The effect of intra-gastric acidity and flora on the concentration of N-nitroso compounds in the stomach

Background Correa's hypothesis proposes that gastric carcinogenesis is due to atrophic gastritis and hypochlorhydria which permit gastric bacterial colonization, the reduction of dietary nitrates to nitrites and the formation of potentially carcinogenic N-nitroso compounds (NOCs). Objective To test the hypothesis that omeprazole-induced hypochlorhydria is associated with increased intra-gastric concentrations of nitrate-reducing bacteria (NRB), nitrites and NOCs. Design Single-blind study in healthy volunteers. Participants Fourteen healthy subjects (seven female, mean age 24 years), free of Helicobacter pylori infection, received a one-week course of placebo followed by a two-week course of omeprazole, 20 mg daily. Methods Fasted gastric samples, aspirated using a sterile double-lumen nasogastric tube at the end of the 1 st week (placebo) and the 2nd and 3rd weeks (omeprazole), were cultured aerobically and anaerobically; gastric pH and intra-gastric concentrations of nitrates, nitrites and NOCs were also determined. Results After weeks 1,2 and 3, the intra-gastric concentrations of nitrate-reducing bacteria exceeded 10(5) colony-forming units (c.f.u.)/ml in 3, 7 and 9 subjects, respectively (P> 0.05). A gastric pH greater than 4.0 was associated with increased NRB (P< 0.05): however, neither increased gastric pH nor increased NRB, alone or in combination, was associated with increased intra-gastric concentrations of nitrites or NOCs (P > 0.05). Conclusions A two-week increase in gastric pH in healthy, H. pylori-negative subjects was associated with increased intra-gastric concentrations of nitrate-reducing bacteria but not of nitrites or N-nitroso compounds. These data suggest that reduced gastric acid secretion is not a necessary precursor to the formation of carcinogenic N-nitroso compounds and that other mechanisms should be invoked to explain gastric carcinogenesis. Eur J Gastroenterol Hepatol 12:165-173 (C) 2000 Lippincott Williams & Wilkins.