Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

Digestion. 2018;97(2):195-204. doi: 10.1159/000481813. Epub 2018 Jan 6.


Background: Gut dysbiosis associated with the use of proton-pump inhibitors (PPIs) has been found to lead to the occurrence of infectious and inflammatory adverse events. A longitudinal observational cohort study has demonstrated the heightened risk of death associated with PPI use.

Summary: We evaluated meta-analyses to determine the association between PPI use and infectious and inflammatory diseases. Meta-analyses showed that PPI use is a potential risk for the development of enteric infections caused by Clostridium difficile, as well as small intestinal bacterial overgrowth, spontaneous bacterial peritonitis, community-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease. We also examined changes in the composition and function of the gut microbiota with the use of PPIs. PPI use significantly increased the presence of Streptococcaceae and Enterococcaceae, which are risk factors for C. difficile infection, and decreased that of Faecalibacterium, a commensal anti-inflammatory microorganism. Key Message: High-throughput, microbial 16S rRNA gene sequencing has allowed us to investigate the association between the gut microbiome and PPI use. Future prospective comparison studies are necessary to confirm this association, and to develop new strategies to prevent complications of PPI use.

Keywords: Clostridium difficile; Dysbiosis; Faecalibacterium; Proton-pump inhibitor; Streptococcaceae.

Publication types

  • Review

MeSH terms

  • Clostridioides difficile / genetics
  • Clostridioides difficile / isolation & purification
  • Clostridioides difficile / pathogenicity*
  • Clostridium Infections / microbiology*
  • DNA, Bacterial / isolation & purification
  • Dysbiosis / microbiology*
  • Enterococcaceae / drug effects
  • Enterococcaceae / genetics
  • Enterococcaceae / isolation & purification
  • Faecalibacterium / drug effects
  • Faecalibacterium / genetics
  • Faecalibacterium / isolation & purification
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Intestinal Diseases / microbiology*
  • Intestines / drug effects
  • Intestines / microbiology
  • Meta-Analysis as Topic
  • Proton Pump Inhibitors / adverse effects*
  • RNA, Ribosomal, 16S / genetics
  • Risk Factors
  • Sequence Analysis, DNA
  • Streptococcaceae / drug effects
  • Streptococcaceae / genetics
  • Streptococcaceae / isolation & purification


  • DNA, Bacterial
  • Proton Pump Inhibitors
  • RNA, Ribosomal, 16S