Elder ages decreases the susceptibility for Helicobacter pylori infection in an animal model

Helicobacter pylori의 감수성과 숙주 연령과의 상관성 연구

  • Lee, Jin-Uk (College of Medicine, Seoul National University) ;
  • Kim, Seung-Hee (College of Medicine, Seoul National University) ;
  • Park, Tan-Woo (College of Life Science and Natural Resources, Wonkwang University) ;
  • Kim, Okjin (College of Life Science and Natural Resources, Wonkwang University)
  • 이진욱 (서울대학교 의과대학 실험동물학교실) ;
  • 김승희 (서울대학교 의과대학 실험동물학교실) ;
  • 박탄우 (원광대학교 생명자원과학대학 동물질병연구실) ;
  • 김옥진 (원광대학교 생명자원과학대학 동물질병연구실)
  • Accepted : 2006.09.19
  • Published : 2007.03.30


Helicobacter pylori (H. pylori) is an important bacterial pathogen that causes chronic gastritisand is associated with gastroduodenal ulcer disease, adenocarcinoma of the distal stomach, and gastricH. pylori infection associated with host agehave not been well-defined in human. To evaluate the difference in host susceptibility to infection in relationto age of acquisition of H. pylori infection, we designed an experiment involving inoculation of H. pyloriATC 43504 at different ages of Mongolian gerbils. H. pylori was inoculated at 5 weeks and 18 monthsof age, as representatives of early and late infection, respectively. Animals were sacrificed 1 week and 4weeks after challenge, and the stomach was removed from each animal for bacterial culture, histologicalexamination, and polymerase chain reaction test. 5 week-old gerbils revealed infection andmaintained continuously its infection until 4 weeks. However, old gerbils did not maintained H. pyloriinfection. These data suggest the insusceptibility of H. pylori in old Mongolian gerbils and the importanceof animal ages for successful animal experimental infection. Also, the results demonstrated that earlyinfection of H. pylori increases its host susceptibility, as compared to the case with later infection, possiblybecause of differences in host gastric mucosal factors and imunologic responses.


Supported by : 한국학술진흥재단


  1. Fox JG, Rogers AB, Ihrig M, Taylor NS, Whary MT, Dockray G, Varro A, Wang TC. Helicobacter pylori-associated gastric cancer in INS-GAS mice is gender specific. Cancer Res 2003, 63, 942-950
  2. Hirayama F, Takagi S, Yokiyama Y, Iwao E, Ikeda Y. Establishment of gastric Helicobacter pylori infection in Mongolian gerbils. J Gastroenterol 1996, 31, 24-28 https://doi.org/10.1007/BF01211183
  3. International Agency for Research on Cancerqb. Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum 1994. 61, 1-241
  4. Lee J, Kim O. NSAID administration preceding Helicobacter pylori inoculationgastrointestinal damage. Korean J Lab Anim Sci 2004, 20, 385-390
  5. Newell DG. Virulence factors of Helicobacter pylori. Scand J Gastroenterol Suppl 1991, 187, 31-38
  6. Spiegelhalder C, Gerstenecker B, Kerstem A, Schiltz E, Kist M. Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. Infect Immun 1993, 61, 5315-5325
  7. Xiang Z, Censini S, Bayeli PF, Telford J, Figura N, Rppuoli R, Covacci A. Analysis of expression of cagA and vacA virulence factor in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that cagA is not necessary for expression of the vacuolating cytotoxin. Infect Immun 1995, 63, 94-98
  8. Bergin IL, Sheppard BJ, Fox JG. Helicobacter pylori infection and high dietary salt independently induce atrophic gastritis and intestinal metaplasia in commercially available outbred Mongolian gerbils. Dig Dis Sci 2003, 48, 475-485 https://doi.org/10.1023/A:1022524313355
  9. Eaton KA, Morgan DR, Krakowks S. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 1991, 59, 2470-2475
  10. Takagi, K, Okabe S. The effects of drugs on the production and recovery processes of the stress ulcer. Jpn J Pharmacol 1968, 18, 9-18 https://doi.org/10.1254/jjp.18.9
  11. Figura N, Guglielmetti P, Rossolini A, Barberi A, Cusi G, Musmanno RA, Russi M, Quaranta S. Cytotoxin production by Campylobacter pylori strains isolated from patients with chronic gastritis only. J Clin Microbiol 1989, 27, 225-226
  12. Tummuru MKR, Cover TL, Blaer MJ. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence for linkage to cytotoxin production. Infect Immun 1993, 61, 1799-1809
  13. Rothenbacher D, Inceoglu J, Bode G, Brenner H. Aquisition of Helicobacter pylori infection in a highrisk population occurs within the first 2 years of life. J Pediatr 2000, 136, 744-748 https://doi.org/10.1067/mpd.2000.105367
  14. Marshall BJ. The future of Helicobacter pylori eradication: a personal perspective. Aliment Pharmacol Ther 1997, 1 Suppl, 109-115
  15. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastric and peptic ulceration. Lancet 1984, 1, 1311-1315
  16. Honda S, Fujioka T, Tokieda M, Satoh R, Nishizono A, Nasu M. Development of Helicobacter pylori induced-gastric carcinoma in Mongolian gerbils. Cancer Res 1998, 58, 4255-4259
  17. Lee S-H, Lim CY, Lee K-H, Yeo S-J, Kim B-J, Kim S-J, Cho M-J, Rhee K-H, Kook Y-H. rpoB Gene analysis of Helicobacter pylori. J Korean Soc Microbiol 1999, 34, 401-408
  18. Yamamoto N, Sakagami T, Fukuda Y, Koizuka H, Hori K, Sawada Y, Hikasa Y, Tanida N, Shimoyama T. Influence of Helicobacter pylori infection on development of stress-induced gastric mucosal injury. J Gastroenterol. 2000, 35, 332-40 https://doi.org/10.1007/s005350050357
  19. Ohkusa T, Okayasu I, Miwa H, Ohtaka K, Endo S, Sato N. Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils. Gut 2003, 52, 797-803 https://doi.org/10.1136/gut.52.6.797
  20. Luzza F, Parrello T, Sebkova L. Expression of proinflammatory and Th1 but not Th2 cytokines is enhanced in gastric mucosa of Helicobacter pylori infected children. Digest Liver Dis 2001, 33, 14-20 https://doi.org/10.1016/S1590-8658(01)80130-4
  21. Minoura T, Kato S, Otsu S, Kodama M, Fujioka T, Linuma K, Nishizono A. Influence of age and duration of infection on bacterial load and immune responses to Helicobacter pylori infection in a murine model. Clin Experim Immunol 2005, 139, 43-47 https://doi.org/10.1111/j.1365-2249.2005.02658.x
  22. Hahm KB, Lee KM, Kim YB, Han SU, Kim MW. Animal models of Helicobacter pylori infection. Korean J Gastroenterol 2001, 37, 399-405
  23. Court M, Robinson PA, Dixon MF, Jeremy AH, Crabtee JE. The effect of gender on Helicobacter felismediated gastritis, epithelial cell proliferation, and apoptosis in the mouse model. J Pathol 2003, 201, 303-311 https://doi.org/10.1002/path.1422
  24. Hansson LE, Nyren O, Hsing AW, Bergstrom R, Josefsson S, Chow WH, Fraumeni JF, Adami HO. The risk of stomach cancer in patients with gastric or duodenal ulcer disease. N Engl J Med 1996, 335, 242-249 https://doi.org/10.1056/NEJM199607253350404
  25. Lee J, Kim O. Ethanol model in Mongolian gerbil for in vivo comparison of pathogenicity of Helicobacter pylori strain. Korean J Lab Anim Sci 2004, 20, 159-164