A Nobel Prize Pathogen
Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that colonises the stomach of approximately half the world's population. Its discovery by Barry Marshall and Robin Warren in 1982 — and Marshall's self-experimentation to prove it caused gastritis — earned the Nobel Prize in Physiology or Medicine in 2005. H. pylori is the primary cause of peptic ulcers (gastric and duodenal) and the strongest known risk factor for gastric adenocarcinoma and gastric MALT lymphoma. It is classified as a Group 1 carcinogen by the WHO's International Agency for Research on Cancer.
How It Survives
The stomach maintains a pH of 1.5 to 3.5 — an environment lethal to most bacteria. H. pylori survives by producing urease, an enzyme that converts urea into ammonia, creating a local alkaline microenvironment around the bacterium. It then uses its flagella to burrow into the gastric mucus layer, where it adheres to epithelial cells and establishes chronic infection that can persist for decades without treatment.
The Damage Pathway
H. pylori virulence depends heavily on strain genetics. Strains carrying the cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) are associated with more severe outcomes. CagA is injected into gastric epithelial cells via a type IV secretion system, where it disrupts cell signalling, promotes inflammation, and initiates the cascade from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately carcinoma — the Correa cascade. Not all infected individuals develop cancer; the lifetime risk is approximately 1 to 2 percent, modulated by bacterial strain, host genetics, diet, and co-infection with other gastric microbiota.
The Other Side of the Coin
Paradoxically, H. pylori prevalence has been declining globally — and this decline correlates with rising rates of gastro-oesophageal reflux disease (GORD), Barrett's oesophagus, and oesophageal adenocarcinoma. H. pylori-induced gastric atrophy reduces acid production, which may have been protective against acid-reflux conditions. Additionally, some epidemiological studies suggest inverse associations between H. pylori infection and allergic diseases (asthma, eczema, allergic rhinitis), possibly through immune modulation. This dual nature — pathogenic in the stomach but potentially protective elsewhere — makes H. pylori one of the most complex human-microbe relationships.
Testing and Eradication
Non-invasive testing includes the urea breath test (sensitivity and specificity both exceeding 95%), stool antigen test, and serology (which cannot distinguish active from past infection). Eradication typically requires triple or quadruple therapy combining a PPI with antibiotics (clarithromycin, amoxicillin, metronidazole, or bismuth-based regimens). Rising antibiotic resistance — particularly to clarithromycin — is a growing concern, prompting susceptibility-guided therapy in regions with resistance rates exceeding 15 percent.