Natural antibiotic against H. pylori in human gastric mucin

Abstract

In a study reported in Science, Dr. Masatomo Kawabuko and co-authors from Japan's Shinshu University School of Medicine and The Burnham Institute, La Jolla, California identified for the first time a component of the gastric mucins, a mucin-type O-glycan that occurs within deeper regions of the gastric mucosa and that has strong antibiotic activity against Helicobacter pylori. H. pylori colonizes the gastric mucosa of about half the world's population and is considered a leading cause of gastric malignancies. However, most infected individuals remain asymptomatic or are affected by chronic active gastritis. Only a fraction develop peptic ulcer, gastric cancer, and malignant lymphoma. According to the authors, “this suggests the presence of host defense mechanisms” against H. pylori pathogenesis. The researchers isolated the O-glycan alpha 1,4-linked N-acetylgucosamine. They noted that it is confined to the stomach's deeper mucosa, which also lacks H. pylori. Further investigation revealed that surface-derived mucin actively supported H. pylori growth, while mucins from the deeper layer inhibited growth. H. pylori in the presence of alpha 1,4-linked N-acetylgucosamine lost its shape, became immobile, and eventually died. Specifically, in H. pylori, this O-glycan inhibited biosynthesis of chloestryl-alpha-D-glucopyranoside, a major cell wall component. The effect appeared similar to that of antibibiotics, which lyse the bacterium's cell wall. Commenting on the findings, Dr. Richard M. Peek, Associate Professor of Medicine (Division of Gastroenterology) and Cancer Biology at Vanderbilt University, notes that previous pathological studies that have investigated the location of H. pylori in the stomach “have consistently noted that the bacteria will bind to particular areas along the gastric epithelium. The area to which they bind most avidly or most frequently are the upper portion of the gastric glands. They're very rarely found, if at all, in the deeper portions of the gastric glands.” Thus, according to Peek, a “complex biosphere” exists within the human stomach, and within that biosphere, “the host has evolved mechanisms to selectively localize bacteria to certain regions of the gastric gland,” and has evolved the ability to produce anti-microbial molecules in the lower part or deeper portions of the gastric gland that actively prevent H. pylori from colonizing those regions. The Science report concludes that the study “reveals a new aspect of mammalian glycan function as a natural antiobiotic.” The authors state that the study “provides a basis for development of novel and potentially safe therapeutic agents to prevent and treat H. pylori infection in humans without adverse reactions.” Says Peek, “This is another example in which mechanistic studies addressing H. pylori pathogenesis have elucidated potential novel therapies which can be utilized as a means of eradication.” For further details, see Science 2004;305:1003–1006.