DOI QR코드

DOI QR Code

Proton Pump Inhibitors and Helicobacter Pylori-Associated Pathogenesis

  • Hagiwara, Tadashi (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science) ;
  • Mukaisho, Ken-Ichi (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science) ;
  • Nakayama, Takahisa (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science) ;
  • Hattori, Takanori (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science) ;
  • Sugihara, Hiroyuki (Department of Pathology, Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science)
  • Published : 2015.03.09

Abstract

The fact that long-term use of proton pump inhibitors (PPIs) aggravates corpus atrophic gastritis in patients with Helicobacter pylori infection has been proven clinically and experimentally. Corpus atrophic gastritis is a known risk factor for gastric cancer. Therefore, gastric neoplasia might be associated with the long-term use of PPIs. One of the causes of worsening corpus atrophic gastritis, leading to the development of adenocarcinoma, might be bacterial overgrowth under conditions of hypochlorhydria. The production of potentially carcinogenic N-nitrosocompounds by nitrosating organisms under conditions of hypochlorhydria might be associated with carcinogenesis. Interactions between bile acids, pH, and H. pylori might also contribute to carcinogenicity, especially in patients with gastro-esophageal reflux disease (GERD). The concentration of soluble bile acids, which have bactericidal or chemorepellent properties toward H. pylori, in gastric contents is considerably higher in patients undergoing continuous PPI therapy than in healthy individuals with normal acid production. Under these circumstances, H. pylori might colonize the stomach body rather than the pyloric antrum. Hypergastrinemia induced by PPI administration might promote the development of gastric cancer. Because the main cause of corpus atrophic gastritis is H. pylori infection, and not PPI administration, H. pylori infection should be eradicated before starting long-term PPI therapy.

Keywords

Helicobacter pylori;proton pump inhibitors;gastric cancer;corpus atrophic gastritis;GERD;gatrin

References

  1. Andersson AF, Lindberg M, Jakobsson H, et al (2008). Comparative analysis of human gut microbiota by barcoded pyrosequencing. PLoS One, 3, 2836. https://doi.org/10.1371/journal.pone.0002836
  2. Bik EM, Eckburg PB, Gill SR, et al (2006). Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci USA, 103, 732-7. https://doi.org/10.1073/pnas.0506655103
  3. Correa P, Haenszel W, Cuello C, et al (1975). Archer M. A model for gastric cancer epidemiology. Lancet, 2, 58-9.
  4. Correa P (1984). Chronic gastritis as a cancer precursor. Scand J Gastroenterol Suppl, 104, 131-6.
  5. Correa P (1992). Human gastric carcinogenesis: a multistep and multifactorial process-- First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res, 52, 6735-40.
  6. Cover TL, Blaser MJ (2009). Helicobacter pylori in health and disease. Gastroenterology, 136, 1863-73. https://doi.org/10.1053/j.gastro.2009.01.073
  7. Dixon MF, Neville PM, Mapstone NP, et al (2001). Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux? Gut, 49, 359-63. https://doi.org/10.1136/gut.49.3.359
  8. Franco AT, Israel DA, Washington MK, et al (2005). Activation of beta-catenin by carcinogenic Helicobacter pylori. Proc. Natl Acad Sci USA, 102, 10646-51. https://doi.org/10.1073/pnas.0504927102
  9. Fox JG, Rogers AB, Ihrig M, et al (2003). Helicobacter pyloriassociated gastric cancer in INS-GAS mice is gender specific. Cancer Res, 63, 942-50.
  10. Fox JG, Kuipers EJ (2011). Long-term proton pump inhibitor administration, H pylori and gastric cancer: lessons from the gerbil. Gut, 60, 567-8. https://doi.org/10.1136/gut.2010.229286
  11. Garcia Rodriguez LA, Lagergren J, Lindblad M, et al (2006). Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK. Gut, 55, 1538-44. https://doi.org/10.1136/gut.2005.086579
  12. Geboes K, Dekker W, Mulder CJ, et al (2001). Long-term lansoprazole treatment for gastro-oesophageal reflux disease: clinical efficacy and influence on gastric mucosa. Aliment Pharmacol Ther, 15, 1819-26. https://doi.org/10.1046/j.1365-2036.2001.01105.x
  13. Graham DY, Opekun AR, Osato MS, et al (2004). Challenge model for Helicobacter pylori infection in human volunteers. Gut, 53, 1235-43. https://doi.org/10.1136/gut.2003.037499
  14. Hagiwara T, Mukaisho M, Ling ZQ, et al (2007). Rebamipide contributes to reducing adverse effects of long-term administration of omeprazole in rats. Dig Dis Sci, 52, 988-94. https://doi.org/10.1007/s10620-006-9415-7
  15. Hagiwara T, Mukaisho M, Nakayama T, et al (2011). Long-term proton pump inhibitor administration worsens atrophic corpus gastritis and promotes adenocarcinoma development in Mongolian gerbils infected with Helicobacter pylori. Gut, 60, 624-30. https://doi.org/10.1136/gut.2010.207662
  16. Hagiwara T, Mukaisho M, Nakayama T, et al (2012). Experimental strategies for induction of gastric adenocarcinomas under long-term proton pump inhibitor administration and Helicobacter pylori infection. Asian Pac J Cancer Prev, 13, 3005-6 https://doi.org/10.7314/APJCP.2012.13.6.3005
  17. Havu N (1986). Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion. Digestion, 35, 42-55. https://doi.org/10.1159/000199381
  18. Havu N, Mattsson H, Ekman L, et al (1990). Enterochromaffinlike cell carcinoids in the rat gastric mucosa following longterm administration of ranitidine. Digestion, 45, 189-95. https://doi.org/10.1159/000200245
  19. Hawkey CJ, Karrasch JA, Szczepanski L, et al (1998). Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group. N Engl J Med, 338, 727-34. https://doi.org/10.1056/NEJM199803123381105
  20. Hill M (1985). Normal and pathological microbial flora of the upper gastrointestinal tract. Scand J Gastroenterol Suppl, 111, 1-6.
  21. Honda S, Fujioka T, Tokieda M, et al (1998a). Gastric ulcer, atrophic gastritis, and intestinal metaplasia caused by Helicobacter pylori infection in Mongolian gerbils. Scand J Gastroenterol, 33, 454-60.
  22. Honda S, Fujioka T, Tokieda M, et al (1998b). Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res, 58, 4255-9.
  23. IARC Monographs on the Evaluation of Carcinogen risk to humans: some industrial chemicals, (1994) No. 60, Lyon: International Agency for Research on Cancer.
  24. Kuipers EJ, Pena AS, Kamp GV, et al (1993). Seroconversion for Helicobacter pylori. Lancet, 342, 328-31. https://doi.org/10.1016/0140-6736(93)91473-Y
  25. Kuipers EJ, Uyterlinde AM, Pena AS, et al (1995). Increase of Helicobacter pylori-associated corpus gastritis during acid suppressive therapy: implications for longterm safety. Am J Gastroenterol, 90, 1401-6.
  26. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al (1996). Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med, 334, 1018-22. https://doi.org/10.1056/NEJM199604183341603
  27. Lee A, Fox AJ, Otto G, et al (1990). A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology, 99, 1315-23. https://doi.org/10.1016/0016-5085(90)91156-Z
  28. Lee A, O'Rourke J, De Ungria MC, et al (1997). A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain. Gastroenterology, 112, 1386-97. https://doi.org/10.1016/S0016-5085(97)70155-0
  29. Li XX, Wong GL, To KF, et al (2009). Bacterial microbiota profiling in gastritis without Helicobacter pylori infection or non-steroidal anti-inflammatory drug use. PLoS One, 4, 7985. https://doi.org/10.1371/journal.pone.0007985
  30. Lofgren JL, Whary MT, Ge Z, et al (2011). Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia. Gastroenterology, 140, 210-20. https://doi.org/10.1053/j.gastro.2010.09.048
  31. Marshall BJ, Warren JR (1984). Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet, 1, 1311-15.
  32. Martinsen TC, Bergh K, Waldum HL (2005). Gastric juice: a barrier against infectious diseases. Basic Clin Pharmacol Toxicol, 96. 94-102. https://doi.org/10.1111/j.1742-7843.2005.pto960202.x
  33. Matsumoto S, Washizuka Y, Matsumoto Y, et al (1997). Induction of ulceration and severe gastritis in Mongolian gerbil by Helicobacter pylori infection. J Med Microbiol, 46, 391-7. https://doi.org/10.1099/00222615-46-5-391
  34. Mattsson H, Havu N, Brautigam J, et al (1991). Partial gastric corpectomy results in hypergastrinemia and development of gastric enterochromaffinlike-cell carcinoids in the rat. Gastroenterol, 100, 311-9. https://doi.org/10.1016/0016-5085(91)90197-S
  35. Meikle DD, Taylor KB, Truelove SC, et al (1976). Gastritis duodenitis, and circulating levels of gastrin in duodenal ulcer patients before and after vagotomy. Gut, 17, 719-28. https://doi.org/10.1136/gut.17.9.719
  36. Mukaisho K, Hagiwara T, Nakayama T, et al (2014). Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD. World J Gastroenterol, 20, 11962-5. https://doi.org/10.3748/wjg.v20.i34.11962
  37. Nair PP, Kritchenvski D (1971). The Bile Acids: Chemistry, Physiology and Metabolism. Chemistry. New York: Plenum Press, 1.
  38. Orlando LA, Lenard L, Orlando RC, et al (2007). Chronic hypergastrinemia: causes and consequences. Dig Dis Sci, 52, 2482-9. https://doi.org/10.1007/s10620-006-9419-3
  39. Polk DB, Peek Jr RM (2010). Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer, 10, 403-14. https://doi.org/10.1038/nrc2857
  40. Shafaghi A, Mansour-Ghanaei F, Joukar F, et al (2013). Serum gastrin and the pepsinogen I/II ratio as markers for diagnosis of premalignant gastric lesions. Asian Pac J Cancer Prev, 14, 3931-6. https://doi.org/10.7314/APJCP.2013.14.6.3931
  41. Stamp DH (2002). Three hypotheses linking bile to carcinogenesis in the gastrointestinal tract: certain bile salts have properties that may be used to complement chemotherapy. Med Hypotheses, 59, 398-405. https://doi.org/10.1016/S0306-9877(02)00125-1
  42. Sheh A, Fox JG (2013). The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis. Gut Microbes, 4, 505-31. https://doi.org/10.4161/gmic.26205
  43. Sordal O, Waldum H, Nordrum IS, et al (2013). The gastrin receptor antagonist netazepide (YF476) prevents oxyntic mucosal inflammation induced by Helicobacter pylori infection in Mongolian gerbils. Helicobacter, 18, 397-405. https://doi.org/10.1111/hel.12066
  44. Targownik LE, Metge CJ, Leung S, et al (2008). The relative efficacies of gastroprotective strategies in chronic users of nonsteroidal anti-inflammatory drugs. Gastroenterology. 134, 937-44. https://doi.org/10.1053/j.gastro.2008.01.010
  45. Tsukamoto H, Mizoshita T, Sasaki M, et al (2011). Longterm high-dose proton pump inhibitor administration to Helicobacter pylori-infected Mongolian gerbils enhances neuroendocrine tumor development in the glandular stomach. Asian Pac J Cancer Prev, 12, 1049-54.
  46. Uemura N, Okamoto S, Yamamoto S, et al (2001). Helicobacter pylori infection and the development of gastric cancer. Engl J Med. 345, 784-9. https://doi.org/10.1056/NEJMoa001999
  47. N. Wang TC, Fox JG (1998). Helicobacter pylori and gastric cancer: Koch's postulates fulfilled? Gastroenterol, 115, 780-3. https://doi.org/10.1016/S0016-5085(98)70159-3
  48. Wang TC, Dangler CA, Chen D, et al (2000). Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology, 118, 36-47. https://doi.org/10.1016/S0016-5085(00)70412-4
  49. Warren JR, Marshall BJ (1983). Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet, 1, 1273-5.
  50. Watanabe T, Tada M, Nagai H, et al (1998). S. Helicobacter pylori infection induces gastric cancer in Mongolian gerbils. Gastroenterol, 115, 642-8. https://doi.org/10.1016/S0016-5085(98)70143-X
  51. Watson SA, Grabowska AM, El-Zaatari M, et al (2006). Gastrin-active participant or bystander in gastric carcinogenesis? Nature Rev Cancer, 6, 936-46. https://doi.org/10.1038/nrc2014
  52. Worku ML, Karim QN, Spencer J, et al (2004). Chemotactic response of Helicobacter pylori to human plasma and bile. J Med Microbiol, 53, 807-11. https://doi.org/10.1099/jmm.0.45636-0
  53. Xu GP, Reed PI (1993). N-nitroso compounds in fresh gastric juice and their relation to intragastric pH and nitrite employing an improved analytical method. Carcinogenesis, 14, 2547-51. https://doi.org/10.1093/carcin/14.12.2547
  54. Yokota K, Kurebayashi Y, Takayama Y, et al (1991). Colonization of Helicobacter pylori in the gastric mucosa of Mongolian gerbils. Microbiol Immunol, 35, 475-80. https://doi.org/10.1111/j.1348-0421.1991.tb01577.x
  55. Ziebarth D, Spiegelhalder B, Bartsch H (1997). N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori. Carcinogenesis, 18, 383-9. https://doi.org/10.1093/carcin/18.2.383

Cited by

  1. Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids vol.6, pp.1664-302X, 2015, https://doi.org/10.3389/fmicb.2015.00412
  2. 26695 to Identify Potential Virulence Factors vol.14, pp.3, 2016, https://doi.org/10.5808/GI.2016.14.3.125
  3. infection in pathogenesis of gastric carcinoma vol.7, pp.1, 2016, https://doi.org/10.4291/wjgp.v7.i1.97
  4. Proton pump inhibitors: Risks of long-term use vol.32, pp.7, 2017, https://doi.org/10.1111/jgh.13737