Ability of Helicobacter pylori to internalize into Candida

The following are our views regarding the“letter to the editor”(Helicobacter is preserved in yeast vacuoles!Does Koch’s postulates confirm it?)by Alipour and Gaeini,and the response“letter to the editor”(Candida accommodates nonculturable Helicobacter pylori in its vacuole-Koch’s postulates aren’t applicable)by Siavoshi and Saniee.Alipour and Gaeini rejected the methods,results,discussion,and conclusions summarized in a review article by Siavoshi and Saniee.The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori(H.pylori)to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse,transporting potentially infectious H.pylori into the stomach of humans.

Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

Helicobacter pylori:High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.

Retrospective analysis of discordant results between histology and other clinical diagnostic tests on helicobacter pylori infection

BACKGROUND A reliable test is essential for diagnosing Helicobacter pylori(H.pylori)infection,and crucial for managing H.pylori-related diseases.Serving as an excellent method for detecting H.pylori infection,histologic examination is a test that clinicians heavily rely on,especially when complemented with immunohistochemistry(IHC).Additionally,other diagnostic tests for H.pylori,such as the rapid urease test(CLO test)and stool antigen test(SA),are also highly sensitive and specific.Typically,the results of histology and other tests align with each other.However,on rare occasions,discrepancy between histopathology and other H.pylori diagnostic tests occurs.AIM To investigate the discordance between histology and other H.pylori tests,the underlying causes,and the impact on clinical management.METHODS Pathology reports of gastric biopsies were retrieved spanning August 2013 and July 2018.Reports were included in the study only if there were other H.pylori tests within seven days of the biopsy.These additional tests include CLO test,SA,and H.pylori culture.Concordance between histopathology and other tests was determined based on the consistency of results.In instances where histology results were negative while other tests were positive,the slides were retrieved for re-assessment,and the clinical chart was reviewed.RESULTS Of 1396 pathology reports were identified,each accompanied by one additional H.pylori test.The concordance rates in detecting H.pylori infection between biopsy and other tests did not exhibit significant differences based on the number of biopsy fragments.117 discrepant cases were identified.Only 20 cases(9 with CLO test and 11 with SA)had negative biopsy but positive results in other tests.Four cases initially stained with Warthin-Starry turned out to be positive for H.pylori with subsequent IHC staining.Among the remaining 16 true discrepant cases,10 patients were on proton pump inhibitors before the biopsy and/or other tests.Most patients underwent treatment,except for two who were untreated,and two patients who were lost to follow-up.CONCLUSION There are rare discrepant cases with negative biopsy but positive in SA or CLO test.Various factors may contribute to this inconsistency.Most patients in such cases had undergone treatment.

Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal carcinoma.The mechanisms underlying this supposedly protective effect remain controversial.AIM To determine the prevalence of H.pylori infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our hospital.METHODS We retrospectively reviewed the prevalence of H.pylori infection in a cohort of patients diagnosed with esophageal carcinoma.Concomitant or previous proton pump inhibitor(PPI)usage was also recorded.RESULTS A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were included.AC was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal body.Overall,54 patients(60.7%)presented at stages III and IV.Previous H.pylori infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous H.pylori infection had stage III-IV.Only one patient had received prior H.pylori eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI treatment.CONCLUSION In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous H.pylori infection.We also reviewed the medical history of the patients,concluding that the majority had received or were on PPI treatment.The minimal prevalence of H.pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis

BACKGROUND Difficulty in obtaining tetracycline,increased adverse reactions,and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy.Therefore,the search for new alternative drugs has become one of the research hotspots.In recent years,minocycline,as a semisynthetic tetracycline,has demonstrated good potential for eradicating Helicobacter pylori(H.pylori)infection,but the systematic evaluation of its role remains lacking.AIM To explore the efficacy,safety,and compliance of minocycline in eradicating H.pylori infection.METHODS We comprehensively retrieved the electronic databases of PubMed,Embase,Web of Science,China National Knowledge Infrastructure,SinoMed,and Wanfang database as of October 30,2023,and finally included 22 research reports on H.pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria.The eradication rates of H.pylori were calculated using a fixed or a random effect model,and the heterogeneity and publication bias of the studies were measured.RESULTS The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H.pylori eradication rates,reaching 82.3%[95%confidence interval(CI):79.7%-85.1%]in the intention-to-treat analysis and 90.0%(95%CI:87.7%-92.4%)in the per-protocol analysis.The overall safety and compliance of the minocycline-containing regimens were good,demonstrating an overall incidence of adverse reactions of 36.5%(95%CI:31.5%-42.2%).Further by traditional meta-analysis,the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects.Most of the adverse reactions were mild to moderate and well-tolerated,and dizziness was relatively prominent in the minocycline-containing regimens(16%).CONCLUSION The minocycline-containing regimens demonstrated good efficacy,safety,and compliance in H.pylori eradication.Minocycline has good potential to replace tetracycline for eradicating H.pylori infection.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

Helicobacter pylori infection alters gastric microbiota structure and biological functions in patients with gastric ulcer or duodenal ulcer

BACKGROUND Helicobacter pylori(H.pylori)infection is closely associated with gastrointestinal diseases.Our preliminary studies have indicated that H.pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer(GU)or duodenal ulcer(DU).AIM To investigate the contributions of H.pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases.METHODS Patients with H.pylori infection and either GU or DU,and healthy individuals without H.pylori infection were included.Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing.The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed.RESULTS Compared with that in the healthy individuals,the gastric mucosal microbiota in the H.pylori-positive patients with GU was dominated by H.pylori,with signi-ficantly reduced biodiversity.The intergroup differential functions,which were enriched in the H.pylori-positive GU patients,were all derived from H.pylori,particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones.A significant enrichment of the uibE gene was detected in the synthesis pathway.There was no significant difference in microbial diversity between the H.pylori-positive DU patients and healthy controls.CONCLUSION H.pylori infection significantly alters the gastric microbiota structure,diversity,and biological functions,which may be important contributing factors for GU.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis

BACKGROUND Helicobacter pylori(H.pylori)infection is a major risk factor for chronic gastritis,affecting approximately half of the global population.H.pylori eradication is a popular treatment method for H.pylori-positive chronic gastritis,but its mecha-nism remains unclear.Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment.However,no clinical study has been conducted on urinary metabolomics of chronic gastritis.AIM To elucidate the urinary metabolic profiles during H.pylori eradication in patients with chronic gastritis.METHODS We applied LC–MS-based metabolomics and network pharmacology to in-vestigate the relationships between urinary metabolites and H.pylori-positive chronic gastritis via a clinical follow-up study.RESULTS Our study revealed the different urinary metabolic profiles of H.pylori-positive chronic gastritis before and after H.pylori eradication.The metabolites regulated by H.pylori eradication therapy include cis-aconitic acid,isocitric acid,citric acid,L-tyrosine,L-phenylalanine,L-tryptophan,and hippuric acid,which were involved in four metabolic pathways:(1)Phenylalanine metabolism;(2)phenylalanine,tyrosine,and tryptophan biosynthesis;(3)citrate cycle;and(4)glyoxylate and dicarboxylate metabolism.Integrated metabolomics and network pharmacology revealed that MPO,COMT,TPO,TH,EPX,CMA1,DDC,TPH1,and LPO were the key proteins involved in the biological progress of H.pylori eradication in chronic gastritis.CONCLUSION Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H.pylori-positive chronic gastritis patients.

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus:A pilot bioinformatics study

BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.

Predictive factors and model validation of post-colon polyp surgery Helicobacter pylori infection

BACKGROUND Recently,research has linked Helicobacter pylori(H.pylori)stomach infection to colonic inflammation,mediated by toxin production,potentially impacting colorectal cancer occurrence.AIM To investigate the risk factors for post-colon polyp surgery,H.pylori infection,and its correlation with pathologic type.METHODS Eighty patients who underwent colon polypectomy in our hospital between January 2019 and January 2023 were retrospectively chosen.They were then randomly split into modeling(n=56)and model validation(n=24)sets using R.The modeling cohort was divided into an H.pylori-infected group(n=37)and an H.pylori-uninfected group(n=19).Binary logistic regression analysis was used to analyze the factors influencing the occurrence of H.pylori infection after colon polyp surgery.A roadmap prediction model was established and validated.Finally,the correlation between the different pathological types of colon polyps and the occurrence of H.pylori infection was analyzed after colon polyp surgery.RESULTS Univariate results showed that age,body mass index(BMI),literacy,alcohol consumption,polyp pathology type,high-risk adenomas,and heavy diet were all influential factors in the development of H.pylori infection after intestinal polypectomy.Binary multifactorial logistic regression analysis showed that age,BMI,and type of polyp pathology were independent predictors of the occurrence of H.pylori infection after intestinal polypectomy.The area under the receiver operating characteristic curve was 0.969[95%confidence interval(95%CI):0.928–1.000]and 0.898(95%CI:0.773–1.000)in the modeling and validation sets,respectively.The slope of the calibration curve of the graph was close to 1,and the goodness-of-fit test was P>0.05 in the two sets.The decision analysis curve showed a high rate of return in both sets.The results of the correlation analysis between different pathological types and the occurrence of H.pylori infection after colon polyp surgery showed that hyperplastic polyps,inflammatory polyps,and the occurrence of H.pylori infection were not significantly correlated.In contrast,adenomatous polyps showed a significant positive correlation with the occurrence of H.pylori infection.CONCLUSION Age,BMI,and polyps of the adenomatous type were independent predictors of H.pylori infection after intestinal polypectomy.Moreover,the further constructed column-line graph prediction model of H.pylori infection after intestinal polypectomy showed good predictive ability.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-negative GML,as well as their potential response to bacterial eradication therapy.

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates

BACKGROUND Resistance to clarithromycin(CLA)and levofloxacin(LFX)of Helicobacter pylori(H.pylori)is increasing in severity,and successful eradication is essential.Presently,the eradication success rate has greatly declined,leaving a large number of patients with previous treatment histories.AIM To investigate secondary resistance rates,explore risk factors for antibiotic resistance,and assess the efficacy of susceptibility-guided therapy.METHODS We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023.Participants underwent a string test after an overnight fast.The gastric juice was obtained and transferred to vials containing storage solution.Subsequently,DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction(qPCR).Demographic information was also analyzed as part of the study.Based on these results,the participants were administered susceptibility-guided treatment.Efficacy was compared with that of the empiric treatment group.RESULTS A total of 132 individuals tested positive for the H.pylori ureA gene by qPCR technique.CLA resistance rate reached a high level of 82.6%(n=109),LFX resistance rate was 69.7%(n=92)and dual resistance was 62.1%(n=82).Gastric symptoms[odds ratio(OR)=2.782;95%confidence interval(95%CI):1.076-7.194;P=0.035]and rural residence(OR=5.152;95%CI:1.407-18.861;P=0.013)were independent risk factors for secondary resistance to CLA and LFX,respectively.A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment,respectively.The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5%(77/102)and 59.0%(59/411)by the intention-to-treat(ITT)analysis and 90.6%(77/85)and 70.2%(59/84)by the per-protocol(PP)analysis,respectively.The eradication rates of these two treatment strategies were significantly different in both ITT(P=0.001)and PP(P=0.012)analyses.CONCLUSION H.pylori presented high secondary resistance rates to CLA and LFX.For patients with previous treatment failures,treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Efficacy and safety of low-dose tetracycline,amoxicillin quadruple therapy in Helicobacter pylori infection:A retrospective single center study

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have declined with the rise of antibiotic-resistant strains in recent years.Although highly effective with a low prevalence of resistance,standard dose tetracycline is associated with frequent adverse events.The efficacy and safety of low-dose tetracycline as part of tetra-cycline and amoxicillin-containing bismuth quadruple therapy are not well described.AIM To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients with H.pylori infection receiving tetracycline,amoxicillin,proton pump inhibitor,and bismuth for 14 days at Sir Run Run Shaw Hospital(1/2022-6/2023)were evaluated.The low-dose tetracycline group received tetracycline 500 mg twice daily(bid)while the standard dose group received 750 mg bid or 500 mg three times daily(tid).Primary endpoints were H.pylori eradication rate and treatment-related adverse events.

Mechanistic research:Selenium regulates virulence factors,reducing adhesion ability and inflammatory damage of Helicobacter pylori

BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlation between them remains unclear.AIM To investigate how selenium acts on virulence factors and reduces their toxicity.METHODS H.pylori strains were induced by sodium selenite.The expression of cytotoxin-associated protein A(CagA)and vacuolating cytotoxin gene A(VacA)was determined by quantitative PCR and Western blotting.Transcriptomics was used to analyze CagA,CagM,CagE,Cag1,Cag3,and CagT.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction,and H.pylori colonization,inflammatory reactions,and the cell adhesion ability of H.pylori were assessed.RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H.pylori strains after sodium selenite treatment.Their expression was significantly and steadily downregulated after the 5th cycle(10 d).Transcriptome analysis revealed that sodium selenite altered the levels affect H.pylori virulence factors such as CagA,CagM,CagE,Cag1,Cag3,and CagT.Of these factors,CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite.Moreover,CagT expression was upregulated before the 3rd cycle(6 d)and significantly downregulated after the 5th cycle.Cag1 and Cag3 expression was upregulated and downregulated,respectively,but no significant change was observed by the 5th cycle.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction.The extent of H.pylori colonization in the stomach increased;however,sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H.pylori-infected mice,and the cell adhesion ability of H.pylori was significantly weakened.CONCLUSION These results demonstrate that H.pylori displayed virulence attenuation after the 10th d of sodium selenite treatment.Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H.pylori,thus mitigating the inflammatory damage to the gastric mucosa.

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population:A prospective,multicenter,randomized,two-stage study

BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.

Evaluation of urea breath test as a diagnostic tool for Helicobacter pylori infection in adult dyspeptic patients

In this editorial,we discuss the article in the World Journal of Gastroenterology.The article conducts a meta-analysis of the diagnostic accuracy of the urea breath test(UBT),a non-invasive method for detecting Helicobacter pylori(H.pylori)infection in humans.It is based on radionuclide-labeled urea.Various methods,both invasive and non-invasive,are available for diagnosing H.pylori infection,inclu-ding endoscopy with biopsy,serology for immunoglobulin titers,stool antigen analysis,and UBT.Several guidelines recommend UBTs as the primary choice for diagnosing H.pylori infection and for reexamining after eradication therapy.It is used to be the first choice non-invasive test due to their high accuracy,specificity,rapid results,and simplicity.Moreover,its performance remains unaffected by the distribution of H.pylori in the stomach,allowing a high flow of patients to be tested.Despite its widespread use,the performance characteristics of UBT have been inconsistently described and remain incompletely defined.There are two UBTs available with Food and Drug Administration approval:The 13C and 14C tests.Both tests are affordable and can provide real-time results.Physicians may prefer the 13C test because it is non-radioactive,compared to 14C which uses a radioactive isotope,especially in young children and pregnant women.Although there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs,13C-UBT consistently outperforms the 14C-UBT.This makes the 13C-UBT the preferred diagnostic approach.Furthermore,the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage,assessment timing,and measurement techniques for both the 13C-UBT and 14C-UBT,to enhance diagnostic precision.