High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis

Abstract

Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pyloriinduced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA ؉ H. pylori strain or an isogenic cagA mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/highsalt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the cagA mutant strain (P < 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1␤ (IL-1␤), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the in vitro results, we detected increased cagA transcription in vivo in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the cagA mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of cagA ؉ H. pylori strains.

Hepcidin as a Major Component of Renal Antibacterial Defenses against Uropathogenic Escherichia coli

“…Indeed, UPEC differs from Helicobacter by the high degree of virulence. 38 And consistent with the influence of the host environment are the results from Gaddy et al 39 showing in gerbils that a high-salt diet led to reverse from induction to repression the effect of H. pylori on hepcidin expression. This observation may also explain our results with UPEC UTI because the kidneys are the exclusive desalting sites with high osmolarity of urine and of the renal medulla counterpart.…”

The gastric microbial community,Helicobacter pyloricolonization, and disease

“…To date the emphasis has been largely on bacterial virulence factors, host genetics, and environmental influences, particularly diet. [5][6][7] But with the recent recognition that the stomach is also colonized by other bacteria, another potential determinant of the outcome of H. pylori infection is the composition or structure of bacterial communities in the stomach, either at the time of exposure or over the course of infection (Fig. 1).…”

Dynamic Expression of the BabA Adhesin and Its BabB Paralog during Helicobacter pylori Infection in Rhesus Macaques

“…Understanding how H. pylori sometimes leads to clinical disease versus asymptomatic infection, or perhaps even mutualism (2), is one of the leading challenges in the field. Emerging evidence suggests the importance of host and bacterial genetics (1), and their interaction (3), as well as dietary (4,5) and other environmental variables, including the gastric microbiota (6). Among the bacterial virulence factors found more commonly in strains isolated from patients with clinical disease, the best studied is the cytotoxin-associated gene pathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS) that is essential for injection of the CagA bacterial oncoprotein (7,8).…”