Is Long-Term Proton Pump Inhibitor Use a Cause of Leaky Gut Syndrome? A Cross-Sectional Case- Control Study

Background and Objective: Although Proton Pump Inhibitors (PPIs) have a good safety profile, they have been shown to be associated with Small Intestinal Bacterial Overgrowth (SIBO) and Clostridium difficile infection if used long-term. Tight junctions in the small intestine epithelium tightly regulate the passage of antigen into the cell. The best-known modulator of tight junctions is the zonulin protein. The gut microbiome is an important factor influencing zonulin release. The aim of current study was to investigate the effect of long-term PPI use on serum zonulin levels, an important indicator of leaky gut syndrome. Materials and Methods: A total of 75 patients were included in the study, 45 long-term PPI users and 30 non-PPI users. Use exceeding one tablet a day for 6 months or one tablet three days a week for 2 years was defined as long-term PPI treatment. The control group was selected from individuals who had never used PPIs. Venous blood samples were obtained from all patients to measure serum zonulin levels. Results: Eighty percent of the patients were using PPIs daily, while twenty percent were using them every other day. No significant difference was observed in the positive/negative ratios of serum zonulin levels between patients with PPI usage and those without PPI usage (p>0.05). Conclusion: The lack of change in zonulin levels in patients on long-term PPI use suggested that PPI use has no significant effect on intestinal permeability. In this context, it can be said that PPI use is safe.