Helicobacter Pylori

8/18/12 Helicobacter pylori - Wikipedia, the free encyclopedia

1/15en.wikipedia.org/wiki/Helicobacter_pylori

Helicobacter pylori infection

Classification and external resources

Immunohistochemical staining of H. pylori from a gastric biopsy

ICD-9 041.86 (http://www.icd9data.com/getICD9Code.ashx?

icd9=041.86)

DiseasesDB 5702 (http://www.diseasesdatabase.com/ddb5702.htm)

MedlinePlus 000229

(http://www.nlm.nih.gov/medlineplus/ency/article/000229.htm)

eMedicine med/962 (http://www.emedicine.com/med/topic962.htm)

MeSH D016481 (http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?

field=uid&term=D016481)

Helicobacter pyloriFrom Wikipedia, the free encyclopedia

Helicobacter pylori

(/ˌhɛlɪkɵˈbæktər paɪˈlɔraɪ/; H.pylori), previously namedCampylobacter pyloridis, is aGram-negative, microaerophilicbacterium found in the stomach.It was identified in 1982 byBarry Marshall and RobinWarren, who found that it waspresent in patients with chronicgastritis and gastric ulcers,conditions that were notpreviously believed to have amicrobial cause. It is also linkedto the development of duodenalulcers and stomach cancer.However, over 80 percent ofindividuals infected with thebacterium are asymptomatic andit has been postulated that it mayplay an important role in the

natural stomach ecology.[1]

More than 50% of the world'spopulation harbor H. pylori intheir upper gastrointestinal tract.Infection is more prevalent in developing countries, and incidence is decreasing in Western countries. H. pylori'shelix shape (from which the generic name is derived) is thought to have evolved to penetrate the mucoid lining of

the stomach.[2][3]

Contents

1 Signs and symptoms

2 Microbiology

2.1 Genome

3 Pathophysiology

4 Diagnosis

5 Prevention5.1 Vaccines

6 Treatment

7 Prognosis

8 Epidemiology

9 Evolution

10 History

11 References



Helicobacter pylori

Scientific classification

Domain: Bacteria

Phylum: Proteobacteria

Class: Epsilonproteobacteria

Order: Campylobacterales

Family: Helicobacteraceae

Genus: Helicobacter

Species: H. pylori

Binomial name

Helicobacter pylori

(Marshall et al. 1985) Goodwin et

al., 1989

Scanning electron

micrograph of H.

pylori

12 External links

Signs and symptoms

Over 80% of people infected with H. pylori show no symptoms.[4] Acute infection may appear as an acute

gastritis with abdominal pain (stomach ache) or nausea.[5] Where this develops into chronic gastritis, thesymptoms, if present, are often those of non-ulcer dyspepsia: stomach pains, nausea, bloating, belching and

sometimes vomiting, black stool.[6][7]

Individuals infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers and a 1 to 2% risk

of acquiring stomach cancer.[8] Inflammation of the pyloric antrum is more likely to lead to duodenal ulcers,while inflammation of the corpus (body of the stomach) is more likely to lead to gastric ulcers and gastric

carcinoma.[9] However, it is possible that H. pylori plays a role only in the first stage that leads to common

chronic inflammation, but not in further stages leading to carcinogenesis.[3]

Microbiology

H. pylori is a helix-shaped (classified as acurved rod, not spirochaete), Gram-negativebacterium, about 3 micrometres long with adiameter of about 0.5 micrometres. It ismicroaerophilic; that is, it requires oxygen, butat lower concentration than is found in theatmosphere. It contains a hydrogenase whichcan be used to obtain energy by oxidizingmolecular hydrogen (H2) produced by

intestinal bacteria.[10] It produces oxidase,catalase, and urease. It is capable of forming

biofilms[11] and can convert from spiral to apossibly viable but nonculturable coccoid

form,[12] both likely to favor its survival and befactors in the epidemiology of the bacterium.

H. pylori possesses five major outer membrane protein (OMP) families.[13]

The largest family includes known and putative adhesins. The other fourfamilies include porins, iron transporters, flagellum-associated proteins andproteins of unknown function. Like other typical Gram-negative bacteria,the outer membrane of H. pylori consists of phospholipids andlipopolysaccharide (LPS). The O antigen of LPS may be fucosylated and

mimic Lewis blood group antigens found on the gastric epithelium.[13] Theouter membrane also contains cholesterol glucosides, which are found in

few other bacteria.[13] H. pylori has four to six lophotrichous flagella; allgastric and enterohepatic Helicobacter species are highly motile due to

flagella.[14] The characteristic sheathed flagellar filaments of Helicobacter

are composed of two copolymerized flagellins, FlaA and FlaB.[15]

Genome



Molecular model of H. pylori urease

enzyme

H. pylori consists of a large diversity of strains, and the genomes of three have been completely

sequenced.[16][17][18][19][20] The genome of the strain "26695" consists of about 1.7 million base pairs, withsome 1,550 genes. The two sequenced strains show large genetic differences, with up to 6% of the nucleotides

differing.[18]

Study of the H. pylori genome is centered on attempts to understand pathogenesis, the ability of this organism tocause disease. Approximately 29% of the loci are in the "pathogenesis" category of the genome database. Twoof sequenced strains have an approximately 40 kb-long Cag pathogenicity island (a common gene sequencebelieved 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.[21]

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.[22] The cagA gene codes for a relatively long (1186 aminoacid) protein. The cag pathogenicity island (PAI) has about 30 genes, part of which code for a complex type IVsecretion system. The low GC-content of the cag PAI relative to the rest of the Helicobacter genome suggests

the island was acquired by horizontal transfer from another bacterial species.[16]

Pathophysiology

To colonize the stomach, H. pylori must survive the acidic pH of thelumen and use its flagella to burrow into the mucus to reach its niche,

close to the stomach's epithelial cell layer.[23] Many bacteria can befound deep in the mucus, which is continuously secreted by mucus-secreting cells and removed on the luminal side. To avoid beingcarried into the lumen, H. pylori senses the pH gradient within themucus layer by chemotaxis and swims away from the acidic contentsof the lumen towards the more neutral pH environment of the

epithelial cell surface.[24] H. pylori is also found on the inner surfaceof the stomach epithelial cells and occasionally inside epithelial

cells.[25] It produces adhesins which bind to membrane-associatedlipids and carbohydrates and help it adhere to epithelial cells. Forexample, the adhesin BabA binds to the Lewis b antigen displayed on

the surface of stomach epithelial cells.[26] H. pylori produces largeamounts of the enzyme urease, molecules of which are localized insideand outside of the bacterium. Urease breaks down urea (which isnormally secreted into the stomach) to carbon dioxide and ammonia.

The ammonia is converted to ammonium by accepting a proton (H+),which neutralizes gastric acid. The survival of H. pylori in the acidicstomach is dependent on urease. The ammonia produced is toxic tothe epithelial cells, and, along with the other products of H. pylori—including proteases, vacuolating cytotoxin A (VacA), and certain

phospholipases—, damages those cells.[27]

Inflammatory processes of H. pylori infections are also mediated by highly disulfide-bridged proteins.Helicobacter cysteine-rich proteins (Hcp), particularly HcpA (hp0211), triggers an immune response throughthe differentiation of human myeloid Thp1 monocytes into macrophages. In analogy to eukaryotic cytokines,they interfere with host cell functions and change the morphology of monocytes, inducing the expression of thesurface marker protein CD11b, phagocytic activity, as well as cell adherence, which are indicative of monocyte

differentiation into macrophages.[28]



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.[29] Duodenal and stomach ulcersresult when the consequences of inflammation allow the acid and pepsin in the stomach lumen to overwhelm themechanisms 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.[30] Theacidity within the stomach lumen affects the colonization pattern of H. pylori, and therefore ultimately determineswhether a duodenal or gastric ulcer will form. In people producing large amounts of acid, H. pylori colonizes theantrum of the stomach to avoid the acid-secreting parietal cells located in the corpus (main body) of the

stomach.[13] 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.[31] Gastrin stimulates the parietal cells in the corpusto 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.[32] The increased acidload damages the duodenum, and ulceration may eventually result. In contrast, gastric ulcers are oftenassociated with normal or reduced gastric acid production, suggesting the mechanisms that protect the gastric

mucosa are defective.[32] In these patients, H. pylori can also colonize the corpus of the stomach, where theacid-secreting parietal cells are located. However chronic inflammation induced by the bacteria causes furtherreduction of acid production and, eventually, atrophy of the stomach lining, which may lead to gastric ulcer and

increases the risk for stomach cancer.[33]

About 50-70% of H. pylori strains in Western countries carry the cag pathogenicity island (cag PAI).[34]

Western patients infected with strains carrying the cag PAI have a stronger inflammatory response in thestomach and are at a greater risk of developing peptic ulcers or stomach cancer than those infected with strains

lacking the island.[13] Following attachment of H. pylori to stomach epithelial cells, the type IV secretion systemexpressed by the cag PAI "injects" the inflammation-inducing agent, peptidoglycan, from their own cell wall intothe epithelial cells. The injected peptidoglycan is recognized by the cytoplasmic pattern recognition receptor

(immune sensor) Nod1, which then stimulates expression of cytokines that promote inflammation.[35]

The type IV secretion apparatus also injects the cag PAI-encoded protein CagA into the stomach's epithelialcells, where it disrupts the cytoskeleton, adherence to adjacent cells, intracellular signaling, cell polarity, and

other cellular activities.[36] Once inside the cell, the CagA protein is phosphorylated on tyrosine residues by ahost cell membrane-associated tyrosine kinase (TK). CagA then allosterically activates protein tyrosine

phosphatase/protooncogene Shp2.[37] Pathogenic strains of H. pylori have been shown to activate theepidermal growth factor receptor (EGFR), a membrane protein with a tyrosine kinase domain. Activation of theEGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells thatmay contribute to pathogenesis. It has also been suggested that a C-terminal region of the CagA protein (aminoacids 873–1002) can regulate host cell gene transcription, independent of protein tyrosine

phosphorylation.[21][22] There is a great deal of diversity between strains of H. pylori, and the strain with whichone is infected is predictive of the outcome.

Two related mechanisms by which H. pylori could promote cancer are under investigation. One mechanisminvolves 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",[38] and involves enhancement of thetransformed host cell phenotype by means of alterations in cell proteins, such as adhesion proteins. H. pylori hasbeen proposed to induce inflammation and locally high levels of TNF-α and/or interleukin 6 (IL-6). Accordingto the proposed perigenetic mechanism, inflammation-associated signaling molecules, such as TNF-α, can altergastric 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.[39]

Diagnosis



H. pylori colonized on the surface of

regenerative epithelium (image from

Warthin-Starry's silver stain)

Colonization with H. pylori is not a disease in and of itself but a condition associated with a number of disorders

of the upper gastrointestinal tract.[13] Testing for H. pylori isrecommended if there is peptic ulcer disease, low grade gastricMALT lymphoma, after endoscopic resection of early gastric cancer,if there are first degree relatives with gastric cancer, and in certain

cases of dyspepsia,[40] not routinely.[13] Several ways of testing exist.One can test noninvasively for H. pylori infection with a bloodantibody test, stool antigen test, or with the carbon urea breath test (in

which the patient drinks 14C- or 13C-labelled urea, which thebacterium metabolizes, producing labelled carbon dioxide that can be

detected in the breath).[40] However, the most reliable method fordetecting H. pylori infection is a biopsy check during endoscopy witha rapid urease test, histological examination, and microbial culture.There is also a urine ELISA test with a 96% sensitivity and 79% specificity. None of the test methods arecompletely 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.[41]

Prevention

H. pylori is a major cause of certain diseases of the upper gastrointestinal tract. Rising antibiotic resistanceincreases the need to search for new therapeutic strategies; this might include prevention in form of

vaccination.[42] Extensive vaccine studies in mouse models have shown promising results.[43] Researchers arestudying different adjuvants, antigens, and routes of immunization to ascertain the most appropriate system of

immune protection; however, most of the research only recently moved from animal to human trials.[44] Anumber of foods may be useful to prevent colonization with H. pylori including: green tea, red wine, broccoli

sprouts, garlic, probiotics and flavonoids.[45]

Vaccines

Vaccines against H. pylori could be used as prophylactic vaccines to prevent the infection or as therapeuticvaccines to cure the infection, to improve the eradication success of standard regimens or to reduce the bacterialdensity in the gastric mucosa and the risk for emergence of antibiotic resistant strains. In recent years, manyattempts, using various H. pylori antigens such as urease, CagA, HP-NAP, HspA or combinations, manyadjuvants and different routes of immunisation have been made to create vaccines against H. pylori infection.Although some attempts are promising, no effective and safe vaccine against H. pylori is currently available forhumans. New directions for immunisation with the use of DNA, living vectors, microspheres etc. are currentlyunder evaluation. The vaccination plan and the groups who should receive vaccination are still to be determined,

but the vaccination will be useful, especially in developing countries.[4] An intramuscular vaccine against H.pylori infection is undergoing Phase I clinical trials, and has shown an antibody response against the bacterium.

Its clinical usefulness requires further study.[46]

Treatment

Further information: Helicobacter pylori eradication protocols

Once H. pylori is detected in a person with a peptic ulcer, the normal procedure is to eradicate it and allow theulcer to heal. The standard first-line therapy is a one week "triple therapy" consisting of proton pump inhibitors

such as omeprazole and the antibiotics clarithromycin and amoxicillin.[47] 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.[48] Such atherapy 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.[49][50]

An increasing number of infected individuals are found to harbour antibiotic-resistant bacteria. This results ininitial treatment failure and requires additional rounds of antibiotic therapy or alternative strategies, such as a

quadruple therapy, which adds a bismuth colloid, such as bismuth subsalicylate.[40][51][52] For the treatment ofclarithromycin-resistant strains of H. pylori, the use of levofloxacin as part of the therapy has been

suggested.[53][54]

An article in the American Journal of Clinical Nutrition found evidence that "ingesting lactic acid bacteriaexerts a suppressive effect on Helicobacter pylori infection in both animals and humans," noting that"supplementing with Lactobacillus- and Bifidobacterium-containing yogurt (AB-yogurt) was shown to improve

the rates of eradication of H. pylori in humans."[55]

Prognosis

H. pylori colonizes the stomach and induces chronic gastritis, a long-lasting inflammation of the stomach. Thebacterium persists in the stomach for decades in most people. Most individuals infected by H. pylori will neverexperience clinical symptoms despite having chronic gastritis. Approximately 10-20% of those colonized by H.

pylori will ultimately develop gastric and duodenal ulcers.[13] 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.[13]

In the absence of treatment, H. pylori infection—once established in its gastric niche—is widely believed to

persist for life.[3] In the elderly, however, it is likely infection can disappear as the stomach's mucosa becomesincreasingly atrophic and inhospitable to colonization. The proportion of acute infections that persist is notknown, but several studies that followed the natural history in populations have reported apparent spontaneous

elimination.[56][57]

Mounting evidence suggests that H. pylori has an important role in protecting from some diseases. Theincidence of acid reflux disease, Barrett's esophagus, and esophageal cancer have been rising dramatically at the

same time as H. pylori's presence decreases.[58] In 1996, Martin J. Blaser advanced the hypothesis that H.

pylori has a beneficial effect: by regulating the acidity of the stomach contents.[31][58] The hypothesis is notuniversally accepted as several randomized controlled trials failed to demonstrate worsening of acid reflux

disease symptoms following eradication of H. pylori.[59][60] Nevertheless, Blaser has refined his view to assert

that H. pylori is a member of the normal flora of the stomach.[61] He postulates that the changes in gastricphysiology caused by the loss of H. pylori account for the recent increase in incidence of several diseases,

including type 2 diabetes, obesity, and asthma.[61][62] His group has recently shown that H. pylori colonization

is associated with a lower incidence of childhood asthma.[63]

Epidemiology

At least half the world's population are infected by the bacterium, making it the most widespread infection in the

world.[64] Actual infection rates vary from nation to nation; the developing world has much higher infection rates

than the West (Western Europe, North America, Australasia), where rates are estimated to be around 25%.[64]

The age at which this bacterium is acquired seems to influence the possible pathologic outcome of the infection :people infected with it at an early age are likely to develop more intense inflammation that may be followed by



atrophic gastritis with a higher subsequent risk of gastric ulcer, gastric cancer or both. Acquisition at an older

age brings different gastric changes more likely to lead to duodenal ulcer.[3] Infections are usually acquired in

early childhood in all countries.[13] However, the infection rate of children in developing nations is higher than inindustrialized nations, probably due to poor sanitary conditions. In developed nations it is currently uncommonto find infected children, but the percentage of infected people increases with age, with about 50% infected for

those over the age of 60 compared with around 10% between 18 and 30 years.[64] The higher prevalence

among the elderly reflects higher infection rates when they were children rather than infection at later ages.[13]

Prevalence appears to be higher in African-American and Hispanic populations, most likely due to

socioeconomic factors.[65][66] The lower rate of infection in the West is largely attributed to higher hygienestandards and widespread use of antibiotics. Despite high rates of infection in certain areas of the world, the

overall frequency of H. pylori infection is declining.[67] However, antibiotic resistance is appearing in H. pylori;

there are already many metronidazole- and clarithromycin-resistant strains in most parts of the world.[68]

H. pylori is contagious, although the exact route of transmission is not known.[69][70] Person-to-persontransmission 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. Findings suggest

that H. pylori is more easily transmitted via gastric mucous than via saliva[3] Transmission occurs mainly within

families in developed nations yet can also be acquired from the community in developing countries.[71] H. pylorimay 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.[3]

Evolution

Helicobacter pylori migrated out of Africa along with its human host circa 60,000 years ago.[72] Its subsequentevolution created seven prototypes - Europe (isolated from Europe, the Middle East, India and Iran), NE Africa(from Northeast Africa), Africa1 (from countries in Western Africa and South Africa), Africa2 (from SouthAfrica), Asia2 (from Northern India and among isolates from Bangladesh, Thailand and Malaysia), Sahul (fromAustralian Aboriginals and Papua New Guineans) and East Asia with the subpopulations E Asia (from EastAsians), Maori (from Taiwanese Aboriginals, Melanesians and Polynesians) and Amerind (Native Americans).The precursors of these prototypes have been named ancestral Europe1, ancestral Europe2, ancestral EastAsia, ancestral Africa1, ancestral Africa2 and ancestral Sahul. These ancestral prototypes appear to haveoriginated in Africa, Central and East Asia. European and African strains were introduced into the Americasalong with its colonisation - both thousands of years ago and more recently - and the slave trade.

History

See also: Timeline of peptic ulcer disease and Helicobacter pylori

Helicobacter pylori was first discovered in the stomachs of patients with gastritis and stomach ulcers in 1982by Dr. Barry Marshall and Dr. Robin Warren of Perth, Western Australia. At the time, the conventional thinkingwas that no bacterium can live in the human stomach, as the stomach produced extensive amounts of acid of astrength similar to the acid found in a car battery. Marshall and Warren rewrote the textbooks with reference towhat causes gastritis and gastric ulcers. In recognition of their discovery, they were awarded the 2005 Nobel

Prize in Physiology or Medicine.[73] 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.[58] The Italianresearcher Giulio Bizzozero described similarly shaped bacteria living in the acidic environment of the stomach of

dogs in 1893.[74] Professor Walery Jaworski of the Jagiellonian University in Kraków investigated sediments ofgastric washings obtained from humans in 1899. Among some rod-like bacteria, he also found bacteria with acharacteristic 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.[75] Several small studies conducted in the early 20thcentury demonstrated the presence of curved rods in the stomach of many patients with peptic ulcers and

stomach cancer.[76] Interest in the bacteria waned, however, when an American study published in 1954 failed

to observe the bacteria in 1180 stomach biopsies.[77]

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.[78] The bacterium had also been observed in1979, by Australian pathologist Robin Warren, who did further research on it with Australian physician BarryMarshall 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 incubatingfor 5 days over the Easter weekend. In their original paper, Warren and Marshall contended that most stomachulcers and gastritis were caused by infection by this bacterium and not by stress or spicy food, as had been

assumed before.[79]

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.[80] To demonstrate H. pylori causedgastritis and was not merely a bystander, Marshall drank a beaker of H. pylori culture. He became ill withnausea and vomiting several days later. An endoscopy ten days after inoculation revealed signs of gastritis andthe presence of H. pylori. These results suggested H. pylori was the causative agent of gastritis. Marshall andWarren went on to demonstrate 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.[81] In 1994, the National Institutes of Health (USA) published an opinion stating most recurrent duodenaland gastric ulcers were caused by H. pylori, and recommended antibiotics be included in the treatment

regimen.[82]

The bacterium was initially named Campylobacter pyloridis, then renamed C. pylori (pylori being the genitiveof pylorus) to correct a Latin grammar error. When 16S ribosomal RNA gene sequencing and other researchshowed 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".[83] The specific epithetpylōri 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.[83]

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 thatindicate the bacteria seem to have spread from East Africa around 58,000 years ago. Their results indicatemodern humans were already infected by H. pylori before their migrations out of Africa, and it has remained

associated with human hosts since that time.[84]

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External links

Information on tests for H. pylori (http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0015937/) from the

National Institutes of Health

Retrieved from "http://en.wikipedia.org/w/index.php?title=Helicobacter_pylori&oldid=505771356"

Categories: Conditions diagnosed by stool test Gastroenterology Gram-negative bacteria

IARC Group 1 carcinogens Proteobacteria

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