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Helicobacter pylori and Peptic Ulcers – an in depth Report

Helicobacter Pylori Report



Helicobacter pylori (H. pylori) is a successful bacterial pathogen that can persist in the stomach of an infected person for their entire life.


It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacterium can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy.


Helicobacter pylori (H. pylori) plays a role in several gastric diseases. Current anti-H. pylori therapy fails in more than 20% of cases, primarily due to antimicrobial resistance and patient non-adherence due to side effects of the treatment regime. This situation has encouraged the search for other approaches to control H. pylori infection.


Helicobacter pylori (H. pylori) infection is an important public health problem in several parts of the world. Because this pathogen is associated with various gastric diseases, ranging from mild discomfort, such as superficial gastritis, to severe ailments, such as chronic atrophic gastritis, gastric cancer or peptic (gastric or duodenal) ulcer, there is much interest in understanding how infection with H. pylori could be prevented.


  1. pylori has virulence factors that are necessary to colonise the acid environment of the stomach and to survive in it. Of these, the most remarkable are urease and the adhesins. Urease metabolises urea into ammonia and carbon dioxide, and it contributes to the neutralisation of gastric acid. In addition, urease is strongly immunogenic and chemotactic for phagocytes (immune cells), and it promotes the production of the proinflammatory cytokines interleukin (IL)-1β, IL-6 and IL-8, as well as tumoural necrosis factor-alpha (TNF-α). H. pylori adheres specifically to the epithelial cells of the gastric mucosa by means of the adhesins. Approximately 20% of the H. pylori population in the stomach adheres to the epithelial cells, whereas the rest is found in the mucosal layer.


In addition, the neutrophil-activating protein of H. pylori (HP-NAP) allows the bacteria to capture iron, which is essential for its growth.


Several H. pylori virulence factors have been associated with gastric carcinogenesis, or the onset of gastric cancer. The most important of these include vacuolating cytotoxin (VacA) and the cytotoxin-associated gen A (CagA) protein. Both are especially relevant for the pathology of the infection by H. pylori because strains that produce them have been more frequently isolated from patients with gastric cancer.


The hallmark of the interaction between H. pylori and the host’s immune system is the persistence of the infection for years, leading to a chronic inflammation of the gastric mucosa. Once the H. pylori infection is established, both cellular and humoural adaptive immunities are developed: naive T helper (Th) CD4+ cells differentiate into Th effector cells (cellular response), and B cells that produce specific antibodies are activated (humoural response).


There is evidence, however, indicating that B cells and antibodies are dispensable for H. pylori control, whereas Th1 and Th17 effector T cell subsets and their cytokines are essential for the control of the infection. Th1 cells produce the pro-inflammatory cytokines gamma interferon (IFN-γ) and tumour necrosis factor α and β that stimulate innate and T-cell immune responses. Th17 cells are a recently identified class of effector T cells that produce pro-inflammatory cytokine IL-17. This interleukin stimulates fibroblasts, endothelial and epithelial cells, and gastric and lamina propria mononuclear cells to produce a diversity of cytokines and chemokines; this process results in neutrophil infiltration that contributes to H. pylori-associated inflammation. Despite the local and systemic response against the infection, H. pylori can subvert and/or modulate the adaptive immunity perpetuating the infection and chronic inflammation. In a small proportion of infected individuals, this chronic inflammation leads to the development of gastric cancer.


In some H. pylori-infected individuals, acid secretion is higher than normal. The acid flows into the duodenum, leading to gastric metaplasia (precancerous gastric lesion). H. pylori cannot colonise a normal duodenum; it preferentially colonises areas of duodenal gastric metaplasia. The numbers of CD4+ FOXP3+ T cells are increased in areas of gastric metaplasia in the duodenum of H. pylori-infected ulcer patients. Interestingly, there is evidence showing reduced cytokine production in the duodenal epithelium of duodenal ulcer patients. These findings suggest that a down-regulation of the immune response, possibly by Treg cells, allows a higher bacterial density in the duodenum that, together with the high secretion of acid, plays a role in the development of H. pylori-associated duodenal ulcer.


In most individuals, the H. pylori infection can continue throughout life as an asymptomatic condition. Unfortunately, its persistence in the stomach causes chronic gastric inflammation and tissue damage, leading to alterations that could evolve to severe gastric diseases such as peptic ulcers, gastric cancer or mucosa associated lymphoid tissue lymphoma. Therefore, eradication appears to offer the most direct approach to reducing the enormous human and economic consequences of H. pylori infection.


In general, several international guidelines for treating patients diagnosed with H. pylori infections are consistent with the use of triple therapy as the first-line treatment. This treatment consists of the administration of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin for 7-14 d[8183].


However, H. pylori eradication treatments following this regimen produce cure rates lower than 80%, mainly due to an increase in clarithromycin resistance. Reinfection rates after twelve months are also very high, at 80%.


As a result, other regimens (second-line therapies) have been proposed. These treatments usually consist of a PPI in combination with two or three antibiotics, among which amoxicillin, clarithromycin, metronidazole, and tetracycline are included. To overcome the antimicrobial resistance problem and to increase the cure rates of initial treatments, new drug combinations are being developed from existing formulas.


The use of a four-drug treatment (i.e., either sequential, concomitant or bismuth-containing) has been recommended.


Sequential treatment consists of a dual therapy (a PPI plus amoxicillin) for 5 days, followed by a 5 day triple therapy with a PPI plus clarithromycin and tinidazole or metronidazole to complete a 10 day treatment.


Concomitant therapy consists of four drugs (a PPI, clarithromycin, metronidazole/tinidazole and amoxicillin) given twice a day for 3-7 days. Bismuth-containing quadruple therapy consists of a bismuth salt, tetracycline HCl, metronidazole/tinidazole, and a PPI given three or four times a day for 7-14 days.


European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity.


After two eradication failures, H. pylori isolates are often resistant to both metronidazole and clarithromycin.


The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be useful.


The main reasons for treatment failure are antimicrobial resistance and patient non-adherence. The lack of treatment compliance by the patient is a basic factor that explains the low rates of bacterial eradication. The cause is the complexity of the therapy, which involves at least three drugs, administered in repeated doses for a long time.


Consequently, there are side effects, which, coupled with a lack of immediate improvement, discourage the patient to continue with the therapy.


The high cost of anti-H. pylori treatments is another drawback.


Finally, the recurrence of H. pylori infection after successful eradication also represents a problem in terms of the efficiency of therapies, especially in developing countries.

Taking into account the problems inherent to anti-H. pylori therapies in clinical practice, new therapeutic approaches have emerged.



Some natural products are in use to tackle H. pylori.



The results of a 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among the subjects in the Shandong trial showed that the treatment with amoxicillin and omeprazole resulted in a statistically significant 39% reduction in gastric cancer incidence. A similar but non-statistically significant decline was observed for gastric cancer mortality. Neither garlic nor vitamin long-term supplementation was associated with a statistically significant decrease in gastric cancer incidence and mortality.

In another case-control study conducted to evaluate the effects of dietary and life-style habits of patients diagnosed with gastric cancer in Turkey, it was found that frequent consumption of garlic did not result in a lower gastric cancer risk.


Green Tea

Green tea extract greatly inhibited H. pylori urease, with an IC50 value of 13 μg/mL. Catechins were identified as the active compounds, and the hydroxyl group at the 5’-position appeared to be important for urease inhibition. Moreover, polyphenols present in green tea inhibited the vacuolisation effect induced by H. pylori VacA toxin.


These data indicate that polyphenols or polyphenol-rich foods or beverages, such as green tea and red wine, may limit some of the symptomatology related to H. pylori infection.



In the only clinical trial made with honey, 12 non-diabetic patients, positive for rapid urease and 14C urea breath tests, but with normal gastroscopies, were recruited. Six of them were treated with a tablespoon of Manuka honey four times a day for 2 weeks and six were treated with honey and omeprazole (20 mg) twice a day for the same period. Four weeks after the completion of treatment, the twelve patients remained positive for H. pylori as demonstrated by 14C urea breath tests.



A clinical trial evaluating a twenty drops/day therapy of a 4% alcoholic preparation of Brazilian propolis in 18 H. pylori positive patients showed that the use of green propolis preparation did not succeed in suppressing or eradicating H. pylori, as determined by a urea breath test at 3 and 40 days after the end of therapy.


The direct role of probiotics in the treatment of gastrointestinal infections is increasingly being documented as an alternative or a complement to antibiotics, with the potential to decrease the use of antibiotics or reduce their side effects. Patel et al. recently reviewed the in vivo clinical trials studying the effect of probiotics on H. pylori infection. They reported 12 human studies investigating the efficacy of antibiotic and probiotic combinations, and 16 studies using probiotics alone as an alternative to antibiotics for the infection treatment. The results indicated that in the majority of the cases, an improvement in H. pylori gastritis and a reduction in bacterial colonisation were associated with probiotics administration, and in any case, eradication could be completely attained. It also appeared that the use of probiotics was helpful to reduce the adverse effects associated with antibiotics. Long-term intakes of products containing probiotic strains may be beneficial in reducing the risk of H. pylori-associated complications.



Finally, a clinical study was performed using Tremella mesenterica, which reportedly has immunomodulatory activities. Fifty-two patients diagnosed with H. pylori infection were treated with 2 g/daily of submerged cultivated T. mesenterica mycelium for 10 days. The treatment was not effective at eradicating H. pylori, as determined by the urea breath test, whether it was administered in the presence or absence of omeprazole.



In general, polysaccharides do not inhibit bacterial growth in vitro, but their anti-adhesive properties could be very valuable to prevent or to treat H. pylori infection, or even to prevent reinfection after antibiotic eradication therapy. Because the sources of these compounds are easily available, carbohydrate-based anti-adhesive treatment could represent a low cost and safe alternative.



Amongst the traditional natural treatments, which have at best a sketchy record of success against H. pylori, is a newcomer, Pylopass. Thanks to a unique mode of action Pylopass can reduce the Helicobacter pylori load of the stomach thus reducing the risk of developing gastritis and gastric ulcers.


Pylopass is obtained through fermentation of a probiotic strain of Lactobacillus reuteri, and is comprised of inactivated cells and is therefore stable at room temperature. Pylopass is able to recognize surface structures on Helicobacter pylori and to form a co-aggregate. Co-aggregates are eliminated from the body normally through the gastrointestinal tract, and this leads to a reduction of Helicobacter pylori load in the stomach. This mode of action is without side effects.

A high percentage of H. pylori-infected individuals remain asymptomatic, but they are still at risk of developing the pathologies associated with H. pylori. The inclusion of Pylopass in the diet of symptomatic and asymptomatic patients could reduce the risk, as well as the development, of an unfavourable outcome of the infection.




There is an inverse relationship between the low rates of H. pylori eradication and the appearance of side effects associated with the current medical therapies. The most common adverse effects observed in patients treated for H. pylori eradication include abdominal discomfort, diarrhoea, nausea, vomiting, headache and weakness; furthermore, these symptoms have an impact on treatment compliance.


The inclusion of alternative treatments in the anti-H. pylori scheme would enhance both the effectiveness of the therapy and the resolution of the pathology. Moreover, eradication rates would increase, and the development of bacterial resistance could be avoided.






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