By Dillon Lim - Medicine Student @ Brasenose College, Oxford
Peptic ulcers are breaks in the gastric or duodenal epithelium that present with symptoms of a burning ache in the abdomen, which worsens on an empty stomach, often with nausea, burping (eructation) and bloating. It was once thought that peptic ulcers were simply caused by lifestyle factors, most popularly stress. However, thanks to the revolutionary work of Barry Marshall and Robin Warren (the 2005 Nobel Laureates in Physiology or Medicine), we now know that the vast majority of peptic ulcers are in fact caused by a pathogen – Helicobacter pylori, a fact once inconceivable to the scientific community.
Warren made the initial findings that the gut mucosal linings of many patients with peptic ulcer had an oddly-shaped bacterium in that he could not identify, and that the area around these colonies of bacteria were often inflamed. Marshall joined the work slightly later to help try and isolate the bacteria they saw, and from there to provide evidence for a causal link between this bacterium and peptic ulcer. After some difficulty, Warren and Marshall managed to culture some of the bacteria after accidentally leaving some of their petri dishes for three times the length of time they had left their other plates to incubate. This was Helicobacter pylori – its genus name giving an indication of its corkscrew-like shape, and its species name the area of the body in which it is found, the pyloric sphincter of the stomach.
To remove any doubt about cause and correlation, Marshall performed a daring self-experiment – he prepared a broth of H. pylori and drank it. Sure enough, he developed symptoms of peptic ulcer five days after drinking the bacterial suspension; endoscopies showed severe gastritis and ulceration. After a short course of antibiotics, the symptoms gradually started to disappear. With this one experiment, Warren and Marshall had overturned centuries of medical thought.
These days, peptic ulcer is most often treated with a combination of antibiotics (to tackle the H. pylori infection) and proton pump inhibitors (to reduce the acidity of the stomach and allow the stomach lining to heal). Interestingly, another risk factor for peptic ulcer is the use of NSAIDs, a class of drugs that include aspirin. Drugs like aspirin inhibit the production of biochemicals called prostaglandins, which cause pain, but are also involved in helping protect the stomach from acid. In combination with an existing H. pylori infection, the use of NSAIDs may be what tip the scales from a subclinical, harmless infection towards ulceration and gastritis. This is of course one of the unanswered questions left in peptic ulcer disease: it is estimated that around 50% of us have H. pylori infections in our stomachs, but only a small fraction of that 50% ever develop a peptic ulcer. We still don’t know what makes that fraction so special!
Chronic inflammation, such as that which can be caused by H. pylori in gastritis, is never good for the body. In inflammation, chemicals are released which can damage cells, the ability of cells to repair their DNA can be affected, and cells are required to proliferate to repair damage. All three of these three together essentially increase the risk of cancer developing – and so H. pylori infection is also associated with types of gastric and oesophageal cancer.
Further reading:
Peptic Ulcer Disease and Helicobacter pylori infection. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140150/
H. pylori & Peptic Ulcer. https://wakegastro.com/patient-info/patient-education/h-pylori-peptic-ulcer/
The Nobel Prize in Physiology of Medicine 2005 Press Release. https://www.nobelprize.org/prizes/medicine/2005/press-release/
Helicobacter pylori: A Nobel pursuit? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661189/
A Humble Bacterium Sweeps This Year’s Nobel Prize. https://www.cell.com/fulltext/S0092-8674(05)01320-6
Helicobacter pylori and cancer. https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet#what-evidence-shows-that-h-pylori-infection-causes-non-cardia-gastric-cancer