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

Background & Aims: Omeprazole produces greater acid inhibition in Helicobac ter pylori-positive than -negative subjects. We investigated whether this i s accompanied by more profound changes in the intragastric milieu that faci litates bacterial synthesis of N-nitroso compounds. Methods: Gastric juice pH; nitrite, ascorbic acid, and total vitamin C concentrations; and coloniz ation by other bacteria were examined before and during omeprazole treatmen t 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 -negativ e subjects were similar for all parameters. During omeprazole, H. pylori-po sitive 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) C FU/mL; P < 0.05). These bacteria included nitrosating species. During omepr azole treatment, H. pylori-positive subjects had higher intragastric nitrit e levels after the nitrate meal (median area under the concentration/time c urve, 12,450 vs. 4708 mu mol/L min; P = 0.04), Omeprazole lowered intragast ric 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-positiv e subjects, omeprazole produces disturbances in intragastric nitrite, vitam in C, and bacterial colonization that facilitate bacterial N-nitrosation, T his may place them at increased risk of mutagenesis and carcinogenesis.