Abstract
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 reviewH. pylori's contribution to the epidemiology and histopathology of both gastric cancer and peptic ulcer disease. Furthermore, we examine the host-pathogen relationship andH. pyloribiology 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 ofH. pyloriin other pathologies—some accepted, for example, MALT lymphoma, and others more controversial, for example, idiopathic thrombocytic purpura. More recently, intriguing suggestions thatH. pylorihas 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.
Highlights
We examine the host-pathogen relationship and H. pylori biology in context of these diseases, focusing on strain differences, virulence factors (CagA and vacuolating cytotoxin (VacA)), immune activation and the challenges posed by resistance to existing therapies
After a long history of discoveries on the pathology and bacterial colonization of the gastric mucosa starting in the beginning of the last century [1], 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 [1,2,3]
H. pylori expresses lipopolysaccharide (LPS) with a very low endotoxic and immunobiological activity compared to LPS of other Gram-negative bacteria [60] that can antagonize signaling mediated by the innate immune receptor, toll-like receptor 4 (TLR4) [61]
Summary
After a long history of discoveries on the pathology and bacterial colonization of the gastric mucosa starting in the beginning of the last century [1], 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 [1,2,3]. 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 (
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
