The small intestine contains billions of cells, which are packed tightly together to keep bacteria, viruses, and other toxins out of the body's tissues. New research findings may have identified the protein that regulates this protective barrier, holding promise for a better understanding of several diseases.

Researchers report that a protein called zonulin appears to be responsible for maintaining the protective barrier in the small intestine, and that high levels of this protein are associated with disruptions in the barrier that allow foreign substances into the body's tissues. When the researchers purified zonulin from human tissue and tested it on intestinal tissue from monkeys, the protein increased the tissue's permeability, allowing molecules of insulin to pass through the cell barrier. Insulin is not normally absorbed when taken by mouth.

Then the investigators turned their attention to celiac disease, a genetic disorder in which people are unable to eat foods that contain gluten, a protein found in wheat and other grains. If they do, the gluten causes a variety of gastrointestinal problems. Celiac disease is an autoimmune disorder, meaning that the immune system overreacts to a foreign substance, and begins to attack normal cells. In celiac disease, the trigger is the protein gluten. If patients avoid gluten-containing foods, they have no symptoms.

The researchers looked at intestinal tissue from seven patients with celiac disease and six healthy people. Patients with the disease had higher levels of zonulin and zonulin antibodies. When the celiac disease patients followed a gluten-free diet, their antibody levels returned to normal. The researchers believe that zonulin makes the space between cells larger, allowing gluten and other substances to pass through. Once these allergens get into the immune system, they are attacked by the antibodies which can lead to all sorts of problems.

The Lancet 2000 355:1518-1519