Ironing out the role of H. pylori in gastric cancer


H. pylori is a bacteria that frequently causes gastric ulcers, is associated with iron deficiency, and is also a significant risk factor for gastric cancer. Noto et al. investigated the influence of iron on H. pylori-induced gastric cancer. Using a gerbil model of the disease, they found that low iron levels accelerated the development of cancerous lesions. The frames above are electron micrographs of H. pylori in gerbils fed a low-iron diet. Interestingly, H. pylori strains isolated from a human population at high risk for gastric cancer were more virulent and produced greater inflammation if they came from patients with low iron levels.

Published December 21, 2012, by Jillian Hurst

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Iron deficiency accelerates Helicobacter pylori–induced carcinogenesis in rodents and humans
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Published December 21, 2012
Citation Information: J Clin Invest. 2013;123(1):479-492. https://doi.org/10.1172/JCI64373.
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Research Article

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. pyloricag+ 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

Jennifer M. Noto, Jennifer A. Gaddy, Josephine Y. Lee, M. Blanca Piazuelo, David B. Friedman, Daniel C. Colvin, Judith Romero-Gallo, Giovanni Suarez, John Loh, James C. Slaughter, Shumin Tan, Douglas R. Morgan, Keith T. Wilson, Luis E. Bravo, Pelayo Correa, Timothy L. Cover, Manuel R. Amieva, Richard M. Peek Jr.

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