High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice

A high-salt diet in humans and experimental animals is known to cause gastr itis, has been associated with a high risk of atrophic gastritis, and is co nsidered a gastric tumor promoter. In laboratory rodents, salt is known to cause gastritis, and when coadministered, it promotes the carcinogenic effe cts of known gastric carcinogens. Because Helicobacter pylori has been asso ciated with a progression from gastritis to gastric cancer, we designed a s tudy to determine whether excessive dietary NaCl would have an effect on co lonization and gastritis in the mouse model of H. pylori infection. Seventy -two, 8-week-old female C57BL/6 mice were infected with H. pylori strain Sy dney, and 36 control mice were dosed with vehicle only, One-half of the inf ected and control mice were fed a high-salt diet (7.5% verses 0.25%) for 2 weeks prior to dosing and throughout the entire experiment. Twelve infected and 6 control animals from the high-salt and normal diet groups were eutha nized at 4, 8, and 16 weeks. At 8 and 16 weeks postinfection (WPI), the col ony-forming units per gram of tissue were significantly higher (P < 0.05) i n the corpus and antrum of animals in the high-salt diet group compared wit h those on the normal diet. Quantitative urease was significantly higher (P < 0.05) at 4 and 8 WPI in the corpus and antrum of animals on the high-sal t diet when compared with controls, At 16 WPI, mice in both the normal and the high-salt diet groups developed moderate to marked atrophic gastritis o f the corpus in response to H. pylori infection. However, the gastric pits of the corpus mucosa in mice on the high-salt diet were elongated and colon ized by H. pylori more frequently than those in mice on the normal diet. Th e high-salt diet was also associated with a significant increase in prolife ration in the proximal corpus and antrum and a multifocal reduction in pari etal cell numbers in the proximal corpus, resulting in the elongation of ga stric pits, We conclude that excessive NaCl intake enhances H, pylori colon ization in mice and in humans and that chronic salt intake may exacerbate g astritis by increasing H, pylori colonization, Furthermore, elevated salt i ntake may potentiate H, pylori-associated carcinogenesis by inducing prolif eration, pit cell hyperplasia, and glandular atrophy.