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A new study found that the proton pump inhibitors (PPIs),
blocking stomach acid can lead to an overgrowth of
intestinal bacteria that likely contributes to liver
inflammation and damage.
The findings suggest that some widely used acid
reflux (heartburn) medications may worsen chronic
liver disease.
In mice, some common acid reflux medications promote
growth of Enterococcus bacteria, shown here
artificially glowing red, in the intestines. These
bacteria can move to the liver and affect its
function. UC San Diego Health.
The liver has many important functions, including
helping to digest food and process and distribute
nutrients.
A healthy liver is necessary for survival.
The liver can regenerate after being damaged.
However, repeated or long-lasting injury can cause
scar tissue to form.
Scarring of the liver may lead to cirrhosis, a
condition in which the liver is unable to function
normally.
Liver cirrhosis is a leading cause of death
worldwide.
Many conditions can contribute to the development of
cirrhosis, including obesity, which is associated
with non-alcoholic fatty liver disease (NAFLD), and
non-alcoholic steatohepatitis (NASH), a form of
NAFLD in which you also have inflammation and liver
cell damage.
But alcohol misuse accounts for about half of
cirrhosis-related deaths.
Changes in your gut’s microorganisms, or microbiota,
can affect the progression of liver disease.
Misusing alcohol alters the microbes in your gut.
So can a commonly used class of heartburn medication
called proton pump inhibitors (PPIs), which block
stomach acid secretion.
PPIs are often used by people who have chronic liver
disease, however, the impact of these medications on
liver disease progression has been unknown.
To investigate whether blocking stomach acid affects
chronic liver disease, a team led by Dr. Bernd
Schnabl at the University of California San Diego
School of Medicine looked at PPIs in mouse models of
three types of liver disease—alcohol-induced liver
disease, NAFLD, and NASH—and in humans.
The team blocked stomach acid in the mice either by
genetically deleting the gene that controls stomach
acid secretion or by administering the PPI
omeprazole (Prilosec).
Liver conditions in all three disease models were
worsened when the mice lacked stomach acid.
The researchers found that mice lacking stomach acid
had higher levels of intestinal bacteria as well as
imbalances among the microbes.
In particular, the mice had increased levels of
Enterococcus in their guts.
Further experiments suggested that these bacteria
can reach the liver, where they can cause liver
inflammation and damage.
In a previous study (Link...)
researchers examined data of 188,323 exposed to ASMs
(proton pump inhibitors PPIs, and H2 receptor
antagonists H2RA) and 376,646 who were not exposed
to ASMs between 1999 and 2013.
Compared to people who didn’t use the drugs, those
who did were at higher risk for a severe form of
diarrhea caused by the Clostridium difficile
bacteria.
Their odds of this infection were 1.4 times higher
when they were hospitalized and 1.7 times higher
when they weren’t in the hospital.
In addition, PPI users had a 4.5 times greater risk
of getting Campylobacter infections, a common form
of food poisoning, if they were hospitalized and a
3.7 times higher risk when they weren’t
hospitalized.
Researchers also tested for Salmonella, Shigella and
Escherichia coli, but didn’t find an association
between PPIs and these infections.
In the new study the team looked at whether also
people taking PPIs have increased levels of
Enterococcus in their guts.
They collected fecal samples from healthy people
before and after PPI treatment.
After two weeks, those taking the PPI treatment also
had a higher number of Enterococcus.
The researchers next investigated whether there
might be a link between PPIs and the development of
alcoholic liver disease.
They looked at 4,830 patients with a diagnosis of
alcohol use disorder.
Among these, 36% had been using PPIs.
The analysis showed that PPI use increased the
10-year risk of developing liver disease (20.7% for
active users; 16.1% for previous users; 12.4% for
those who had never used PPIs).
Proton pump inhibitors (PPIs) have also been shown
to be potentially involved in cognitive decline
in a study of the German Center for
Neurodegenerative Diseases in Bonn, Germany (Link...)
“Our findings indicate that the recent rise in use
of [stomach] acid-suppressing medications might have
contributed to the increased incidence of chronic
liver disease,” Schnabl says, “We believe clinicians
should consider withholding medications that
suppress [stomach] acid unless there is a strong
medical indication.”
See also
Heartburn pills tied to bacterial gastroenteritis
(2017-01-22)
Link...
Popular heartburn pills known as proton pump
inhibitors (PPIs) tied to greater mortality
(2017-07-24)
Link...
For more information
Gastric acid suppression promotes alcoholic liver
disease by inducing overgrowth of intestinal
Enterococcus.
Llorente C, Jepsen P, Inamine T, Wang L, Bluemel S,
Wang HJ, Loomba R, Bajaj JS, Schubert ML, Sikaroodi
M, Gillevet PM, Xu J, Kisseleva T, Ho SB, DePew J,
Du X, Sørensen HT, Vilstrup H, Nelson KE, Brenner
DA, Fouts DE, Schnabl B. Nat Commun. 2017 Oct
16;8(1):837. doi: 10.1038/s41467-017-00796-x. PMID:
29038503.
Link...
NIH U.S. National Institutes of Health
Link...
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