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
The Lancet 2000 355:1518-1519