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The Duration of Proton Pump Inhibitor Therapy and the Risk of Small Intestinal Bacterial Overgrowth: A Systematic

Alsu R Khurmatullina1, Dmitrii N Andreev1, Yury A Kucheryavyy2

  • 1Department of Internal Disease Propaedeutics and Gastroenterology, Russian University of Medicine, 127473 Moscow, Russia.

Journal of Clinical Medicine
|July 12, 2025
PubMed

Insights

Proton pump inhibitor (PPI) use significantly elevates the risk of small intestinal bacterial overgrowth (SIBO). Longer PPI treatment duration correlates with a higher likelihood of developing SIBO, highlighting a dose-dependent relationship.

Area of Science:

  • Gastroenterology
  • Pharmacology

Background:

  • Proton pump inhibitors (PPIs) are widely used medications.
  • Small intestinal bacterial overgrowth (SIBO) is a known complication associated with PPI use.
  • The impact of PPI treatment duration on SIBO risk is not well-established.

Purpose of the Study:

  • To conduct a meta-analysis evaluating the temporal association between the duration of proton pump inhibitor (PPI) use and the risk of developing small intestinal bacterial overgrowth (SIBO).

Main Methods:

  • Systematic literature search across multiple databases (MEDLINE/PubMed, EMBASE, Cochrane Library, RSCI, Google Scholar) from 1985 to June 2025.
  • Inclusion of observational studies and clinical trials assessing SIBO in adult PPI users, adhering to PRISMA 2020 guidelines.
  • Meta-regression analysis to explore the relationship between PPI treatment duration and SIBO prevalence.

Main Results:

  • Twenty-nine studies comprising 3682 PPI patients and 2907 controls were analyzed.
  • Pooled SIBO prevalence was significantly higher in PPI users (36.8%) compared to controls (19.9%).
  • PPI use increased SIBO risk (OR = 2.143), with a significant positive association between treatment duration and SIBO prevalence (4.265% increase per month).

Conclusions:

  • Proton pump inhibitor (PPI) therapy is associated with a substantially increased risk of small intestinal bacterial overgrowth (SIBO).
  • A clear duration-dependent trend indicates that longer PPI treatment durations correlate with a higher prevalence and risk of SIBO.
Keywords:
PPI durationmeta-analysisproton pump inhibitorssmall intestinal bacterial overgrowthsystematic review

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