Physicians have described and treated patients suffering from epigastric pain and gastrointestinal bleeding since time immemorial. In 1793, Matthew Baillie published one of the earliest illustrations of stomach ulcers in The Morbid Anatomy of Some of the Most Important Parts of the Human Body. In France, in 1835, Jean Cruveilhier distinguished benign peptic ulcers from cancer. These ulcers remained uncommon before 1850 but exploded between 1850 and 1950 into the most common cause of admission to medical and surgical hospital wards.

Treatment was long guided by Karl Schwarz’s 1910 dictum, “no acid, no ulcer,” and relied mainly on antacids and bland diets. In 1915, Dr. Bertram Sippy introduced the “Sippy” diet, which required patients to take hourly mixtures of milk and cream with alkaline powders. Although these measures provided temporary relief, they generally did not heal ulcers. Around 1976, they were supplemented by the H2-receptor antagonists cimetidine and ranitidine, after which surgery became less common. Another breakthrough came in 1982, when Australians Barry Marshall and Robin Warren isolated a spiral bacterium from patients with chronic gastritis. Initially called Campylobacter pyloridis, it was later renamed Helicobacter pylori.

To address initial skepticism, Marshall famously ingested a culture of H. pylori in 1984; developed acute gastritis; documented it endoscopically; and cured it with antibiotics, proving that it was not simply an innocent bystander in an acid-damaged stomach but a primary causative agent. For their discovery, Marshall and Warren were awarded the Nobel Prize in Physiology or Medicine in 2005.

We now know that H. pylori is a urease-producing bacterium uniquely adapted to survive in the acidic gastric mucus layer, where it hydrolyzes urea into ammonia and carbon dioxide. Ammonia is toxic to gastric epithelial cells. The H. pylori flagella enable the bacteria to burrow through the viscous mucus layer and adhere to the gastric epithelial cells, facilitating chronic colonization and triggering a sustained host immune response that includes neutrophil and mononuclear cell infiltration, cytokine release, and progressive epithelial damage. Thus, peptic ulcer disease came to be understood primarily as an infectious condition, with most cases in developed countries caused by H. pylori.

Meanwhile, epidemiologists had noted that the actual incidence of peptic ulcers had already begun to decline by 1950, quite a few years before the first drug treatments could have had a significant impact. They eventually settled on an explanation that initially peptic ulcers had become frequent because deteriorating social conditions were favoring the spread of H. pylori at an early age. A century later, however, in the 1950s, social conditions had improved and favored the spread of the bacterium to an older age group, where its effects would be less harmful.

The decline in H.pylori infection, however, has not occurred uniformly. Infection with H. pylori remains more common in less-developed regions, where childhood crowding and infection persist. Elsewhere, in more developed parts of the world, peptic ulcers have become a more frequent complication of the increased use of NSAID drugs, especially in the elderly. Ulcers may also occur without demonstrable H. pylori infection in various infections, undisclosed medication use, severe systemic illness, ischemia, Crohn’s disease, or rare hypersecretory disorders. As a specific epidemiological phenomenon, H. pylori may therefore have become less important than in its days of glory.