Zonulin, a protein discovered in 2000 that regulates the permeability of the intestine, and which has already been linked to celiac disease, may also play a role in non-celiac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS), a new Italian study has found.
“We were intrigued to find that blood levels of zonulin were almost as high in patients with NCGS as in those with celiac disease,” said Giovanni Barbara a professor at University of Bologna in a news release.
The protein zonulin has been at the center of drug development research in recent years, particularly aiming at controlling and inhibiting the protein’s effects on the intestinal walls. One of the drugs in development, larazotide acetate, works by inhibiting zonulin from increasing the permeability of the intestine, and thus stopping the flow of gluten into the body, which in turn can help reduce inflammation, gastrointestinal and other celiac disease symptoms.
Barbara and his team recruited 27 patients with gluten sensitivity, 15 patients with IBS, 15 more with celiac disease, and 15 healthy control volunteers. When they did blood tests, researchers found that the group with celiac disease showed the highest levels of zonulin (0.033 ng/mg), followed closely by the levels for the gluten-sensitive group (0.030 ng/mg). The IBS patients (0.012 ng/mg) also showed higher levels than those for the healthy cohort (0.007 ng/mg).
Barbara, while noting that intestinal permeability has been cited as a contributing factor in conditions ranging from type 1 diabetes to multiple sclerosis, said the protein may play a role in those conditions, too. With regards to celiac disease, gluten sensitivity and other related bowel conditions, however, Barbara is most excited about the possible treatment interventions that may come out of it, allowing people with these conditions to supplement existing strategies, such as the gluten-free diet.
“Hopefully, our work will lead to new diagnostic and therapeutic strategies for patients with these and possibly other autoimmune conditions,” Barbara said when he presented the study at the United European Gastroenterology Week conference in October.
Allergic Living asked renowned celiac expert Dr. Alessio Fasano how a definitive test for NCGS would change the care he is able to offer patients. He said: “Dramatically.”
Fasano, director of the Center for Celiac Research at Massachusetts General Hospital and a pioneer researcher on the zonulin molecule, said that for NCGS patients and their doctors, having a test would mean being able to be confident about prescribing a strict elimination diet.
“Going gluten-free is a real investment,” Fasano said. “And it’s a great investment if you have a return, like better quality of life and improvement of your symptoms. But it’s not a great investment if it’s going to be of questionable return. Having a test that will tell you, ‘Yep, I’m heading the right direction. I’m doing what I’m supposed to do,’ will give everybody piece of mind.”
While a test is an important piece of the puzzle, the ultimate goal in this area of gluten-sensitivity research would be development of a treatment that brings zonulin to heel. For Fasano, that means continuing to follow closely the clinical trials for larazotide acetate in the months and years to come.
“Larazotide [acetate] will give to people with celiac disease and gluten sensitivity the same kind of function that those not suffering those conditions have, back to the way everything was supposed to be,” he said. “That’s pretty much the goal, if these clinical trials lead to a drug that will be commercialized.”
Q&A with celiac expert Alessio Fasano
Q&A with celiac expert Joseph Murray