Helicobacter pylori

GASTROENTEROLOGY 2008;134:306 –323

REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY
Wafik El-Diery and David Metz, Section Editors

Host-Bacterial Interactions in Helicobacter pylori Infection
MANUEL R. AMIEVA* and EMAD M. EL–OMAR‡
*Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, and ‡Department of Medicine and Therapeutics, AberdeenUniversity, Aberdeen, Scotland

Helicobacter pylori are spiral-shaped gram-negative bacteria with polar flagella that live near the surface of the human gastric mucosa. They have evolved intricate mechanisms to avoid the bactericidal acid in the gastric lumen and to survive near, to attach to, and to communicate with the human gastric epithelium and host immune system. This interaction sometimesresults in severe gastric pathology. H pylori infection is the strongest known risk factor for the development of gastroduodenal ulcers, with infection being present in 60%– 80% of gastric and 95% of duodenal ulcers.1 H pylori is also the first bacterium to be classified as a definite carcinogen by the World Health Organization’s International Agency for Research on Cancer because of its epidemiologicrelationship to gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma.2 In the last 25 years, since H pylori was first described and cultured, a complete paradigm shift has occurred in our clinical approach to these gastric diseases, and more than 20,000 scientific publications have appeared on the subject. From the medical point of view, H pylori is a formidable pathogenresponsible for much morbidity and mortality worldwide. However, H pylori infection occurs in approximately half of the world population, with disease being an exception rather than the rule. Understanding how this organism interacts with its host is essential for formulating an intelligent strategy for dealing with its most important clinical consequences. This review offers an insight into Hpylori host-bacterial interactions. elicobacter pylori infection is usually acquired early in childhood and lasts for a lifetime, and the majority of those infected (80%–90%) will carry and transmit H pylori without any symptoms of disease. In many ways, H pylori can be defined as a commensal and not a pathogen, making it difficult to determine who should be treated to prevent serious sequelae.3 Manyclinical and basic re-

search studies have been undertaken to define what makes H pylori a pathogen. It is now clear that both bacterial virulence factors and host susceptibility play a role. However, as investigators explore the intricate relationship between H pylori and the gastric mucosa at the cellular and molecular level, we find that the pathogenesis of H pylori is much more complex thansimply defining how it “damages” the stomach. In this review, we will discuss recent findings and concepts underlying the “virulence” mechanisms of H pylori pathogenesis but discuss them within the context of their known biologic properties, their role in the bacterial life cycle, and what these virulence factors have told us about the biology of the human stomach. We will also discuss how host riskfactors for disease illustrate biologic principles of the function of the gastric mucosa that were previously unrecognized.

Bacterial Factors Transmission and Entry
The very large number of people colonized throughout the world suggests that H pylori evolved a very robust strategy of transmission. However, our understanding of how H pylori infections are acquired and which bacterial factors areinvolved in transmission is limited. Unlike many organisms that have free-living forms in environmental reservoirs and unlike those that can infect many different animal and plant species, natural H pylori infection is restricted to humans and closely related primates. (Other species of gastric Helicobacters have been described in many other mammals ranging from cheetahs to polar bears and...