Using Mathematics to Understand a Species of Bacteria That
Can Add Up to Big Trouble: Helicobacter pylori is Sometimes
Hard to Stomach
About half of all adult Americans have an intimate companionone
they carry with them everywherethat usually keeps its
presence unknown but can prove to be a most unwelcome guest.
Its proper name is Helicobacter pyloria species of bacteria
which usually produces no symptoms in the humans carrying it,
but which can cause ulcers and stomach cancer in some individuals.
it is an organism widespread in the human population, scientists
know very little about H. pylori. To learn how it coexists for
long periods of time with people, Medical School 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, 1999, issue of the
Proceedings of the National Academy of Sciences.
While several mathematical models have been developed to study
HIV, the virus that causes AIDS, this is the first model for
Helicobacter pylori, according to Kirschner. The most
important factor in the relationship is the capacity of the
host response to the bacteria, says Kirschner, an assistant
professor of microbiology and immunology in the Medical School.
Some people have the ability to flush it from their systems
and some dont. We dont know why these individual
differences exist and we dont understand exactly how the
host responds to the bacterias 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 says. 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 one 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 timebut not
for long. One strain will always be dominant over the
other, Kirschner says. But any change in stomach
conditions can create advantages for a different strain and
allow it to predominate.
Mathematical models like this one are especially valuable
in biomedical research when clinical experiments are difficult
or impossible, Kirschner says. They help us focus
study on areas most likely to produce a positive result and
allow us to test experimental treatments quickly and inexpensively
to guide 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.
Kirschner can be reached at