Proton pump inhibitor-induced gut dysbiosis and immunomodulation: current knowledge and potential restoration by probiotics

Pharmacol Rep. 2023 Aug;75(4):791-804. doi: 10.1007/s43440-023-00489-x. Epub 2023 May 4.


Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs), esophagitis, peptic ulcer disease (PUD), Zollinger-Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), non-ulcer dyspepsia, and Helicobacter pylori eradication therapy. The drugs have the effect of inhibiting acid production in the stomach. According to research, PPIs can affect the composition of gut microbiota and modulate the immune response. Recently, there has been a problem with the over-prescription of such drugs. Although PPIs do not have many side effects, their long-term use can contribute to small intestinal bacterial overgrowth (SIBO) or C. difficile and other intestinal infections. Probiotic supplementation during PPIs therapy may provide some hope in the reduction of emerging therapy side effects. This review aims to present the most important effects of long-term PPI use and provides critical insights into the role of probiotic intervention in PPI therapy.

Keywords: Clostridioides difficile infection; Gut microbiota; Immunomodulation; PPI; Probiotics; Proton pump inhibitors; SIBO; Salmonella infection.

Publication types

  • Review

MeSH terms

  • Clostridioides difficile*
  • Dysbiosis / chemically induced
  • Gastroesophageal Reflux* / chemically induced
  • Gastroesophageal Reflux* / drug therapy
  • Humans
  • Immunity
  • Immunomodulation
  • Probiotics* / therapeutic use
  • Proton Pump Inhibitors / adverse effects


  • Proton Pump Inhibitors