Helicobacter pylori

from Wikipedia, the free encyclopedia
Helicobacter pylori
Helicobacter pylori

Helicobacter pylori

Systematics
Department : Proteobacteria
Class : Epsilonproteobacteria
Order : Campylobacterales
Family : Helicobacteraceae
Genre : Helicobacter
Type : Helicobacter pylori
Scientific name
Helicobacter pylori
( Marshall et al. 1985) Goodwin et al. 1989

Helicobacter pylori is a gram-negative , microaerophilic rod bacterium thatcan colonizethe human stomach . The spirally curved germ moves by means of its lophotrich arranged flagella . The organism is completely DNA-sequenced .

history

Before the discovery of Helicobacter pylori as the cause of ulcers in the stomach and duodenum (gastroduodenal ulcer disease), “hyperacidity of the stomach” and psychological factors were assumed to be the cause of the diseases. You have been treated with drugs that neutralize stomach acid (antacids) or block its production ( stomach acid blockers ). It was assumed that the acidic gastric environment excludes gastric flora (cf. the preliminary investigations and findings of Georg Ernst Konjetzny ), although Walter Krienitz had already observed bacteria in the stomach in 1905 .

Barry Marshall and John Robin Warren from Perth , Western Australia , discovered H. pylori in 1983 , but this was not taken seriously by medical research for a long time. It wasn't until 1989 that the breakthrough came and the bacterium was recognized worldwide as the cause of ulcers . In December 2005, Warren and Marshall were awarded half the Nobel Prize in Physiology or Medicine for their work on H. pylori .

Originally the germ was called " Campylobacter pyloridis " (after the pylorus ). It was later renamed " Campylobacter pylori ". This name fits better with the names of other pathogenic germs in the gastrointestinal tract. In 1989 it was given its current name because of its spiral shape (helix = spiral).

Further Helicobacter species have since been discovered in the stomachs of other mammals and birds.

Frequency and distribution

With a prevalence of around 50% worldwide, Helicobacter pylori infection is one of the most common chronic bacterial infections . The infection rate in developing countries is much higher than in industrialized nations . In Germany a total of about 33 million people are infected with H. pylori , of which about 10 to 20% develop a peptic ulcer .

It has been suggested at times that the occurrence of the bacterium was related to socio-economic status. However, studies from Switzerland and Germany have not been able to support this view. About seven percent of young people in Switzerland and Germany are infected with H. pylori , regardless of their status. According to previous studies, around 50 percent of older adults are contaminated with the bacterium, but not everyone develops gastroduodenal ulcer disease .

A study on 2,219 children in Leipzig found that about 2/3 of the parents of H. pylori -infected preschoolers were infected - twice as high as was statistically expected. About 40% of the children reported stomach pain. The infected children were on average 1.4 cm smaller and 1.3 kg lighter than the uninfected children.

A total of 370 strains with very large differences in the details of their DNA sequences could be detected for the bacterium, which is widespread worldwide . When comparing the bacterial genome , it was found that it is preferably passed on within families. This means that bacterial strains can be genetically differentiated in different geographical population groups. By comparing the bacterial genetic makeup, it is possible for epidemiologists and ethnologists to trace the spread of bacteria and thus indirectly the migration of mankind for at least 60,000 years.

illness

Infections with H. pylori are blamed for a number of gastrointestinal diseases associated with an increased secretion of gastric acid associated. This includes, for example, type B gastritis , around 75 percent of gastric ulcers and around 90–95% of duodenal ulcers . The examination for an infection with H. pylori is therefore an essential part of the diagnosis of gastric diseases today. Chronic H. pylori infection is a risk factor for the development of gastric cancer and MALT lymphoma . For this reason, the WHO classified H. pylori in group I of defined carcinogens in 1994 . In addition, H. pylori has been linked to many other diseases, such as: B. idiopathic chronic urticaria, chronic immune thrombocytopenia , etiologically inexplicable iron deficiency anemia, Parkinson's disease.

colonization

Helicobacter on an epithelial surface (silver color)
Gastric biopsy specimen with immunohistochemical staining

The transmission route of H. pylori has not yet been clarified. It appears to spread via the faecal-oral route, i.e. excretion of the bacterium in the stool and reabsorption through water or contaminated food. Epidemiological data also indicate the possibility of an oral-oral or gastro-oral (contact with gastric mucus infected by H. pylori during vomiting). According to the current state of knowledge, the stomach is considered to be the main reservoir for germs, which strengthens the latter views.

A possible transmission through blowflies is also discussed. The colonization with H. pylori occurs from the antrum cardiacum of the esophagus aborally in the direction of the gastric entrance ( cardia ) and gastric porter ( antrum pyloricum ). Here the germ moves by scourge strike. Specialized adhesive structures enable it to have a particularly firm connection to the epithelial cells of the gastric mucosa, which is the prerequisite for the inflammatory process.

In the stomach, the acid-sensitive H. pylori protects itself from being destroyed by gastric acid

Pathomechanism

Helicobacter pylori damage

The amount of ammonia formed by the urease reaction is normally small and, if the gastric mucous barrier is intact, it is non-toxic. Rather, the following damaging processes are described.

  • H. pylori secretes a number of enzymes that damage the mucous membrane and paralyze the body's immune system . The inflammation leads to increased gastrin - and consequently to increased gastric acid production. However, many type B gastritis have no symptoms. It is not uncommon for an additional weakening of the gastric mucosal barrier (for example, through alcohol consumption , nicotine , drugs , stress , etc.), which temporarily causes the germ to produce more ammonia in order to protect itself (ammonia crack), to develop an ulcer, usually in the area of ​​the Pylorus or in the duodenum.
  • H. pylori strains of type I have additional pathogenicity factors and are highly pathogenic with regard to gastroduodenal ulcer disease and cancer. A basic trigger is the expression of the inflammation- promoting so-called vacuolating cytotoxin (VacA gene product ). As Cesare Montecucco demonstrated between 1993 and 2000, it causes the formation of small cell sap spaces ( vacuoles ) in the epithelial cells, which fill with acid until they burst and thus destroy the tissue.
  • Researchers at the Pasteur Institute in Paris found another mechanism . As a result , the bacterium injects a peptidoglycan into the interior of the gastric epithelial cell via a needle-like extension . There it docks to a receptor and sets in motion a chain of reactions that ultimately leads to inflammation of the gastric mucosa. The mechanism is genetically coded , the corresponding section on the bacterial chromosome is referred to as the " cytotoxin-associated genes (cag) pathogenicity island ".
    Infections with H. pylori strains of type II, which lack the cag pathogenicity island and VacA secretion, are much less associated with gastroduodenal ulcer disease than infections with strains of type I.
  • In 2016, researchers at the German Center for Infection Research discovered which receptors are involved in the binding between the H. pylori bacterium and the host cell. In doing so, they were able to identify receptors on the surface of the epithelial cells, the so-called CEACAMs (carcinoembryonic antigen-cell adhesion molecules, English: carcinoembryonic antigen-related cell adhesion molecules). On the bacterial side, the protein HopQ (the abbreviation Hop stands for 'H. pylori outer membrane protein') mediates the binding, i.e. acts as an adhesin. CEACAMs are not found in healthy stomach tissue, but mainly in the case of an inflammation of the gastric mucosa caused by an infection with Helicobacter pylori . The CEACAM-HopQ molecule pair is not only important for the binding of bacteria to their host cells, but also for the pathogenic effect of the bacteria. The cause of the disease is the bacterial protein CagA .

Diagnosis

H. pylori in the electron microscope

The direct detection of H. pylori is done by taking samples (biopsies) from the lower gastrointestinal third and microscopy . The Helicobacter urease test can also be used to draw conclusions about the presence of urease from the samples and thus indirectly about the presence of the bacterium.

The germ can also be detected with a high degree of probability using a breath test . To do this, the patient swallows 13 C or 14 C isotope-labeled urea in the form of a solution together with some juice (extension of the contact time between urease and substrate by delayed gastric emptying) or in the form of a capsule with a little water. If there is an existing infection, the urea is cleaved by the urease produced by H. pylori and the 13 C or 14 C labeled carbon dioxide that is produced is detected in the exhaled air. Detection takes place at 13 C by mass spectroscopy in the laboratory or by means of infrared spectroscopy in the doctor's office, at 14 C by means of suitable radiation detectors .

The H. pylori antigen test in the stool and the detection of antibodies in the serum ( ELISA , Western blot ) are also diagnostic . Fecal antigen tests are good for children and adults and are a cost-effective method for Helicobacter pylori diagnosis.

Therapy (eradication)

Until Helicobacter pylori infection was discovered as the cause of gastric mucosal inflammation and gastroduodenal ulcer disease, therapy consisted of the administration of antacids or gastric acid blockers (proton pump inhibitors) . Today, an infection with H. pylori is first examined. (In the case of endoscopically proven duodenal ulcer, a clearly positive urease rapid test is sufficient to indicate antibiotic eradication ). In the event of infection, eradication therapy is effective to eliminate the bacterium.

According to the Maastricht guidelines of the European Helicobacter pylori Study Group (EHPSG), the eradication of H. pylori is indicated in:

  • symptomatic Helicobacter pylori gastritis
  • atrophic Helicobacter pylori gastritis , giant fold gastritis
  • gastroduodenal ulcer disease with evidence of Helicobacter pylori
  • positive family history of gastric cancer
  • after partial stomach resection
  • malignant MALT lymphoma (maltoma)
  • after resection of an early gastric cancer
  • before long-term therapy with NSAIDs (ulcer prophylaxis)

Eradication therapy for H. pylori consists of a combination of a proton pump inhibitor (omeprazole, pantoprazole, lansoprazole, esomeprazole or rabeprazole) with at least two antibiotics , since antibiotic monotherapy is not sufficiently successful.

There are different therapy schemes. Depending on the resistance situation , a proton pump inhibitor in combination with amoxicillin , metronidazole and clarithromycin (PAMC), or a proton pump inhibitor with bismuth citrate potassium , metronidazole and tetracycline (PBMT) ( combined quadruple therapy or bismuth-containing quadruple therapy ) is used. In areas of low resistance to clarithromycin, triple therapy may be used consisting of a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole ( “French” or “Italian” standard triple therapy ). Reserve therapies are PBMT or a combination of a proton pump inhibitor with levofloxacin and amoxicillin ( fluoroquinololone triple therapy, moxifloxacin is also possible as an alternative to levofloxacin ). Rifabutin- containing therapies should only be used with patients who have failed to respond to three different other therapies.

Eradication often fails because reinfection takes place via the oral plaque. As early as 1999, Riggio et al. demonstrated that H. pylori was present in the subgingival plaque of 38 percent of the periodontal disease patients examined. Zari et al. show the advantage of a combination of periodontitis therapy to reduce germs in the oral cavity and triple drug therapy.

In addition to a lack of compliance , antibiotic resistance can also be considered as causes of failure . Before attempting a new therapy, the pathogen should therefore be cultivated and a resistance determination carried out.

With the 13 C or 14 C urea breath test (see diagnostics), the success of eradication can be proven about four to six weeks after the end of therapy. The reinfection rate is low and is around 1% per year.

Prophylaxis - Outlook

In 2005, Helicobacter experts from North America, China and Europe met at the Max Planck Institute for Infection Biology in Berlin to discuss the development and use of a vaccine. According to Thomas F. Meyer, director of the institute, “the dangerousness of H. pylori is still generally underestimated. More than half of all people are infected with it and it must be assumed that around ten percent of the world's population will develop a gastric ulcer once in their life. ”Some of them then suffer from gastric cancer, which claims around 750,000 victims worldwide each year. It is ten to twenty times more common than the rare esophageal cancer . Before deciding on the vaccination strategy, the connection between this form of cancer, heartburn and the disappearance of the gastric germ H. pylori is important.

The Berlin researchers warn against premature hope for the possibility of vaccination. A reliable vaccine was not yet available in 2011 either. One of the problems with developing a vaccine is that anyone infected with Helicobacter will show an antibody response against the bacterium, even if the infection is often symptom-free. Obviously, the body's reaction is insufficient to eliminate the germ. One mechanism is that Helicobacter produces the enzyme γ-glutamyltransferase (GGT), which blocks T cells . Structural elements of the enzyme are researched as epitopes for the induction of antibodies , which can then paralyze the enzyme in a targeted manner.

The first successes in vaccine development were reported from China in 2013 . Here, a vaccine against Helicobacter pylori was developed, which causes good local and humoral immunity.

Genome research

The first complete genome sequence of a representative of the species H. pylori was published as early as 1997 . A second sequence was published in 1999, making it possible for the first time to compare the genome sequences of two isolates of the same bacterial species. It was found that the two isolates differed in about 10% of the genes.

literature

Specialist literature

Guidelines

Popular science

Web links

Commons : Helicobacter pylori  - collection of pictures, videos and audio files

Individual evidence

  1. ↑ J. Stein, M. Kist: Helicobacter heilmannii (formerly: Gastrospirillium hominis) and other Helicobacter species. In: Infektiologie des Gastrointestinal Tract 2006, pp. 185–187.
  2. ↑ W. Krienitz: About the appearance of spirochetes of various forms in the stomach contents in carcinoma ventriculi. In: Dtsch. Med. Wochenschr. Volume 32, 1906, p. 872.
  3. ^ Tilo Richter: Investigations on the epidemiology and clinic of Helicobacter pylori infection in Leipzig school children and family members (a population-based study). Dissertation. Medical Faculty of the University of Leipzig , Leipzig 2002.
  4. ↑ gastric bacteria. People have carried stowaways in their stomachs for 60,000 years. In: Der Spiegel . Hamburg February 8, 2007.
  5. ↑ SE Miederer u. a .: Digestive diseases and sciences. New York 1996, pp. 41 and 944.
  6. ↑ Jérôme Viala et al. a., in: Nature Immunology 5.2004, 11 (Nov.), 1166-1174. ISSN  1529-2908
  7. ↑ a b c d Lea Charlotte Holsten: Characterization of new adhesin receptors of Helicobacter pylori and their role in the translocation of the cytotoxin CagA. (PDF) Ludwig Maximilians University Munich, July 7, 2015, p. V-VI (list of abbreviations) , accessed on October 19, 2016 (dissertation at the Max von Pettenkofer Institute for Hygiene and Medical Microbiology).
  8. ↑ Verena Königer, Lea Holsten, Ute Harrison, Benjamin Busch, Eva Loell, Qing Zhao, Daniel A. Bonsor, Alexandra Roth, Arnaud Kengmo-Tchoupa, Stella I. Smith, Susanna Mueller, Eric J. Sundberg, Wolfgang Zimmermann, Wolfgang Fischer , Christof R. Hauck, Rainer Haas: Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA. In: Nature Microbiology 2, Article Number: 16188. October 17, 2016, accessed October 19, 2016 .
  9. ↑ Anahita Javaheri, Tobias Kruse, Kristof Moonens, Raquel Mejías-Luque, Ayla Debraekeleer, Carmen I. Asche, Nicole Tegtmeyer, Behnam Kalali, Nina C. Bach, Stephan A. Sieber, Darryl J. Hill, Verena Königer, Christof R. Hauck, Roman Moskalenko, Rainer Haas, Dirk H. Busch, Esther Klaile, Hortense Slevogt , Alexej Schmidt, Steffen Backert, Han Remaut, Bernhard B. Singer, Markus Gerhard: Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs . In: Nature Microbiology 2, Article Number: 16189. October 17, 2016, accessed October 19, 2016 .
  10. ↑ J. Keller et al .: Clinically relevant breath tests. In: Z Gastroenterol. Volume 42, 2005, pp. 1071-1090. DOI10.1055 / s-2005-858479
  11. ^ JP Gisbert, JM Pajares: Stool antigen tests for the diagnosis of Helicobacter pylori infection. A systemic review. In: Helicobacter. 2004; 9, 347-368.
  12. ↑ Stool antigen tests for H. pylori diagnosis? In: Deutsches Ärzteblatt. 102, issue 39 of September 30, 2005, page A-2649 / B-2239 / C-2115
  13. ↑ Marianne Abele-Horn (2009), p. 202.
  14. ↑ European Helicobacter pylori Study Group (EHPSG)
  15. ↑ Marianne Abele-Horn (2009), p. 203.
  16. ↑ a b c d C. A. Fallone, N. Chiba, SV van Zanten, L. Fischbach, JP Gisbert, RH Hunt, NL Jones, C. Render, GI Leontiadis, P. Moayyedi, JK Marshall: The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. In: Gastroenterology. Volume 151, number 1, July 2016, pp. 51-69.e14, doi: 10.1053 / j.gastro.2016.04.006 , PMID 27102658 .
  17. ↑ a b c guideline Helicobacter pylori and gastroduodenal ulcer disease of the German Society for Gastroenterology, Digestive and Metabolic Diseases eV (DGVS). In: AWMF online (as of February 5, 2016)
  18. ↑ Vaccine against the bacterium Helicobacter pylori
  19. ↑ Stomach cancer - vaccination against Helicobacter pylori , Pharmazeutische Zeitung Online, 10/2010
  20. ↑ F. .. Hongying, W. .. Xianbo, Y. .. Fang, B. .. Yang, L. .. Beiguo: Oral immunization with recombinant Lactobacillus acidophilus expressing the adhesin hp0410 of Helicobacter pylori induces mucosal and systemic immune responses . In: Clinical and Vaccine Immunology. , S., doi: 10.1128 / CVI.00434-13 .
  21. ↑ J.-F. Tomb u. a .: The complete genome sequence of the gastric pathogen Helicobacter pylori . in: Nature . London 388.1997, 539-547. ISSN  0028-0836
  22. ↑ RA Alm u. a., in: Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori . in: Nature . London 397.1999, 176-180. ISSN  0028-0836