|Immunohistochemical staining of H. pylori from a gastric biopsy|
|Specialty||Infectious disease, gastroenterology|
|Symptoms||None, abdominal pain, nausea|
|Complications||Stomach ulcer, stomach cancer|
|Causes||Helicobacter pylori spread by fecal oral route|
|Diagnostic method||Urea breath test, fecal antigen assay, tissue biopsy|
|Medication||Proton pump inhibitor, clarithromycin, amoxicillin, metronidazole|
Helicobacter pylori, previously known as Campylobacter pylori, is a Gram-negative, microaerophilic bacterium usually found in the stomach. It was identified in 1982 by Australian scientists Barry Marshall and Robin Warren, who found that it was present in a person 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.
A microaerophile is a microorganism that requires oxygen to survive, but requires environments containing lower levels of oxygen than are present in the atmosphere (i.e. <21% O2; typically 2–10% O2). Many microaerophiles are also capnophiles, requiring an elevated concentration of carbon dioxide (e.g. 10% CO2 in the case of Campylobacter species).
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital digestive organ. In the digestive system the stomach is involved in the second phase of digestion, following mastication (chewing).
Barry James Marshall, AC, FRACP, FRS, FAA is an Australian physician, Nobel Prize Laureate in Physiology or Medicine, and Professor of Clinical Microbiology at the University of Western Australia. Marshall and Robin Warren showed that the bacterium Helicobacter pylori plays a major role in causing many peptic ulcers, challenging decades of medical doctrine holding that ulcers were caused primarily by stress, spicy foods, and too much acid. This discovery has allowed for a breakthrough in understanding a causative link between Helicobacter pylori infection and stomach cancer.
More than 50% of the world's population has H. pylori in their upper gastrointestinal tracts.Infection is more common in developing countries than Western countries. H. pylori's helical shape (from which the genus name derives) is thought to have evolved to penetrate the mucoid lining of the stomach.
The gastrointestinal tract is an organ system within humans and other animals which takes in food, digests it to extract and absorb energy and nutrients, and expels the remaining waste as feces. The mouth, esophagus, stomach and intestines are part of the gastrointestinal tract. Gastrointestinal is an adjective meaning of or pertaining to the stomach and intestines. A tract is a collection of related anatomic structures or a series of connected body organs.
A genus is a taxonomic rank used in the biological classification of living and fossil organisms, as well as viruses, in biology. In the hierarchy of biological classification, genus comes above species and below family. In binomial nomenclature, the genus name forms the first part of the binomial species name for each species within the genus.
Mucus is a polymer. It is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is a viscous colloid containing inorganic salts, antiseptic enzymes, immunoglobulins, and glycoproteins such as lactoferrin and mucins, which are produced by goblet cells in the mucous membranes and submucosal glands. Mucus serves to protect epithelial cells in the respiratory, gastrointestinal, urogenital, visual, and auditory systems; the epidermis in amphibians; and the gills in fish, against infectious agents such as fungi, bacteria and viruses. Most of the mucus produced is in the gastrointestinal tract.
Up to 85% of people infected with H. pylori never experience symptoms or complications.Acute infection may appear as an acute gastritis with abdominal pain (stomach ache) or nausea. Where this develops into chronic gastritis, the symptoms, if present, are often those of nonulcer dyspepsia: stomach pains, nausea, bloating, belching, and sometimes vomiting or black stool.
In medicine, describing a disease as acute denotes that it is of short duration and, as a corollary of that, of recent onset. The quantitation of how much time constitutes "short" and "recent" varies by disease and by context, but the core denotation of "acute" is always qualitatively in contrast with "chronic", which denotes long-lasting disease. In addition, "acute" also often connotes two other meanings: sudden onset and severity, such as in acute myocardial infarction (AMI), where suddenness and severity are both established aspects of the meaning. It thus often connotes that the condition is fulminant, but not always. The one thing that acute MI and acute rhinitis have in common is that they are not chronic. They can happen again, but they are not the same case ongoing for months or years.
Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain. Other possible symptoms include nausea and vomiting, bloating, loss of appetite and heartburn. Complications may include bleeding, stomach ulcers, and stomach tumors. When due to autoimmune problems, low red blood cells due to not enough vitamin B12 may occur, a condition known as pernicious anemia.
Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues.
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.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. However, H. pylori possibly plays a role only in the first stage that leads to common chronic inflammation, but not in further stages leading to carcinogenesis. A meta-analysis conducted in 2009 concluded the eradication of H. pylori reduces gastric cancer risk in previously infected individuals, suggesting the continued presence of H. pylori constitutes a relative risk factor of 65% for gastric cancers; in terms of absolute risk, the increase was from 1.1% to 1.7%.
Stomach cancer, also known as gastric cancer, is a cancer which develops from the lining of the stomach. Early symptoms may include heartburn, upper abdominal pain, nausea and loss of appetite. Later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes, vomiting, difficulty swallowing and blood in the stool among others. The cancer may spread from the stomach to other parts of the body, particularly the liver, lungs, bones, lining of the abdomen and lymph nodes.
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine may be used instead of duodenum. In mammals the duodenum may be the principal site for iron absorption.
Carcinoma is a category of types of cancer that develop from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.
Helicobacter pylori has been associated with colorectal polyps and colorectal cancer.It may also be associated with eye disease.
Colorectal cancer (CRC), also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum. A cancer is the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and feeling tired all the time.
Pain typically occurs when the stomach is empty, between meals, and in the early morning hours, but it can also occur at other times. Less common ulcer symptoms include nausea, vomiting, and loss of appetite. Bleeding can also occur; prolonged bleeding may cause anemia leading to weakness and fatigue. If bleeding is heavy, hematemesis, hematochezia, or melena may occur.
Hematemesis is the vomiting of blood. The source is generally the upper gastrointestinal tract, typically above the suspensory muscle of duodenum. Patients can easily confuse it with hemoptysis, although the latter is more common. Hematemesis "is always an important sign".
Hematochezia is the passage of fresh blood through the anus, usually in or with stools. The term is from Greek αἷμα ("blood") and χέζειν. Hematochezia is commonly associated with lower gastrointestinal bleeding, but may also occur from a brisk upper gastrointestinal bleed. The difference between hematochezia and rectorrhagia is that, in the latter, rectal bleeding is not associated with defecation; instead, it is associated with expulsion of fresh bright red blood without stools. The phrase bright red blood per rectum (BRBPR) is associated with hematochezia and rectorrhagia.
Melena refers to the dark black, tarry feces that are associated with upper gastrointestinal bleeding. The black color and characteristic strong odor are caused by hemoglobin in the blood being altered by digestive enzymes and intestinal bacteria.
(Marshall et al. 1985) Goodwin et al., 1989
Helicobacter pylori is a helix-shaped (classified as a curved rod, not spirochaete) Gram-negative bacterium about 3 μm long with a diameter of about 0.5μm. H. pylori can be demonstrated in tissue by Gram stain, Giemsa stain, haematoxylin–eosin stain, Warthin–Starry silver stain, acridine orange stain, and phase-contrast microscopy. It is capable of forming biofilms and can convert from spiral to a possibly viable but nonculturable coccoid form.
Helicobacter pylori has four to six flagella at the same location; all gastric and enterohepatic Helicobacter species are highly motile owing to flagella.The characteristic sheathed flagellar filaments of Helicobacter are composed of two copolymerized flagellins, FlaA and FlaB.
Helicobacter pylori is microaerophilic—that is, it requires oxygen, but at lower concentration than in the atmosphere. It contains a hydrogenase that can produce energy by oxidizing molecular hydrogen (H2) made by intestinal bacteria.It produces oxidase, catalase, and urease.
H. pylori possesses five major outer membrane protein families.The largest family includes known and putative adhesins. The other four families are 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 are present in few other bacteria.
Helicobacter pylori consists of a large diversity of strains, and hundreds of genomes have been completely sequenced.The genome of the strain "26695" consists of about 1.7 million base pairs, with some 1,576 genes. The pan-genome, that is a combined set of 30 sequenced strains, encodes 2,239 protein families (orthologous groups, OGs). Among them, 1248 OGs are conserved in all the 30 strains, and represent the universal core. The remaining 991 OGs correspond to the accessory genome in which 277 OGs are unique (i.e., OGs present in only one strain).
In 2010, Sharma et al. presented a comprehensive analysis of transcription at single-nucleotide resolution by differential RNA-seq that confirmed the known acid induction of major virulence loci, such as the urease (ure) operon or the cag pathogenicity island (see below).More importantly, this study identified a total of 1,907 transcriptional start sites, 337 primary operons, and 126 additional suboperons, and 66 monocistrons. Until 2010, only about 55 transcriptional start sites (TSSs) were known in this species. Notably, 27% of the primary TSSs are also antisense TSSs, indicating that—similar to E. coli —antisense transcription occurs across the entire H. pylori genome. At least one antisense TSS is associated with about 46% of all open reading frames, including many housekeeping genes. Most (about 50%) of the 5' UTRs are 20–40 nucleotides (nt) in length and support the AAGGag motif located about 6 nt (median distance) upstream of start codons as the consensus Shine–Dalgarno sequence in H. pylori.
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 have a colonization defect when mutated. 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.
The cagA gene codes for one of the major H. pylori virulence proteins. Bacterial strains with 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 the island was acquired by horizontal transfer from another bacterial species.
To avoid the acidic environment of the interior of the stomach (lumen), H. pylori uses its flagella to burrow into the mucus lining of the stomach to reach the epithelial cells underneath, where it is less acidic.H. pylori is able to sense the pH gradient in the mucus and move towards the less acidic region (chemotaxis). This also keeps the bacteria from being swept away into the lumen with the bacteria's mucus environment, which is constantly moving from its site of creation at the epithelium to its dissolution at the lumen interface.
H. pylori is found in the mucus, on the inner surface of the epithelium, and occasionally inside the epithelial cells themselves.It adheres to the epithelial cells by producing adhesins, which bind to lipids and carbohydrates in the epithelial cell membrane. One such adhesin, BabA, binds to the Lewis b antigen displayed on the surface of stomach epithelial cells. H. pylori adherence via BabA is acid sensitive and can be fully reversed by increased pH. It has been proposed that BabA's acid responsiveness enables adherence while also allowing an effective escape from unfavorable environment at pH that is harmful to the organism. Another such adhesin, SabA, binds to increased levels of sialyl-Lewis x antigen expressed on gastric mucosa.
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. These react with the strong acids in the environment to produce a neutralized area around H. pylori.Urease knockout mutants are incapable of colonization. In fact, urease expression is not only required for establishing initial colonization but also for maintaining chronic infection.
Helicobacter pylori harms the stomach and duodenal linings by several mechanisms. The ammonia produced to regulate pH is toxic to epithelial cells, as are biochemicals produced by H. pylori such as proteases, vacuolating cytotoxin A (VacA) (this damages epithelial cells, disrupts tight junctions and causes apoptosis), and certain phospholipases.Cytotoxin associated gene CagA can also cause inflammation and is potentially a carcinogen.
Colonization of the stomach by H. pylori can result in chronic gastritis, an inflammation 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 inflammation.. H. Pylori has been shown to increase the levels of COX2 in H. Pylori positive gastritis. Chronic gastritis is likely to underlie H. pylori-related diseases.
Ulcers in the stomach and duodenum result when the consequences of inflammation 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 affects the location of the ulcer, depends on the acidity of the stomach.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). In people producing normal or reduced amounts of acid, H. pylori can also colonize the rest of the stomach.
The inflammatory response caused by bacteria colonizing near the pyloric antrum induces G cells in the antrum to secrete the hormone gastrin, which travels through the bloodstream to parietal cells in the fundus.Gastrin stimulates the parietal cells to secrete more acid into the stomach lumen, and over time increases the number of parietal cells, as well. The increased acid load damages the duodenum, which may eventually result in ulcers forming in the duodenum.
When H. pylori colonizes other areas of the stomach, the inflammatory response can result in atrophy of the stomach lining and eventually ulcers in the stomach. This also may increase the risk of stomach cancer.
The pathogenicity of H. pylori may be increased by genes of the cag pathogenicity island; about 50–70% of H. pylori strains in Western countries carry it.Western people 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 inflammation-inducing agent, peptidoglycan, from their own cell walls into the 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.
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, cell polarity, and other cellular activities.Once inside the cell, the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase (TK). CagA then allosterically activates protein tyrosine phosphatase/protooncogene Shp2. 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 873–1002) has also been suggested to be able to regulate host cell gene transcription, independent of protein tyrosine phosphorylation. A great deal of diversity exists between strains of H. pylori, and the strain that infects a person can predict the outcome.
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. H. pylori has been proposed to induce inflammation and locally high levels of TNF-α and/or interleukin 6 (IL-6). According to the proposed perigenetic mechanism, inflammation-associated signaling molecules, such as TNF-α, 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.
The strain of H. pylori a person is exposed to may influence 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 under way. As a result of the bacterial presence, neutrophils and macrophages set up residence in the tissue to fight the bacteria assault.
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.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.
Vulnerability to oxidative stress and oxidative DNA damage occurs commonly in many studied bacterial pathogens, including Neisseria gonorrhoeae, Hemophilus influenzae, Streptococcus pneumoniae, S. mutans, and H. pylori.For each of these pathogens, surviving the DNA damage induced by oxidative stress appears supported by transformation-mediated recombinational repair. Thus, transformation and recombinational repair appear to contribute to successful infection.
Transformation (the transfer of DNA from one bacterial cell to another through the intervening medium) appears to be part of an adaptation for DNA repair. H. pylori is naturally competent for transformation. While many organisms are competent only under certain environmental conditions, such as starvation, H. pylori is competent throughout logarithmic growth.All organisms encode genetic programs for response to stressful conditions including those that cause DNA damage. In H. pylori, homologous recombination is required for repairing DNA double-strand breaks (DSBs). The AddAB helicase-nuclease complex resects DSBs and loads RecA onto single-strand DNA (ssDNA), which then mediates strand exchange, leading to homologous recombination and repair. The requirement of RecA plus AddAB for efficient gastric colonization suggests, in the stomach, H. pylori is either exposed to double-strand DNA damage that must be repaired or requires some other recombination-mediated event. In particular, natural transformation is increased by DNA damage in H. pylori, and a connection exists between the DNA damage response and DNA uptake in H. pylori, suggesting natural competence contributes to persistence of H. pylori in its human host and explains the retention of competence in most clinical isolates.
RuvC protein is essential to the process of recombinational repair, since it resolves intermediates in this process termed Holliday junctions. H. pylori mutants that are defective in RuvC have increased sensitivity to DNA-damaging agents and to oxidative stress, exhibit reduced survival within macrophages, and are unable to establish successful infection in a mouse model.Similarly, RecN protein plays an important role in DSB repair in H. pylori. An H. pylorirecN mutant displays an attenuated ability to colonize mouse stomachs, highlighting the importance of recombinational DNA repair in survival of H. pylori within its host.
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.Testing for H. pylori is not routinely recommended. Testing is recommended if peptic ulcer disease or low-grade gastric MALT lymphoma is present, after endoscopic resection of early gastric cancer, for first-degree relatives with gastric cancer, and in certain cases of dyspepsia. Several methods of testing exist, including invasive and noninvasive testing methods.
Noninvasive tests for H. pylori infection may be suitable and include blood antibody tests, stool antigen test s, or 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).It is not known which non-invasive test is more accurate for diagnosing a H. pylori infection, and the clinical significance of the levels obtained with these tests are not clear. Some drugs can affect H. pylori urease activity and give false negatives with the urea-based tests.
An endoscopic biopsy is an invasive means to test for H. pylori infection. Low-level infections can be missed by biopsy, so multiple samples are recommended. The most accurate 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.
Helicobacter 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 the form of vaccination.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. Researchers are studying 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. 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-effective for the prevention of peptic ulcer and stomach cancer. A similar approach has also been studied for the United States.
The presence of bacteria in the stomach may be beneficial, reducing the prevalence of asthma,rhinitis, dermatitis, inflammatory bowel disease, gastroesophageal reflux disease, and esophageal cancer by influencing systemic immune responses.
Recent evidence suggests that nonpathogenic strains of H. pylori may be beneficial, e.g., by normalizing stomach acid secretion,and may play a role in regulating appetite, since its presence in the stomach results in a persistent but reversible reduction in the level of ghrelin.
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 first-line therapy is a one-week "triple therapy" consisting of proton-pump inhibitors such as omeprazole and the antibiotics clarithromycin and amoxicillin.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. In areas with higher rates of clarithromycin resistance, other options are recommended. 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 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.For the treatment of clarithromycin-resistant strains of H. pylori, the use of levofloxacin as part of the therapy has been suggested.
Ingesting lactic acid bacteria exerts a suppressive effect on H. pylori infection in both animals and humans, and supplementing with Lactobacillus - and Bifidobacterium -containing yogurt improved the rates of eradication of H. pylori in humans.Symbiotic butyrate-producing bacteria which are normally present in the intestine are sometimes used as probiotics to help suppress H. pylori infections as an adjunct to antibiotic therapy. Butyrate itself is an antimicrobial which destroys the cell envelope of H. pylori by inducing regulatory T cell expression (specifically, FOXP3) and synthesis of an antimicrobial peptide called LL-37, which arises through its action as a histone deacetylase inhibitor.
The substance sulforaphane, which occurs in broccoli and cauliflower, has been proposed as a treatment.Periodontal therapy or scaling and root planing has also been suggested as an additional treatment.
Helicobacter 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 never experience clinical symptoms, despite having chronic gastritis. About 10–20% of those colonized by H. pylori 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.
In the absence of treatment, H. pylori infection—once established in its gastric niche—is widely believed to persist for life.In the elderly, however, infection likely 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.
Mounting evidence suggests H. pylori has an important role in protection from some diseases. 's presence decreases. In 1996, Martin J. Blaser advanced the hypothesis that H. pylori has a beneficial effect by regulating the acidity of the stomach contents. 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 reasserted his view 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.The incidence of acid reflux disease, Barrett's esophagus, and esophageal cancer have been rising dramatically at the same time as H. pylori
At least half the world's population is infected by the bacterium, making it the most widespread infection in the world.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%.
The age when someone acquires this bacterium seems to influence the pathologic outcome of the infection. People infected 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.Infections are usually acquired in early childhood in all countries. 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 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. The higher prevalence among the elderly reflects higher infection rates in the past when the individuals were children rather than more recent infection at a later age of the individual. In the United States, prevalence appears higher in African-American and Hispanic populations, most likely due to socioeconomic factors. 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. However, antibiotic resistance is appearing in H. pylori; many metronidazole- and clarithromycin-resistant strains are found in most parts of the world.
Helicobacter 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. Findings suggest H. pylori is more easily transmitted by gastric mucus than saliva. 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.
Helicobacter pylori migrated out of Africa along with its human host circa 60,000 years ago.Recent research states that genetic diversity in H. pylori, like that of its host, decreases with geographic distance from East Africa. 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.
H. pylori was first discovered in the stomachs of patients with gastritis and ulcers in 1982 by Drs. Barry Marshall and Robin Warren of Perth, Western 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.
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.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 by lavage 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. His 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 20th century demonstrated the presence of curved rods in the stomachs of many people with peptic ulcers and stomach cancers. Interest in the bacteria waned, however, 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 stomachs of people with gastric ulcers.The bacteria had also been observed in 1979, by Robin Warren, who researched it further with Barry Marshall from 1981. After 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 five 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.
Some skepticism was expressed initially, but within a few years multiple research groups had verified the association of H. pylori with gastritis and, to a lesser extent, ulcers.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 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 stated most recurrent duodenal and gastric ulcers were caused by H. pylori, and recommended antibiotics be included in the treatment regimen.
The bacterium was initially named Campylobacter pyloridis, then renamed C. pylori in 1987 (pylori being the genitive of pylorus , the circular opening leading from the stomach into the duodenum, from the Ancient Greek word πυλωρός, which means gatekeeper.). 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 hělix/έλιξ "spiral" or "coil".
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.The Group is involved with the Annual International Workshop on Helicobacter and Related Bacteria, the Maastricht Consensus Reports (European Consensus on the management of H. pylori), and other educational and research projects, including two international long-term projects:
Results from in vitro studies suggest that fatty acids, mainly polyunsaturated fatty acids, have a bactericidal effect against H. pylori, but their in vivo effects have not been proven.
The urea breath test is a rapid diagnostic procedure used to identify infections by Helicobacter pylori, a spiral bacterium implicated in gastritis, gastric ulcer, and peptic ulcer disease. It is based upon the ability of H. pylori to convert urea to ammonia and carbon dioxide. Urea breath tests are recommended in leading society guidelines as a preferred non-invasive choice for detecting H. pylori before and after treatment.
Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, first part of the small intestine or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while that in the first part of the intestines is a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain or upper abdominal pain that improves with eating. With a gastric ulcer the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms. Complications may include bleeding, perforation and blockage of the stomach. Bleeding occurs in as many as 15% of people.
Helicobacter is a genus of Gram-negative bacteria possessing a characteristic helical shape. They were initially considered to be members of the genus Campylobacter, but in 1989, Goodwin et al. published sufficient reasons to justify the new genus name Helicobacter. The genus Helicobacter contains about 35 species.
Virulence is a pathogen's or microbe's ability to infect or damage a host.
Achlorhydria, also known as hypochlorhydria, refers to states where the production of hydrochloric acid in gastric secretions of the stomach and other digestive organs is absent or low, respectively. It is associated with various other medical problems.
Atrophic gastritis (also known as type A or type B gastritis) is a process of chronic inflammation of the stomach mucous membrane (mucosa), leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems. The most common are vitamin B12 deficiency which results in a megaloblastic anemia and malabsorption of iron, leading to iron deficiency anaemia. It can be caused by persistent infection with Helicobacter pylori, or can be autoimmune in origin. Those with the autoimmune version of atrophic gastritis are statistically more likely to develop gastric carcinoma, Hashimoto's thyroiditis, and achlorhydria.
MALT lymphoma (MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be afflicted. It is a cancer originating from B cells in the marginal zone of the MALT, and is also called extranodal marginal zone B cell lymphoma.
Martin J. Blaser(born 1948) is the Muriel G. and George W. Singer Professor of Translational Medicine, Director of the NYU Human Microbiome Program, former Chair of the Department of Medicine, and Professor of Microbiology at New York University School of Medicine. In mid-January 2019, Blaser will become the next director of the Center for Advanced Biotechnology and Medicine (CABM) at Rutgers (NJ) Biomedical and Health Sciences (RBHS) and the Henry Rutgers Chair of the Human Microbiome and professor of medicine and microbiology at the Rutgers Robert Wood Johnson Medical School in New Jersey.
Ménétrier disease is a rare, acquired, premalignant disease of the stomach characterized by massive gastric folds, excessive mucous production with resultant protein loss, and little or no acid production. The disorder is associated with excessive secretion of transforming growth factor alpha (TGF-α). It is named after a French physician Pierre Eugène Ménétrier, 1859–1935.
This is a timeline of the events relating to the discovery that peptic ulcer disease and some cancers are caused by H. pylori. In 2005, Barry Marshall and Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery that peptic ulcer disease (PUD) was primarily caused by Helicobacter pylori, a bacterium with affinity for acidic environments, such as the stomach. As a result, PUD that is associated with H. pylori is currently treated with antibiotics used to eradicate the infection. For decades prior to their discovery, it was widely believed that PUD was caused by excess acid in the stomach. During this time, acid control was the primary method of treatment for PUD, to only partial success. Among other effects, it is now known that acid suppression alters the stomach milieu to make it less amenable to H. pylori infection.
Cancer bacteria are bacteria infectious organisms that are known or suspected to cause cancer. While cancer-associated bacteria have long been considered to be opportunistic, there is some evidence that bacteria may be directly carcinogenic. The strongest evidence to date involves the bacterium H. pylori and its role in gastric cancer.
Helicobacter pylori eradication protocols is a standard name for all treatment protocols for peptic ulcers and gastritis; the primary goal is not only temporary relief of symptoms, but also total elimination of Helicobacter pylori infection. Patients with active duodenal or gastric ulcers and those with a prior ulcer history should be tested for H. pylori. Appropriate therapy should be given for eradication. Patients with MALT lymphoma should also be tested and treated for H. pylori since eradication of this infection can induce remission in many patients when the tumor is limited to the stomach. Several consensus conferences, including the Maastricht Consensus Report, recommend testing and treating several other groups of patients but there is limited evidence of benefit. This includes patients diagnosed with gastric adenocarcinoma, patients found to have atrophic gastritis or intestinal metaplasia, as well as first-degree relatives of patients with gastric adenocarcinoma since the relatives themselves are at increased risk of gastric cancer partly due to the intrafamilial transmission of H. pylori. To date, it remains controversial whether to test and treat all patients with functional dyspepsia, gastroesophageal reflux disease, or other non-GI disorders as well as asymptomatic individuals.
Stomach diseases include gastritis, gastroparesis, diarrhea, Crohn's disease and various cancers.
Troxipide is a drug used in the treatment of gastroesophageal reflux disease. Troxipide is a systemic non-antisecretory gastric cytoprotective agent with anti-ulcer, anti-inflammatory and mucus secreting properties irrespective of pH of stomach or duodenum. Troxipide is currently marketed in Japan (Aplace), China (Shuqi), South Korea (Defensa), and India (Troxip). It is used for the management of gastric ulcers, and amelioration of gastric mucosal lesions in acute gastritis and acute exacerbation of chronic gastritis.
The hopC RNA motif is a predicted cis-regulatory element identified by a bioinformatic screen for conserved RNA secondary structures. hopC RNAs are exclusively found within bacteria classified within the genus Helicobacter, some of which are human pathogens that infect the stomach and can cause ulcers.
Helicobacter pylori virulence factor CagA is a 120–145kDa protein encoded on the 40kb cag pathogenicity island (PAI). H. pylori strains can be divided into CagA positive or negative strains. Approximately 60% of H. pylori strains isolated in Western countries carry cag PAI, whereas almost all of the East Asian isolates are cag PAI-positive
Chronic gastritis is a chronic inflammation of the gastric mucosa.
Pepsinogen 3, group I is a protein that in humans is encoded by the PGA3 gene.
The establishment of a link between light therapy, vitamin D and human cathelicidin LL-37 expression provides a completely different way for infection treatment. Instead of treating patients with traditional antibiotics, doctors may be able to use light or vitamin D [291,292]. Indeed using narrow-band UV B light, the level of vitamin D was increased in psoriasis patients (psoriasis is a common autoimmune disease on skin) . In addition, other small molecules such as butyrate can induce LL-37 expression . Components from Traditional Chinese Medicine may regulate the AMP expression as well . These factors may induce the expression of a single peptide or multiple AMPs . It is also possible that certain factors can work together to induce AMP expression. While cyclic AMP and butyrate synergistically stimulate the expression of chicken β-defensin 9 , 4-phenylbutyrate (PBA) and 1,25-dihydroxyvitamin D3 (or lactose) can induce AMP gene expression synergistically [294,298]. It appears that stimulation of LL-37 expression by histone deacetylase (HDAC) inhibitors is cell dependent. Trichostatin and sodium butyrate increased the peptide expression in human NCI-H292 airway epithelial cells but not in the primary cultures of normal nasal epithelial cells . However, the induction of the human LL-37 expression may not be a general approach for bacterial clearance. During Salmonella enterica infection of human monocyte-derived macrophages, LL-37 is neither induced nor required for bacterial clearance .
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