Dyspepsia has been recognized as a symptom complex since antiquity, but its mechanisms began to be understood only after peptic ulcer disease became a recognizable clinicopathologic entity. The isolation of Helicobacter pylori by Warren and Marshall in 1982 established that most chronic gastritis and peptic ulcer disease are infectious and curable.^[1] This discovery led to the classification of H. pylori as a group 1 human carcinogen in 1994,^[2] the noninvasive “test-and-treat” strategy for uninvestigated dyspepsia,^[3] and the current framing of H. pylori eradication as a gastric cancer prevention strategy.^[4]

• In 1799, Matthew Baillie described the pathology of gastric ulcer; the development of barium contrast radiography by Walter Cannon in 1897 later allowed peptic ulcer disease to be recognized in living patients and correlated with symptoms.
• In 1916, Walter Alvarez (Mayo Clinic) applied the term “functional dyspepsia” to patients with ulcer-like symptoms and a normal X-ray. This concept is the forerunner of the current definition of functional dyspepsia as dyspepsia without organic pathology at upper gastrointestinal endoscopy.^[3]

• In 1889, Walery Jaworski (Jagiellonian University, Kraków) described spiral-shaped organisms in human gastric washings; similar organisms were later observed in animals by Bizzozero, but the findings were not taken seriously because the stomach was presumed sterile.^[5]
• In the late 1970s, J. Robin Warren, a pathologist in Perth, Australia, observed spiral bacteria overlying the gastric mucosa, predominantly over inflamed tissue.^[5]
• In 1982, Warren and Barry Marshall cultured the organism from 11 patients with gastritis and demonstrated a strong association between its presence and gastric mucosal inflammation; individuals without gastritis did not harbor the organism.^[5] Their 1984 report proposed a causal role in gastritis and peptic ulcer, challenging the prevailing view that ulcers were driven mainly by stress and diet.^[1]
• The organism was initially named Campylobacter pyloridis, then Campylobacter pylori, and finally Helicobacter pylori when its morphologic, structural, and genetic features justified a new genus.^[5]
• Marshall ingested a culture of the organism and developed acute gastritis, fulfilling Koch’s postulates for H. pylori-associated gastritis; the experiment was published in 1985.^[6]
• In 1993, Covacci and colleagues characterized the CagA gene product, an immunodominant antigen associated with cytotoxicity and duodenal ulcer, the first molecular evidence that strain-specific virulence factors influence disease risk.^[7]
• In 1997, the complete H. pylori genome was sequenced, accelerating identification of virulence determinants.^[8]
• In 2005, Warren and Marshall were awarded the Nobel Prize in Physiology or Medicine for the discovery of H. pylori and its role in gastritis and peptic ulcer disease.^[9]

• In 1992, Pelayo Correa summarized the multistep model of intestinal-type gastric carcinogenesis: chronic gastritis → atrophy → intestinal metaplasia → dysplasia, with the initial stages linked to H. pylori infection and high salt intake.^[10]
• In 1991, Wotherspoon and colleagues reported H. pylori-associated gastritis in patients with primary gastric B-cell lymphoma.^[11] In 1993, the same group showed regression of low-grade gastric MALT lymphoma after H. pylori eradication in 5 of 6 patients, the first demonstration that a malignancy could respond to antibiotic therapy alone.^[12]
• In 1994, Parsonnet and colleagues confirmed a prospective association between H. pylori infection and gastric non-Hodgkin lymphoma.^[13]
• In 1994, the International Agency for Research on Cancer classified H. pylori infection as carcinogenic to humans (group 1).^[2]

• In 2002, the Maastricht 2-2000 Consensus Report endorsed a noninvasive “test-and-treat” strategy for H. pylori in younger patients with uninvestigated dyspepsia.^[14]
• In 2001, Chan and colleagues showed that in H. pylori-infected patients with prior ulcer bleeding, eradication alone was comparable to omeprazole in preventing recurrent bleeding with low-dose aspirin, whereas omeprazole was superior for patients taking naproxen.^[15]
• In 2017, the joint ACG/CAG dyspepsia guideline recommended upper endoscopy for patients aged ≥60 years and noninvasive H. pylori testing with treatment if positive for patients <60 years, with eradication also offered to infected patients with functional dyspepsia.^[3]
• In 2024, the ACG H. pylori guideline designated 14-day bismuth quadruple therapy as the preferred first-line regimen when antibiotic susceptibility is unknown and emphasized universal post-treatment test-of-cure.^[16]
• In 2025, an updated meta-analysis of randomized and observational studies found that eradication therapy reduces gastric cancer incidence in healthy H. pylori-positive individuals and in patients after endoscopic mucosal resection of gastric neoplasia, and reduces gastric cancer mortality (RR 0.78 in randomized trials of healthy individuals).^[17]
• In 2025, the Taipei Global Consensus II concluded that H. pylori eradication is an effective gastric cancer prevention strategy that should be offered to all infected adults, with the greatest risk reduction when performed before premalignant changes develop.^[4]