Helicobacter pylori but not high salt induces gastric intraepithelial neoplasia in B6129 mice.

Helicobacter pylori is responsible for most human stomach cancers. Gastric cancer also is overrepresented in populations consuming high-salt diets. Attempts to test the hypothesis that high salt promotes H. pylori carcinogenesis have been hindered by the lack of a wild-type mouse model. Based on pilot observations of unexpectedly early gastric adenocarcinoma in C57BL/6 x 129S6/SvEv (B6129) mice infected with Helicobacter felis, we conducted a study to characterize H. pylori infection in these mice and to determine whether high salt promotes tumorigenesis. Male and female mice were gavaged with H. pylori Sydney strain-1 or vehicle only and divided into four groups based on infection status and maintenance on a basal (0.25%) or high (7.5%) salt diet. In uninfected mice, the high-salt diet enhanced proliferation and marginally increased parietal cell mucous metaplasia with oxyntic atrophy. Lesions in H. pylori infected mice without regard to diet or gender were of equivalent severity and characterized by progressive gastritis, oxyntic atrophy, hyperplasia, intestinal metaplasia, and dysplasia. Infected mice on the high-salt diet exhibited a shift in antimicrobial humoral immunity from a Th1 to a Th2 pattern, accompanied by significantly higher colonization and a qualitative increase in infiltrating eosinophils. No mice developed anti-parietal cell antibodies suggestive of autoimmune gastritis. At 15 months of age infected mice in both dietary cohorts exhibited high-grade dysplasia consistent with gastric intraepithelial neoplasia. In summary, we report for the first time H. pylori-induced gastric intraepithelial neoplasia in a wild-type mouse model and show no additive effect of high-salt ingestion on tumor progression.