Researchers find increased zonulin levels among celiac disease patients

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Researchers find increased zonulin levels among celiac disease patients

Researchers at the University of land School of Medicine have found

that the human protein zonulin, which regulates the permeability of the

intestine, is at increased levels during the acute phase of celiac

disease. The discovery suggests that increased levels of zonulin are a

contributing factor to the development of celiac disease and other

autoimmune disorders such as insulin dependent diabetes, multiple

sclerosis, and rheumatoid arthritis. The findings are published in the

April 29 issue of the journal Lancet.

" Zonulin works like the traffic conductor or the gatekeeper of our

body's tissues, " says lead author Alessio Fasano, M.D., professor of

pediatrics and physiology at the University of land School of

Medicine, and director of Pediatric Gastroenterology and Nutrition at

the University of land Hospital for Children. " Our largest gateway

is the intestine with its billions of cells. Zonulin opens the spaces

between cells allowing some substances to pass through while keeping

harmful bacteria and toxins out, " explains Dr. Fasano.

Earlier research conducted by Dr. Fasano discovered that zonulin is also

involved in the regulation of the impenetrable barrier between the blood

stream and the brain, known as the blood-brain barrier. Celiac disease

offered Dr. Fasano and his team a unique model for understanding the

dynamic interaction between zonulin and the immune system. Celiac

disease is a genetic disorder that affects one out of every 300 people

in Europe, but its prevalence in the United States is not fully known.

People who suffer from the disorder are unable to eat foods that contain

the protein gluten, which is found in wheat and other grains. The gluten

sets off a reaction that can cause diarrhea, abdominal pain,

malabsorption of nutrients, and other gastrointestinal problems. Celiac

disease can be easily treated by avoiding foods with gluten.

With celiac disease, the body reacts to gluten by creating antibodies

that attack the intestine and cause severe damage over time. Unlike

other autoimmune disorders, scientists also know that celiac disease is

triggered by a specific antigen, which is the protein gluten. Celiac

disease is also known to cause increased permeability of the intestine.

In addition, many people who suffer from celiac disease also suffer from

other autoimmune disorders.

The research team examined the intestinal tissue of seven people with

celiac disease, and six patients without the disease. Patients with

active celiac disease showed higher levels of zonulin and anti-zonulin

antibodies compared to non-celiac patients and patients in remission,

who were eating a gluten-free diet.

" With celiac disease, we could never understand how a big protein like

gluten was getting through to the immune system. Now we have the

answer, " explains Dr. Fasano. " People with celiac have an increased

level of zonulin, which opens the junctions between the cells. In

essence, the gateways are stuck open, allowing gluten and other

allergens to pass. Once these allergens get into the immune system, they

are attacked by the antibodies, " adds Dr. Fasano.

" I believe that zonulin plays a critical role in the modulation of our

immune system. For some reason, the zonulin levels go out of whack, and

that leads to autoimmune disease, " explains Fasano.

Dr. Fasano adds that more research is needed. He is currently conducting

experiments with diabetic rats. Preliminary results from his experiments

show that insulin dependent diabetes occurs in lab rats about three to

four weeks after increased intestinal permeability. The researchers

believe the increased intestinal permeability is associated with

increased levels of zonulin.

" We are at the threshold of exciting discoveries in this field, " says

Dr. Fasano. " We now have a new way of looking at our cells. Our cells

are not stacked together like bricks. They are a dynamic field, which is

constantly in flux. " ###