Helicobacter felis-associated gastric pathology in gnotobiotic mice (46.8)

Abstract

Human gastric infection with Helicobacter pylori is associated with pathologic consequences, such as gastritis, dysplasia, and adenocarcinoma. This led to the classification of H. pylori as a type-1 carcinogen, but the role of additional non-helicobacter factors in the disease is unclear. In this study we utilized three models in C57BL/6(B6) mice to evaluate the role of gastric microbiota in H. felis disease development: germfree/gnotobiotic(B6.GB), colonized with Altered Schaedler Flora®(B6.ASF), and specific pathogen free model(B6.SPF). Despite similar histological changes over 24 weeks of infection, bacterial colonization of the three groups was different. While B6.GB and B6.ASF mice did not eradicate the helicobacter, the B6.SPF mice cleared it and acquired Lactobacillus spp, indicating that H. felis is sufficient to cause a dysplastic phenotype but alone is not causing histological damage seen in the B6.SPF mice. Over 24 weeks, IL-17 transcription decreased significantly in the B6.SPF and B6.ASF, whereas in B6.GB mice continued to be upregulated. Additionally, B6.SPF mice had very high IgG2c, while in the other two groups, IgG1 was dominant. This data suggests that though H. felis is sufficient to cause gastric inflammation, bacterial clearance is mediated not only by a CD4+ response, but also by other bacteria taking advantage of the gastric environment that has been established by the helicobacter infection.