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.
Atherton
John C
JC
Wolfson Digestive Diseases Centre and Institute of Infections, Immunity, and Inflammation, University of Nottingham, Nottingham NG7 2UH, United Kingdom. john.atherton@nottingham.ac.uk
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