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We have a remedy (stop eating gluten) // We know the cause (a faulty gene, faulty antibodies) // And now the disease is providing a window into how autoimmunity occurs.

Celiac Disease: Eating Away at You

By Cathryn Delude // Photo Illustrations by Hugh Kretschmer // Winter 2010
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hugh kretschmer for proto

In medical school in Naples, in the late 1970s, Alessio Fasano learned a thing or two about human intestines. More than twenty feet long, with an interior surface a bit bigger than a tennis court (about 3,000 square feet if you include the shaggy, finger-shaped villi that grab nutrients from digested food and drink), the intestines are lined with epithelial cells that were thought to be sealed permanently by groutlike junctions. Tiny nutrients are absorbed through the cells, but the “grout” was credited with creating an impermeable barrier preventing larger, harmful material from entering the gut. Then, in the late 1980s, when Fasano was working on a cholera vaccine, he began to wonder how large molecules, such as the cholera toxin, got past the intestinal wall and into the bloodstream, and learned that the space between cells was not sealed after all. His suspicions were confirmed in 1988, when a Japanese research group discovered that the “tight” junctions are actually perfectly fitted doors that open and close under special circumstances.

Fasano, who now directs the Mucosal Biology Research Center and the Center for Celiac Research at the University of Maryland School of Medicine, hypothesized that the cholera bacterium, Vibrio cholerae, had evolved a key to that door, and he proved the notion in 1991. Using Latin for tight junction, the key was named “zonula occludens toxin,” or Zot. “Vibrio uses Zot to make the intestine permeable,” he says, “and intestinal permeability allows access to the things that can harm us.”

In 2000, Fasano discovered that the body produces its own key, a molecule he called zonulin. Scientists are still trying to determine zonulin’s normal function, but they do know that bacteria and inflammatory molecules can stimulate its production to make the intestines “leak.” It turns out that certain undigested portions of gluten, the storage protein of wheat, barley and rye, may have the same effect.

This accumulating understanding of how, when and under what circumstances the intestines can be breached ultimately led Fasano to an innovative and somewhat controversial theory about autoimmunity—in which the body mistakenly turns on itself—and about one of its clearest examples, celiac disease, in which the autoimmune response is triggered by gluten. He had become interested in celiac disease after searching the scientific literature for references to intestinal permeability and finding that it occurs in many autoimmune diseases—from type 1 diabetes and multiple sclerosis to rheumatoid arthritis and inflammatory bowel diseases, including celiac. That people with autoimmune diseases also have elevated levels of zonulin in their gut could partially explain this leakiness, Fasano reasoned.

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Celiac Disease Timeline: A Glutinous History

The story of gluten stretches from humans’ first taste of wheat 10,000 years ago to modern advances in treating celiac disease.


1. “Celiac Disease and Autoimmunity in the Gut and Elsewhere,” by Susan H. Barton and Joseph A. Murray, Gastroenterology Clinics of North America, June 2008.These experts discuss the theory that environmental triggers can interact with the immune system in the gut, leading to the loss of tolerance and autoimmune diseases.

2. “Review: New and Developing Therapies for Celiac Disease,” by Christina A. Tennyson, Suzanne K. Lewis and Peter H.R. Green, Therapeutic Advances in Gastroenterology, Sept. 1, 2009. This article makes the case for new therapies for celiac disease (because a gluten-free diet is so difficult to maintain) and describes the most promising approaches in development.

3. “Tight Junctions, Intestinal Permeability, and Autoimmunity: Celiac Disease and Type 1 Diabetes Paradigms,” by Jeroen Visser, Jan Rozing, Anna Sapone, Karen Lammers and Alessio Fasano, Annals of the New York Academy of Sciences, May 2009. In this review, the authors present the controversial hypothesis that intestinal permeability underlies not just celiac disease but other autoimmune conditions as well, including type 1 diabetes.

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