Helicobacer Pylori (HP) is a Gram-negative bacterium in a spiral shape that colonizes the stomach . Helicobacter infection is the most common chronic bacterial infection in the world and is often asymptomatic .
However in some cases it can cause chronic inflammatory damage to the stomach mucosa (active chronic gastritis) up to the development of ulcers . Ulcers can affect both the mucous membrane of the stomach and that of the duodenum. It is estimated that around 90% of duodenal ulcers and 80% of gastric ulcers are associated with Helicobacter infection . HP infection is also an important onerisk factor for stomach cancer and gastric lymphoma
Find out more about this pathogen, how it is transmitted, what diseases and complications it causes and possible therapies.
Helicobacter Pylori : what it is
Helicobacter Pylori is a common Gram-negative gastric pathogen. It is a spiral-shaped microorganism that has adapted to grow in the gastric environment, very acidic, thanks to an enzyme, urease , which increases the surrounding pH . In addition, the particular helix shape , from which its name derives, allows it to penetrate the mucus layer , to settle under it, where the acidity is lower.
Thanks to some proteins present on the outer membrane it is able to adhere to the epithelial cells of the stomach, damaging them through the expression of some virulence factors directed against the epithelium of the stomach and through the activation of the inflammatory response.
Helicobacter Pylori is found in about half of the world’s population. The prevalence of infection is higher in developing countries.
Its presence was only observed in the late 1980s. Before then, the stomach environment was considered too acidic for germ survival .
This erroneous belief meant that when Helicobacter Pylori was first detected in gastric tissues from surgery or gastroscopy, an error or contamination was thought of.
It was Barry Marshall and Robin Warren, two Australian researchers , who hypothesized that this bacterium could actually be in the stomach and deepened its studies. The name Helicobacter Pylori is due to them, due to its spiral shape and the fact that it prefers the pylorus , the point of passage from the stomach to the intestine.
Helicobacter and gastric ulcer: the discovery of the link
It also took time to recognize the role of Helicobacter in the development of gastric ulcer . Throughout the twentieth century, in fact, it was believed that it was mainly caused by stress or, sometimes, by the intake of acidic or very spicy foods.
The merit of this association always goes to the two Australian researchers and their commitment to overcome the skepticism of doctors, who did not believe in an infectious origin of this pathology . To prove this, Marshall self-infected by drinking the broth from a bacterial culture, then fell ill with gastritis, isolated the bacterium from his ulcer and recovered with antibiotic therapy.
Only in 1994, the American National Institute of Health (NIH) declared a close relationship between gastroduodenal ulcer and Helicobacter infection. In 1996 the Food and Drug Administration (FDA) approved the first specific antibiotic treatment in the United States.
In 2005 , Marshall and Warren were awarded the Nobel Prize for medicine thanks to the discovery of Helicobacter .
Also in 1994, the International Agency for Research on Cancer (IARC) included Helicobacter among the carcinogens , recognizing its role in the development of stomach cancers.
Helicobacter Pylori: strains
To date, several strains of Helicobacter Pylori are known , more or less virulent . The main classification is that which distinguishes between positive or negative CagA strains . This definition derives from the presence, in the genome of the bacterium, of a region coding for the CagA protein.
This protein is found on average in 60% of western bacterial strains and in about 90% of Asian bacterial strains.
The CagA protein is largely responsible for inducing the chronic inflammatory response. The CagA + strains therefore generate a greater inflammatory response than the negative CagA strains lacking this protein.
In addition to being ” pro-inflammatory “, this protein is also called “oncoprotein” as it is involved in the carcinogenesis process , that is, the process by which a “healthy” cell is transformed into a neoplastic cell.
It is important to underline how, although CagA + strain infections are associated with a higher risk of complications (ulcers and stomach cancer), the development of these conditions derives from a more complex process . In addition to other virulence factors of the bacterium , environmental factors and genetic factors of the host (man) also come into play in this mechanism .
Habitat and colonization method of the gastric mucosa
The peculiarity of Helicobacter Pylori lies in its ability to settle in the stomach in conditions that are unfavorable for most bacteria due to the highly acidic environment (pH ~ 2-4).
The property of Helicobacter Pylori to resist in the gastric lumen is due to two factors :
- the presence of flagella that allow the bacterium to move and pass through the mucus layer above the gastric epithelium to settle under it and adhere to the epithelial cells
- the ability to produce an enzyme, “urease”, thanks to which it neutralizes the pH of the gastric cavity making the habitat more “comfortable” . Urea splits urea, which is abundantly contained in the stomach, in carbon dioxide and ammonia. The latter neutralizes the acid produced by the gastric cavity.
Other factors that allow the colonization and survival of the bacterium at the stomach level are some proteins, present in the external membrane of the bacterium, which allow it to adhere to the gastric epithelial cells . These proteins, in addition to adhering to the mucosa, are able to damage cells , both directly, through the activation of cell death mechanisms, and indirectly, inducing a state of chronic inflammation that is harmful over time.
Helicobacter Pylori: transmission mode
Currently, humans are the only known reservoir of Helicobacter. The transmission modalities of the bacterium are not yet clear. The most common ways of contagion are the gold-gastric and the gold-fecal one. The bacterium has been isolated in the stool and to a greater extent in vomiting, suggesting such possible ways of contagion.
It is also possible to become infected by ingesting contaminated food or water . The bacterium can in fact survive in water at room temperature for up to 10 days. Other possible routes of infection are contact with contaminated endoscopic instruments . In some countries (Peru, Egypt) the bacterium has been found in the water of the distribution network. Specific studies, however, have excluded the presence of Helicobacter Pylori in the Italian network, where the water is treated with chlorine.
Helicobacter Pylori infection can affect anyone, but there are risk factors, that is, environmental conditions that favor contagion. Among them, living in a country with a low socio-health level or in an unhygienic environment . In developing countries, this bacterium is usually acquired in childhood : in Africa , for example, mothers who have a habit of pre-mixing food before passing it on to children can pass on the infection to them .
In Italy and in most other developed countries , however, with the improvement of socio-economic conditions in the 1950s and 1960s, there was a drastic reduction in the prevalence of Helicobacter in the general population. Today, the bacterium is present in 40-50% of subjects who are over 60 years old and only in 10-20% of younger ones.
The categories at greatest risk of infection include nurses and gastroenterologists , because bacteria can be transmitted by improperly disinfected endoscopes. But thanks to the application of adequate hygienic precautions (hand washing, standard disinfection of instruments) this risk is now greatly reduced.
Helicobacter Pylori : which diseases it causes
Helicobacter Pylori infection is the most frequent cause of chronic active gastritis and peptic ulcer.
Helicobacter Pylori is the most important cause of chronic active gastritis . Almost all people with Helicobacter Pylori infection have this condition, which can affect the entire stomach or only its lower part (antrum).
By gastritis is meant an inflammation of the mucous membrane of the stomach which can be asymptomatic, in most cases, or symptomatic. Chronic inflammation over time determines the accumulation of harmful molecules that can damage the cells of the stomach and in some cases, based on factors related to both the bacterium and the host (man), determine complications such as the formation of ulcers (both in the stomach and in the duodenum), gastric lymphoma associated with MALT (lymphoid tissue associated with mucous membranes, also called Maltoma) and stomach cancer.
HP infection and the resulting chronic inflammation can determine erosive gastritis and lead to the development of gastroduodenal ulcers, characterized by a continuous lesion of the epithelium, which affects the mucous membrane of the digestive system exposed to the action of the secretion stomach acid.
HP infection is believed to be responsible for 80-90% of cases of gastric (if erosion affects the mucous membrane of the stomach) or duodenal (if erosion affects the first centimeters of the duodenum) ulcers.
As for duodenal ulcer , it develops following an increased exposure of the mucosa of the duodenum to acid, consequent to an increased gastric secretion . Usually, the antral localization of the bacterium favors a condition of acid hypersecretion which therefore increases the risk of development of the duodenal ulcer.
L ‘ gastric ulcer , however, occurs in the presence of active chronic gastritis that affects the entire stomach . In this case, the development of the ulcer, rather than an increased gastric acid secretion, is linked to a reduction in the defensive mechanisms of the mucosa (including the production of mucus).
Symptoms and signs
HP infection is in many cases asymptomatic . According to data from the Higher Institute of Health, Helicobacter Pylori is present in the stomach of about 25 million Italians, but in most individuals the infection does not cause symptoms.
The most common symptoms of Helicobacter infection are burning or pain in the upper part of the abdomen (epigastrium) and the so-called “difficulty digesting”, that is, the feeling of a full stomach after eating, even in the case of non-abundant meals .
More rarely, symptoms such as nausea, vomiting, loss of appetite, swelling can occur .
Bleeding may occur in an ulcer .
When HP infection involves the whole stomach ( active chronic pangastritis ), over time it can lead to malabsorption of some micronutrients (such as iron and vitamin B12) and therefore to chronic deficiency anemia .
Helicobacter Pylori and stomach cancer
About 90% of stomach cancers are associated with HP infection . Long-term HP infection increases the risk of gastric cancer : infected people are in fact 2 to 6 times more likely to develop stomach cancer.
It is important to note, however, that although Helicobacter Pylori infection is recognized as a risk factor for stomach cancer, the development of this complication results from a more complex process . Environmental, genetic and bacterial factors (virulence and duration of infection) all have a more or less known role in determining the aggressiveness of the infection and the associated neoplastic risk. Among environmental factors, cigarette smoking appears to increase the risk of developing cancer.
Helicobacter Pylori is classified by the International Agency for Research on Cancer as a class I carcinogen, i.e. an agent whose carcinogenicity is recognized in humans .
HP infection determines a state of chronic inflammation and the production of substances that damage the cells of the stomach over time, causing a series of cellular changes that can progress towards the tumor.
The progression from chronic active gastritis (Hp infection) to adenocarcinoma has been widely studied in the literature. This made it possible to develop surveillance strategies aimed at identifying and possibly treating changes in the mucous membrane of the stomach before it develops the tumor (the so-called precancerous conditions and lesions).
The indication for antibiotic therapy against the bacterium must always take into consideration the presence of conditions at risk of evolution in cancer, as early eradication of the infection has been shown to reduce the risk of developing stomach cancer .
Helicobacter and lymphomas
Other malignancies associated with Helicobacter Pylori infection include MALT lymphoma (lymphoid tissue associated with the mucous membranes), a rare form of cancer that affects the immune system cells that are found in the stomach.
For the diagnosis of Helicobacter Pylori infection it is possible to carry out several tests, more or less invasive .
- Breath test, or breath test : after giving the patient radioactively labeled urea with carbon, the amount of carbon dioxide emitted by exhalation is measured. This gas is in fact the metabolic product of the bacterium. The sensitivity and specificity of this test reaches 94-98% . It is important that this test is performed under the advice of the doctor after stopping the possible intake of pump inhibiting drugs and antibiotics, as they could compromise their diagnostic accuracy.
- Fecal Antigen Test : This test consists of finding Helicobacter Pylori Ag in the stool and appears to have a sensitivity and specificity similar to that of the urea breath test .
- Endoscopy : during the examination, samples (biopsies) of the stomach mucosa are taken , then analyzed under a microscope in search of the bacterium and / or inflammation cells present in case of chronic infection. This examination is considered the optimal standard for the diagnosis of HP infection, ulcer and other complications associated with it (such as pre-neoplastic and neoplastic conditions) .
- Serological tests : consist in the research in the blood of IgG antibodies specifically directed against Helicobacter Pylori . These tests have a sensitivity and specificity of 80% -95%, depending on the kit used . The test can be used for the diagnosis of HP infection, but it should not be used to control eradication as its positivity is indicative of infection, but does not distinguish an “active” infection from a pass .
The pharmacological therapy of infection is made to the eradication of the bacterium and is recommended in the presence of complications, such as ulcers or neoplasia .
Treatment typically consists of antibiotic-based therapy , selected from amoxicillin, metronidazole, tetracycline or clarithromycin, for 1-2 weeks associated with a proton pump inhibitor . The choice of therapy is guided by any previous antibiotic therapies and local resistance to antibiotics (specifically clarithromycin).
Treatment of asymptomatic infection has been controversial, but recognition of Helicobacter Pylori’s role in cancer development has led to suggest therapy even in the absence of symptoms .
The choice of the doctor in this case will be based on the presence of individual risk factors and on the evaluation of the benefits deriving from the eradication of the infection. Vaccines are under development, with both preventive and therapeutic effects (i.e. to be used in addition to the treatment of infected patients).
There are currently no specific dietary indications in the presence of chronic active gastritis . Dietary restrictions, where indicated, should be based on the presence and type of symptoms possibly associated.
Information on how Helicobacter is transmitted is still quite scarce, so there are no specific infection prevention measures . Certainly it is useful to observe the common rules of personal hygiene, first of all wash your hands well . It is also important to wash food well and drink safe water , not at risk of contamination.