Male Syrian Hamsters Experimentally Infected with Helicobacter spp. of the H. bilis Cluster Develop MALT-Associated Gastrointestinal Lymphomas

Helicobacter. 2016 Jun;21(3):201-17. doi: 10.1111/hel.12265. Epub 2015 Sep 8.

Abstract

Background: Aged hamsters naturally infected with novel Helicobacter spp. classified in the H. bilis cluster develop hepatobiliary lesions and typhlocolitis.

Methods: To determine whether enterohepatic H. spp. contribute to disease, Helicobacter-free hamsters were experimentally infected with H. spp. after suppression of intestinal bacteria by tetracycline treatment of dams and pups. After antibiotic withdrawal, weanlings were gavaged with four H. bilis-like Helicobacter spp. isolated from hamsters or H. bilis ATCC 43879 isolated from human feces and compared to controls (n = 7 per group).

Results: Helicobacter bilis 43879-dosed hamsters were necropsied at 33 weeks postinfection (WPI) due to the lack of detectable infection by fecal PCR; at necropsy, 5 of 7 were weakly PCR positive but lacked intestinal lesions. The remaining hamsters were maintained for ~95 WPI; chronic H. spp. infection in hamsters (6/7) was confirmed by PCR, bacterial culture, fluorescent in situ hybridization, and ELISA. Hamsters had mild-to-moderate typhlitis, and three of the male H. spp.-infected hamsters developed small intestinal lymphoma, in contrast to one control. Of the three lymphomas in H. spp.-infected hamsters, one was a focal ileal mucosa-associated lymphoid tissue (MALT) B-cell lymphoma, while the other two were multicentric small intestinal large B-cell lymphomas involving both the MALT and extra-MALT mucosal sites with lymphoepithelial lesions. The lymphoma in the control hamster was a diffuse small intestinal lymphoma with a mixed population of T and B cells.

Conclusions: Results suggest persistent H. spp. infection may augment risk for gastrointestinal MALT origin lymphomas. This model is consistent with H. pylori/heilmannii-associated MALT lymphoma in humans and could be further utilized to investigate the mechanisms of intestinal lymphoma development.

Keywords: Helicobacter; hamster; mucosa-associated lymphoid tissue lymphoma.

MeSH terms

  • Age Factors
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / blood
  • Cecum / pathology
  • Colon / pathology
  • Cricetinae
  • Disease Models, Animal
  • Female
  • Gastrointestinal Diseases / microbiology*
  • Helicobacter / immunology
  • Helicobacter / pathogenicity*
  • Helicobacter Infections / complications*
  • Helicobacter Infections / microbiology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liver / pathology
  • Lymphoma, B-Cell, Marginal Zone / microbiology*
  • Male
  • Mesocricetus
  • Specific Pathogen-Free Organisms

Substances

  • Anti-Bacterial Agents
  • Antibodies, Bacterial