Omeprazole, Helicobacter pylori status, and alterations in the intragastric milieu facilitating bacterial N-nitrosation

Background & Aims: Omeprazole produces greater acid inhibition in Helicobacter pylori-positive than -negative subjects. We investigated whether this is accompanied by more profound changes in the intragastric milieu that facilitates bacterial synthesis of N-nitroso compounds. Methods: Gastric juice pH; nitrite, ascorbic acid, and total vitamin C concentrations; and colonization by other bacteria were examined before and during omeprazole treatment in subjects with and without H. pylori infection. Studies were performed in the fasting state and after consumption of 2 mmol nitrate (equivalent to a salad meal). Results: Before omeprazole, H. pylori-positive and -negative subjects were similar for all parameters. During omeprazole, H. pylori-positive subjects had a higher intragastric pH (7.8 vs. 3.0; P < 0.00001) and greater colonization with non-H. pylori species (5 x 10(7) vs. 5 x 10(5) CFU/mL; P < 0.05). These bacteria included nitrosating species. During omeprazole treatment, H. pylori-positive subjects had higher intragastric nitrite levels after the nitrate meal (median area under the concentration/time curve, 12,450 vs. 4708 mu mol/L min; P = 0.04), Omeprazole lowered intragastric vitamin C levels in H. pylori-positive but not -negative subjects (1.8 vs. 3.4 mu g/mL, respectively; P = 0.02). Conclusions: In H. pylori-positive subjects, omeprazole produces disturbances in intragastric nitrite, vitamin C, and bacterial colonization that facilitate bacterial N-nitrosation, This may place them at increased risk of mutagenesis and carcinogenesis.