Neonatal co-infection with helicobacter species markedly accelerates the development of inflammation-associated colonic neoplasia in IL-10(-/-) mice

Helicobacter. 2007 Dec;12(6):598-604. doi: 10.1111/j.1523-5378.2007.00552.x.


Background: Inflammatory bowel disease (IBD) is hypothesized to represent an aberrant immune response against enteric bacteria that occurs in a genetically susceptible host. Humans and mice with IBD are at markedly increased risk for colonic neoplasia. However, the long lead time required before development of inflammation-associated colon neoplasia in commonly used murine models of IBD slows the development of effective chemopreventative therapies.

Materials and methods: Neonatal coinfection with Helicobacter typhlonius and Helicobacter rodentium was used to trigger the onset of IBD in mice deficient in the immunoregulatory cytokine interleukin (IL)-10. The severity of colon inflammation and incidence of neoplasia was determined histologically.

Results: IL-10(-/-) mice demonstrated early onset, severe colon inflammation following neonatal infection with H. typhlonius and H. rodentium. The incidence of inflammation-associated colon neoplasia was approximately 95% at a mean age of 21 +/- 2 weeks. Mutation of endoglin, an accessory receptor for TGF-beta, did not affect the severity of IBD or the incidence of neoplasia in this model.

Conclusions: The rapid onset of severe colon inflammation and multiple neoplastic lesions in the colons of IL-10(-/-) mice neonatally coinfected with H. typhlonius and H. rodentium makes this model well-suited for investigating the mechanisms involved in inflammation-associated colon cancer as well as its chemoprevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / complications
  • Colitis / genetics
  • Colitis / microbiology*
  • Colonic Neoplasms / complications
  • Colonic Neoplasms / microbiology*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Disease Progression
  • Endoglin
  • Genetic Predisposition to Disease
  • Helicobacter Infections / complications*
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / microbiology
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-10 / genetics*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation


  • Endoglin
  • Eng protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Interleukin-10