- ANN ARBOR, Mich. -
When it comes to cooling the burning pain of gastritis or an inflamed stomach
lining, reducing the amount of acid in the stomach may seem like a good
idea. But two new studies with laboratory mice, conducted by Howard Hughes
Medical Institute scientists at the University of Michigan Medical School,
indicate it could be exactly the wrong thing to do.
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- U-M scientists found that antibiotics were the best way
to kill the bacteria that cause gastritis and eliminate stomach inflammation
in their experimental mice. Mice treated with prescription drugs called
proton pump inhibitors or PPIs, which block acid production, acquired more
bacteria and developed more inflammatory changes in their stomach linings
than untreated mice.
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- "These animal studies indicate that it is the inflammatory
response - triggering the overproduction of hydrochloric acid - which is
the stomach's primary response to bacterial colonization," says Juanita
L. Merchant, M.D., Ph.D., an HHMI assistant investigator and U-M associate
professor of internal medicine and physiology. "Inflammation of the
stomach lining coincides with production of peptides called cytokines,
which stimulate production of a hormone called gastrin. Gastrin triggers
parietal cells in the stomach lining to produce more hydrochloric acid,
which kills off most invading microbes. If you inhibit gastric acid production,
you interfere with the stomach's natural defense mechanism."
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- Merchant cautions that without controlled clinical trials,
it is impossible to know whether the results would be exactly the same
in humans. She also emphasizes that a type of bacteria called Helicobacter
pylori, the most common cause of gastritis, was excluded from these studies.
Since reduced gastric acidity does appear to make the mammalian stomach
more vulnerable to bacterial invasion and gastritis, however, Merchant
says physicians may want to re-evaluate the long-term use of omeprazole
and other proton-pump-inhibiting drugs in their patients.
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- Together with Yana Zavros, Ph.D., an HHMI post-doctoral
fellow, Merchant and colleagues compared stomach cells from normal mice
with those from a strain of transgenic mice, developed at U-M, that lack
the gene for producing gastrin. Their goal was to understand the feedback
relationship between bacteria, pro-inflammatory factors, hormones and acid
secretion in the stomach. Results are published in the January 2002 issues
of Gastroenterology and The American Journal of Physiology.
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- Mice in the U-M studies contracted gastritis just like
people do - from eating food or drinking water contaminated with bacteria.
While 75 percent of people with gastritis test positive for Helicobacter
pylori, many other species of bacteria can trigger inflammatory changes,
too, and often co-exist with Helicobacter. No matter what type of bacteria
causes the problem, it is a serious medical condition. If untreated, chronic
gastritis can lead to peptic ulcers and stomach cancer.
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- H. pylori is the only bacterial organism in the stomach
that cannot be killed by hydrochloric acid. Since Merchant wanted to study
the relationship between other bacteria and gastric acid, she needed to
exclude the presence of H. pylori. U-M scientists cultured and analyzed
bacteria from stomach washings of all normal and gastrin-deficient mice
to confirm the absence of Helicobacter. Major types of bacteria identified
included Lactobacillus, Enterobacter and Staphylococcus.
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- U-M scientists treated infected gastrin-deficient mice
and normal control mice with antibiotics for 20 days. Other mice were treated
for two months with a proton-pump-inhibiting drug called omeprazole or
with a combination of omeprazole and antibiotics. At the end of the treatment
period, researchers compared cell changes and bacterial counts from the
stomach linings of all mice.
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- Major findings from the U-M studies include:
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- * Stomach cell samples from both the transgenic gastrin-deficient
mice and the normal mice whose ability to produce gastric acid was inhibited
by omeprazole all showed significant inflammatory changes -- including
more immune cells called lymphocytes -- and greater numbers of bacteria.
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- * Gastritis that developed in mice on omeprazole resolved
after 20 days of antibiotic treatment, despite continued omeprazole treatment
and low stomach acidity.
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- * The number of acid-producing parietal cells and gastrin-secreting
G-cells in the stomach increased in all mice with abnormally low levels
of hydrochloric acid. Elevated numbers of parietal and G-cells correlated
with the presence of inflammation, not with stomach acidity.
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- * Elevated levels of gastrin during chronic inflammation
suppressed production of a growth hormone called somatostatin, which inhibits
parietal and G-cell function. When the inflammation subsided following
antibiotic treatment, gastrin levels returned to normal releasing the hormonal
brake inhibiting somatostatin.
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- "Our findings show that changes observed in gastrin-deficient
mice are caused by inflammation triggered by an overgrowth of many bacterial
species," Zavros explains. "An abnormally low level of acidity
in the stomach is the factor initiating all these events."
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- "The bottom-line message is that a two-week course
of antibiotics to treat the inflammation is essential for a successful
cure," Merchant adds. "Once you get rid of the inflammation,
the gastric acid levels should return to normal. It is crucial to take
antibiotics for the entire two weeks exactly as your physician has prescribed,
however. People often stop taking their medication early or skip doses,
which helps the bacteria to develop antibiotic resistance."
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- In addition to the Howard Hughes Medical Institute, this
research was supported by the National Institutes of Health. Linda C. Samuelson,
Ph.D., an associate professor of physiology in the Medical School, developed
the strain of transgenic mice used in the experiments. Former U-M post-doctoral
fellows Gabriele Rieder, Ph.D., and Amy Ferguson, Ph.D., collaborated in
the study.
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- Editor's Note: The original news release can be found
at http://www.med.umich.edu/opm/newspage/stomachacid.htm
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- Note: This story has been adapted from a news release
issued by University Of Michigan Health System for journalists and other
members of the public. If you wish to quote from any part of this story,
please credit University Of Michigan Health System as the original source.
You may also wish to include the following link in any citation: http://www.sciencedaily.com/releases/2002/01/020115074441.htm
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