Pylori-related Gastric Diseases Research Articles

Periodontal therapy as adjunctive treatment for gastric Helicobacter pylori infection.

Helicobacter pylori is estimated to affect about half the world's population and is considered as the main cause of chronic gastritis and peptic ulcer disease. Eradication of H. pylori infection accelerates ulcer healing and prevents relapse, reducing incidence of H. pylori-related gastric diseases. Numerous studies have provided evidence that the oral cavity could be a potential reservoir for H. pylori. The presence of oralH. pylori might affect the efficiency of eradication therapy and act as a causal force for its recurrence. Conversely, other investigators have indicated that the colonization and growth of H. pylori differs between the oral cavity and the stomach. Considering the open debate on the topic, it's necessary to clarify whether periodontal therapy is an effective adjunctive treatment for gastric H. pylori infection. To assess the effects of periodontal therapy plus eradication therapy versus eradication therapy alone for gastric H. pylori infection. The secondary objective is to compare the non-recurrence rate at long-term follow up in different treatment groups. We identified randomized controlled trials (RCTs) by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 8), MEDLINE (1946 to August 2015), EMBASE (1980 to August 2015), and the Chinese Biomedical Database (1978 to August 2015). We also searched both ClinicalTrials.gov and the WHO ICTRP portal in October 2015. We handsearched the reference lists of included studies to identify relevant trials. RCTs comparing periodontal therapy plus eradication treatment with eradication treatment alone, regardless of language of publication. Two reviewers selected the trials that met the inclusion criteria and extracted the details of each study independently. The data were pooled using both fixed-effect and random-effects models and results calculated as odds ratios (OR) with their 95% confidence intervals (CIs) based on an intention-to-treat analysis. However, because there was little difference in the results from these two models, we only reported the results from the fixed-effect model. We included seven small RCTs involving 691 participants aged 17 to 78 years in our meta analyses. The primary result showed that periodontal therapy combined with H. pylori eradication treatment increased the eradication rate of gastric H. pylori compared with eradication treatment alone (OR 2.15; 95% CI 1.47 to 3.14; P < 0.0001) in people with H. pylori infection. In addition, periodontal therapy also had benefits on long-term gastric H. pylori eradication. After eradication of H. pylori, the non-recurrence rate of gastric H. pylori infection increased in participants treated with periodontal therapy compared with those who received eradication therapy alone (OR 3.60; 95% CI 2.11 to 6.15; P < 0.00001). According to the GRADE approach, the overall quality of the evidence was 'moderate' for eradication rate of gastric H.pylori and 'low' for non-recurrence rate of gastric H. pylori. Overall, periodontal therapy could increase the efficiency of H. pylori eradication and the non-recurrence rate of gastricH. pylori. In view of the limited number and quality of included studies, it will be necessary to conduct more well-designed, multicenter, and large-scale RCTs to determine the effects of periodontal therapy in eradicating gastric H. pylori and suppressing the recurrence of this bacterium in the stomach.

The Anti-inflammatory Effects of Acidic Polysaccharide from Artemisia capillaris on Helicobacter pylori Infection.

Background:Helicobacter pylori infection is associated with diverse upper gastrointestinal diseases, such as peptic and duodenal ulcers as well as gastric cancer. Longstanding period of infection impose great risk of H. pylori-related gastric disease, based on the evidence that early childhood infection is responsible for ensuing atrophic gastritis and gastric cancer related to H. pylori infection. Artemisiahas been known to be beneficial for heath for a long time. In spite of well-acknowledged cytoprotective and anti-inflammatory actions of Artemisia, the effects of the acidic polysaccharide fractions on the gastroprotection remain to be investigated.Methods:In the current study, we compared anti-inflammatory actions of the acidic polysaccharide fraction between Artemisia and Panax ginseng against H. pylori infection in vitro. The polysaccharide fractions were pretreated 1 h before H. pylori infection on normal gastric mucosal RGM-1 cells and gastric cancer MKN-28 cells. RT-PCR and Western blot was performed to check anti-inflammatory actions.Results:The expressions of inflammatory markers including COX-2, iNOS and IL-8 increased after H. pylori infection, of which levels were significantly decreased when treating with the polysaccharide fractions from Artemisia and ginseng in RGM1 and gastric cancer MKN-28 cells. In addition, the polysaccharide fractions significantly ameliorated H. pylori-induced angiogenic and invasive markers such as HIF-1α and ICAM1. Moreover, H. pylori-induced apoptosis were prevented by pretreatment with the polysaccharide fractions. The polysaccharide fraction from Artemisia showed the most protective effects among the several polysaccharide fractions used in this study.Conclusions:The polysaccharide fraction of Artemisia capillariscan is a candidate substance which can attenuate either H. pylori-induced gastritis or tumorigenesis based on potent anti-inflammatory action.

The Effects of Two Novel Copper-Based Formulations on Helicobacter pylori.

We investigated the effects of two novel copper-based inorganic formulations for their activity against 60 isolates of Helicobacter pylori (Hp). The two copper-based formulations were tested against three NCTC Helicobacter pylori isolates and 57 clinical strains isolated from the UK and Italy in time-kill assays. Both copper-based formulations were bio-cidal against all Helicobacter pylori strains tested reducing the viable count by 4–5 log within 2 h. These two copper-based anti-microbial agents deserve further study in relation to the treatment of H. pylori-related gastric disease.

Helicobacter pylori infection

This review is aimed at describing the main findings of 2011 on the aspects of Helicobacter pylori-related gastric disease linked to CagA and to T-regulatory cells (Treg), and on the attempts to improve the treatment efficacy. Recent findings presented in this review are as follows: CagA interferes with tumor suppression; tolerance protects from H. pylori-induced disease; modified H. pylori treatments/regimens can afford higher efficacy than the standard triple therapy. H. pylori colonizes the human stomach causing gastritis and severe diseases including gastric cancer. One of the most dangerous H. pylori factors, CagA, has been investigated in relation to gastric cancer: recently this relationship was strongly reinforced by the finding that CagA interacts with the tumor suppressor apoptosis-stimulating protein of p53-2 (ASPP2), promoting p53 degradation. Treg have been proposed to be involved in H. pylori infection and gastric disease: recent findings suggest that Treg-induced tolerance, rather than immunity to H. pylori, may result in less severe disease. The eradication rates achieved with the standard triple therapy dropped below 80%, mainly due to antibiotic resistance, while no vaccines are currently licensed; new treatments/regimens were subjected to clinical trials, in some cases strongly increasing the eradication rates.

Advances in relationship between gastric disease and polymorphisms in both helicobacter pylori virulence factors and host genetics

Helicobacter pylori infection may cause many gastric disease, such as peptic ulcers, chronic atrophic gastritis, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The different clinical outcomes of Helicobacter pylori infection are related to H. pylori virulence factors and host gene polymorphism. H.pylori had been confirmed to be the class I carcinogen by the World Health Organization and International Agency for Research on Cancer Consensus Group (IARC) in1994. Most severe diseases always occur in the background that certain microbial virulence markers (e.g. cagA, vacA) and susceptible host genetic polymorphisms harboured together. Herein, we reviewed the association with H. pylori-related gastric diseases in relation to diffirent H. pylori types and the host polymorphisms.

The Effect of Probiotics forHelicobacter pylori

Background/Aims: Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis and peptic ulcer and a risk factor of gastric malignancy. Antibiotics based H. pylori eradication treatment is 90% effective, however, it is expensive and causes side effects and antibiotics resistance. Probiotics could present a low-cost, alternative solution to prevent or decrease H. pylori colonization. Materials and Methods: Eligible articles were indentified by researches of electronic databases. Results: In vitro studies demonstrated an inhibitory activity of probiotics on H. pylori growth and that this effect is extremely strain specific. The probiotics seem to be efficacious for the prevention of antibiotics associated side effects and might be of help for the prevention of H. pylori complications by decreasing H. pylori density and gastritis, and for the prevention of H. pylori colonization or re-infection by inhibiting adhesion to gastric epithelial cells. There was no significant evidence that probiotics may increase the H. pylori eradication rate. Conclusion: Probiotics could be an accessory treatment for H. pylori related gastric diseases, but more researches will be needed. (The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2011;11:26-36)

Sibship size, Helicobacter pylori infection and chronic atrophic gastritis: a population-based study among 9444 older adults from Germany

Early-life social environment has been suggested to play an important role during the development of Helicobacter pylori-related gastric diseases. We aimed to assess the association of sibship size with H. pylori infection and chronic atrophic gastritis (CAG) in a population-based study from Germany. In the baseline examination of ESTHER, a study conducted in Saarland, serological measurements of pepsinogen I and II and H. pylori antibodies were taken in 9444 participants aged 50-74 years. Information on potential risk factors and medical history were obtained by self-administered standardized questionnaire. A strong dose-response relationship between sibship size and H. pylori seroprevalence was observed (P < 0.01). Adjusted odds ratios (ORs) 95% confidence interval (CI) for H. pylori seropositivity for subjects with 4, 5, 6 and 7 or more siblings compared with subjects without siblings were 1.45 (1.20-1.77), 1.83 (1.50-2.22) and 1.84 (1.47-2.31), respectively. A large sibship size was also associated with an increased risk of CAG with an adjusted OR of 1.42 (1.01-2.01) for 7 or more compared with less than or equal to 2 siblings. This association was attenuated but not entirely eliminated after additional adjustment for H. pylori infection. Notably, a significant association between large sibship size and CAG was also found among H. pylori-negative subjects. Our results suggest that large sibship size is associated with increased H. pylori prevalence and CAG risk. The association with CAG risk may be mediated at least in part by H. pylori infection. However, mechanisms other than H. pylori infection may contribute to the 'sibling effect' as well.

Differential phosphoproteome profiling reveals a functional role for VASP inHelicobacter pylori-induced cytoskeleton turnover in gastric epithelial cells

Infection with Helicobacter pylori induces various gastric diseases, including ulceration, gastritis and neoplasia. As H. pylori-induced cellular mechanisms leading to these disease states are widely unclear, we analysed the phosphoproteome of H. pylori-infected gastric epithelial cells. Phosphoproteins from infected cells were enriched using affinity columns and analysed by two-dimensional gel electrophoresis and mass spectrometry. Eleven novel phosphoproteins that showed differentially regulated phosphorylation levels during H. pylori infection were identified. Interestingly, the identified proteins were actin-binding, transport and folding, RNA/DNA-binding or cancer-associated proteins. We analysed functions of one identified H. pylori-regulated candidate, the vasodilator-stimulated phosphoprotein (VASP). H. pylori induced VASP phosphorylation at residues Ser157, Ser239 and Thr278, which was enhanced by the bacterial oncogene cytotoxin-associated gene A. Overexpression of a phosphorylation-resistant VASP mutant efficiently blocked host cell elongation. We identified cGMP-dependent protein kinase G-mediated Ser239 and Thr278 phosphorylation of VASP as a crucial event in H. pylori-dependent host cell elongation. These results suggest that phosphorylated VASP could be a novel target candidate for therapeutic intervention in H. pylori-related gastric diseases.

Interleukin-13 mucosal production in Helicobacter pylori-related gastric diseases

A shift from Th1 (IFN-γ) towards Th2 (IL-4)-type immune response was found in patients with gastric cancer and dysplasia. Recently, IL-13 has been described as a central mediator of Th2-dominant immune response in different inflammatory diseases. Aim and Methods to analyse, by Enzyme-Linked-Immuno-SPOT (ELISPOT) assay and immunohistochemistry, the IL-13 production of mononuclear cells obtained from gastric biopsies of 19 H. pylori-negative subjects and 23 H. pylori-positive patients. Results By ELISPOT, we did not find any significant variation of the spot range number of IL-13, IL-4 and IFN-γ secreting cells, irrespective of H. pylori status. After antigenic exposition, the spot range for IL-13, IL-4 and IFN-γ significantly increased ( p < .0001) only in H. pylori-positive patients. A prevalent Th1 (IFN-γ) immunoresponse was observed in 2/23 cases with active gastritis, while a prevalent Th2 (IL-13 and IL-4) was detected in 5/23 cases all with atrophic chronic gastritis of whom two with intestinal metaplasia. By immunohistochemistry, IL-13, IL-4 and IFN-γ were detectable in all cases directly related to the inflammatory infiltrate. In the two cases with intestinal metaplasia, IL-13 and IL-4 were localised in both inflammatory and epithelial cells. This immunopattern was confirmed in selected additional 10 cases of H. pylori-positive chronic atrophic gastritis with intestinal metaplasia and 10 cases of intestinal type gastric cancer. Conclusion These preliminary results suggest that IL-13 could be implicated in the different outcome of H. pylori infection.

Helicobacter pylori as a class I carcinogen: Physiopathology and management strategies

The gram-negative bacterium Helicobacter pylori is known as a persistent colonizer of the human stomach, and probably less known is that it is also involved in extraintestinal diseases. Public awareness of its contribution in the development of gastric cancer is less than 15 years old. The efficacy of the current therapies based on antibiotics against H. pylori has been limited by difficulties such as antibiotic resistance and recurrence. As a consequence, the development of promising vaccines was prompted as the best preventive measure. Unfortunately, so far vaccines failed the transition from animal models to human trials. This keynote presentation is to provide a bird's eye view of H. pylori-related gastric diseases, including gastric cancer, with a synthesis of the molecular mechanisms involved, and an exhaustive presentation and discussion of the current therapeutic guidelines and future strategies for prevention or therapy.

Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility

Helicobacter pylori induces a strong motogenic response in infected gastric epithelial host cells, which is enhanced by translocation of the pathogenic factor cytotoxin-associated gene A (CagA) into host cells via a specialized type IV secretion system. Once injected into the cytosol CagA is rapidly tyrosine phosphorylated by Src family kinases followed by Src inactivation. Hence, it remained unknown why CagA is constantly phosphorylated in sustained H. pylori infections to induce cell migration, whereas other substrates of Src kinases are dephosphorylated. Here, we identify the non-receptor tyrosine kinase c-Abl as a crucial mediator of H. pylori-induced migration and novel CagA kinase in epithelial cells. Upon H. pylori infection c-Abl directly interacts with CagA and localizes in focal adhesion complexes and membrane ruffles, which are highly dynamic cytoskeletal structures necessary for cell motility. Selective inhibition of c-Abl kinase activity by STI571 or shRNA abrogates sustained CagA phosphorylation and epithelial cell migration, indicating a pivotal role of c-Abl in H. pylori infection and pathogenicity. These results implicate c-Abl as a novel molecular target for therapeutic intervention in H. pylori-related gastric diseases.

Gastrokine 1 expression in patients with and without Helicobacter pylori infection

Background To understand the molecular changes underlying Helicobacter pylori-related gastric diseases is mandatory to prevent gastric cancer. Proteomic technology is providing a rapid expansion of the basic knowledge, particularly in the discovery of new biomarkers involved in the tumourigenesis. Aim To characterise changes in protein expression level of the gastric mucosa in H. pylori-infected patients. Methods The population enrolled comprised 41 dyspeptic patients. Proteins extracted from gastric mucosal specimens were analysed by 2-dimensional electrophoresis, sequenced by MALDI-TOF and identified by Edman's degradation. Results Twenty-one out of 41 patients had H. pylori infection of whom 17 had anti-CagA IgG antibodies. Several proteins were identified, of which Rho guanosine diphosphatase dissociation inhibitor α and heat shock protein 27 increased and glutathione transferase and antrum mucosa protein-18 decreased in H. pylori-positive in respect to H. pylori-negative patients. Interestingly, antrum mucosa protein-18, currently referred as gastrokine-1, showed two isoforms differing in the first N-terminal amino acid residue. Both gastrokine-1 isoforms were observed in the H. pylori-negative group whereas a lower expression or even absence of the gastrokine-1 basic isoform was found in a subgroup (7/21) of H. pylori-positive patients with moderate–severe gastritis. Conclusion Our study demonstrated the presence of gastrokine-1 isoforms of which the basic isoform was reduced in a subset of patients with H. pylori infection.

Suppressive effect of rice extract on Helicobacter pylori infection in a Mongolian gerbil model

Rice extract has been shown to protect gastric mucosa from stress-induced damage. In this study, the antibiotic effect and the anti-inflammatory effect of orally administered aqueous rice extract on Helicobacter pylori infection and H. pylori-induced gastritis, respectively, in Mongolian gerbils were investigated. Fifty specific-pathogen-free male Mongolian gerbils, seven weeks old, were divided into four groups: uninfected, untreated animals (group A); uninfected, rice extract-treated animals (group B); H. pylori-infected, untreated animals (group C); and H. pylori-infected, rice extract-treated animals (group D). Group C and D animals were killed 12 weeks after H. pylori infection (i.e., at 19 weeks of age) and group A and B animals were also killed at age 19 weeks. The stomachs were removed for histopathological examination with hematoxylin-and-eosin staining and anti-5'-bromo-2'-deoxyuridine (BrdU) immunostaining, and to determine the bacterial burden. Serum anti-H. pylori antibody titers were also tested. In groups A and B, the gastric mucosa showed no inflammatory cell infiltration and a few BrdU-reactive cells. Group C animals developed marked chronic active gastritis in the gastric mucosa, and BrdU-labeled cells in the gastric mucosa markedly increased in number. In group D animals, a significant reduction occurred in the degree of neutrophilic polymorphonuclear cell infiltration into the gastric mucosa, in the BrdU-labeling indices of gastric epithelial cells, and in anti-H. pylori antibody titers in the serum (P < 0.01), compared with although H. pylori was not completely eradicated. The rice extract was effective in suppressing inflammation and epithelial cell proliferation in the gastric mucosa in H. pylori-infected Mongolian gerbils. The rice extract has potential to exhibit a protective effect on H. pylori-related gastric mucosal diseases.

Effect of Helicobacter pylori infection on gastric mucosal pathologic change and level of nitric oxide and nitric oxide synthase.

To investigate the level of nitric oxide (NO) and nitrous oxide synthase (NOS) enzyme and its effect on gastric mucosal pathologic change in patients infected with Helicobacter pylori (H pylori), and to study the pathogenic mechanism of H pylori. The mucosal tissues of gastric antrum were taken by endoscopy, then their pathology, H pylori and anti-CagA-IgG were determined. Fifty H pylori positive cases and 35 H pylori negative cases were randomly chosen. Serum level of NO and NOS was detected. One hundred and seven cases (71.33%) were anti-CagA-IgG positive in 150 H pylori positive cases. The positive rate was higher especially in those with pre-neoplastic diseases, such as atrophy, intestinal metaplasia and dysplasia. The level of NO and NOS in positive group was higher than that in negative group, and apparently lower in active gastritis than in pre-neoplastic diseases such as atrophy, intestinal metaplasia and dysplasia. H pylori is closely related with chronic gastric diseases, and type I H pylori may be the real factor for H pylori-related gastric diseases. Infection with H pylori can induce elevation of NOS, which produces NO.

B-Raf/Rap1 signaling, but not c-Raf-1/Ras, induces the histidine decarboxylase promoter in Helicobacter pylori infection.

Histidine decarboxylase (HDC) is the key enzyme for gastric histamine synthesis, and enhanced HDC expression is critically involved in the pathogenesis of gastric disorders, including gastroduodenal ulcer disease. We characterized the pathogenicity mechanism underlying activation of the HDC promoter in H. pylori-infected gastric epithelial cells and performed a detailed analysis of the participating signaling elements. We found that H. pylori infection of gastric epithelial cells activated the MEK1-2/ERK1-2 cascade through cAMP-dependent stimulation of Rap1 and B-Raf, but not Ras/c-Raf-1, leading to potent transactivation of the human HDC promoter. H. pylori-triggered elevation of adenylate cyclase activity was directed by GalphaS-subunits of heterotrimeric G proteins. Stimulation of this signaling cascade was triggered independent of bacterial-cell contact by a small molecular- weight component(s) (approximately 1 kDa) released by H. pylori and did not require a functional type IV secretion system. Thus, our studies demonstrate for the first time to our knowledge that the GalphaS-->cAMP-->Rap1--->B-Raf-->MEK1/2-->ERK1/2 pathway is critical for H. pylori-dependent epithelial gene regulation, which can be induced via a bioactive component(s) apart from the site of bacterial colonization. These results further elucidate the molecular mechanisms underlying interaction of H. pylori with gastric epithelial cells and help to define potential molecular targets for therapeutic interventions in the context of H. pylori-related gastric diseases.