The Duration of Proton Pump Inhibitor Therapy and the Risk of Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta-Analysis.

Small intestinal bacterial overgrowth (SIBO) is frequently observed in patients treated with proton pump inhibitors (PPIs), yet the role of treatment duration in modulating SIBO risk remains unclear. This meta-analysis aims to evaluate the temporal association between PPI use duration and SIBO risk. Following the PRISMA 2020 guidelines, a systematic search was conducted across MEDLINE/PubMed, EMBASE, the Cochrane Library, the Russian Science Citation Index, and Google Scholar from 1985 to June 2025 and was previously registered in PROSPERO under the registration number CRD420251031719. Eligible studies included observational designs or clinical trials assessing SIBO in adult PPI users. Twenty-nine studies ( = 3682 PPI patients; n = 2907 controls) were included. The pooled SIBO prevalence among PPI-treated patients was 36.839% (95% CI: 29.703-44.277), significantly higher than that among controls (19.887%; 95% CI: 12.027-29.399). PPI use was associated with increased SIBO risk (OR = 2.143; 95% CI: 1.446-3.175), with high heterogeneity (I = 77.61%). A duration-dependent trend was observed: our meta-regression analysis demonstrated a significant positive association between PPI treatment duration and SIBO prevalence with the regression coefficient 4.265% (95% CI: 1.827-6.384; = 0.0024), indicating that each additional month of PPI therapy was associated with a 4.265 percentage increase in SIBO risk. PPI use significantly increases the risk of SIBO, with longer treatment durations associated with higher odds.