and damage. Here’s what the scientists discovered and how this could lead to better treatments for people who can’t tolerate gluten.
Where gluten reactions begin
Celiac disease affects about 1 in 100 people worldwide. Even a crumb of gluten can trigger intense symptoms like bloating, diarrhea, abdominal pain, and fatigue. Over time, repeated exposure can damage the small intestine and interfere with nutrient absorption. Until now, avoiding gluten entirely was the only treatment available.
In this new study, the McMaster team used genetically engineered mice that carry the same immune-related genes seen in people with celiac disease—HLA-DQ2.5 and HLA-DQ8. These genes are known to help the immune system recognize harmful invaders, but in celiac disease, they mistakenly identify gluten as a threat.
Using these animal models, scientists found that the cells lining the small intestine, known as epithelial cells, play a direct role in launching the immune response. These cells release an enzyme that binds to gluten fragments and changes their structure. Once altered, those gluten pieces become easier for immune cells to detect, sparking the inflammation that damages intestinal tissue.
“This allowed us to narrow down the specific cause and effect and prove exactly whether and how the reaction takes place“, said study co-author Tohid Didar, a biomedical engineer at McMaster.
The research team also created miniature lab-grown versions of the gut, called organoids, to observe this interaction in real time. When these gut cells were exposed to gluten and certain bacteria, they began presenting gluten fragments to immune cells, confirming that the gut lining itself is where the reaction begins.
What this means for people with celiac disease
The discovery changes how scientists think about gluten sensitivity and the body’s response to it. Until now, most research has focused on the immune cells that attack the gut, assuming the intestinal lining was only a casualty of that process. This study shows those lining cells are actually key players in the disease, helping to “present” gluten to the immune system and trigger inflammation.
That insight opens new possibilities for treatment. Instead of focusing solely on suppressing the immune response, future therapies might aim to change how the gut’s lining cells process gluten. For instance, targeting the enzyme that alters gluten fragments, or modifying the way gut bacteria interact with those enzymes, could stop the reaction before it starts.
If future treatments can interrupt this early stage of the disease, people with celiac disease may one day tolerate gluten without risking damage to their intestines. It could mean eating bread, pasta, or pastries again safely. For now, the findings offer hope and a clearer understanding of where this autoimmune disorder begins, right in the gut’s first line of defense.