Helicobacter pylori

Helicobacter pylori (/hlkbktrpalra/), previ- and colorectal cancer.[15]

ously named Campylobacter pylori, is a Gram-negative,
microaerophilic bacterium found in the stomach, and
may be present in other parts of the body, such as the
2 Microbiology
eye.[1][2][3] It was identied in 1982 by Australian scientists Barry Marshall and Robin Warren with further
research led by British scientist Stewart Goodwin, who
found that it was present in patients with chronic gastritis
and gastric ulcers, conditions not previously believed to
have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. However,
over 80% of individuals infected with the bacterium are
asymptomatic and it may play an important role in the
natural stomach ecology.[4]
More than 50% of the worlds population harbor H. pylori in their upper gastrointestinal tract. Infection is more
prevalent in developing countries, and incidence is decreasing in Western countries. H. pylori's helical shape
(from which the generic name is derived) is thought
to have evolved to penetrate the mucoid lining of the
stomach.[5][6]

Signs and symptoms

Up to 85% of people infected with H. pylori never experience symptoms or complications.[7] Acute infection may
appear as an acute gastritis with abdominal pain (stomach ache) or nausea.[8] Where this develops into chronic
gastritis, the symptoms, if present, are often those of
non-ulcer dyspepsia: stomach pains, nausea, bloating,
belching, and sometimes vomiting or black stool.[9][10]
Scanning electron micrograph of H. pylori
Individuals infected with H. pylori have a 10 to 20%
lifetime risk of developing peptic ulcers and a 1 to H. pylori is a helix-shaped (classied as a curved rod, not
2% risk of acquiring stomach cancer.[11] [12] Inam- spirochaete) Gram-negative bacterium about 3 m long
mation of the pyloric antrum is more likely to lead to with a diameter of about 0.5 m. It is microaerophilic;
duodenal ulcers, while inammation of the corpus (body that is, it requires oxygen, but at lower concentration than
of the stomach) is more likely to lead to gastric ulcers is found in the atmosphere. It contains a hydrogenase
and gastric carcinoma.[13] However, H. pylori possibly which can be used to obtain energy by oxidizing molecplays a role only in the rst stage that leads to common ular hydrogen (H2 ) produced by intestinal bacteria.[16]
chronic inammation, but not in further stages leading It produces oxidase, catalase, and urease. It is capato carcinogenesis.[6] A meta-analysis conducted in 2009 ble of forming biolms[17] and can convert from spiral
concluded the eradication of H. pylori reduces gastric to a possibly viable but nonculturable coccoid form,[18]
cancer risk in previously infected individuals, suggesting both likely to favor its survival and be factors in the
the continued presence of H. pylori constitutes a relative epidemiology of the bacterium.
risk factor of 65% for gastric cancers; in terms of absolute H. pylori possesses ve major outer membrane prorisk, the increase was from 1.1% to 1.7%.[14]
tein families.[12] The largest family includes known and
H. pylori has also been associated with colorectal polyps putative adhesins. The other four families are porins,
1

3 PATHOPHYSIOLOGY

iron transporters, agellum-associated proteins, and pro- 3.1

teins of unknown function. Like other typical Gramnegative 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.[12]
The outer membrane also contains cholesterol glucosides,
which are found in few other bacteria.[12] H. pylori has
four to six lophotrichous agella; all gastric and enterohepatic Helicobacter species are highly motile owing to
agella.[19] The characteristic sheathed agellar laments
of Helicobacter are composed of two copolymerized agellins, FlaA and FlaB.[20]

2.1

Microscopy

Adaptation to the stomachs acidic environment

Diagram showing how H. pylori reaches the epithelium of the

stomach

H. pylori can be demonstrated in tissue by Gram stain,

Giemsa stain, haematoxylin-eosin stain, Warthin-Starry To avoid the acidic environment of the interior of the
silver stain, acridine-orange stain, and phase-contrast mi- stomach (lumen), H. pylori uses its agella to burrow into
croscopy.
the mucus lining of the stomach to reach the epithelial
cells underneath, where the pH is more neutral.[28] H. pylori is able to sense the pH gradient in the mucus and
move towards the less acidic region (chemotaxis). This
2.2 Genome
also keeps the bacteria from being swept away into the
H. pylori consists of a large diversity of strains, lumen with the bacterias mucus environment, which is
the epitheand the genomes of three have been completely constantly moving from its site of creation at[29]
[21][22][23][24][25]
lium
to
its
dissolution
at
the
lumen
interface.
sequenced.
The genome of the strain
26695 consists of about 1.7 million base pairs, with
some 1,550 genes. The two sequenced strains show large
genetic dierences, with up to 6% of the nucleotides
diering.[23]
Study of the H. pylori genome is centered on attempts
to understand pathogenesis, the ability of this organism
to cause disease. About 29% of the loci are in the
pathogenesis category of the genome database. Two
of sequenced strains have an around 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.[26]

H. pylori is found in the mucus, on the inner surface

of the epithelium, and occasionally inside the epithelial
cells themselves.[30] It adheres to the epithelial cells by
producing adhesins, which bind to lipids and carbohydrates in the epithelial cell membrane. One such adhesion, BabA, binds to the Lewis b antigen displayed on the
surface of stomach epithelial cells.[31] Another such adhesion, SabA, binds to increased levels of sialyl-Lewis x
antigen expressed on gastric mucosa.[32]

In addition to using chemotaxis to avoid areas of low pH,

H. pylori also neutralizes the acid in its environment by
producing large amounts of urease, which breaks down
the urea present in the stomach to carbon dioxide and
ammonia. The ammonia, which is basic, then neutralizes
The cagA gene codes for one of the major H. pylori stomach acid.
virulence proteins. Bacterial strains with the cagA gene
are associated with an ability to cause ulcers.[27] The cagA
3.2 Inammation, gastritis, and ulcer
gene codes for a relatively long (1186-amino acid) protein. The cag pathogenicity island (PAI) has about 30
H. pylori harms the stomach and duodenal linings by
genes, part of which code for a complex type IV secreseveral mechanisms. The ammonia produced to regtion system. The low GC-content of the cag PAI relative
ulate pH is toxic to epithelial cells, as are biochemto the rest of the Helicobacter genome suggests the island
icals produced by H. pylori such as proteases, vacwas acquired by horizontal transfer from another bacteuolating cytotoxin A (VacA) [this damages epithelial
[21]
rial species.
cells, disrupts tight junctions and causes apoptosis],
and certain phospholipases.[33] Cytotoxin associated gene
CagA can also cause inammation and is potentially a
carcinogen.[34]
3 Pathophysiology
Colonization of the stomach by H. pylori can result in

3.4

Cancer

chronic gastritis, an inammation of the stomach lining,

at the site of infection. Helicobacter cysteine-rich proteins
(Hcp), particularly HcpA (hp0211), are known to trigger
an immune response, causing inammation.[35] Chronic
gastritis is likely to underlie H. pylori-related diseases.[36]

3
CagA then allosterically activates protein tyrosine phosphatase/protooncogene Shp2.[44] Pathogenic strains of H.
pylori have been shown to activate the epidermal growth
factor receptor (EGFR), a membrane protein with a TK
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. A C-terminal region of the CagA protein (amino
acids 8731002) has also been suggested to be able to
regulate host cell gene transcription, independent of protein tyrosine phosphorylation.[26][27] A great deal of diversity exists between strains of H. pylori, and the strain
with which one is infected is predictive of the outcome.

Ulcers in the stomach and duodenum result when the consequences of inammation allow stomach acid and the digestive enzyme pepsin to overwhelm the mechanisms that
protect the stomach and duodenal mucous membranes.
The location of colonization of H. pylori, which aects
the location of the ulcer, depends on the acidity of the
stomach.[37] In people producing large amounts of acid,
H. pylori colonizes near the pyloric antrum (exit to the
duodenum) to avoid the acid-secreting parietal cells at the
fundus (near the entrance to the stomach).[12] In people
producing normal or reduced amounts of acid, H. pylori 3.4 Cancer
can also colonize the rest of the stomach.
Two related mechanisms by which H. pylori could proThe inammatory response caused by bacteria coloniz- mote cancer are under investigation. One mechanism
ing near the pyloric antrum induces G cells in the antrum involves the enhanced production of free radicals near
to secrete the hormone gastrin, which travels through the H. pylori and an increased rate of host cell mutation.
bloodstream to parietal cells in the fundus.[38] Gastrin The other proposed mechanism has been called a peristimulates the parietal cells to secrete more acid into the genetic pathway,[45] and involves enhancement of the
stomach lumen, and over time increases the number of transformed host cell phenotype by means of alterations
parietal cells, as well.[39] The increased acid load dam- in cell proteins, such as adhesion proteins. H. pylori has
ages the duodenum, which may eventually result in ulcers been proposed to induce inammation and locally high
forming in the duodenum.
levels of TNF- and/or interleukin 6 (IL-6). According
When H. pylori colonizes other areas of the stomach, the to the proposed perigenetic mechanism, inammationinammatory response can result in atrophy of the stom- associated signaling molecules, such as TNF-, can alter
ach lining and eventually ulcers in the stomach. This also gastric epithelial cell adhesion and lead to the dispersion
and migration of mutated epithelial cells without the need
may increase the risk of stomach cancer.[40]
for additional mutations in tumor suppressor genes, such
as genes that code for cell adhesion proteins.[46]

3.3

The Cag pathogenicity island

The strain of H. pylori to which a person is exposed may

inuence the risk of developing gastric cancer. Strains of
H. pylori that produce high levels of two proteins, vacuolating toxin A (VacA) and the cytotoxin-associated gene
A (CagA), appear to cause greater tissue damage than
those that produce lower levels or that lack those genes
completely.These proteins are directly toxic to cells lining the stomach and signal strongly to the immune system
that an invasion is underway. As a result of the bacterial
presence, neutrophils and macrophages set up residence
in the tissue to ght the bacteria assault. [47]

The pathogenicity of H. pylori may be increased by genes

of the cag pathogenicity island. About 5070% of H. pylori strains in Western countries carry the cag pathogenicity island (cag PAI).[41] Western patients infected with
strains carrying the cag PAI have a stronger inammatory 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.[12] Following attachment of H. pylori to stomach epithelial cells, the
type IV secretion system expressed by the cag PAI injects the inammation-inducing agent, peptidoglycan,
from their own cell wall into the epithelial cells. The
injected peptidoglycan is recognized by the cytoplas- 4 Diagnosis
mic pattern recognition receptor (immune sensor) Nod1,
which then stimulates expression of cytokines that pro- Colonization with H. pylori is not a disease in and of itmote inammation.[42]
self, but a condition associated with a number of disorThe type-IV secretion apparatus also injects the cag ders of the upper gastrointestinal tract.[12] Testing for H.
PAI-encoded protein CagA into the stomachs epithe- pylori is recommended if there is peptic ulcer disease,
lial cells, where it disrupts the cytoskeleton, adherence low grade gastric MALT lymphoma, after endoscopic
to adjacent cells, intracellular signaling, cell polarity, resection of early gastric cancer, if there are rst deand other cellular activities.[43] Once inside the cell, the gree relatives with gastric cancer, and in certain cases
CagA protein is phosphorylated on tyrosine residues by of dyspepsia,[48] not routinely.[12] Several ways of testing
a host cell membrane-associated tyrosine kinase (TK). exist. One can test noninvasively for H. pylori infection

TREATMENT

Recent evidence suggests that H. pylori may be benecial

by helping regulate levels of stomach acids, thus creating
an environment that suits itself and its host. If the stomach churns out too much acid for the bacteria to thrive,
for example, strains of the bacteria that contain a gene
called cagA start producing proteins that signal the stomach to tone down the ow of acid, in susceptible people,
however, cagA has an unwelcome side eect: provoking
the ulcers that earned H. pylori its nasty rap.[58]

H. pylori colonized on the surface of regenerative epithelium (image from Warthin-Starrys silver stain)

with a blood antibody test, stool antigen test, or with the

carbon urea breath test (in which the patient drinks 14 C
or 13 C-labelled urea, which the bacterium metabolizes,
producing labelled carbon dioxide that can be detected in
the breath).[48] Also, a urine ELISA test with a 96% sensitivity and 79% specicity is available. 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 aect H. pylori urease activity and give false negatives
with the urea-based tests. The most reliable method for
detecting H. pylori infection is with a histological examination from two sites after endoscopic biopsy, combined
with either a rapid urease test or microbial culture.[49]

Prevention

H. pylori is a major cause of certain diseases of the upper gastrointestinal tract. Rising antibiotic resistance increases the need to search for new therapeutic strategies; this might include prevention in form of vaccination. [50] Much work has been done on developing viable vaccines aimed at providing an alternative strategy to
control H. pylori infection and related diseases, including
stomach cancer. [51] Researchers are studying dierent
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. [52] An economic evaluation of
the use of a potential H. pylori vaccine in babies found
its introduction could, at least in the Netherlands, prove
cost-eective for the prevention of peptic ulcer and stomach cancer. [53] A similar approach has also been studied
for the United States. [54]

H. pylori may play a role in regulating appetite When

you have H. pylori, you have a postprandial decrease in
ghrelin. When you eradicate H. pylori, you lose that.
Ghrelin is a hormone which tells the brain that the body
needs to eat. [58]

6 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 the ulcer to heal. The standard rst-line therapy is a one-week
triple therapy consisting of proton pump inhibitors such
as omeprazole and the antibiotics clarithromycin and
amoxicillin.[59] Variations of the triple therapy have been
developed over the years, such as using a dierent proton
pump inhibitor, as with pantoprazole or rabeprazole, or
replacing amoxicillin with metronidazole for people who
are allergic to penicillin.[60] 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.[61][62]
An increasing number of infected individuals are found
to harbor 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,
such as bismuth subsalicylate.[48][63][64] For the treatment of clarithromycin-resistant strains of H. pylori, the
use of levooxacin as part of the therapy has been
suggested.[65][66]

Ingesting lactic acid bacteria exerts a suppressive eect

The presence of bacteria in the stomach may be ben- on H. pylori infection in both animals and humans, and
ecial, reducing the prevalence of asthma, [55] rhinitis, supplementing with Lactobacillus- and Bidobacteriumimproved the rates of eradication of H.
[55]
dermatitis, [55] inammatory bowel disease, [55] containing yogurt[67]
pylori
in
humans.
[56]
gastroesophageal reux disease,
and esophageal cancer [56] by inuencing systemic immune responses. [55] The substance sulforaphane, which occurs in broccoli and
[57]
cauliower, has been proposed as a treatment.[68][69][70]

Prognosis

Survival of H. pylori

pathogens, surviving the DNA damage induced by oxidative stress appears to be supported by transformationH. pylori colonizes the stomach and induces chronic mediated recombinational repair. Thus, transformation
gastritis, a long-lasting inammation of the stomach. The and recombinational repair appear to contribute to sucbacterium persists in the stomach for decades in most cessful infection.
people. Most individuals infected by H. pylori will never Transformation (the transfer of DNA from one bacteexperience clinical symptoms despite having chronic gas- rial cell to another through the intervening medium) aptritis. About 1020% of those colonized by H. pylori pears to be part of an adaptation for DNA repair. H.
will ultimately develop gastric and duodenal ulcers.[12] H. pylori is naturally competent for transformation. While
pylori infection is also associated with a 12% lifetime many organisms are competent only under certain envirisk of stomach cancer and a less than 1% risk of gastric ronmental conditions, such as starvation, H. pylori is comMALT lymphoma.[12]
petent throughout logarithmic growth.[82] All organisms
In the absence of treatment, H. pylori infectiononce es- encode genetic programs for response to stressful[82]conIn
tablished in its gastric nicheis widely believed to per- ditions including those that cause DNA damage.
H.
pylori,
homologous
recombination
is
required
for
re[6]
sist for life. In the elderly, however, infection likely can
disappear as the stomachs mucosa becomes increasingly pairing DNA double-strand breaks (DSBs). The AddAB
atrophic and inhospitable to colonization. The proportion helicase-nuclease complex resects DSBs and loads RecA
of acute infections that persist is not known, but several onto single-strand DNA (ssDNA), which then mediates
studies that followed the natural history in populations strand exchange, leading to homologous recombination
and repair. The requirement of RecA plus AddAB
have reported apparent spontaneous elimination.[71][72]
for ecient gastric colonization suggests, in the stomMounting evidence suggests H. pylori has an important ach, H. pylori is either exposed to double-strand DNA
role in protection from some diseases. The incidence of damage that must be repaired or requires some other
acid reux disease, Barretts esophagus, and esophageal recombination-mediated event. In particular, natural
cancer have been rising dramatically at the same time transformation is increased by DNA damage in H. pyas H. pylori's presence decreases.[73] In 1996, Martin lori, and a connection exists between the DNA damage
J. Blaser advanced the hypothesis that H. pylori has a response and DNA uptake in H. pylori,[82] suggesting natbenecial eect: by regulating the acidity of the stom- ural competence contributes to persistence of H. pylori in
ach contents.[38][73] The hypothesis is not universally ac- its human host and explains the retention of competence
cepted as several randomized controlled trials failed to in most clinical isolates.
demonstrate worsening of acid reux disease symptoms
following eradication of H. pylori.[74][75] Nevertheless, RuvC protein is essential to the process of recombinaBlaser has reasserted his view that H. pylori is a member tional repair since it resolves intermediates in this proof the normal ora of the stomach.[76] He postulates that cess termed Holliday junctions. H. pylori mutants that
the changes in gastric physiology caused by the loss of are defective in RuvC have increased sensitivity to DNAH. pylori account for the recent increase in incidence of damaging agents and to oxidative stress, exhibit reduced
to estabseveral diseases, including type 2 diabetes, obesity, and survival within macrophages, and are unable
[83]
lish
successful
infection
in
a
mouse
model.
Similarly,
[76][77]
asthma.
His group has recently shown that H. pyprotein plays an important role in DSB repair in H.
lori colonization is associated with a lower incidence of RecN [84]
pylori.
An H. pylori recN mutant displays an attenu[78]
childhood asthma.
ated ability to colonize mouse stomachs, highlighting the
importance of recombinational DNA repair in survival of
H. pylori within its host.[84]

The pathogenesis of H. pylori depends on its ability to

survive in the harsh gastric environment characterized by
acidity, peristalsis, and attack by phagocytes accompanied by release of reactive oxygen species.[79] In particular, H. pylori elicits an oxidative stress response during
host colonization. This oxidative stress response induces
potentially lethal and mutagenic oxidative DNA adducts
in the H. pylori genome.[80]
Vulnerability to oxidative stress and oxidative DNA
damage occurs commonly in many studied bacterial
pathogens, including Neisseria gonorrhoeae, Hemophilus
inuenzae, Streptococcus pneumoniae, Streptococcus mutans and Helicobacter pylori.[81] For each of these

9 Epidemiology
At least half the worlds population is infected by the
bacterium, making it the most widespread infection in
the world.[85] 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%.[85] The age at which this bacterium is acquired
seems to inuence the possible pathologic outcome of the
infection : people infected with it at an early age are likely
to develop more intense inammation that may be followed by atrophic gastritis with a higher subsequent risk

11 HISTORY

of gastric ulcer, gastric cancer, or both. Acquisition at an

older age brings dierent gastric changes more likely to
lead to duodenal ulcer.[6] Infections are usually acquired
in early childhood in all countries.[12] However, the infection rate of children in developing nations is higher
than in industrialized nations, probably due to poor sanitary conditions, perhaps combined with lower antibiotics
usage for unrelated pathologies. In developed nations, it
is currently uncommon to nd 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.[85] The
higher prevalence among the elderly reects higher infection rates in the past when the individuals were children
rather than more recent infection at a later age of the
individual.[12] In the United States, prevalence appears
to be higher in African-American and Hispanic populations, most likely due to socioeconomic factors.[86][87]
The lower rate of infection in the West is largely attributed to higher hygiene standards 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.[88] However, antibiotic resistance is appearing in H. pylori; many metronidazole- and
clarithromycin-resistant strains are found in most parts of
the world.[89]
H. pylori is contagious, although the exact route of transmission is not known.[90][91] 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. Findings suggest H.
pylori is more easily transmitted by gastric mucus than
saliva[6] Transmission occurs mainly within families in
developed nations, yet can also be acquired from the community in developing countries.[92] 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.[6]

10

Evolution

H. pylori migrated out of Africa along with its human

host circa 60,000 years ago.[93] Its subsequent evolution
created seven prototypesEurope (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 South Africa),
Asia2 (from Northern India and among isolates from
Bangladesh, Thailand, and Malaysia), Sahul (from Australian Aboriginals and Papua New Guineans) and East
Asia with the subpopulations E Asia (from East Asians),
Maori (from Taiwanese Aboriginals, Melanesians and
Polynesians) and Amerind (Native Americans). The precursors of these prototypes have been named ancestral
Europe1, ancestral Europe2, ancestral East Asia, an-

cestral Africa1, ancestral Africa2, and ancestral Sahul.

These ancestral prototypes appear to have originated in
Africa and Central and East Asia. European and African
strains were introduced into the Americas along with its
colonisationboth thousands of years ago and more recently in the slave trade.
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, researchers have created simulations that indicate
the bacteria seem 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, and it has remained associated with human
hosts since that time.[94]

11 History
See also: Timeline of peptic ulcer disease and Helicobacter pylori
H. pylori was rst discovered in the stomachs of patients with gastritis and ulcers in 1982 by Drs. Barry
Marshall and Robin Warren of Perth, Australia. At the
time, the conventional thinking was that no bacterium
could live in the acid environment of the human stomach. In recognition of their discovery, Marshall and Warren were awarded the 2005 Nobel Prize in Physiology or
Medicine.[95]
Before the research of Marshall and Warren, German
scientists found spiral-shaped bacteria in the lining of
the human stomach in 1875, but they were unable to
culture them, and the results were eventually forgotten.[73]
The Italian researcher Giulio Bizzozero described similarly shaped bacteria living in the acidic environment of
the stomach of dogs in 1893.[96] Professor Walery Jaworski of the Jagiellonian University in Krakw 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 rst to suggest a
possible role of this organism in the pathogenesis of gastric diseases. His work was included in the Handbook of
Gastric Diseases, but it had little impact, as it was written
in Polish.[97] Several small studies conducted in the early
20th century demonstrated the presence of curved rods
in the stomach of many patients with peptic ulcers and
stomach cancer.[98] Interest in the bacteria waned, however, when an American study published in 1954 failed
to observe the bacteria in 1180 stomach biopsies.[99]
Interest in understanding the role of bacteria in stomach
diseases was rekindled in the 1970s, with the visualization
of bacteria in the stomachs of gastric ulcer patients.[100]
The bacteria had also been observed in 1979, by Robin
Warren, who researched it further with Barry Marshall

7
from 1981. After unsuccessful attempts at culturing the
bacteria from the stomach, they nally succeeded in visualizing colonies in 1982, when they unintentionally left
their Petri dishes incubating for ve days over the Easter
weekend. In their original paper, Warren and Marshall
contended that most stomach ulcers and gastritis were
caused by bacterial infection and not by stress or spicy
food, as had been assumed before.[101]
Although some skepticism was expressed initially, within
several years multiple research groups had veried the association of H. pylori with gastritis and, to a lesser extent,
ulcers.[102] To demonstrate H. pylori caused gastritis and
was not merely a bystander, Marshall drank a beaker of
H. pylori culture. He became ill with nausea and vomiting several days later. An endoscopy 10 days after inoculation revealed signs of gastritis and the presence of H.
pylori. These results suggested H. pylori was the causative
agent. Marshall and Warren went on to demonstrate antibiotics are eective in the treatment of many cases of
gastritis. In 1987, the Sydney gastroenterologist Thomas
Borody invented the rst triple therapy for the treatment
of duodenal ulcers.[103] In 1994, the National Institutes of
Health stated most recurrent duodenal and gastric ulcers
were caused by H. pylori, and recommended antibiotics
be included in the treatment regimen.[104]
The bacterium was initially named Campylobacter pyloridis, then renamed C. pylori (pylori being the genitive
of pylorus, the circular opening leading from the stomach into the duodenum, from the Ancient Greek word
, which means gatekeeper.[105] ). When 16S
ribosomal RNA 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 from the ancient Greek hlix/ spiral
or coil.[105]
In October 1987, a group of experts met in Copenhagen to found the European Helicobacter Study Group
(EHSG), an international multidisciplinary research
group and the only institution focused on H. pylori.[106]
The Group is involved with the Annual International
Workshop on Helicobacter and Related Bacteria,[107] the
Maastricht Consensus Reports (European Consensus on
the management of H. pylori),[108][109][110][111] and other
educational and research projects, including two international long-term projects:
European Registry on H. pylori Management
(Hp-EuReg) a database systematically registering the routine clinical practice of European
gastroenterologists.[112]
Optimal H. pylori management in primary care (OptiCare) a long-term educational project aiming
to disseminate the evidence based recommendations of the Maastricht IV Consensus to primary
care physicians in Europe, funded by an educational
grant from United European Gastroenterology.[113]

12 See also
List of oncogenic bacteria
Infectious causes of cancer

13 References
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with central serous chorioretinopathy: Hypotheses regarding pathogenesis. Medical Hypotheses 63 (3): 524
7. doi:10.1016/j.mehy.2004.02.020. PMID 15288381.
[2] Ahnoux-Zabsonre A, Quaranta M, Mauget-Fasse M
(2004). Prvalence de l'Helicobacter pylori dans la
choriortinopathie sreuse centrale et l'pithliopathie
rtinienne diuse [Prevalence of Helicobacter pylori
in central serous chorioretinopathy and diuse retinal epitheliopathy: a complementary study]. Journal Franais d'Ophtalmologie (in French) 27 (10):
112933. doi:10.1016/S0181-5512(04)96281-X. PMID
15687922.
[3] Cotticelli L, Borrelli M, D'Alessio AC, Menzione M, Villani A, Piccolo G, Montella F, Iovene MR, Romano M
(2006). Central serous chorioretinopathy and Helicobacter pylori. European journal of ophthalmology 16 (2):
2748. PMID 16703546.
[4] Blaser MJ (2006). Who are we? Indigenous microbes
and the ecology of human diseases (PDF). EMBO Reports
7 (10): 95660. doi:10.1038/sj.embor.7400812. PMC
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14

EXTERNAL LINKS

14 External links
Information on tests for H. pylori from the National
Institutes of Health
European Helicobacter Study Group (EHSG)

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15
15.1

Text and image sources, contributors, and licenses

Text

Helicobacter pylori Source: http://en.wikipedia.org/wiki/Helicobacter%20pylori?oldid=659821122 Contributors: AxelBoldt, Alex.tan,

Josh Grosse, Kowloonese, Azhyd, Zocky, Zashaw, GTBacchus, J'raxis, JWSchmidt, Marco Krohn, Ehn, Dcoetzee, Peregrine981, Tpbradbury, Taxman, SEWilco, Oaktree b, Pollinator, Phil Boswell, Robbot, Dale Arnett, Fredrik, Peak, Mirv, UtherSRG, Fuelbottle,
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File:Ulcer-causing_Bacterium_(H.Pylori)_Crossing_Mucus_Layer_of_Stomach.jpg Source:
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