Researchers explore protein linked to gluten sensitivity

While only about 1% of Americans have tested positive for celiac disease, another 6% are estimated to be sensitive to gluten — the stretchy protein that makes wheat bread fluffy and pie crusts crisp. Why those without the disease still have adverse reactions when ingesting gluten has been a question researchers have been trying to answer for years. However, a new study hopes to answer this question as researchers have been homing in on markers in the body responsible for gluten sensitivity.

A study from Giovanni Barbara and his team at the University of Bologna, Italy, suggests that gluten-sensitive individuals may harbor high levels of a molecule called zonulin that is linked to inflammation, a recent article states. Levels of zonulin in the blood have been shown to be high in celiacs already and in Barbara’s study, levels in gluten-sensitive individuals almost matched those of celiacs. Though the results are preliminary, they point in a hopeful direction for future tests to help diagnose this condition.

The article explains that zonulin is an inflammatory protein first discovered in 2000. It helps regulate leakiness in the gut by opening and closing the spaces or “junctions” between cells in the lining of the digestive tract. Zonulin is triggered by harmful bacteria, and offers important protection to the body: If you accidentally eat a food contaminated with Salmonella, for example, you rely on zonulin to help trigger diarrhea and flush out the pathogen. Once the pathogen is gone, zonulin levels drop and the junctions close.

So what does it have to do with gluten? It turns out that gluten is a strong trigger of zonulin in some individuals, which explains the symptoms many people with gluten sensitivity experience. These are similar to irritable bowel syndrome (IBS) and include abdominal pain, bloating, alternating diarrhea or constipation, “brain fog,” headache, fatigue, as well as joint and muscle pain.

“No human being completely digests gluten,” gastroenterologist Alessio Fasano said in the article. “And in a small percentage of us, that undigested gluten triggers the release of zonulin,” leading to high levels of it.

To test the theory, Barbara and a team of researchers at the University of Bologna measured blood levels of zonulin in four groups of individuals: those with celiac disease, those with irritable bowel syndrome marked by diarrhea, those with self-diagnosed gluten sensitivity, and healthy volunteers. Both celiacs and gluten-sensitives turned up with remarkably high levels of zonulin in their blood. Those with IBS had elevated levels but less than half the levels of celiacs or gluten-sensitive individuals. Healthy volunteers had negligible blood levels of zonulin.

“I was very surprised, but not only by the zonulin levels,” Barbara said in the article. “In our study, gluten-sensitive individuals who responded to a gluten-free diet had a genetic predisposition to celiac disease. They had no evidence of celiac, but they did have the vulnerable genes that put a person at risk of celiac.”

Despite having found two potential biomarkers, Barbara cautions that it’s far too soon to recommend any kind of clinical testing. “We need more research to determine the clinical usefulness of these markers. Other laboratories need to reproduce our data, and we need to repeat our own experiment with gluten-sensitive patients who have been identified by strict criteria in double-blind studies.” Barbara adds in the article that his center only sees the most severe patients who have been unsuccessful finding treatment elsewhere, which may have influenced the results.

Fasano, who was not involved in Barbara’s study, says the discovery of zonulin is part of a larger, evolving picture.

“This molecule is extremely important in a lot of illness, from Type 1 diabetes to other autoimmune diseases. Many illnesses link back to loss of barrier function in the gut.” Soon, a trial will begin to test whether it’s possible to shut down zonulin production in the gut for a few hours.

“It would be really great if we had a safe medication that could keep this molecule at bay and offer help for celiac disease, gluten sensitivity and perhaps other conditions,” he added.

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