Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts

Abstract

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) have a major impact on gut microbiome and immune function, which in turn, may increase the risk of inflammatory bowel disease (IBD). Our aim in this study was to evaluate PPI use and subsequent risk of IBD and subtypes (ie, Crohn's disease and ulcerative colitis). METHODS: This was a pooled analysis of the Nurses' Health Study (NHS, n ¼ 82,869), NHS II (n ¼ 95,141), and UK Biobank (n ¼ 469,397). We included participants with information on personal use of PPIs and free of IBD or cancer at baseline. We evaluated hazard ratios and 95% confidence intervals (CIs) with Cox regression adjusting for lifestyle factors, PPI indications, comorbidities, and other medications. RESULTS: We documented 271 cases of IBD (median follow-up, 12 years) in the pooled NHS cohorts and 1419 cases (median follow-up, 8.1 years) in the UK Biobank. For both pooled NHS cohorts and UK Biobank, regular use of PPIs consistently showed a significantly positive association with IBD, Crohn's disease, and ulcerative colitis risk. Combined analyses of 3 cohorts showed that regular PPI users had an increased risk of IBD as compared with nonusers (hazard ratio, 1.42; 95% CI, 1.22-1.65; number needed to harm, 3770; 95% CI, 3668-4369). Direct comparison with H2 receptor antagonist, a less potent acid suppressor, showed that PPI use was also associated with higher IBD risk (hazard ratio, 1.38; 95% CI, 1.16-1.65). CONCLUSIONS: Regular use of PPIs was associated with an increased risk of IBD and its subtypes. The findings should be interpreted with caution because the absolute risk was low and the clinical benefits of PPIs are substantial.

Sugar‐sweetened beverages, artificially sweetened beverages and natural juices and risk of inflammatory bowel disease: a cohort study of 121,490 participants

“…Second, self‐reported exposures assessed by the 24‐h diet recall questionnaires were subject to inevitable measurement error and recall bias, although the questionnaire has been validated 22,23 and we tried to address this issue by including participants with at least two assessments. Third, diagnosis for IBD, CD and UC was ascertained by ICD code, as in previous studies, 46,47 which may have limited specificity. In the current study, we further ascertained IBD patients as more than twice diagnosis in the sensitivity analysis.…”

Manipulation of Gut Microbiota as a Key Target for Crohn's Disease

“…Although PPIs exhibit a sound safety profile and have demonstrated significant benefits in acid-related gastrointestinal disorders, there are controversial data regarding their safety in IBD. In an observational analysis of three cohorts made up of 6,40,000 subjects, long-term PPI use was associated with an increased risk of developing IBD ( 91 ). This association was also found in multiple other studies correlating PPI use to increased risk of enteric infections such as Clostridoides difficile and IBD.…”

Association Between Regular Use of Gastric Acid Suppressants and Subsequent Risk of Cholelithiasis: A Prospective Cohort Study of 0.47 Million Participants

“…Detailed description of this cohort can be found elsewhere (Sudlow et al, 2015). The UK Biobank has been used to investigate the association between regular use of PPIs and risk of diabetes (He et al, 2020), inflammatory bowel disease (Xia et al, 2021), and mortality (He et al, 2021).…”