Researchers studying the effects of proton pump inhibitors (PPIs), a type of drug used to block stomach acid secretions and relieve heartburn, have uncovered evidence that use of the drug may promote progression of three types of chronic liver disease. The study was published yesterday in Nature Communications.
PPI’s, which go by the brand name Prilosec, Nexium and Prevacid are among the most commonly prescribed medications and have been taken by approximately 10% of the population to relieve acid reflux. Notably, they are often prescribed as a treatment for chronic liver disease.
Knowing that the gut microbiome can influence liver disease risk, the researchers, from the University of California San Diego School of Medicine, decided to explore the effect of gastric acid suppression on liver disease risk.
To test the effects, the team blocked gastric acid production either by genetic engineering or use of PPIs in a mouse model of chronic liver disease. They then sequenced microbe-specific genes collected from the mouse’s stool to assess the gut microbiome.
In mice with gastric acid suppression, the researchers found an increase in the number of Enterococus bacteria. An increase in liver inflammation and injury was also observed, accelerating the progression of three types of liver disease in mice: alcohol-induced liver disease, NAFLD and NASH.
When Enterococcus faecalis was introduced to mice in a separate experiment, mild steatosis and increase alcohol-induced liver disease was observed, confirming the bacteria’s role in disease onset.
To further explore the association, the team analyzed a cohort of 4,830 patients with a diagnosis of chronic alcohol abuse—1,024 (21%) were active PPI users, 745 (15%) were previous users and 3061 (63%) had never used PPIs.
The researchers found an increase in stool concentrations of Enterococcus in subjects taking a PPI. It was also observed that the 10-year risk of a diagnosis of alcoholic liver disease was 20.7 percent for active users of PPIs, 16.1 percent for previous users and 12.4 for those who had never used them.
The researchers caution that, while these results do appear to be correlative, further studies are needed to eliminate the possibility that a conflicting factor is behind the association between PPIs and chronic liver disease. Still, they feel the evidence is strong enough to encourage clinicians to exercise restraint when prescribing PPIs unless there is a strong need.
The research note that these findings may someday be provide a therapeutic basis for treating chronic liver disease through modulation of Enterococcus faecalis.
Image: In mice, some common acid reflux medications promote growth of Enterococcus bacteria (like those shown here artificially glowing red in a petri dish) in the intestines. These bacteria also translocate to the liver, where they exacerbate inflammation and worsen chronic liver disease. Image courtesy of UC San Diego Health.