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Body's own defense against H. pylori, cause of stomach ulcers and stomach cancer

(La Jolla, California) An international team led by The Burnham Institute's Minoru Fukuda, Ph.D., has discovered that a human glycoprotein inhibits Helicobacter pylori ("H. pylori"), the bacterium that causes stomach ulcers and is linked with 90% of stomach cancers. Published on August 13th in Science magazine, these results present a new way of looking at treating chronic inflammation associated with stomach ulcers, and introduces the possibility of preventing stomach cancer associated with H. pylori.

Over fifty percent of the world's population is infected with H. pylori, yet only 2% are afflicted with stomach ulcers and only 1% with stomach cancer. A collaboration between The Burnham Institute and Japan's Shinsu University has discovered the defense mechanism that protects the stomach against H. pylori infection.

H. pylori is found in mostly in the stomach, where it thrives in the superficial mucin layer lining the stomach. The bacterium is rarely found in the deeper portion of the mucin layer, where the mucous cells produce a particular class of glycoproteins, called O-glycans, linked with the carbohydrate alpha 1,4-N-acetylglusoseamine, cloned previously in Dr. Fukuda's laboratory.

Because the alpha 1,4-linked N-acetylgucosamine is confined to the stomach's deeper mucosa lining, which also lacks H. pylori, the scientists investigated the possibility that it might play a role against infection by H. pylori.

They isolated mucin from the upper and lower layers and found a key difference: surface-derived mucin actively supported H. pylori growth, while mucins from the second layer inhibited growth. H. pylori in the presence of alpha 1,4-linked N-acetylgucosamine lost its shape, became immobile, and eventually died. This cell-growth immobilizing effect is very similar to the effect of antibiotics, which dissolve or "lyse" the bacterium's cell wall.

The researchers lysed H. py
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Contact: Nancy Beddingfield
nbeddingfield@burnham.org
858-449-9940
Burnham Institute
12-Aug-2004


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