title: 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. pylori-induced 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/high-salt-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 1β (IL-1β), 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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gaddy
authors.forename: Jana N
authors.initials: JN
authors.lastname: Radin
authors.forename: John T
authors.initials: JT
authors.lastname: Loh
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Holly M Scott
authors.initials: HM
authors.lastname: Algood
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
mesh_terms: D000126:Achlorhydria; D000230:Adenocarcinoma / Q000209:etiology*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D005849:Gerbillinae; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000633:toxicity*; D013270:Stomach / Q000737:chemistry / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D053583:Interleukin-1beta; D017673:Sodium Chloride, Dietary; C080866:cagA protein, Helicobacter pylori; D017506:H(+)-K(+)-Exchanging ATPase