The bacterium was initially named Campylobacter pyloridis, then renamed C. pylori to fix a Latin grammar error. When 16S rRNA gene sequencing and other research showed in 1989 that the bacterium did not belong in the genus Campylobacter, it was placed in its own genus, Helicobacter. The genus derived from the Ancient Greek hělix/έλιξ "spiral" or "coil". The specific epithet pylōri means "of the pylorus" or pyloric valve (the circular opening leading from the stomach into the duodenum), from the Ancient Greek word πυλωρός, which means gatekeeper.
More than 50% of the world's population harbour H. pylori in their upper gastrointestinal tract. Infection is more prevalent in developing countries. The route of transmission is unknown, although individuals become infected in childhood. H. pylori's helix shape (from which the generic name is derived) is thought to have evolved to penetrate the mucoid lining of the stomach.
Most individuals with chronic H. pylori infection have no symptoms. Some individuals develop more serious problems, including stomach or duodenal ulcers. Ulcers can cause a variety of symptoms or no symptoms at all. Common complaints include pain or discomfort (usually in the upper abdomen), bloating, feeling full after eating a small amount of food, lack of appetite, nausea, vomiting, and dark or tar-colored stools. Ulcers that bleed can cause a low blood count and fatigue.
H. pylori is a helix-shaped Gram-negative bacterium, about 3 micrometres long with a diameter of about 0.5 micrometre. It is microaerophilic; it requires oxygen although at lower concentration than is found in the atmosphere. It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) that is produced by intestinal bacteria. It produces oxidase, catalase, and urease. It is capable of forming biofilms and can convert from spiral to a possibly viable but nonculturable coccoid form, both likely to favor its survival and be factors in the epidemiology of the bacterium. The coccoid form can adhere to gastric epithelial cells in vitro.
H. pylori possesses five major outer membrane protein (OMP) families. The largest family includes known and putative adhesins. The other four families include porins, iron transporters, flagellum-associated proteins, and proteins of unknown function. Like other typical Gram-negative bacteria, the outer membrane of H. pylori consists of phospholipids and lipopolysaccharide (LPS). The O antigen of LPS may be fucosylated and mimic Lewis blood group antigens found on the gastric epithelium. The outer membrane also contains cholesterol glucosides, which is found in few other bacteria. H. pylori has 4–6 flagella; all gastric and enterohepatic Helicobacter species are highly motile due to flagella. The characteristic sheathed flagellar filaments of helicobacters are composed of two copolymerized flagellins, FlaA and FlaB.
Study of the H. pylori genome is centered on attempts to understand pathogenesis, the ability of this organism to cause disease. Approximately 29% of the loci are in the "pathogenesis" category of the genome database. Both sequenced strains have an approximately 40 kb-long Cag pathogenicity island (a common gene sequence believed responsible for pathogenesis) that contains over 40 genes. This pathogenicity island is usually absent from H. pylori strains isolated from humans who are carriers of H. pylori but remain asymptomatic.
The cagA gene codes for one of the major H. pylori virulence proteins. Bacterial strains that have the cagA gene are associated with an ability to cause ulcers. The cagA gene codes for a relatively long (1186 amino acid) protein. The cag pathogenicity island (PAI) has about 30 genes, part of which code for a complex type IV secretion system. The low GC content of the cag PAI relative to the rest of the helicobacter genome suggests that the island was acquired by horizontal transfer from another bacterial species.
To colonize the stomach H. pylori must survive the acidic pH of the lumen and burrow into the mucus to reach its niche, close to the stomach's epithelial cell layer. The bacterium has flagella and moves through the stomach lumen and drills into the mucoid lining of the stomach. Many bacteria can be found deep in the mucus, which is continuously secreted by mucous cells and removed on the luminal side. To avoid being carried into the lumen, H. pylori senses the pH gradient within the mucus layer by chemotaxis and swims away from the acidic contents of the lumen towards the more neutral pH environment of the epithelial cell surface. H. pylori is also found on the inner surface of the stomach epithelial cells and occasionally inside epithelial cells. It produces adhesins which bind to membrane-associated lipids and carbohydrates and help it adhere to epithelial cells. For example, the adhesin BabA binds to the Lewis b antigen displayed on the surface of stomach epithelial cells. H. pylori produces large amounts of the enzyme urease, molecules of which are localized inside and outside of the bacterium. Urease breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia (which neutralizes gastric acid). The survival of H. pylori in the acidic stomach is dependent on urease, and it would eventually die without the enzyme. The ammonia that is produced is toxic to the epithelial cells, and, along with the other products of H. pylori—including protease, vacuolating cytotoxin A (VacA), and certain phospholipases—damages those cells.
Colonization of the stomach by H. pylori results in chronic gastritis, an inflammation of the stomach lining. The severity of the inflammation is likely to underlie H. pylori-related diseases. Duodenal and stomach ulcers result when the consequences of inflammation allow the acid and pepsin in the stomach lumen to overwhelm the mechanisms that protect the stomach and duodenal mucosa from these caustic substances. The type of ulcer that develops depends on the location of chronic gastritis, which occurs at the site of H. pylori colonization. The acidity within the stomach lumen affects the colonization pattern of H. pylori and therefore ultimately determines whether a duodenal or gastric ulcer will form. In people producing large amounts of acid, H. pylori colonizes the antrum of the stomach to avoid the acid-secreting parietal cells located in the corpus (main body) of the stomach. The inflammatory response to the bacteria induces G cells in the antrum to secrete the hormone gastrin, which travels through the bloodstream to the corpus. Gastrin stimulates the parietal cells in the corpus to secrete even more acid into the stomach lumen. Chronically increased gastrin levels eventually cause the number of parietal cells to also increase, further escalating the amount of acid secreted. The increased acid load damages the duodenum, and ulceration may eventually result. In contrast, gastric ulcers are often associated with normal or reduced gastric acid production, suggesting that the mechanisms that protect the gastric mucosa are defective. In these patients H. pylori can also colonize the corpus of the stomach, where the acid-secreting parietal cells are located. However chronic inflammation induced by the bacteria causes further reduction of acid production and, eventually, atrophy of the stomach lining, which may lead to gastric ulcer and increases the risk for stomach cancer.
About 50-70% of H. pylori strains in Western countries carry the cag pathogenicity island (cag PAI). Western patients infected with strains carrying the cag PAI have a stronger inflammatory response in the stomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains lacking the island. Following attachment of H. pylori to stomach epithelial cells the type IV secretion system expressed by the cag PAI "injects" the inflammatory inducing agent peptidoglycan from their own cell wall into the epithelial cells. The injected peptidoglycan is recognized by the cytoplasmic immune sensor Nod1, which then stimulates expression of cytokines that promote inflammation.
The type IV secretion apparatus also injects the cag PAI-encoded protein CagA into the stomach's epithelial cells, where it disrupts the cytoskeleton, adherence to adjacent cells, intracellular signaling, and other cellular activities. Once inside the cell the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase. Pathogenic strains of H. pylori have been shown to activate the epidermal growth factor receptor (EGFR), a membrane protein with a tyrosine kinase domain. Activation of the EGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells that may contribute to pathogenesis. It has also been suggested that a c-terminal region of the CagA protein (amino acids 873–1002) can regulate host cell gene transcription independent of protein tyrosine phosphorylation.
Two related mechanisms by which H. pylori could promote cancer are under investigation. One mechanism involves the enhanced production of free radicals near H. pylori and an increased rate of host cell mutation. The other proposed mechanism has been called a "perigenetic pathway and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins such as adhesion proteins. It has been proposed that H. pylori induces inflammation and locally high levels of TNF-alpha and/or interleukin 6. According to the proposed perigenetic mechanism, inflammation-associated signaling molecules such as TNF-alpha can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in tumor suppressor genes such as genes that code for cell adhesion proteins.
Diagnosis of infection is usually made by checking for dyspeptic symptoms and by tests which can indicate H. pylori infection. One can test noninvasively for H. pylori infection with a blood antibody test, stool antigen test, or with the carbon urea breath test (in which the patient drinks 14C- or 13C-labelled urea, which the bacterium metabolizes, producing labelled carbon dioxide that can be detected in the breath). However, the most reliable method for detecting H. pylori infection is a biopsy check during endoscopy with a rapid urease test, histological examination, and microbial culture. None of the test methods is completely failsafe. Even biopsy is dependent on the location of the biopsy. Blood antibody tests, for example, range from 76% to 84% sensitivity. Some drugs can affect H. pylori urease activity and give false negatives with the urea-based tests.
Once H. pylori is detected in patients with a peptic ulcer, the normal procedure is to eradicate it and allow the ulcer to heal. The standard first-line therapy is a one week triple therapy consisting of the antibiotics amoxicillin and clarithromycin, and a proton pump inhibitor such as omeprazole. Variations of the triple therapy have been developed over the years, such as using a different proton pump inhibitor, as with pantoprazole or rabeprazole, or replacing amoxicillin with metronidazole for people who are allergic to penicillin. Such a therapy has revolutionized the treatment of peptic ulcers and has made a cure to the disease possible; previously the only option was symptom control using antacids, H2-antagonists or proton pump inhibitors alone.
An increasing number of infected individuals are found to harbour antibiotic-resistant bacteria. This results in initial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies such as a quadruple therapy, which adds a bismuth colloid. For the treatment of clarithromycin-resistant strains of H. pylori the use of levofloxacin as part of the therapy has been suggested.
H. pylori colonizes the stomach and induces chronic gastritis, a long-lasting inflammation of the stomach. The bacterium persists in the stomach for decades in most people. Most individuals infected by H. pylori will never experience clinical symptoms despite having chronic gastritis. Approximately 10-20% of those colonized by H. pylori will ultimately develop gastric and duodenal ulcers. H. pylori infection is also associated with a 1-2% lifetime risk of stomach cancer and a less than 1% risk of gastric MALT lymphoma.
It is widely believed that in the absence of treatment, H. pylori infection—once established in its gastric niche—persists for life. In the elderly, however, it is likely infection can disappear as the stomach's mucosa becomes increasingly atrophic and inhospitable to colonization. The proportion of acute infections that persist is not known, but several studies that followed the natural history in populations have reported apparent spontaneous elimination.
While H. pylori has been disappearing from the stomach of humans, the incidence of the related disorders acid reflux disease, Barrett's esophagus, and esophageal cancer have been rising dramatically. In 1996, Martin J. Blaser advanced the hypothesis that H. pylori has a beneficial effect: by regulating the acidity of the stomach contents, it lowers the impact of regurgitation of gastric acid into the esophagus. The hypothesis is not universally accepted as several randomized controlled trials failed to demonstrate worsening of acid reflux disease symptoms following eradication of H. pylori. Nevertheless, Blaser has refined his view to assert that H. pylori is a member of the normal flora of the stomach. He postulates that the changes in gastric physiology caused by the loss of H. pylori account for the recent increase in incidence of several diseases, including type 2 diabetes, obesity, and asthma. His group has recently shown that H. pylori colonization is associated with a lower incidence of childhood asthma.
H. pylori is contagious, although the exact route of transmission is not known. Person-to-person transmission by either the oral-oral or fecal-oral route is most likely. Consistent with these transmission routes, the bacteria have been isolated from feces, saliva and dental plaque of some infected people. Transmission occurs mainly within families in developed nations yet can also be acquired from the community in developing countries. H. pylori may also be transmitted orally by means of fecal matter through the ingestion of waste-tainted water, so a hygienic environment could help decrease the risk of H. pylori infection.
German scientists found spiral-shaped bacteria in the lining of the human stomach in 1875, but they were unable to culture it and the results were eventually forgotten. The Italian researcher Giulio Bizzozero described similarly shaped bacteria living in the acidic environment of the stomach of dogs in 1893. Professor Walery Jaworski of the Jagiellonian University in Kraków investigated sediments of gastric washings obtained from humans in 1899. Among some rod-like bacteria, he also found bacteria with a characteristic spiral shape, which he called Vibrio rugula. He was the first to suggest a possible role of this organism in the pathogenesis of gastric diseases. This work was included in the Handbook of Gastric Diseases, but it had little impact as it was written in Polish. Several small studies conducted in the early 1900s demonstrated the presence of curved rods in the stomach of many patients with peptic ulcers and stomach cancer. However interest in the bacteria waned when an American study published in 1954 failed to observe the bacteria in 1180 stomach biopsies.
Interest in understanding the role of bacteria in stomach diseases was rekindled in the 1970s with the visualization of bacteria in the stomach of gastric ulcer patients. The bacterium had also been observed in 1979 by Australian pathologist Robin Warren, who did further research on it with Australian physician Barry Marshall beginning in 1981. After numerous unsuccessful attempts at culturing the bacteria from the stomach, they finally succeeded in visualizing colonies in 1982 when they unintentionally left their Petri dishes incubating for 5 days over the Easter weekend. In their original paper, Warren and Marshall contended that most stomach ulcers and gastritis were caused by infection by this bacterium and not by stress or spicy food as had been assumed before.
Although there was some skepticism initially, within several years, numerous research groups verified the association of H. pylori with gastritis and to a lesser extent ulcers. To demonstrate that H. pylori caused gastritis and was not merely a bystander, Marshall drank a beaker of H. pylori. He became ill several days later with nausea and vomiting. An endoscopy ten days after inoculation revealed signs of gastritis and the presence of H. pylori. These results proved that H. pylori was the causative agent of gastritis. Marshall and Warren went on to show that antibiotics are effective in the treatment of many cases of gastritis. In 1987 the Sydney gastroenterologist Thomas Borody invented the first triple therapy for the treatment of duodenal ulcers. In 1994, the National Institutes of Health (USA) published an opinion stating that most recurrent duodenal and gastric ulcers were caused by H. pylori and recommended that antibiotics be included in the treatment regimen. Warren and Marshall were awarded the Nobel Prize in Medicine in 2005 for their work on H. pylori.
Recent research states that genetic diversity in H. pylori decreases with geographic distance from East Africa, the birthplace of modern humans. Using the genetic diversity data, the researchers have created simulations that indicate the bacteria seems to have spread from East Africa around 58,000 years ago. Their results indicate modern humans were already infected by H. pylori before their migrations out of Africa, remaining associated with human hosts since that time.