Pathobiology of Helicobacter pylori–Induced Gastric Cancer

Abstract

Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism.

Prevalence of Helicobacter Pylori Among Asymptomatic Populations in Sana'a, Yemen

“…Over 80% of individuals infected with the bacterium are asymptomatic, and it may play an important role in the natural stomach ecology 1 . More than 50% of the world's populations have H. pylori in their upper gastrointestinal tract 2 . Infection is more common in developing countries than Western countries 3 .…”

In Vivo Analysis of the Viable Microbiota and Helicobacter pylori Transcriptome in Gastric Infection and Early Stages of Carcinogenesis

“…It is well established that atrophy of the corpus mucosa, leading to decreased acid secretion, is highly associated with GC development. How the chronic infection and inflammation lead to cancer in some individuals but leave the majority without symptoms is still not outlined but is thought to depend on a combination of host susceptibility, environmental factors, and bacterial pathogenicity (14).…”

The synergy of Helicobacter pylori and lipid metabolic disorders in induction of Th17-related cytokines in human gastric cancer

“…[1,2] The overall 5-year survival rate of GC patients is only between 15 to 35%. [3] Epidemiological studies show that persistent Helicobacter pylori (H. pylori) infection accounts for approximate 75% of confound risk factors for GC.…”

“…pylori, a gram-negative spiral-shaped pathogenic bacterium, specifically colonizes and induces damage to the gastric epithelium leading to chronic gastritis, ulcers and even cancer. [2,7,8] Considerable studies have demonstrated that a mixed response of Th1 and Th17 cells plays a critical role in H. pylori-induced inflammatory gastric diseases and cancer. [9,10] The phenotypes of T helper subsets are determined by the local cytokine milieu and their lineage-specific transcription factors.…”