July 21, 1999 ANN ARBOR --- Half of all American adults have an alien life form growing in their stomachs. Most of us will live our entire lives unaware that we have been colonized by Helicobacter pylori---a species of bacteria which usually produces no symptoms, but can cause ulcers and stomach cancer in some individuals.
For a bug that is so widespread in the human population, scientists know very little about H. pylori. To learn how it coexists for long periods of time with people, University of Michigan scientist Denise Kirschner, Ph.D., created a mathematical model, based on experimental evidence, of the symbiotic relationship between bacterium and host.
Results from the model were published in an article by Kirschner and Martin Blaser, M.D., of Vanderbilt University Medical Center in the July 20 issue of the Proceedings of the National Academy of Sciences.
While several mathematical models have been developed to study the HIV virus that causes AIDS, this is the first model for H. pylori, according to Kirschner.
"The most important factor in the relationship is the capacity of the host response to the bacteria," said Kirschner, an assistant professor of microbiology and immunology in the U-M Medical School. "Some people have the ability to flush the bug from their systems and some don't. We don't know why these individual differences exist and we don't understand exactly how the host responds to H. pylori's presence. The response may or may not be directly related to the immune system."
"Everything about the model works and is consistent with indirect experimental data," Blaser said. "We describe the initial transition from one organism to a bloom of organisms. Then as immunity kicks in, the organisms settle down and reach equilibrium. In essence, bacteria and host are dancing together; each one is signaling the other."
Helicobacter pylori bacteria live in the thick mucus layer lining the inside of the stomach, which protects epithelial cells from stomach acid, Kirschner explained. When bacteria enter the stomach, probably through fecal-oral transmission, some penetrate the mucus layer and attach to epithelial cells. These bacteria release molecules that irritate and degrade epithelial cells, which creates food for the bacterial colony.
"Our most surprising discovery is the key role played by this small group of adherent bacteria," Kirschner said. "They only make up 1 percent of the entire colony, but they must be present or colonization will not take place."
The model also indicates that two competing strains of H. pylori can live together in the stomach at the same time---but not for long. "One strain will always be dominant over the other," Kirschner said. "But any change in stomach conditions can create advantages for a different strain and allows it to predominate."
Kirschner added that H. pylori's ability to live in such close, long-term relationships with people indicates that the bacteria may have been evolving with humans for thousands of years. The advantages of this relationship to the bacteria are obvious. But could there be advantages for the human host, as well?
Kirschner hopes future research with the model will answer that question, as well as many others related to the nature of the human response and the mechanism of transmission. Kirschner also hopes the model will help scientists discover what upsets the bacterial-host equilibrium leading to ulcers or stomach cancer in some people.
"Mathematical models like this one are especially valuable in biomedical research when clinical experiments are difficult or impossible," Kirschner said. "They help us focus study on areas most likely to produce a positive result and allow us to test experimental treatments quickly and inexpensively without human clinical trials."
Model development was supported by the National Institutes of Health, the Medical Research Service of the Department of Veterans Affairs, and Astra-Merck, Inc.
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