Effect of gastric acid on Helicobacter pylori ecology

  • A. Lee
  • B. Mellgård
  • H. Larsson


The discovery of Helicobacter pylori has altered for ever our perceptions of gastro-duodenal disease, and has dramatically influenced patient management. However, we have much to learn. We still cannot explain the rather politically incorrect observation of nearly 40 years ago which was referring to differences in distribution of peptic ulcers between the rich and the poor. While all would now accept H. pylori as a cause of peptic ulcer, most gastric ulcers (GU), many gastric cancers (GC) and all mucosa-associated lymphoid tissue (MALT) lymphomas, we cannot explain what is illustrated in Figure 1, i.e., that there are different patterns of H. pylori-associated disease and these patterns vary in different populations. Indeed, some of the pathways of disease appear to be mutually exclusive. In the developed world the pattern tends towards duodenal ulcer (DU), while in the developing world gastric cancer may be more likely to develop. In this latter group, gastric ulcers will outnumber duodenal ulcers, as is implied in the opening quote. This chapter attempts to address this issue by suggesting that a major difference in these populations is variation in local acid output.


Duodenal Ulcer Gastric Ulcer Pylorus Infection Parietal Cell Transitional Zone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anon. Gastric ulcer and the ulcer equation. Lancet. 1959;1:1131–3.Google Scholar
  2. 2.
    Crabtree JE. Gastric mucosal inflammatory responses to Helicobacter pylori. Aliment Pharmacol Ther. 1996;10(Suppl. 1):29–37.PubMedGoogle Scholar
  3. 3.
    Tummuru M, Sharma SA, Blaser MJ. Helicobacter pylori picb, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells. Mol Microbiol. 1995;18:867–76.PubMedCrossRefGoogle Scholar
  4. 4.
    Lee A. Peptic ulceration — H. prylori-initiated ulcerogenesis — look to the host. Lancet. 1993;341: 280–1.PubMedCrossRefGoogle Scholar
  5. 5.
    Azuma T, Konishi J, Ito Y et al. Genetic differences between duodenal ulcer patients who were positive or negative for Helicobacter pylori. J Clin Gastroenterol. 1995;21(Suppl. 1):S151–4.PubMedGoogle Scholar
  6. 6.
    Azuma T, Konishi J, Tanaka Y et al. Contribution of HLA-dqa gene to hosts response against Helicobacter pylori. Lancet. 1994;343:542–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Lee A, Dixon MF, Danon SJ et al. Local acid production and Helicobacter pylori: a unifying hypothesis of gastroduodenal disease. Eur J Gastroenterol Hepatol. 1995;7:461–5.PubMedGoogle Scholar
  8. 8.
    Miller JF, Mekalanos JJ, Falkow S. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science. 1989;243:916–22.PubMedCrossRefGoogle Scholar
  9. 9.
    Kroll JK. Bacterial virulence: an environmental response. Arch Dis Child. 1990;65:361–3.CrossRefGoogle Scholar
  10. 10.
    Aagaard P, Andreassen M, Kurz L. Duodenal and gastric ulcer in the same patient. Lancet. 1959;1:1111–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Bonnevie O. Changing demographics of peptic ulcer disease. Dig Dis Sci. 1985;30:8–14S.CrossRefGoogle Scholar
  12. 12.
    Schrager J, Spink R, Mitra S. The antrum in patients with duodenal and gastric ulcers. Gut. 1967;8:497–508.PubMedCrossRefGoogle Scholar
  13. 13.
    Marks IN, Shay H. Observations on the pathogenesis of gastric ulcer. Lancet. 1959;1:107–11.Google Scholar
  14. 14.
    Ball PAJ. The secretory background to gastric ulcer. Lancet. 1961;1:1363–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Magnus HA. The pathology of simple gastritis. J Pathol Bacteriol. 1946;58:431–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Oi M, Oshida K, Sugimura S. The location of gastric ulcer. Gastroenterology. 1959;36:45–56.PubMedGoogle Scholar
  17. 17.
    Stave R, Brandtzaeg P, Nygaard K, Fausa O. The transitional body — antrum zone in resected human stomachs. Scand J Gastroenterol. 1978;13:685–91.PubMedCrossRefGoogle Scholar
  18. 18.
    Sonnenberg A. Temporal trends and geographical variations of peptic ulcer disease. Aliment Pharmacol Ther. 1995;9(Suppl. 2):3–12.PubMedGoogle Scholar
  19. 19.
    Anon. Treatment of acid-related diseases. A century of change. Oxford: Oxford Clinical Communications;1995.Google Scholar
  20. 20.
    Bayerdorffer E, Lehn N, Hatz R et al. Differences in expression of Helicobacter pylori gastritis in antrum and body. Gastroenterology. 1992;102:1575–82.PubMedGoogle Scholar
  21. 21.
    Stolte M, Eidt S, Ohnsmann A. Differences in Helicobacter pylori associated gastritis in the antrum and body of the stomach. Z. Gastroenterol. 1990;28:229–33.Google Scholar
  22. 22.
    Khulusi S, Mendall MA, Patel P, Levy J, Badve S, Northfield TC. Helicobacter pylori infection density and gastric inflammation in duodenal ulcer and non-ulcer subjects. Gut. 1995;37:319–24.PubMedCrossRefGoogle Scholar
  23. 23.
    Thomas E, Farnum JB, Rohrbach M. Helicobacter pylori infection and inflammation of the gastric corpus. Gastroenterology. 1991;101:1454–5.PubMedGoogle Scholar
  24. 24.
    Genta RM, Robason GO, Graham DY. Inflammatory responses and intensity of Helicobacter pylori infection in patients with duodenal and gastric ulcer — histopathologic analysis with a new stain. Acta Histochem Cytochem. 1995;28:67–72.CrossRefGoogle Scholar
  25. 25.
    Meikle DD, Taylor KB, Truelove SC, Whithead R. Gastritis duodenitis, and circulating levels of gastrin in duodenal ulcer before and after vagotomy. Gut. 1976;17:719–28.PubMedCrossRefGoogle Scholar
  26. 26.
    Peetsalu A, Maaroos HI, Sipponen P, Peetsula M. Long-term effect of vagotomy on gastric mucosa and Helicobacter pylori in duodenal ulcer patients. Scand J Gastroenterol. 1991;26:77–83.CrossRefGoogle Scholar
  27. 27.
    Vigneri S, Termini R, Scialabba A, Pisciotta G, di Mario F. Omeprazole therapy modifies the gastric localization of Helicobacter pylori. Am J Gastroenterol. 1991;86:1276.PubMedGoogle Scholar
  28. 28.
    Kuipers EJ, Uyterlinde AM, Pena AS et al. Increase of Helicobacter prylori-associated corpus gastritis during acid suppressive therapy — implications for long-term safety. Am J Gastroenterol. 1995;90:1401–6.PubMedGoogle Scholar
  29. 29.
    Logan RPH, Walker MM, Misiewicz JJ, Gummett PA, Karim QN, Baron JH. Changes in the intragastric distribution of Helicobacter pylori during treatment with omeprazole. Gut. 1995;36: 12–16.PubMedCrossRefGoogle Scholar
  30. 30.
    Marzio L, Biasco G, Cifani F et al. Short-and long-term omeprazole for the treatment and prevention of duodenal ulcer, and effect on Helicobacter pylori. Am J Gastroenterol. 1995;90: 2172–6.PubMedGoogle Scholar
  31. 31.
    Paster BJ, Lee A, Fox JG et al. Phylogeny of Helicobacter felis sp. nov., Helicobacter mustelae, and related bacteria. Int J Syst Bacteriol. 1991;41:31–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Dick-Hegedus E, Lee A. Use of a mouse model to examine anti-Helicobacter pylori agents. Scand J Gastroenterol. 1991;26:909–15.PubMedCrossRefGoogle Scholar
  33. 33.
    Lee A, Fox JG, Otto G, Murphy J. A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology. 1990;99:1315–23.PubMedGoogle Scholar
  34. 34.
    Lee A. The use of a mouse model in the study of Helicobacter sp.-associated gastric cancer. Eur J Gastroenterol Hepatol. 1994;6(Suppl. 1):S67–71.PubMedGoogle Scholar
  35. 35.
    Michetti P, Corthesy-Theulaz I, Davin C et al. Immunisation of BALB/c mice against Helicobacter felis infection with H. pylori urease. Gastroenterology. 1994;107:1002–11.PubMedGoogle Scholar
  36. 36.
    Enno A, O’Rourke J, Lee A, Jack A, Dixon MF. Maltoma-like lesions in the stomach resulting from long-standing Helicobacter infection in the mouse. Am J Gastroenterol. 1994;1994:1357.Google Scholar
  37. 37.
    Ferrero RL, Labigne A. Cloning, expression and sequencing of Helicobacter felis urease genes. Mol Microbiol. 1993;9:323–33.PubMedCrossRefGoogle Scholar
  38. 38.
    Danon SJ, O’Rourke JL, Moss ND, Lee A. The importance of local acid production in the distribution of Helicobacter felis in the mouse stomach. Gastroenterology. 1995;108:1386–95.PubMedCrossRefGoogle Scholar
  39. 39.
    Mellgard B, Arvidsson S, Lee A, Sundell G, Larsson H. The H. felis-infected rat as a model for human H. pylori infection — colonisation pattern and inflammatory response. Am J Gastroenterol. 1994;89:1320.Google Scholar
  40. 40.
    Cave DR, King WW, Hoffman JS. Production of two chemically distinct and inhibitory factors produced by H. pylori. Eur J Gastroenterol Hepatol. 1993;5(Suppl.):23–7.Google Scholar
  41. 41.
    Morris A, Nicholson G. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol. 1987;82:192–9.PubMedGoogle Scholar
  42. 42.
    Ramsey EJ, Carey KV, Peterson WL, Jackson JJ, Murphy FK, Read NWT. Epidemic gastritis with hypochlorhydria. Gastroenterology. 1979;76:1449–57.PubMedGoogle Scholar
  43. 43.
    Graham DY, Alpert LC, Smith JL, Yoshimura HH. Iatrogenic Campylobacter pylori infection is a cause of epidemic achlorhydria. Am J Gastroenterol. 1988;83:974–80.PubMedGoogle Scholar
  44. 44.
    Sóbala GM, Crabtree JE, Dixon MF et al. Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations. Gut. 1991;32:1415–18.PubMedCrossRefGoogle Scholar
  45. 45.
    Graham DY, Lew GM, Lechago J. Antral G-cell and D-cell numbers in Helicobacter pylori infection — effect of H. pylori eradication. Gastroenterology. 1993;104:1655–60.PubMedGoogle Scholar
  46. 46.
    El-Omar E, Penman I, Ardill JES, Chittajallu RS, Howie C, McColl KEL. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology. 1995;109:681–91.PubMedCrossRefGoogle Scholar
  47. 47.
    Ferrero RL, Lee A. The importance of urease in acid protection for the gastric-colonising bacteria Helicobacter pylori and Helicobacter felis sp. nov. Microbiol Ecol Health Dis. 1991;4:121–34.CrossRefGoogle Scholar
  48. 48.
    Clyne M, Labigne A, Drumm B. Helicobacter pylori requires an acidic environment to survive in the presence of urea. Infect Immun. 1995;63:1669–73.PubMedGoogle Scholar
  49. 49.
    Sjostrom JE, Larsson H. Factors affecting growth and antibiotic susceptibility of Helicobacter pylori: effect of pH and urea on the survival of a wild-type strain and a urease deficient mutant. J Med Microbiol. 1996;44:1–9.CrossRefGoogle Scholar
  50. 50.
    Williams C, Neithercut WD, Hossack M, Hair J, McColl KEL. Urease-mediated destruction of bacteria is specific for Helicobacter urease and results in total cellular disruption. FEMS Immunol Med Microbiol. 1994;9:273–80.PubMedCrossRefGoogle Scholar
  51. 51.
    Greig MA, Neithercut WD, Hossack M, McColl KE. Harnessing of urease activity of Helicobacter pylori to induce self-destruction of the bacterium. J Clin Pathol. 1991;44:157–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Neithercut WD, Williams C, Hossack MS, McColl KEL. Ammonium metabolism and protection from urease mediated destruction in Helicobacter pylori infection. J Clin Pathol. 1993;46:75–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Matin A, Zychlinsky E, Keyhan M, Sachs G. Capacity of Helicobacter pylori to generate ionic gradients at low pH is similar to that of bacteria which grow under strongly acidic conditions. Infect Immun. 1996;64:1434–6.PubMedGoogle Scholar
  54. 54.
    Dixon M. Acid, ulcers, and H. pylori. Lancet. 1993;342:384–5.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers and Axcan Pharma 1996

Authors and Affiliations

  • A. Lee
  • B. Mellgård
  • H. Larsson

There are no affiliations available

Personalised recommendations