Systematic Review

The Effects of Proton Pump Inhibitors on the Microbiome of the Digestive Tract

Evidence From Next-generation Sequencing Studies

Lukas Macke; Christian Schulz; Leandra Koletzko; Peter Malfertheiner


Aliment Pharmacol Ther. 2020;51(5):505-526. 

In This Article


We conducted a systematic review following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.[66] A Database search in PubMed until 1 February 2019, using the search terms ((ppi OR (proton pump)) AND (microbiome OR microbiota)) yielded 197 results.

After removal of records not in English, all findings were screened for eligibility based on title and abstract. Only articles using next-generation sequencing techniques, being conducted in humans and containing a sample size of n > 5 were included in the review. Review articles and studies assessing effects of PPIs in combination with other medications, eg H pylori eradication protocols, non-steroidal anti-inflammatory drugs, statins or psychiatric drugs, were excluded. Potentially relevant articles were reviewed in full text. Furthermore, the reference lists of eligible publications were screened for studies that might have been missed. Nineteen studies met the pre-specified criteria and were included in the review (Figure 1; Appendix S1).

Figure 1.

PRISMA Flowchart

The study results were categorized according to study design into prospective interventional and retrospective observational trials. The strength of the evidence for the association between PPI therapy and adverse events was graded according to the system used previously (Table 1).[67]