The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases.
Helicobacter pylori is the main cause of peptic ulceration, distal gastric adenocarcinoma, and gastric lymphoma. Only 15% of those colonized develop disease, and pathogenesis depends upon strain virulence, host genetic susceptibility, and environmental cofactors. Virulence factors include the cag pathogenicity island, which induces proinflammatory, pro-proliferative epithelial cell signaling; the cytotoxin VacA, which causes epithelial damage; and an adhesin, BabA. Host genetic polymorphisms that lead to high-level pro-inflammatory cytokine release in response to infection increase cancer risk. Pathogenesis is dependent upon inflammation, a Th-1 acquired immune response and hormonal changes including hypergastrinaemia. Antral-predominant inflammation leads to increased acid production from the uninflamed corpus and predisposes to duodenal ulceration; corpus-predominant gastritis leads to hypochlorhydria and predisposes to gastric ulceration and adenocarcinoma. Falling prevalence of H. pylori in developed countries has led to a falling incidence of associated diseases. However, whether there are disadvantages of an H. pylori-free stomach, for example increased risk of esosphageal adenocarcinoma, remains unclear.
Wolfson Digestive Diseases Centre and Institute of Infections, Immunity, and Inflammation, University of Nottingham, Nottingham NG7 2UH, United Kingdom. john.atherton@nottingham.ac.uk
John C
JC
Atherton
D000230:Adenocarcinoma / Q000382:microbiology / Q000473:pathology; D004381:Duodenal Ulcer / Q000382:microbiology / Q000473:pathology; D004942:Esophagitis, Peptic / Q000382:microbiology / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications* / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology; D013276:Stomach Ulcer / Q000382:microbiology / Q000473:pathology