MI - 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.
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.
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."
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.
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.
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
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
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.
from the U-M studies include:
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
that developed in mice on omeprazole resolved after 20 days of
antibiotic treatment, despite continued omeprazole treatment and
low stomach acidity.
- 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
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.
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."
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
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."
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.
122:119-133, 2002 - text available at:
Am J Physiol
Gastrointest Liver Physiol 282:G175-G183, 2002
A press release
from the Howard Hughes Medical Institute is available at http://www.hhmi.org/news/merchant.html
Written by Sally Pobojewski
information, contact Sally Pobojewski or Kara Gavin, UMHS Public
Relations, 734-764-2220, or by e-mail.
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