With the momentous discovery in the 1980's that a bacterium, Helicobacter pylori, can cause peptic ulcer disease and gastric cancer, antibiotic therapies and prophylactic measures have been successful, only in part, in reducing the global burden of these diseases. To date, ~700,000 deaths worldwide are still attributable annually to gastric cancer alone. Here, we review H. pylori's contribution to the epidemiology and histopathology of both gastric cancer and peptic ulcer disease. Furthermore, we examine the host-pathogen relationship and H. pylori biology in context of these diseases, focusing on strain differences, virulence factors (CagA and VacA), immune activation and the challenges posed by resistance to existing therapies. We consider also the important role of host-genetic variants, for example, in inflammatory response genes, in determining infection outcome and the role of H. pylori in other pathologies—some accepted, for example, MALT lymphoma, and others more controversial, for example, idiopathic thrombocytic purpura. More recently, intriguing suggestions that H. pylori has protective effects in GERD and autoimmune diseases, such as asthma, have gained momentum. Therefore, we consider the basis for these suggestions and discuss the potential impact for future therapeutic rationales.
After a long history of discoveries on the pathology and bacterial colonization of the gastric mucosa starting in the beginning of the last century, the gastroenterologist Barry Marshall and the pathologist Robin Warren, in the 1980’s, fulfilled Koch’s postulates for the association between gastritis and the human gastric pathogen Helicobacter pylori. This decisive demonstration substantially changed our views of the microbiology and pathology of the human stomach and resulted in Marshall and Warren receiving the 2005 Nobel Prize in Physiology and Medicine. Marshall and Warren’s discovery founded the concept that infection with H. pylori , and not (if at all, very indirectly) stress, can lead to a variety of upper gastrointestinal disorders (Figure 1) such as gastric inflammation (gastritis), peptic ulcer disease (10%–20%), distal gastric adenocarcinoma (1%-2%), and gastric mucosal-associated lymphoid tissue (MALT) lymphoma (<1%). These insights not only dramatically improved the management and therapy of gastric diseases but also provided an invaluable key for deeper insights into the pathogenesis of chronic infections. Moreover, during the past 20 years of research, the initially tentative association between persistent H.