Proton pump inhibitor use is not independently associated with colonic diverticulosis in an asymptomatic screening population

Proton pump inhibitors (PPIs) are widely used medications that alter gut microbiota. Given the high prevalence of colonic diverticulosis and its increasing incidence in younger populations, we investigated whether PPI use is associated with diverticulosis prevalence in an asymptomatic screening population. This retrospective observational study analyzed data from 6,153 asymptomatic individuals undergoing colorectal cancer screening in Austria. Colonoscopies assessed diverticulosis presence, while PPI use was determined via structured medical history. Statistical analyses, including Poisson regression models and sensitivity analyses, were conducted to evaluate the association between PPI use and diverticulosis, with adjustments for confounding factors such as age, sex, BMI, comorbidities, and lifestyle characteristics. Among 6,153 participants, 37% were found to have diverticulosis, with a significantly higher prevalence observed in PPI users (48%) compared to non-users (36%, p < 0.001). PPI users were generally older, had a higher BMI, and were more likely to have cardiometabolic comorbidities. Univariate analysis demonstrated a significant association between PPI use and diverticulosis (RR 1.326, 95% CI: 1.199-1.476, p < 0.001). However, this association was not sustained in multivariable models adjusted for age, sex, BMI, comorbidities, and lifestyle factors, indicating that the observed relationship is likely attributable to confounding rather than a direct causal effect. In this large screening cohort, the initially observed association between PPI use and diverticulosis was likely attributable to confounding. These findings suggest that PPI use is not independently associated with diverticulosis.