In vitro anti-Helicobacter pylori activity of Syzygium aromaticum and the preliminary mechanism of action.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried flower bud of Syzygium aromaticum (L.) Merr. & L.M Perry (S. aromaticum) (Myrtaceae), also known as clove, was used in Traditional Chinese Medicine (TCM) to aid gastrointestinal function and treat stomach disorders including vomiting, flatulence and nausea. And it is a food homology medicine which is a promising candidate for H. pylori treatment. H. pylori is a Gram-negative bacterium that infects approximately 50% of the human population worldwide, which is closely related to multiple gastric diseases, including gastric cancer. However, there are still no sufficient studies on the anti-H. pylori activity of S. aromaticum, especially for the mechanism of action. AIM OF STUDY: This study aimed to study the antibacterial activities of S. aromaticum extracts on both antibiotic-sensitive and -resistant H. pylori strains, and to explore the underlying mechanisms of action. MATERIALS AND METHODS: The S. aromaticum extracts were obtained by heat reflux extraction and lyophilized to powder form. The phytochemical analyses were performed by High-performance liquid chromatography (HPLC) and UPLC-electrospray ionization mass spectrometry (ESI-MS). In vitro anti-H. pylori activity was evaluated by broth microdilution method. Mechanism of action studies included morphological observation using electron microscopy, determination of expression of virulence genes by reverse transcription quantitative polymerase chain reaction (RT-qPCR), genes expression profile identification by transcriptomic analysis, and exploration of anti-H. pylori infection mechanisms by network pharmacology analysis and western blotting validation. RESULTS: The S. aromaticum extracts, aqueous extract (AE) and 75% hydroalcoholic extract (HE), exerted significant antibacterial activities against both antibiotic-sensitive and -resistant H. pylori strains with MICs of 160∼320 µg/ml, without developing drug resistance. Among them, AE was bactericide to all the tested strains with MBCs of less than 4MIC, while HE was merely bacteriostatic to most of the tested strains with MBCs of 2MIC∼16MIC. Besides, they showed no antagonistic effects in combination with clarithromycin, metronidazole, levofloxacin, and amoxicillin. Additionally, these extracts altered the morphology and ultrastructure and down-regulated the virulence genes expression of H. pylori. And transcriptomic analysis showed that they regulated genes expression of multiple H. pylori biological processes, including tricarboxylic acid cycle (TAC) and pyruvate metabolic pathways. Furthermore, these extracts combated the abnormal activation of PI3K-Akt and MAPK signaling pathways caused by H. pylori infection. CONCLUSIONS: Overall, the present study firstly analyzed the chemical compositions of S. aromaticum extracts, and then confirmed their activities on both antibiotic-sensitive and -resistant H. pylori strains. In addition, the mechanisms of action of S. aromaticum extracts against H. pylori were found to be destroying the bacterial structure, down-regulating the expression of virulence genes, and interfering TAC and pyruvate metabolic pathways. Finally, S. aromaticum extracts were found to combated the abnormal activation of PI3K-Akt and MAPK signaling pathways to treat H. pylori infection. This study should accelerate further research and application of S. aromaticum against H. pylori infection.

Traditional Chinese medicine for Helicobacter pylori infection: A protocol for a systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (Hp) is the only bacterium in the stomach. It is characterized by its ability to adhere to gastric mucosa and cause a series of pathological changes in the gastric mucosa. Modern research shows that Hp is an important pathogenic factor for chronic gastritis, gastroduodenal ulcer, and gastric cancer. Triple, quadruple, and triple combinations of antibacterial drugs, proton pump inhibitors, and bismuth aluminate preparations have been developed in modern medical research. Sequential therapy is used to treat Hp, but antibiotic resistance and repeated infections still exist. A large number of clinical trials have proved that traditional Chinese medicine has a good therapeutic effect on Hp. In this systematic review, we aim to evaluate the efficacy and safety of traditional Chinese medicine in the treatment of Hp. METHODS AND ANALYSIS: We will search for publications from Web of Science, PubMed, Science Direct, Wan Fang Data Knowledge Service Platform, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), China National Knowledge Infrastructure (CNKI) and EMBASE, which should be published from inception to December 2020. Two researchers will independently perform the selection of the studies, data extraction, and synthesis. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias in the randomized controlled trials. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.3) software. The I2 test will be used to identify the extent of heterogeneity. We will use the Egger funnel chart to evaluate possible publication biases, in addition, when possible we will perform a subgroup/meta-regression analysis. The strength of the evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS AND CONCLUSIONS: This study will systematically evaluate the efficacy of traditional Chinese medicine in the treatment of Hp infection, and provide evidence for the clinical application of this treatment. The results of the research will be published in a peer-reviewed journal. ETHICS: This systematic review will evaluate the efficacy of traditional Chinese medicine for Hp infection. Because all data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. TRIAL REGISTRATION NUMBER: INPLASY2020120057.

Banxia Xiexin Decoction in the treatment of Hp-associated peptic ulcer: A protocol for systematic review and meta-analysis.

BACKGROUND: Studies suggested Banxia Xiexin Decoction is effective in the treatment of helicobacter pylori (HP) positive peptic ulcer. The present meta-analysis aimed at evaluating the efficacy and safety of Banxia Xiexin decoction in the treatment HP positive peptic ulcer. METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the November 30th, 2020. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14.0 software will be used for data analysis. RESULTS: This systematic review will determine the efficacy and safety of Banxia Xiexin decoction in the treatment HP positive peptic ulcer. CONCLUSION: Its findings will provide helpful evidence for the efficacy and safety of Banxia Xiexin decoction in the treatment HP positive peptic ulcer. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020120002.

Helicobacter pylori: Perturbation and restoration of gut microbiome.

Alternate remedies with natural products provides unlimited opportunities for new drug development. These can be either as pure compounds or as standardized set of compounds. The phytochemicals and secondary metabolites are in great demand for screening bioactive compounds and plays an important role towards drug development. Natural products have many advantages over to synthetic chemical drugs. Helicobacter pylori (H. pylori) a Gram-negative bacteria has been classified as Class I carcinogen by World Health Organization in 1994. Current treatment regimens for H. pylori is 'triple therapy' administrated for two weeks which includes a combination of two antibiotics like Amoxicillin and Clarithromycin and a proton pump inhibitor (PPI) like Lansoprazole, and for 'quadruple therapy' in addition to antibiotics and a PPI, Bismuth is used. Antibiotic resistance can be named as the main factor for failure of treatment of H. pylori infection. The need of the hour is to develop a herbal remedy that could combat the growth of H. pylori. Probiotics can also be used as 'feasible' tool for H. pylori infection management. Present review is an attempt to briefly discuss about the pathogenicity, genetic predisposition, perturbation of gut microbiota due to antibiotic treatment and restoration of healthy gut microbiota with phytochemicals and probiotics.

Blue light emitting diodes enhance the antivirulence effects of Curcumin against Helicobacter pylori.

Introduction. Growing concern about the increasing frequency of resistance of Helicobacter pylori to the available antimicrobial agents worldwide has encouraged the search for new strategies in treating and eradicating H. pylori infections. Endoscopic blue-light therapy has been used in patients with H. pylori gastritis with limited success due to subsequent repopulation with H. pylori. Clinical trials using Curcumin could not eradicate infection either.Aim. We studied the effect of blue light emitting diodes (LEDs) in conjunction with Curcumin on H. pylori, since this has not been previously reported.Methodology. We examined the effect of Curcumin with and without irradiation with blue LEDs on the viability of H. pylori and four key factors important for colonization and establishment of H. pylori infection, namely urease production, motility, adhesion and biofilm formation.Results. We found that a combination of Curcumin and blue LEDs caused significant reductions in viability, urease production, motility, haemagglutination activity, as well as increased disruption of mature preformed biofilms of H. pylori, in comparison to Curcumin alone (P<0.0001), at sublethal concentrations of Curcumin.Conclusion. Targeting the virulence factors of H. pylori with blue LED photoactivated Curcumin would theoretically cripple this pathogen from colonizing and causing tissue damage and perhaps overcome the problem of repopulation with H. pylori that often occurs following endoscopic blue-light therapy.

Mechanism of berberine in treating Helicobacter pylori induced chronic atrophic gastritis through IRF8-IFN-γ signaling axis suppressing.

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.

GPR30-Expressing Gastric Chief Cells Do Not Dedifferentiate But Are Eliminated via PDK-Dependent Cell Competition During Development of Metaplasia.

BACKGROUND & AIMS: Gastric chief cells, a mature cell type that secretes digestive enzymes, have been proposed to be the origin of metaplasia and cancer through dedifferentiation or transdifferentiation. However, studies supporting this claim have had technical limitations, including issues with the specificity of chief cell markers and the toxicity of drugs used. We therefore sought to identify genes expressed specifically in chief cells and establish a model to trace these cells. METHODS: We performed transcriptome analysis of Mist1-CreERT-traced cells, with or without chief cell depletion. Gpr30-rtTA mice were generated and crossed to TetO-Cre mice, and lineage tracing was performed after crosses to R26-TdTomato mice. Additional lineage tracing experiments were performed using Mist1-CreERT, Kitl-CreERT, Tff1-Cre, and Tff2-Cre mice crossed to reporter mice. Mice were given high-dose tamoxifen or DMP-777 or were infected with Helicobacter pylori to induce gastric metaplasia. We studied mice that expressed mutant forms of Ras in gastric cells, using TetO-KrasG12D, LSL-KrasG12D, and LSL-HrasG12V mice. We analyzed stomach tissues from GPR30-knockout mice. Mice were given dichloroacetate to inhibit pyruvate dehydrogenase kinase (PDK)-dependent cell competition. RESULTS: We identified GPR30, the G-protein-coupled form of the estrogen receptor, as a cell-specific marker of chief cells in gastric epithelium of mice. Gpr30-rtTA mice crossed to TetO-Cre;R26-TdTomato mice had specific expression of GPR30 in chief cells, with no expression noted in isthmus stem cells or lineage tracing of glands. Expression of mutant Kras in GPR30+ chief cells did not lead to the development of metaplasia or dysplasia but, instead, led to a reduction in labeled numbers of chief cells and a compensatory expansion of neck lineage, which was derived from upper Kitl+ clones. Administration of high-dose tamoxifen, DMP-777, or H pylori decreased the number of labeled chief cells. Chief cells were eliminated from epithelia via GPR30- and PDK-dependent cell competition after metaplastic stimuli, whereas loss of GRP30 or inhibition of PDK activity preserved chief cell numbers and attenuated neck lineage cell expansion. CONCLUSIONS: In tracing studies of mice, we found that most chief cells are lost during metaplasia and therefore are unlikely to contribute to gastric carcinogenesis. Expansion of cells that coexpress neck and chief lineage markers, known as spasmolytic polypeptide-expressing metaplasia, does not occur via dedifferentiation from chief cells but, rather, through a compensatory response from neck progenitors to replace the eliminated chief cells.

Effects of addition of probiotic and/or bismuth to triple therapy of H. pylori and analysis of genetic variation of 23S rRNA gene between patients with clarithromycin sensitivity and resistance.

The aim of the study was to compare the effects of three treatment regimens for H. pylori in patients sensitive to clarithromycin and analyze the polymorphism of 23S rRNA gene between patients who were sensitive or resistant to clarithromycin in a Chinese Han population. 204 H. pylori sensitive cases and 45 H. pylori resistant Han patients were selected as subjects of the research. All H. pylori sensitive cases were divided into three groups based on their different therapies. The polymerase chain reaction-ligase detection reaction (PCR) was used to identify the genotype at the A2143G of the 23S rRNA gene. SPSS18.0 software was applied to analyze the data statistically. The success rate of H. pylori eradication in the TTP (TT + probiotic) group was higher when compared with the triple therapy (TT) group, and the difference was statistically significant. The incidence of abdominal pain, headache and diarrhea in TTP group was significantly lower than that in the TT group and the TTB (TT+ bismuth) group. Moreover, patients in the TTP group suffered less taste impairment than patients in the other two groups. In addition, there was significant difference in genotype frequency distribution between the clarithromycin-resistant group and the clarithromycin-sensitive group. It was suggested in the results of Chinese Han population that the TTP regimen was significantly superior to the other two regimens in the treatment of clarithromycin-sensitive H.PYLORI infection. In addition, potential genotypic differences between clarithromycin-sensitive and drug-resistant patients provided a theoretical basis for gene therapy in patients with clarithromycin resistance.

Blue light emitting diodes cripple Helicobacter pylori by targeting its virulence factors.

BACKGROUND: The endogenous photosensitizing porphyrins in Helicobacter pylori (H. pylori), make blue light therapy an attractive addition to the armamentarium in the war against this very prevalent and difficult to treat infectious agent. METHODS: In the current study we examined in vitro the effect of blue LED (Light Emitting Diode) irradiation for 1-6 minutes on the viability and virulence factors of H. pylori, which allow this microorganism to colonize and establish infection. Specifically, we examined the effects of blue LED on urease production, motility, adhesion and biofilm formation. RESULTS: We found that exposure to blue LED for 1-6 minutes significantly decreased the viability of H. pylori and caused decreased urease activity, as well as, swarming motility. Furthermore, blue LED irradiation for 6 minutes caused greater than 50% disruption of preformed mature biofilms of H. pylori, relative to controls. CONCLUSIONS: Collectively, the results of our in-vitro study indicate that therapy with blue LED may be an added weapon in the eradication of H. pylori by targeting the virulence factors of this very common pathogen. We envisage that phototherapy will have an adjuvant effect on conventional anti-H. pylori therapy, especially considering its efficacy in biofilm disruption and the fact that microorganisms are unlikely to develop resistance as a result of the multi-target effects.

Artemisinin and its derivatives prevent Helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-κB signaling.

BACKGROUND: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated. PURPOSE: We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA. METHODS: The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action. RESULTS: ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation. CONCLUSION: ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.

Effect of Celastrus orbiculatus in inhibiting Helicobacter pylori induced inflammatory response by regulating epithelial mesenchymal transition and targeting miR-21/PDCD4 signaling pathway in gastric epithelial cells.

BACKGROUND: The extract of Celastrus orbiculatus (COE) have been studied for anti-Helicobacter pylori (H. pylori) activity and anti-cancer effects in vitro and in vivo. However, the molecular mechanism by which COE inhibits H. pylori-induced inflammatory response has not been fully elucidated so far. METHODS: The effects of COE on viability, morphological changes, inflammatory cytokine secretion, protein and mRNA expression were analyzed by MTT assay, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, western blot and real-time PCR (RT-PCR), respectively. The methylation level of programmed cell death 4 (PDCD4) promoter was investigated by methylation-specific PCR. (MSP) . RESULTS: COE effectively inhibited the H.pylori-induced inflammatory response by regulating epithelial-mesenchymal transition (EMT). The methylation level of PDCD4 promoter was suppressed by COE, which increased the expression ofPDCD4. Moreover, COE could inhibit microRNA-21 (miR-21) expression, as shown by an enhancement of its target gene PDCD4. Furthermore, both miR-21 over-expression and PDCD4 silencing attenuated the anti-inflammatory effect. of COE. CONCLUSIONS: COE inhibits H. pylori induced inflammatory response through regulating EMT, correlating with inhibition of miR-21/PDCD4 signal pathways in gastric epithelial cells.

Bovine lactoferrin enhances the efficacy of levofloxacin-based triple therapy as first-line treatment of Helicobacter pylori infection: an in vitro and in vivo study.

OBJECTIVES: To evaluate the in vitro antimicrobial/antivirulence action of bovine lactoferrin and its ability to synergize with levofloxacin against resistant Helicobacter pylori strains and to analyse the effect of levofloxacin, amoxicillin and esomeprazole with and without bovine lactoferrin as the first-line treatment for H. pylori infection. METHODS: The bovine lactoferrin antimicrobial/antivirulence effect was analysed in vitro by MIC/MBC determination and twitching motility against six clinical H. pylori strains and a reference strain. The synergism was evaluated using the chequerboard assay. The prospective therapeutic trial was carried out on two separate patient groups, one treated with esomeprazole/amoxicillin/levofloxacin and the other with esomeprazole/amoxicillin/levofloxacin/bovine lactoferrin. Treatment outcome was determined with the [13C]urea breath test. RESULTS: In vitro, bovine lactoferrin inhibited the growth of 50% of strains at 10 mg/mL and expressed 50% bactericidal effect at 40 mg/mL. The combination of levofloxacin and bovine lactoferrin displayed a synergistic effect for all strains, with the best MIC reduction of 16- and 32-fold for levofloxacin and bovine lactoferrin, respectively. Bovine lactoferrin at one-fourth MIC reduced microbial motility significantly for all strains studied. In the in vivo study, 6 of 24 patients recruited had treatment failure recorded with esomeprazole/amoxicillin/levofloxacin (75% success, 95% CI 57.68%-92.32%), and in the group with esomeprazole/amoxicillin/levofloxacin/bovine lactoferrin, 2 out of 53 patients recruited had failure recorded (96.07% success, 95% CI 90.62%-101.38%). CONCLUSIONS: Bovine lactoferrin can be considered a novel potentiator for restoring susceptibility in resistant H. pylori strains. Bovine lactoferrin added to a triple therapy in first-line treatment potentiates the therapeutic effect.

Synthesis of terpenoid oxo derivatives with antiureolytic activity.

Urease is an important virulence factor for a variety of pathogenic bacteria strains such as Helicobacter pylori, which colonizes human gastric mucosa, and Proteus sp., responsible for urinary tract infections. Specific inhibition of urease activity could be a promising adjuvant strategy for eradication of these pathogens. Due to the interesting antiureolytic activity of carvone and the scant information regarding the inhibitory properties of corresponding monoterpenes, we decided to study selected monoterpenic ketones and their oxygen derivatives. Several monoterpenes and their terpenoid oxygen derivatives were evaluated in vitro against Sporosarcina pasteurii urease. The most effective inhibitors-derivatives of ß-cyclocitral (ester 10 and bromolactone 14)-were described with [Formula: see text] of 46.7 µM and 45.8 µM, respectively. Active inhibitors of native urease were tested against H. pylori and Proteus mirabilis whole cells. Here, the most active inhibitor, 14, was characterized with IC50 values of 0.32 mM and 0.61 mM for P. mirabilis and H. pylori, respectively. The antibacterial activity of a few tested inhibitors was also observed. Compound 14 limited the growth of E. coli ([Formula: see text]= 250 µg/mL). Interestingly, 10 was the only compound that was effective against both Gram-negative and Gram-positive bacteria. It had a [Formula: see text] of 150 µg/mL against E. coli and S. aureus. In the presented study a group of novel antiureolytic compounds was characterised. Besides carvone stereoisomers, these are the only terpenoid urease inhibitors described so far.

The association of garlic with Helicobacter pylori infection and gastric cancer risk: A systematic review and meta-analysis.

BACKGROUND: Garlic may be protective against Helicobacter pylori infection and gastric cancer development. We conducted this study to quantitatively update evidence on garlic intake and gastric cancer with the inclusion of most recent cohort studies and qualitatively summarize epidemiological studies of garlic consumption and Helicobacter pylori infection. MATERIALS AND METHODS: PubMed, Embase, MEDLINE, and Cochrane Library were searched on April 2018. We conducted a meta-analysis to determine whether garlic intake reduced gastric cancer risk using random-effect models and a systematic review to summarize evidence on the association between garlic consumption and Helicobacter pylori infection. Risk of bias was assessed using tools of Cochrane risk of bias and Robins-I for randomized and nonrandomized studies, respectively. RESULTS: Meta-analysis of 18 studies (142 921 subjects) demonstrated high garlic consumption (as comparing the highest category to the lowest) was associated with a reduced gastric cancer risk (OR = 0.51, 95% CI = 0.44-0.57). This association became nonsignificant if only derived from the prospective studies (OR = 0.95, 95% CI = 0.66-1.24). Thirteen studies (4889 participants) were included in the systematic review for garlic consumption and Helicobacter pylori infection; ten of which found no significant results. The majority of these studies were poor in quality given the small sample size and high risk of bias. CONCLUSIONS: Pooled evidence, mainly from case-control studies, suggested a significant inverse association of garlic intake with gastric cancer risk. Given the limitations of included studies, current epidemiological evidence is not sufficient to reach any definite conclusion regarding the association of garlic with Helicobacter pylori infection.

Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy. DESIGN: Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10-day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony-forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates. RESULTS: A total of 209 patients (33% triple therapy, 66% non-bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (ß -0.023, P 0.738). Female gender (P < 0.001) and quadruple therapy (P 0.007) were independent predictors of side effects. No differences in compliance were observed, regardless of the study group or eradication therapy. Eradication rates were similar between groups [placebo 95% (95% confidence interval (CI), 89% to 98%) vs probiotic 97% (95% CI, 92% to 99%), P 0.721]. There were no relevant differences in cure rates (>90% in all cases) between triple and quadruple concomitant therapy. CONCLUSION: Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.

Evaluación del suplemento de vitaminas C y E en el tratamiento antibiótico contra Helicobacter pylori: revisión sistemática y metaanálisis / Assessment of the use of vitamin C and E supplements concomitantly to antibiotic treatment against Helicobacter pylori: A systematic review and meta-analysis

Introducción: La prevalencia de la infección por Helicobacter pylori afecta casi al 50% de la población mundial, siendo un factor de riesgo para enfermedades benignas y malignas gastrointestinales. El aumento de la resistencia al tratamiento antibiótico contra esta infección ha presentado un dilema en el abordaje de otras alternativas en la terapéutica. Objetivo: Determinar la eficacia del suplemento de vitaminasC y E añadido al tratamiento antibiótico en la erradicación de la infección por H. pylori. Métodos: Se realizó una revisión sistemática en las bases de datos de MedLine, Embase y Cochrane Central Register of Clinical Trials (CENTRAL), para estudios que evaluaran la eficacia del suplemento de vitaminasC y/o E en el tratamiento antibiótico de infección por H. pylori. El resultado principal fue erradicación de la infección y el secundario fueron efectos adversos. El metaanálisis fue elaborado mediante el método de efectos aleatorios. Resultados: Se incluyeron 10 estudios y se hicieron 2 grupos. El primero comparó el uso de suplemento de vitaminasC y E incluyendo 973 pacientes, en el cual sin discriminar el número de antibióticos no se obtuvo una relación con la erradicación de la infección (OR: 1,98 [IC95%: 0,92-4,29], p=0,08). La terapia triple o cuádruple antibiótica no tuvo un efecto sobre la erradicación (OR: 1,80 [IC95%: 0,64-5,08], p=0,26, y OR: 2,84 [IC95%: 0,51-15,56], p=0,22, respectivamente). En el grupo en que solo se evaluó el uso de vitaminaC se incluyeron 702pacientes, pero no se obtuvo un efecto sobre la erradicación (OR: 1,17 [IC95%: 0,58-2,31], p=0,65). Los efectos adversos solo fueron reportados en 4 estudios, siendo el más frecuente las náuseas. Conclusiones: El suplemento de vitaminasC y E en la terapia antibiótica contra H. pylori no tuvo ningún efecto. Sin embargo, los estudios presentaron bastantes sesgos y diferencias en la posología de los suplementos y antibióticos

Introduction: Helicobacter pylori infections affect almost 50% of the world population, constituting a risk factor for benign and malignant gastrointestinal diseases. The increased resistance to antibiotic treatment against this infection represents a dilemma in the search of other therapeutic alternatives. Objective: To determine the efficacy of the use of vitaminC and E supplements concomitantly to antibiotic treatment against H. pylori infections. Methods: We performed a systematic review on the MedLine (PubMed), Embase and Cochrane Central Register of Clinical Trials (CENTRAL) databases, searching for studies evaluating the efficacy of vitaminC and/or E supplements in the antibiotic treatment of H. pylori infections. The primary outcome was eradication of the infection. The secondary outcome was the adverse effects. The meta-analysis was conducted using the random effects method. Results: Ten studies were included and analyzed in two groups. The first group, which was comprised by 973patients, compared the use of supplementation with vitaminC and E, showing that, without discriminating the number of antibiotics used, there was no relationship with the eradication of the infection (OR: 1.98 [95%CI: 0.92-4.29] P=.08). The triple or quadruple antibiotic therapy had no effect on eradication rates either (OR 1.80 [95%CI: 0.64-5.08] P=.26 and OR: 2.84 [95%CI: 0.51-15.56] P=.22, respectively). No effect on the eradication rates was observed either in the group that only assessed the use of vitaminC, comprised by 702patients (OR: 1.17 [95%CI: 0.58-2.31] P=.65). Only four studies reported adverse effects, the most common one being nausea. Conclusions: Supplementation with vitaminC and E in the antibiotic treatment against H. pylori has no effect. However, the reviewed studies had several biases and differences in the dosage of the supplements and antibiotics administered

The Diagnosis and Treatment of Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 10-20%. It affectsthe gastrointestinal tract. METHODS: This article is based on publications retrieved by a selective search of PubMed, with special attention to controlled trials, guidelines, and reviews. RESULTS: Typical dyspeptic symptoms in functional dyspepsia include epigastric pain, sensations of pressure and fullness, nausea, and early subjective satiety. The etiology of the disorder is heterogeneous and multifactorial. Contributory causes include motility disturbances, visceral hypersensitivity, elevated mucosal permeability, and disturbances of the autonomic and enteric nervous system. There is as yet no causally directed treatment for functional dyspepsia. Its treatment should begin with intensive patient education regarding the benign nature of the disorder and with the establishment of a therapeutic pact for long-term care. Given the absence of a causally directed treatment, drugs to treat functional dyspepsia should be given for no more than 8-12 weeks. Proton-pump inhibitors, phytotherapeutic drugs, and Helicobacter pylori eradication are evidence-based interventions. For intractable cases, tricyclic antidepressants and psychotherapy are further effective treatment options. CONCLUSION: The impaired quality of life of patients with functional dyspepsia implies the need for definitive establishment of the diagnosis, followed by symptom-oriented treatment for the duration of the symptomatic interval.

Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

AIM: To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori (H. pylori)-infected patients in Ireland. METHODS: DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype HelicoDR assay. cagA and vacA genotypes were investigated using PCR. RESULTS: Primary, secondary and overall resistance rates for clarithromycin were 50.5% (n = 53/105), 78.3% (n = 47/60) and 60.6% (n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2% (n = 16/105) and 28.3% (n = 17/60) and 20% (n = 33/165), respectively. Resistance to both antibiotics was 12.4% (n = 13/105) in treatment-naïve patients, 25% (n = 15/60) in those previously treated and 17% (n = 28/165) overall. A cagA-positive genotype was detected in 22.4% (n = 37/165) of patient samples. The dominant vacA genotype was S1/M2 at 44.8% (n = 74/165), followed by S2/M2 at 26.7% (n = 44/165), S1/M1 at 23.6% (n = 39/165) and S2/M1 at 4.8% (n = 8/165). Primary clarithromycin resistance was significantly lower in cagA-positive strains than in cagA-negative strains [32% (n = 8/25) vs 56.3% (n = 45/80) P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vacA s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vacA s2 genotype, [41% (n = 32/78) vs 77.8% (n = 21/27) P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status. CONCLUSION: Genotypic H. pylori clarithromycin resistance is high and cagA-negative strains are dominant in our population. Less virulent (cagA-negative and vacA S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.

Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis. AIM OF THE STUDY: The emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model. MATERIALS AND METHODS: H. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis. RESULTS: Our in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1ß, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB). CONCLUSIONS: Our findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity against H. pylori and could be an alternative to antibiotics for preventing H. pylori infection.