New research suggests that drugs used to reduce gastric acid reflux may promote a type of gut bacteria tied to chronic liver disease.
Proton pump inhibitors (PPIs) are drugs that reduce the production of gastric, or stomach, acid in the long-term. PPIs are often used to treat gastroesophageal reflux disease, which is a condition wherein gastric acid travels up to the esophagus, producing an uncomfortable burning sensation.
One study suggests that PPI prescriptions in the United States are on the rise, despite the fact that they are tied to a series of adverse events. Another recent article even linked PPIs with an increased risk of death.
Now, emerging research from the University of California, San Diego School of Medicine in La Jolla suggests that PPIs may also have a role to play in the development of liver diseases.
"Our stomachs produce gastric acid to kill ingested microbes," explains senior study author Dr. Bernd Schnabl, "and taking a medication to suppress gastric acid secretion can change the composition of the gut microbiome."
"We found," he continues, "that the absence of gastric acid promotes growth of Enterococcus bacteria in the intestines and translocation [transfer] to the liver, where they exacerbate inflammation and worsen chronic liver disease."
The study's findings have now been published in the journal Nature Communications.
PPIs may promote Enterococcus population
The team studied the effect of gastric acid suppression in the promotion of a series of chronic liver diseases - alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH) - using mouse models.
For every model, they either genetically engineered the animals to produce less gastric acid, or they reduced production by giving the mice the PPI omeprazole.
Then, the researchers collected stool samples from the mice to see how the gut microbiome had been affected in each case.
They found that in mice who had been administered the PPI, the Enterococcus faecalis bacteria, which are tied to inflammation of the liver, were more abundant. The animals were therefore more exposed to the symptoms of alcohol-induced liver disease, NAFLD, and NASH.
Dr. Schnabl and his team also colonized a group of mice with Enterococcus to replicate the effect of PPIs on the gut microbiome. As a result, the scientists were able to confirm the bacteria's role in causing steatosis - that is, the buildup of excess fat in the liver, which marks fatty liver diseases.
An abundance of Enterococcus also aggravated alcoholic liver disease in the mouse model.
Abundant Enterococcus in guts of PPI users
Finally, the researchers wanted to confirm the effect of PPIs in humans, analyzing stool samples from individuals who had been diagnosed with chronic alcohol abuse.
They worked with a total 4,830 people, of whom 1,024 were taking PPIs, 745 had previously used gastric acid suppressors, and 3,061 had never taken PPIs. Once more, the team found abundant Enterococcus in the stool samples they analyzed.
They also found that the risk of being diagnosed with alcoholic liver disease within 10 years was 20.7 percent for those currently taking PPIs, and 16.1 percent for those who used to take PPIs but had since ceased this treatment.
Individuals who had never used PPIs had the lowest risk, at 12.4 percent.
"Our findings indicate that the recent rise in use of gastric acid-suppressing medications might have contributed to the increased incidence of chronic liver disease," suggests Dr. Schnabl.
The results may point to a link between PPI use and the risk of developing or worsening a chronic liver disease, but the team admits that currently unidentified confounding factors may also play a role.
Dr. Schnabl and his colleagues say that, in the future, a randomized controlled clinical trial should be conducted to confirm a causal relationship between PPI usage and the risk of liver disease.
'Clinicians should consider withholding PPIs'
Still, as a preventive measure, healthcare professionals may want to reconsider prescribing such medication if other options are available, suggests Dr. Schnabl.
"Although obesity and alcohol use predispose a person to acid reflux requiring antacid [gastric acid suppressive] medication," he says, "many patients with chronic liver disease take gastric acid suppressive medications without appropriate indication."
"We believe clinicians should consider withholding medications that suppress gastric acid unless there is a strong medical indication."
Dr. Bernd Schnabl
The researchers hope that their current findings, should they be confirmed by future research, may eventually lead the way to more effective and targeted therapies for chronic liver diseases.
"We might someday be able to manipulate the gut microbiome, and in particular Enterococcus faecalis, to attenuate alcohol-related liver disease associated with gastric acid suppression," Dr. Schnabl concludes.