Efficacy of Probiotics as Adjuvant to the Standard Triple Therapy for the Treatment of Helicobacter Pylori-Associated Peptic Ulcer Disease: A Randomized-Control Trial.

Helicobacter pylori (H. pylori) is a major cause of peptic ulcer disease (PUD), which needs effective eradication of the organism to heal ulcers and prevent a recurrence. In recent years, increasing resistance of H. pylori to clarithromycin and amoxicillin have decreased peptic ulcer cure rate following treatment with standard triple therapy worldwide. The addition of probiotics with standard triple therapy has shown excellent efficacy in H. pylori eradication and has appeared to be an alternative treatment strategy. This study aimed to assess the efficacy of standard triple therapy plus probiotics for H. pylori eradication and ulcer healing compared to standard triple therapy alone. This double-blind, randomized placebo-controlled clinical trial included 158 with endoscopically proven H. pylori-positive PUD who were randomly allocated equally into two groups; Group A was treated with standard triple therapy plus probiotics, and Group B was treated with standard triple therapy plus placebo for 14 days. The outcome was evaluated at the end of treatment (14th day) (symptoms plus adverse events) and after 60 days of treatment completion (H. pylori eradication and ulcer healing). One hundred forty four (144) study subjects (73 in Group A and 71 in Group B) completed the study. Significantly higher H. pylori eradication rate (82.2%vs. 67.6%, p=0.043) and ulcer healing rate (92.3% vs. 60.0%, p=0.049) were observed in the standard triple therapy plus probiotic group than the standard triple therapy plus placebo group. Early relief of epigastric pain was also seen among patients getting probiotics than the placebo in addition to standard triple therapy (42.3% vs. 15.1%, p<0.001).The addition of probiotics significantly improves the H. pylori eradication rate and ulcer healing rate among the patients getting standard triple therapy. Further large-scale, multi-center studies are needed to recommend routine use of probiotics with standard triple therapy for H. pylori eradication.

AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice: Expert Review.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert Best Practice Advice on the integration of potassium-competitive acid blockers (P-CABs) in the clinical management of foregut disorders, specifically including gastroesophageal reflux disease, Helicobacter pylori infection, and peptic ulcer disease. METHODS: This expert review was commissioned and approved by the AGA Institute Governing Board and CPU Committee to provide timely guidance on a topic of high clinical importance to the AGA membership. This CPU expert review underwent internal peer review by the CPU Committee and external peer review through the standard procedures of Gastroenterology. These Best Practice Advice statements were developed based on review of the published literature and expert consensus opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Based on nonclinical factors (including cost, greater obstacles to obtaining medication, and fewer long-term safety data), clinicians should generally not use P-CABs as initial therapy for acid-related conditions in which clinical superiority has not been shown. BEST PRACTICE ADVICE 2: Based on current costs in the United States, even modest clinical superiority of P-CABs over double-dose proton pump inhibitors (PPIs) may not make P-CABs cost-effective as first-line therapy. BEST PRACTICE ADVICE 3: Clinicians should generally not use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 4: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line on-demand therapy for patients with heartburn symptoms who have previously responded to antisecretory therapy, their rapid onset of acid inhibition raises the possibility of their utility in this population. BEST PRACTICE ADVICE 5: Clinicians should generally not use P-CABs as first-line therapy in patients with milder erosive esophagitis (EE) (Los Angeles classification of erosive esophagitis grade A/B EE). Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 6: Clinicians may use P-CABs as a therapeutic option for the healing and maintenance of healing in patients with more severe EE (Los Angeles classification of erosive esophagitis grade C/D EE). However, given the markedly higher costs of the P-CAB presently available in the United States and the lack of randomized comparisons with double-dose PPIs, it is not clear that the benefits in endoscopic outcomes over standard-dose PPIs justify the routine use of P-CABs as first-line therapy. BEST PRACTICE ADVICE 7: Clinicians should use P-CABs in place of PPIs in eradication regimens for most patients with H pylori infection. BEST PRACTICE ADVICE 8: Clinicians should generally not use P-CABs as first-line therapy in the treatment or prophylaxis of peptic ulcer disease. BEST PRACTICE ADVICE 9: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line therapy in patients with bleeding gastroduodenal ulcers and high-risk stigmata, their rapid and potent acid inhibition raises the possibility of their utility in this population.

Dysbiosis of gut microbiota is associated with pathogenesis of peptic ulcer diseases through inflammatory proteins: A Mendelian randomization study.

The gut microbiota and inflammatory proteins may affect the development of peptic ulcer disease. However, this association remains unclear. We analyzed genome-wide association study data of gut microbiota, inflammatory proteins, and peptic ulcer disease using Mendelian randomization with instrumental variables to assess causal relationships. Various statistical methods, including inverse variance weighting, Mendelian randomization Egger regression, and sensitivity analysis were employed to evaluate the data and calculate mediation ratios. Our findings reveal that the genus Butyriciccus plays a role in mitigating the adverse effects of gastric ulcers by 7.9%, primarily through reducing beta-negative growth factor levels. Additionally, the genus Lachnospiraceae UCG004 can significantly alleviate the negative outcomes of gastric ulcers and reduces hepatocyte growth factor and beta-reserve growth factor levels by 6.39% and 7.45%, respectively. This study highlights the independent and mediating effects of the gut microbiota and inflammatory proteins on peptic ulcers, offering insights on potential pathways and targets for future preventive interventions.

Effect of MDR1 C3435T and CYP2C19 genetic polymorphisms on the outcome of Helicobacter pylori eradication treatment in children with gastritis and peptic ulcer, Vietnam.

BACKGROUND: Helicobacter pylori eradication therapy based on antimicrobial susceptibility in Vietnamese children currently get low efficiency. There are causes of treatment failure, among host genetic factors namely MDR1 C3435T and CYP2C19 affect the absorption and metabolism of proton pump inhibitors - a crucial component of eradication therapy. The study aimed to investigate the effect of MDR1 C3435T and CYP2C19 genetic polymorphisms on the cure rate. METHODS: 207 pediatric patients with gastritis and peptic ulcer infecting Helicobacter pylori completed the eradication therapy based on antimicrobial susceptibility with proton pump inhibitor esomeprazole. Eradication efficacy was assessed after at least 4 weeks by the urease breath test. MDR1 C3435T genetic polymorphism and CYP2C19 genotype were determined using a sequencing method based on Sanger's principle. RESULTS: Among 207 children recruited in this study, the ratio of CYP2C19 EM, IM, and PM phenotypes was 40.1%, 46.4%, and 16.9%, respectively. The patient with MDR1 3435 C/C polymorphism accounted for 43.0%, MDR1 3435 C/T was 40.1%, and MDR1 3435T/T was 16.9%. The cure rate of Helicobacter pylori infection in patients with CYP2C19 EM genotype was 78.3%; 83.3% of those with the IM genotype, and PM genotype was 96,4% (p = 0.07). Successful eradication rates for Helicobacter pylori were 85.4%, 86.7%, and 68.6% in patients with the MDR1 3435 C/C, C/T, and T/T, respectively (p = 0.02). Multiple logistic regression analysis found that MDR1 C3435T genetic polymorphisms of patients were significant independent risk factors for treatment failure, and CYP2C19 genotype did not affect Helicobacter pylori eradication. CONCLUSIONS: The Helicobacter pylori eradication rates by regimens based on antibiotic susceptibility and esomeprazole were not significantly different between the CYP2C19 phenotypes. The MDR1 C3435T polymorphism is one of the factors impacting Helicobacter pylori eradication results in children.

Efficacy and Safety of Vonoprazan-Based Quadruple Therapy for the Eradication of Helicobacter pylori in Patients with Peptic Ulcers: A Pooled Analysis of Two Randomized, Double-Blind, Double-Dummy, Phase 3 Trials.

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).

Detection of Helicobacter pylori strain types and analysis of risk factors among subjects from Hainan Province, China.

OBJECTIVE: To explore the prevalence of type I and type II Helicobacter pylori infection and investigate risk factors in a population from Hainan Province in China. METHODS: Data came from a large, cross-sectional study conducted from August 2022 to April 2023 involving five cities of Hainan. Subjects with confirmed 14C-urea breath test (UBT) and positive serological assay were included. All subjects had a gastroscopy. According to presence or absence of CagA/VacA proteins, subjects were classified as either type I (present) or type II strains (absent). Gastroscopic findings and several socio-demographic factors were examined for correlation with antibody serotyping. RESULTS: In total, 410 subjects were investigated for H. pylori strain types. The overall prevalence of the highly virulent, type I H. pylori strain was 79% (324/410) and type II strain was 21% (86/410). There was a strong association between type I strain and peptic ulcer disease. Of several sociodemographic factors investigated, only smoking and data over baseline (DOB) values showed significant differences between type 1 and type II strains. Logistic regression analysis showed a lower risk of type I H. pylori infection in smokers compared with non-smokers, and a higher risk of H. pylori type I infection in subjects with medium and high data over baseline (DOB) values compared with subjects who had low DOB values. CONCLUSION: Highly virulent, type I H. pylori infections predominate in Hainan and the co-positivity of CagA and VacA antibodies are related to type I H. pylori infection. We found that Type I H. pylori was closely associated with peptic ulcer disease and the DOB values were generally high.

Antibiotic resistance and virulence genes in Helicobacter pylori strains isolated from children in Shanghai, China (2019-2022).

BACKGROUND: The increasing prevalence of antibiotic-resistant Helicobacter pylori strains poses a significant threat to children's health. This study investigated antibiotic resistance rates in Helicobacter pylori strains isolated from children in Shanghai and analyzed the presence of virulence genes in these strains. METHODS: We obtained 201 Helicobacter pylori strains from pediatric patients with upper gastrointestinal symptoms who underwent gastrointestinal endoscopy between 2019 and 2022. Subsequently, we performed antibiotic susceptibility tests and virulence gene PCR assays on these strains. RESULTS: Helicobacter pylori resistance rates of 45.8%, 15.4%, 1.0%, and 2.5% were detected for metronidazole, clarithromycin, amoxicillin, and levofloxacin, respectively. Among all isolates, 64.7% exhibited resistance to at least one antibiotic. Resistance to metronidazole and clarithromycin increased from 2019 to 2022. The predominant vacA gene subtype was vacA s1a/m2. The prevalence of vacA m2 and dupA exhibited an upward trend, while oipA presented a decreasing trend from 2019 to 2022. The prevalence of dupA was significantly higher in gastritis than peptic ulcer disease, and in non-treatment compared to treatment groups. CONCLUSIONS: Helicobacter pylori antibiotic resistance remains high in children and has risen in recent years. Therefore, the increasing use of metronidazole and clarithromycin requires increased monitoring in children. No association was observed between antibiotic resistance and virulence gene phenotypes.

Efficacy and safety of seven Chinese patent medicines combined with conventional triple/quadruple therapy for Helicobacter pylori-positive peptic ulcers: a systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy and safety of seven Chinese patent medicines (CPMs) combined with conventional triple/quadruple therapy (T/Q) for Helicobacter pylori-positive peptic ulcers. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: China National Knowledge Infrastructure, VIP database, Wanfang database, ScienceDirect, EBSCO, EMBASE, Web of Science, Cochrane Library and PubMed were searched through 1 June 2022. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) testing CPMs combined with T/Q for H. pylori-positive peptic ulcers were included. The CPMs included Anweiyang capsule, Jianweiyuyang tablets/capsule/granule, Jinghuaweikang capsule, Kangfuxin liquid, Puyuanhewei capsule, Weifuchun tablets/capsule and Weisu granule. At least one of the following outcome indicators was recorded: complete ulcer healing rate (CUHR), effective rate (ER), H. pylori eradication rate (HPER), rate of peptic ulcer recurrence (RPUR) and incidence of adverse reactions (IAR). DATA EXTRACTION AND SYNTHESIS: Two researchers independently conducted the study selection and extracted data for included studies. The risk of bias was assessed using the Cochrane risk of bias tool. A pairwise meta-analysis was performed using RevMan V.5.3. Network meta-analysis was performed using STATA/MP V.15.0. Confidence in the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation. RESULTS: A total of 36 RCTs involving 3620 patients were included. Compared with T/Q alone, Weisu+T/Q, Weifuchun+T/Q and Puyuanhewei+T/Q had the highest CUHR, ER and HPER, respectively. Weisu+T/Q and Jianweiyuyang+T/Q had the lowest RPUR and IAR, respectively. The cluster analysis results showed Jianweiyuyang+T/Q might be the best choice concerning efficacy and safety simultaneously, followed by Kangfuxin+T/Q. CONCLUSION: Among the combination therapies with the CPMs, Jianweiyuyang+T/Q might be the most favourable option for H. pylori-positive peptic ulcers, followed by Kangfuxin+T/Q. Considering the limited quantity and quality of the included RCTs, the results should be interpreted with caution. PROSPERO REGISTRATION NUMBER: CRD42022327687.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Helicobacter pylori Infection: A 40-Year Journey through Shifting the Paradigm to Transforming the Management.

BACKGROUND: Helicobacter pylori (H. pylori) was discovered 40 years ago and has set a milestone in human medicine. The discovery led to rejection of the dogma of the acidic stomach as a sterile organ and requested to rewrite the chapters on gastric pathophysiology and gastroduodenal diseases. SUMMARY: Over a period of 40 years following the discovery, more than 50,000 articles can be retrieved in PubMed as of today and illustrate the amount and the intensity of research around the role of this bacterium. H. pylori emerged as cause of chronic gastritis and principal cause of peptic ulcer disease (PUD). Eradication of H. pylori became standard of care in management in PUD. The importance of this was highlighted in 2005 with the Nobel Prize in Medicine awarded to Barry Marshall and Robin Warren. H. pylori became eventually recognized for its oncogenic potential in the stomach and as the main risk factor for gastric cancer development. KEY MESSAGES: H. pylori gastritis is defined as infectious disease and requires therapy in all infected individuals. Strategies of gastric cancer prevention and development of therapies to overcome the increasing antibiotic resistance are main targets in clinical research of today.

Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity.

PURPOSE: This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. METHODS: Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. RESULTS: H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. CONCLUSION: This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.

Aiding gastrointestinal diagnostic laboratory by designing a device for the non invasive detection of peptic ulcer.

Peptic ulcer (PU) has been recognized as an utmost gastrointestinal problem that affects the lining of the stomach and duodenum, specifically triggering soreness. It is a life-threatening condition, while roots of the infection are not identified yet. There are various risk factors for the cause of peptic ulcer disease, but the most significant is "Helicobacter pylori" (H. pylori). The detection of this disease involves different invasive procedures which are painful and not feasible for everyone. The aim of this device is to identify the peptic ulcer non-invasively by unmasking the presence of H. Pylori bacterium by monitoring crucial parameters of the disease which include respiration rate, heart rate, ECG, pH of Saliva, and temperature. Multiple investigations related to PU authenticate the alteration in these physicochemical aspects of the body. The increase in the level of stomach acid in PU is responsible for belching and bloating. Heart rate, temperature, and respiratory rate are also elevated during peptic ulcers while the pH of Saliva is decreased toward the acidic side. The disturbance in the QRS complex of the ECG wave is also observed. These biosignals are examined as analog input from the body, sent into MCP3008, and converted into digital input signals. Then these digital inputs are directed toward Raspberry pi 3 which processes, received inputs, and shows output on the LCD. The values of parameters obtained are then compared with standard values and a conclusion is made that whether a patient has a peptic ulcer or not.

Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori.

INTRODUCTION: Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED: In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION: For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).

PDE5 inhibitors and gastric mucosa: implications for the management of peptic ulcer disease.

Peptic ulcer disease (PUD) continues to be a cause of significant morbidity and mortality worldwide. Almost two-thirds of PUD cases are asymptomatic. In symptomatic patients, epigastric pain is the most common presenting symptom of PUD, which is manifested by nausea, abdominal fullness, bloating, and dyspepsia. Most PUD cases are associated with the use of COX inhibitors or Helicobacter pylori infection, or both. The traditional management of PUD includes the use of proton pump inhibitors to reduce the gastric acid secretion and antibacterial drugs to combat H. pylori. Timely diagnosis and treatment of PUD are vital to reduce the risk of associated morbidity and mortality, as is prevention of PUD among patients at high risk, including COX inhibitors users and those infected with H. pylori. PDE5 inhibitors have been used for the management of erectile dysfunction and pulmonary hypertension for decades. In recent years, studies have mentioned tremendous pleiotropic effects of PDE5 inhibitors on gastrointestinal, urogenital, musculoskeletal, reproductive, cutaneous, and neurologic disorders. Recent data shows that PDE5 inhibition augments gastric mucosa protection, and here, we review the most recent findings regarding the use of PDE5 inhibitors for the prevention and management of PUD.

New CagL Amino Acid Polymorphism Patterns of Helicobacter pylori in Peptic Ulcer and Non-Ulcer Dyspepsia.

Background and Objectives: Helicobacter pylori infection is associated with chronic gastritis, ulcers, and gastric cancer. The H. pylori Type 4 secretion system (T4SS) translocates the CagA protein into host cells and plays an essential role in initiating gastric carcinogenesis. The CagL protein is a component of the T4SS. CagL amino acid polymorphisms are correlated with clinical outcomes. We aimed to study the association between CagL amino acid polymorphisms and peptic ulcer disease (PUD) and non-ulcer dyspepsia (NUD). Materials and Methods: A total of 99 patients (PUD, 46; NUD, 53) were enrolled and screened for H. pylori by qPCR from antrum biopsy samples. The amino acid polymorphisms of CagL were analyzed using DNA sequencing, followed by the MAFFT sequence alignment program to match the amino acid sequences. Results: Antrum biopsy samples from 70 out of 99 (70.7%) patients were found to be H. pylori DNA-positive. A positive band for cagL was detected in 42 out of 70 samples (PUD, 23; NUD, 19), and following this, these 42 samples were sequenced. In total, 27 different polymorphisms were determined. We determined three CagL amino acid polymorphism combinations, which were determined to be associated with PUD and NUD. Pattern 1 (K35/N122/V134/T175/R194/E210) was only detected in PUD patient samples and was related to a 1.35-fold risk (p = 0.02). Patterns 2 (V41/I134) and 3 (V41/K122/A171/I174) were found only in NUD patient samples and were linked to a 1.26-fold increased risk (p = 0.03). Conclusions: We observed three new patterns associated with PUD and NUD. Pattern 1 is related to PUD, and the other two patterns (Patterns 2 and 3) are related to NUD. The patterns that we identified include the remote polymorphisms of the CagL protein, which is a new approach. These patterns may help to understand the course of H. pylori infection.

Effects of Quadruple Therapy Combined with Probiotics on Helicobacter Pylori-Related Peptic Ulcer.

The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.

[The history of the discovery of the Helicobacter pylori].

Helicobacter pylori is a spiral-shaped gram-negative bacterium that colonizes the stomach lining. The presence of a microorganism in humans was described more than a century ago, but from detection to recognition of its role in the etiology and pathogenesis of diseases of the stomach, researchers had to overcome a long path of criticism and mistrust. Coiled bacteria have been mentioned several times in the medical literature, but these bacteria were thought to be contaminants, and any evidence of the bacteria in the stomach was ignored by the medical community. The discovery of H. pylori led to a revolutionary rethinking of the mechanisms of development of a number of diseases: the role of bacteria in the development of chronic gastritis, peptic ulcer disease, stomach cancer and MALT lymphoma was proved. The principles of their prevention and treatment have changed. For this discovery in 2005, Barry Marshall and Robin Warren were awarded the Nobel Prize in Medicine and Physiology.

Benzimidazole derivatives: A versatile scaffold for drug development against Helicobacter pylori-related diseases.

Helicobacter pylori (H. pylori) is a microaerophilic gastric pathogen and a major contributor to chronic atrophic gastritis, peptic ulcer, and gastric malignancies. The increasing prevalence of H. pylori infection and its related diseases, such as gastric cancer (GC), motivates medicinal chemists to seek for more effective multi-targeting drugs to prevent and treat H. pylori-related clinical complications. Benzimidazole, a hetero-aromatic bicyclic ring compound, has claimed a prominent role in medicinal chemistry owing to its broad range of biological activities, including antibacterial, antiviral, antidiabetic, and anticancer activities. Studies highlight the promising therapeutic potential of benzimidazole derivatives in the treatment of H. pylori-related clinical complications such as gastric infection, gastritis, peptic ulcer, and GC. Accordingly, we here aimed to scrutinize the role of active molecules of benzimidazole derivatives as potential antibacterial, anti-urease, anti-inflammatory, anti-ulcerative, and anticancer agents, which are expected to find their ways to the clinical setting sooner or later. Due to the role of structural moieties in determining the biological behaviors of benzimidazole derivatives, we explored the structure-activity relationship (SAR) of these compounds to further expand the scope of design of and research on new drugs against H. pylori-related diseases.

Mapping microbiome-redox spectrum and evaluating Microbial-Redox Index in chronic gastritis.

Peptic ulcer disease (PUD) and chronic gastritis are prevalent in developing countries. The role of oxidative stress in the pathogenesis of gastrointestinal mucosal disorders is well recognized. In PUD, the gastric mucosa and its associated microbiome are subject to diet and stress-induced oxidative perturbations. Tissue redox potential (ORP) measurement can quantify oxidative stress, reflecting the balance between prooxidants and antioxidants. This study hypothesizes that the oxidative stress quantified by tissue ORP will be associated with characteristic changes in the mucosa-associated microbiome in PUD and gastritis. In addition, we propose using relative microbial abundance as a quantitative marker of mucosal health. Endoscopy was performed to obtain gastric mucosal biopsies from ten PUD and ten non-ulcer dyspepsia (NUD) patients. The tissue ORP was measured directly with a microelectrode using a biopsy specimen. A second specimen from an adjacent site was subjected to 16s rRNA gene sequencing. From the OTUs, the relative abundance of the microbial taxon in each of the samples was derived. We analyzed the genome of the predominant species for genes encoding the utilization of oxygen as an electron acceptor in respiration and for the presence of antioxidant defense mechanisms. The organisms were then grouped based on their established and inferred redox traits. Shannon diversity index and Species richness were calculated on rarefied data. The relative abundance of organisms that prefer high ORP over those that favor low ORP is conceived as the "Microbial Redox Index (MRI)," an indicator of mucosal health. In the gastric mucosa, aerobic species predominate and are more diverse than the anaerobes. The predominant aerobes are Helicobacter pylori and Sphingobacterium mizutaii. The abundance of these two species had an inverse correlation with the abundance of low ORP preferring anaerobes. Their relative abundance ratio (Microbial Redox Index) correlated with the tissue oxidation-reduction potential (ORP), a direct measure of oxidative stress. Correlation analysis also revealed that the abundance of all anaerobes inversely correlated with the dominant aerobic taxa. In addition, Shannon and Species richness diversity indices, the probable indicators of mucosal health, were negatively correlated with Microbial Redox Index. Using PUD as a prototype mucosal disease, this article describes a generalized approach to infer and quantify mucosal oxidative stress by analyzing the relative abundance of microorganisms that preferentially grow at the extremes of the tissue redox potential. This ratiometric Microbial Redox Index can also be assessed using simple qPCR without the need for sequencing. The approach described herein may be helpful as a widely applicable quantitative measure of mucosal health with prognostic and therapeutic implications.