title: Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans.
abstract: Gastric adenocarcinoma is strongly associated with Helicobacter pylori infection; however, most infected persons never develop this malignancy. H. pylori strains harboring the cag pathogenicity island (cag+), which encodes CagA and a type IV secretion system (T4SS), induce more severe disease outcomes. H. pylori infection is also associated with iron deficiency, which similarly augments gastric cancer risk. To define the influence of iron deficiency on microbial virulence in gastric carcinogenesis, Mongolian gerbils were maintained on iron-depleted diets and infected with an oncogenic H. pylori cag+ strain. Iron depletion accelerated the development of H. pylori-induced premalignant and malignant lesions in a cagA-dependent manner. H. pylori strains harvested from iron-depleted gerbils or grown under iron-limiting conditions exhibited enhanced virulence and induction of inflammatory factors. Further, in a human population at high risk for gastric cancer, H. pylori strains isolated from patients with the lowest ferritin levels induced more robust proinflammatory responses compared with strains isolated from patients with the highest ferritin levels, irrespective of histologic status. These data demonstrate that iron deficiency enhances H. pylori virulence and represents a measurable biomarker to identify populations of infected persons at high risk for gastric cancer.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Noto
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gaddy
authors.forename: Josephine Y
authors.initials: JY
authors.lastname: Lee
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.forename: David B
authors.initials: DB
authors.lastname: Friedman
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Colvin
authors.forename: Judith
authors.initials: J
authors.lastname: Romero-Gallo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Suarez
authors.forename: John
authors.initials: J
authors.lastname: Loh
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.forename: Shumin
authors.initials: S
authors.lastname: Tan
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Morgan
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bravo
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Amieva
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000097:blood* / Q000235:genetics; D044404:Genomic Islands / Q000235:genetics; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000097:blood / Q000150:complications / Q000235:genetics / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D000090463:Iron Deficiencies; D008297:Male; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C080866:cagA protein, Helicobacter pylori; D005293:Ferritins