Omeprazole Induces a Transepithelial Leak in Gastric Mucosa

Abstract

Purpose: Having observed a paracellular leak to oral sucrose in esophagitis patients, we tested if PPI therapy would decrease (paracellular) sucrose leak by allowing for mucosal healing. Methods: 23 study subjects presenting to their primary care physician with symptoms of GERD were placed on an 8 week course of esomeprazole (40 mg daily). Subjects were PPI and H-2 blocker naive. All subjects reported symptom alleviation by 4 weeks. Before beginning esomeprazole therapy and at the end of therapy, subjects consumed at bedtime a solution of the disacharide, sucrose (100 gms in 200 cc tap water), and collected an overnight urine specimen. Sucrose, as a disacharide, can enter the bloodstream only by leaking paracellularly out of the upper GI lumen. Once in the blood, sucrose is filtered quantitatively into urine. Sucrose concentration in urine was measured by enzymatic/spectrophotometric means. The sucrose concentration × the total urine volume yields the total amount of sucrose in the urine, which equals the the amount of sucrose which leaked paracellularly from the upper GI lumen. Results: We observed that 17 of 23 patients exhibited a marked increase in sucrose leak by 8 weeks of omeprazole therapy (667% increase). Similar sucrose leak is observed after only 8 days of esomeprazole therapy. Considering all 23 patients, the Wilcoxon Signed Rank Test indicated a significant increase in sucrose leak (P= 0.007). In rat gastric mucosa, 200 μM omeprazole induces an immediate paracellular leak to D-mannitol, with a simultaneous decrease in transepithelial electrical resistance. Both phenomena indicate that omeprazole is likely producing a tight junction leak in gastric mucosa. Conclusion: PPI therapy may be associated with a paracellular leak in the acid secreting region of the stomach. Future studies will examine the characteristics of this leak and the mechanism by which omeprazole induces the leak.