PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of gutGutView this articleSubmit a manuscriptReceive email alertsContact usBMJ
 
Gut. 1999 April; 44(4): 468–475.
PMCID: PMC1727447

Helicobacter pylori infection potentiates the inhibition of gastric acid secretion by omeprazole

Abstract

BACKGROUND—Omeprazole has a greater intragastric pH elevating effect in Helicobacter pylori positive than negative subjects. Ammonia production by H pylori has been suggested as a probable mechanism.
AIMS—To assess the effect of H pylori status on gastric acid secretion during omeprazole treatment, and to examine the possible role of ammonia neutralisation of intragastric acid in increased omeprazole efficacy in infected subjects.
METHODS—Twenty H pylori positive and 12 H pylori negative healthy volunteers were examined before and six to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma gastrin and acid output were measured basally and in response to increasing doses of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured.
RESULTS—Prior to omeprazole, measurements were similar in the H pylori positive and negative subjects. During omeprazole, median basal intragastric pH was higher in the H pylori positive (7.95) versus negative (3.75) subjects (p<0.002). During omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800 pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h respectively) versus negative subjects (0.3,14.2, 18.6 mmol/h) (p<0.03 for each). This effect was not explained by neutralisation by ammonia.
CONCLUSION—The presence of H pylori infection leads to a more profound suppression of acid secretion during omeprazole treatment. The effect cannot be explained by neutralisation of intragastric acid by bacterial ammonia production and its precise mechanism has to be explained.

Keywords: omeprazole; Helicobacter pylori; ammonia; acid secretion

Full Text

The Full Text of this article is available as a PDF (145K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Olbe L, Haglund U, Leth R, Lind T, Cederberg C, Ekenved G, Elander B, Fellenius E, Lundborg P, Wallmark B. Effects of substituted benzimidazole (H 149/94) on gastric acid secretion in humans. Gastroenterology. 1982 Jul;83(1 Pt 2):193–198. [PubMed]
  • Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjöstrand SE, Wallmark B. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase. Nature. 1981 Mar 12;290(5802):159–161. [PubMed]
  • Garner A, Fadlallah H, Parsons ME. 1976 and all that!--20 years of antisecretory therapy. Gut. 1996 Dec;39(6):784–786. [PMC free article] [PubMed]
  • Howden CW, Forrest JA, Reid JL. Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man. Gut. 1984 Jul;25(7):707–710. [PMC free article] [PubMed]
  • Walt RP, Gomes MD, Wood EC, Logan LH, Pounder RE. Effect of daily oral omeprazole on 24 hour intragastric acidity. Br Med J (Clin Res Ed) 1983 Jul 2;287(6384):12–14. [PMC free article] [PubMed]
  • Howden CW, Hunt RH. The relationship between suppression of acidity and gastric ulcer healing rates. Aliment Pharmacol Ther. 1990 Feb;4(1):25–33. [PubMed]
  • Koop H, Arnold R. Long-term maintenance treatment of reflux esophagitis with omeprazole. Prospective study in patients with H2-blocker-resistant esophagitis. Dig Dis Sci. 1991 May;36(5):552–557. [PubMed]
  • Maton PN, Vinayek R, Frucht H, McArthur KA, Miller LS, Saeed ZA, Gardner JD, Jensen RT. Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study. Gastroenterology. 1989 Oct;97(4):827–836. [PubMed]
  • Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984 Jun 16;1(8390):1311–1315. [PubMed]
  • Graham DY. Campylobacter pylori and peptic ulcer disease. Gastroenterology. 1989 Feb;96(2 Pt 2 Suppl):615–625. [PubMed]
  • Armstrong D. Helicobacter pylori infection and dyspepsia. Scand J Gastroenterol Suppl. 1996;215:38–47. [PubMed]
  • Graham DY, Klein PD, Opekun AR, Boutton TW. Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the [13C]urea breath test in normal subjects and patients with peptic ulcer disease. J Infect Dis. 1988 Apr;157(4):777–780. [PubMed]
  • The British Society of Gastroenterology spring meeting 20-22 March 1996. Abstracts. Gut. 1996;38 (Suppl 1):A1–73. [PMC free article] [PubMed]
  • McGowan CC, Cover TL, Blaser MJ. The proton pump inhibitor omeprazole inhibits acid survival of Helicobacter pylori by a urease-independent mechanism. Gastroenterology. 1994 Sep;107(3):738–743. [PubMed]
  • 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 May;108(5):1386–1395. [PubMed]
  • Logan RP, Walker MM, Misiewicz JJ, Gummett PA, Karim QN, Baron JH. Changes in the intragastric distribution of Helicobacter pylori during treatment with omeprazole. Gut. 1995 Jan;36(1):12–16. [PMC free article] [PubMed]
  • Kuipers EJ, Uyterlinde AM, Peña AS, Hazenberg HJ, Bloemena E, Lindeman J, Klinkenberg-Knol EC, Meuwissen SG. Increase of Helicobacter pylori-associated corpus gastritis during acid suppressive therapy: implications for long-term safety. Am J Gastroenterol. 1995 Sep;90(9):1401–1406. [PubMed]
  • Eissele R, Brunner G, Simon B, Solcia E, Arnold R. Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia. Gastroenterology. 1997 Mar;112(3):707–717. [PubMed]
  • Verdú EF, Armstrong D, Fraser R, Viani F, Idström JP, Cederberg C, Blum AL. Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole. Gut. 1995 Apr;36(4):539–543. [PMC free article] [PubMed]
  • Verdú EF, Armstrong D, Idström JP, Labenz J, Stolte M, Dorta G, Börsch G, Blum AL. Effect of curing Helicobacter pylori infection on intragastric pH during treatment with omeprazole. Gut. 1995 Dec;37(6):743–748. [PMC free article] [PubMed]
  • Labenz J, Tillenburg B, Peitz U, Idström JP, Verdú EF, Stolte M, Börsch G, Blum AL. Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcer. Gastroenterology. 1996 Mar;110(3):725–732. [PubMed]
  • Koop H, Kuly S, Flüg M, Eissele R, Mönnikes H, Rose K, Lühmann R, Schneider A, Fischer R, Arnold R. Intragastric pH and serum gastrin during administration of different doses of pantoprazole in healthy subjects. Eur J Gastroenterol Hepatol. 1996 Sep;8(9):915–918. [PubMed]
  • Ferrero RL, Hazell SL, Lee A. The urease enzymes of Campylobacter pylori and a related bacterium. J Med Microbiol. 1988 Sep;27(1):33–40. [PubMed]
  • Mowat C, Murray L, Hilditch TE, Kelman A, Oien K, McColl KE. Comparison of helisal rapid blood test and 14C-urea breath test in determining Helicobacter pylori status and predicting ulcer disease in dyspeptic patients. Am J Gastroenterol. 1998 Jan;93(1):20–25. [PubMed]
  • Hassan MA, Hobsley M. Positioning of subject and of nasogastric tube during a gastric secretion study. Br Med J. 1970 Feb 21;1(5694):458–460. [PMC free article] [PubMed]
  • Mulholland G, Ardill JE, Fillmore D, Chittajallu RS, Fullarton GM, McColl KE. Helicobacter pylori related hypergastrinaemia is the result of a selective increase in gastrin 17. Gut. 1993 Jun;34(6):757–761. [PMC free article] [PubMed]
  • Neithercut WD, el Nujumi AM, McColl KE. Measurement of urea and ammonium concentrations in gastric juice. J Clin Pathol. 1993 May;46(5):462–464. [PMC free article] [PubMed]
  • Gillen D, el-Omar EM, Wirz AA, Ardill JE, McColl KE. The acid response to gastrin distinguishes duodenal ulcer patients from Helicobacter pylori-infected healthy subjects. Gastroenterology. 1998 Jan;114(1):50–57. [PubMed]
  • Fändriks L, Stage L. Simultaneous measurements of gastric motility and acid-bicarbonate secretions in the anaesthetized cat. Acta Physiol Scand. 1986 Dec;128(4):563–573. [PubMed]
  • Ladas SD, Katsogridakis J, Malamou H, Giannopoulou H, Kesse-Elia M, Raptis SA. Helicobacter pylori may induce bile reflux: link between H pylori and bile induced injury to gastric epithelium. Gut. 1996 Jan;38(1):15–18. [PMC free article] [PubMed]
  • Yasunaga Y, Shinomura Y, Kanayama S, Yabu M, Nakanishi T, Miyazaki Y, Murayama Y, Bonilla-Palacios JJ, Matsuzawa Y. Improved fold width and increased acid secretion after eradication of the organism in Helicobacter pylori associated enlarged fold gastritis. Gut. 1994 Nov;35(11):1571–1574. [PMC free article] [PubMed]
  • Feldman M, Cryer B, McArthur KE, Huet BA, Lee E. Effects of aging and gastritis on gastric acid and pepsin secretion in humans: a prospective study. Gastroenterology. 1996 Apr;110(4):1043–1052. [PubMed]
  • El-Omar EM, Oien K, El-Nujumi A, Gillen D, Wirz A, Dahill S, Williams C, Ardill JE, McColl KE. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology. 1997 Jul;113(1):15–24. [PubMed]
  • Robert A, Olafsson AS, Lancaster C, Zhang WR. Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying. Life Sci. 1991;48(2):123–134. [PubMed]
  • Wallace JL, Cucala M, Mugridge K, Parente L. Secretagogue-specific effects of interleukin-1 on gastric acid secretion. Am J Physiol. 1991 Oct;261(4 Pt 1):G559–G564. [PubMed]
  • Taché Y, Saperas E. Potent inhibition of gastric acid secretion and ulcer formation by centrally and peripherally administered interleukin-1. Ann N Y Acad Sci. 1992;664:353–368. [PubMed]
  • Sachs G. Gastritis, Helicobacter pylori, and proton pump inhibitors. Gastroenterology. 1997 Mar;112(3):1033–1036. [PubMed]
  • Lorentzon P, Jackson R, Wallmark B, Sachs G. Inhibition of (H+ + K+)-ATPase by omeprazole in isolated gastric vesicles requires proton transport. Biochim Biophys Acta. 1987 Feb 12;897(1):41–51. [PubMed]
  • Cave DR, Vargas M. Effect of a Campylobacter pylori protein on acid secretion by parietal cells. Lancet. 1989 Jul 22;2(8656):187–189. [PubMed]
  • Beil W, Birkholz C, Wagner S, Sewing KF. Interaction of Helicobacter pylori and its fatty acids with parietal cells and gastric H+/K(+)-ATPase. Gut. 1994 Sep;35(9):1176–1180. [PMC free article] [PubMed]
  • Giannella RA, Broitman SA, Zamcheck N. Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro. Gut. 1972 Apr;13(4):251–256. [PMC free article] [PubMed]
  • Drasar BS, Shiner M, McLeod GM. Studies on the intestinal flora. I. The bacterial flora of the gastrointestinal tract in healthy and achlorhydric persons. Gastroenterology. 1969 Jan;56(1):71–79. [PubMed]
  • Boyd JF. Pathology of the alimentary tract in Salmonella typhimurium food poisoning. Gut. 1985 Sep;26(9):935–944. [PMC free article] [PubMed]
  • Unreviewed reports. Br Med J (Clin Res Ed) 1984 Nov 10;289(6454):1272–1272. [PMC free article] [PubMed]
  • Ruddell WS, Losowsky MS. Severe diarrehoea due to small intestinal colonisation during cimetidine treatment. Br Med J. 1980 Jul 26;281(6235):273–273. [PMC free article] [PubMed]
  • KUNZ LJ, WADDELL WR. Association of Salmonella enteritis with operations on the stomach. N Engl J Med. 1956 Sep 20;255(12):555–559. [PubMed]
  • Axon AT, Poole D. Salmonellosis presenting with cholera-like diarrhoea. Lancet. 1973 Apr 7;1(7806):745–746. [PubMed]
  • Kubben FJ, Peeters-Haesevoets A, Engels LG, Baeten CG, Schutte B, Arends JW, Stockbrügger RW, Blijham GH. Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation. Gut. 1994 Apr;35(4):530–535. [PMC free article] [PubMed]
  • Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992 Dec 15;52(24):6735–6740. [PubMed]
  • Klinkenberg-Knol EC, Festen HP, Jansen JB, Lamers CB, Nelis F, Snel P, Lückers A, Dekkers CP, Havu N, Meuwissen SG. Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med. 1994 Aug 1;121(3):161–167. [PubMed]
  • Hetzel DJ, Dent J, Reed WD, Narielvala FM, Mackinnon M, McCarthy JH, Mitchell B, Beveridge BR, Laurence BH, Gibson GG, et al. Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology. 1988 Oct;95(4):903–912. [PubMed]
  • Klinkenberg-Knol EC, Jansen JB, Lamers CB, Nelis F, Snel P, Meuwissen SG. Use of omeprazole in the management of reflux oesophagitis resistant to H2-receptor antagonists. Scand J Gastroenterol Suppl. 1989;166:88–94. [PubMed]
  • Lundell L, Backman L, Ekström P, Enander LH, Fausa O, Lind T, Lönroth H, Sandmark S, Sandzén B, Unge P, et al. Omeprazole or high-dose ranitidine in the treatment of patients with reflux oesophagitis not responding to 'standard doses' of H2-receptor antagonists. Aliment Pharmacol Ther. 1990 Apr;4(2):145–155. [PubMed]
  • Bell NJ, Burget D, Howden CW, Wilkinson J, Hunt RH. Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion. 1992;51 (Suppl 1):59–67. [PubMed]
  • Sontag SJ, Hirschowitz BI, Holt S, Robinson MG, Behar J, Berenson MM, McCullough A, Ippoliti AF, Richter JE, Ahtaridis G, et al. Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: the U.S. Multicenter Study. Gastroenterology. 1992 Jan;102(1):109–118. [PubMed]
  • Vigneri S, Termini R, Leandro G, Badalamenti S, Pantalena M, Savarino V, Di Mario F, Battaglia G, Mela GS, Pilotto A, et al. A comparison of five maintenance therapies for reflux esophagitis. N Engl J Med. 1995 Oct 26;333(17):1106–1110. [PubMed]
  • Leite LP, Johnston BT, Just RJ, Castell DO. Persistent acid secretion during omeprazole therapy: a study of gastric acid profiles in patients demonstrating failure of omeprazole therapy. Am J Gastroenterol. 1996 Aug;91(8):1527–1531. [PubMed]

Figures and Tables

Figure 1
Basal fasting gastric juice pH in H pylori negative and positive subjects before and during omeprazole treatment. Medians are represented by horizontal bars.
Figure 2
Basal plasma gastrin concentrations in the H pylori negative and positive subjects before and during omeprazole treatment. Medians are represented by horizontal bars.
Figure 3
Basal acid output in H pylori negative and positive subjects before and during omeprazole treatment. Medians are represented by horizontal bars.
Figure 4
Maximal acid output in the H pylori negative and positive subjects before and during omeprazole treatment. Medians are represented by horizontal bars.
Figure 5
Median acid outputs (and ranges) to the submaximal doses of G-17 in H pylori negative and positive subjects (A) before and (B) during omeprazole treatment.
Figure 6
Median plasma gastrin concentration versus median acid output curves for the H pylori negative and positive subjects before and during omeprazole treatment.

Articles from Gut are provided here courtesy of BMJ Group