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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.
University of Michigan 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, like Prilosec and Prevacid, which block acid production, acquired
more bacteria and developed more inflammatory changes in their stomach
linings than untreated mice.
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. 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."
Since reduced gastric acidity
does appear to make the mammalian stomach more vulnerable to bacterial
invasion and gastritis, however, Physicians may want to re-evaluate the
long-term use of Prilosec and other proton-pump-inhibiting drugs in their
patients.
Researchers compared stomach
cells from normal mice with those from a strain of transgenic mice 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.
Mice 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.
H. pylori is the only bacterial
organism in the stomach that cannot be killed by hydrochloric acid. Since
investigators wanted to study the relationship between other bacteria
and gastric acid, they needed to exclude the presence of H. pylori.
They 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.
Researchers 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.
Major findings from the studies
include:
- Stomach cell samples from
both the transgenic gastrin-deficient mice and the normal mice whose
ability to produce gastric acid was inhibited by Prilosec all showed
significant inflammatory changes -- including more immune cells called
lymphocytes -- and greater numbers of bacteria.
- Gastritis that developed
in mice on Prilosec resolved after 20 days of antibiotic treatment,
despite continued Prilosec 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 acidity.
- 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.
The findings show that changes
observed in gastrin-deficient mice are caused by inflammation triggered
by an overgrowth of many bacterial species,. An abnormally low level of
acidity in the stomach is the factor initiating all these events.
Gastroenterology and The
American Journal of Physiology January 2002
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