The impact of proton pump inhibitors on the human gastrointestinal microbiome

Abstract

Potent gastric acid suppression using proton pump inhibitors (PPIs) is common in clinical practice but may have important effects on human health that are mediated through changes in the gastrointestinal microbiome. In the esophagus, PPIs change the normal bacterial milieu to decrease distal esophageal exposure to inflammatory gram-negative bacteria. In the stomach, PPIs alter the abundance and location of gastric Helicobacter pylori and other bacteria. In the small bowel, PPIs cause polymicrobial small bowel bacterial overgrowth and have been associated with the diagnosis of celiac disease. In the colon, PPIs associate with incident but not recurrent Clostridium difficile infection.

Keywords: Barrett's esophagus; Clostridium difficile infection; Gastric acid suppression; Helicobacter pylori; Human microbiome; Hypergastrinemia; Proton pump inhibitors; Small bowel bacterial overgrowth.

Figure 1

Common structure of proton pump inhibitors (PPIs). All PPIs share a common backbone, with a pyridine linked to a benzimadazole.

Figure 2

Corresponding rises in the incidence of C. difficile infection (CDI) and rate of proton pump inhibitor (PPI) use, during a time of decreasing antibiotic use. Adapted from: Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. Dec 21 2005;294(23):2989–2995.

Figure 3

Bacteria that may be affected by proton pump inhibitors (PPIs) are shown by anatomical area; small arrows indicate directionality of changes with PPIs.