Math model helps trace bacterium's invasion pattern
Dr. Martin Blaser used a mathematical model to examine how the bacterium Helicobacter pylori colonizes the stomach. (photo by John Howser)
Human bodies are teeming with bacteria, and yet the relationship we share with our normal flora – the organisms that live in and on us – is poorly understood.
Scientists at Vanderbilt University Medical Center and the University of Michigan are shedding some light on the subject by using mathematics to examine how the bacterium Helicobacter pylori colonizes the stomach, even in the presence of an immune response. They report a mathematical model that describes the dynamics of H. pylori infection in the July 20th issue of the Proceedings of the National Academy of Sciences.
H. pylori colonizes the stomachs of half of all humans. Although it has been linked to ulcer disease and stomach cancer, most people with the organism are well.
"An outstanding feature of H. pylori colonization is that there is an immune response, which means the host recognizes that the organism is there, and yet H. pylori persists, essentially for life, in everybody carrying it," said Dr. Martin J. Blaser, Addison B. Scoville Jr. Professor of Medicine, director of the division of Infectious Diseases, and professor of Microbiology and Immunology.
"So the question is, how do the host and the bacteria co-exist?"
In an earlier paper, Blaser and his collaborator, Denise Kirschner, Ph.D., developed a model to examine the relationship between H. pylori and the human host at equilibrium – some years after the organism has been acquired, when the system is balanced. The model demonstrated that bacteria and host were related in a feedback loop. The bacteria produce factors that cause the host to have inflammation, which in turn provides nutrients for the bacteria.
"In essence, the two are dancing together; each one is signaling the other. And that's a novel concept; that our normal flora are actually working in concert with us," Blaser said.
Blaser and Kirschner's earlier studies did not account for the early stages of infection or the host's immune response. The current model includes time – moving from one bacterium to an entire community, and terms for immunity – changing from a naive host to an immunologically aware host.
"Everything about the model works, and it is consistent with indirect experimental data. We're able to describe the initial transition from one organism to a bloom of organisms, and then as immunity kicks in, the organisms settle down and reach equilibrium," Blaser said.
Work is now in progress to test the mathematical model in a mouse experimental model.
The study illustrates the power of mathematics as a tool to analyze and lend insight into host-microbial interactions and other biological issues. The model can also be used to explain the dynamics of other bacterial colonizations and may clarify why people who have AIDS rarely are infected by their own bacterial flora.
"In addition to its own medical importance, H. pylori serves as a model system for understanding the interrelationships that we have with our normal flora," Blaser said. "I would project that studies of our normal flora are going to become increasingly important to medical research in future decades.
"Just as we house and feed them, these organisms provide important functions for us."
H. pylori's "important functions" remain largely undefined, but there is evidence that while the bacteria increase the risk of gastric disease, they may actually protect the esophagus from cancer and other diseases.
"We have to find ways that we can discriminate amongst people – something to tell which group is at high risk and which group is at low risk for a given disease. I believe that the development and refinement of mathematical models like ours will allow us ultimately to generate better markers for disease," Blaser said.
This work was supported by the NIH, the Medical Research Service of the Department of Veterans Affairs, and by Astra-Merck Inc.