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1.
J Int Med Res ; 52(5): 3000605241248041, 2024 May.
Article En | MEDLINE | ID: mdl-38775336

OBJECTIVE: To investigate factors related to the risk of developing irritable bowel syndrome (IBS) or Helicobacter pylori infection. METHODS: This cross-sectional, questionnaire-based study analysed the responses from participants that completed an online questionnaire, which asked about their knowledge of the causes and risk factors associated with IBS and H. pylori infection. RESULTS: The study analysed responses from 230 participants: 181 females (of 227 participants; 79.7%) and 190 aged 18-40 years (of 228; 83.3%). Of the 230 participants, 40 (17.4%) had been diagnosed by a physician with IBS and 57 (24.8%) had been diagnosed with H. pylori infection. Of 226 participants, 93 (41.2%) had self-medicated with antibiotics in the past 6 months for various reasons. The overall mean ± SD knowledge score about IBS and H. pylori infection for the study cohort (n = 230) was 35.8 ± 19.2%. Wald χ2-test analysis demonstrated that chronic diseases, antibiotic use and having an endoscopy were significantly associated with developing IBS. Male sex and chronic diseases were significantly associated with H. pylori infection. Logistic regression analysis showed no relationship between IBS and H. Pylori infection. CONCLUSION: Chronic diseases was the only risk factor common for IBS and H. pylori infection.


Health Knowledge, Attitudes, Practice , Helicobacter Infections , Helicobacter pylori , Irritable Bowel Syndrome , Humans , Irritable Bowel Syndrome/microbiology , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/diagnosis , Irritable Bowel Syndrome/psychology , Female , Male , Helicobacter Infections/diagnosis , Helicobacter Infections/microbiology , Helicobacter Infections/complications , Helicobacter Infections/epidemiology , Adult , Helicobacter pylori/isolation & purification , Adolescent , Risk Factors , Surveys and Questionnaires , Young Adult , Cross-Sectional Studies , Anti-Bacterial Agents/therapeutic use
2.
Arq Gastroenterol ; 61: e23139, 2024.
Article En | MEDLINE | ID: mdl-38775582

BACKGROUND: Helicobacter pylori (H. pylori) is a gram-negative bacterium associated with the etiology of several gastrointestinal tract pathologies, and cagA-positive (cagA+) strains are found in populations with gastric ulcers and precancerous lesions, inducing pro-inflammatory responses. The development of neoplasms is related to microRNA (miRNA) dysregulation, indicating highly expressed miRNA-629. The article aims to correlate the expression level of miRNA-629 with the presence of H. pylori and the pathogenicity marker cagA. METHODS: 203 gastric biopsy samples were evaluated from individuals with normal gastric tissue (n=60), gastritis (n=96), and gastric cancer (n=47) of both genders and over 18 years old. The samples were subdivided according to the presence or absence of H. pylori, detected by polymerase chain reaction (PCR). RNA was extracted using a commercial kit and quantified. Complementary DNA (cDNA) was synthesized using commercial kits, and the relative expression was calculated using the 2-ΔΔCt method. RESULTS: Individuals infected with H. pylori are nine times more likely to develop gastric cancer. Cancer patients appeared to have decreased expression of miRNA-629; however, the presence of the bacterium would not influence this reduction. Individuals in the cancer group showed lower miRNA-629 expression when cagA+; however, in the control group, the expression was higher when cagA+. CONCLUSION: H. pylori is a factor involved in the etiology and progression of gastric diseases. Reduction in miRNA-629 expression in cancer patients occurs independent of the presence of the bacterium, but when the cagA pathogenicity marker is present, it induces changes in the gene expression of the respective miRNA.


Antigens, Bacterial , Bacterial Proteins , Helicobacter Infections , Helicobacter pylori , MicroRNAs , Stomach Neoplasms , Humans , Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Stomach Neoplasms/microbiology , Stomach Neoplasms/genetics , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , MicroRNAs/genetics , MicroRNAs/analysis , Female , Male , Helicobacter Infections/microbiology , Middle Aged , Adult , Aged , Gastritis/microbiology
3.
Korean J Intern Med ; 39(3): 439-447, 2024 May.
Article En | MEDLINE | ID: mdl-38715232

BACKGROUND: Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection. METHODS: A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set. RESULTS: The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed. CONCLUSION: Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.


Helicobacter Infections , Helicobacter pylori , Predictive Value of Tests , Humans , Helicobacter Infections/diagnosis , Helicobacter Infections/microbiology , Helicobacter Infections/drug therapy , Retrospective Studies , Male , Female , Middle Aged , Helicobacter pylori/isolation & purification , Helicobacter pylori/drug effects , Adult , Aged , Breath Tests , Endoscopy, Gastrointestinal , Reproducibility of Results , Gastritis/microbiology , Gastritis/diagnosis , Risk Assessment , Decision Support Techniques
4.
BMC Gastroenterol ; 24(1): 157, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720287

BACKGROUND: At present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH. METHODS: Subjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient. RESULTS: PCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases. CONCLUSIONS: In NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI's acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated. STUDY REGISTRATION: This study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).


Anti-Bacterial Agents , Drug Therapy, Combination , Gastritis , Helicobacter Infections , Helicobacter heilmannii , Proton Pump Inhibitors , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/therapeutic use , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Male , Female , Middle Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Gastritis/drug therapy , Gastritis/microbiology , Adult , Aged , Helicobacter heilmannii/isolation & purification , Helicobacter pylori/drug effects , Helicobacter pylori/isolation & purification , Amoxicillin/administration & dosage , Amoxicillin/therapeutic use , Clarithromycin/administration & dosage , Clarithromycin/therapeutic use , Helicobacter/isolation & purification , Helicobacter/drug effects , Treatment Outcome , Gastric Mucosa/microbiology , Gastric Mucosa/pathology
5.
World J Gastroenterol ; 30(16): 2281-2284, 2024 Apr 28.
Article En | MEDLINE | ID: mdl-38690016

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 non-culturable 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.


Helicobacter Infections , Helicobacter pylori , Helicobacter pylori/pathogenicity , Humans , Helicobacter Infections/microbiology , Candida/physiology , Candida/growth & development , Candida/pathogenicity , Vacuoles/microbiology , Vacuoles/metabolism , Stomach/microbiology , Gastric Mucosa/microbiology
6.
Helicobacter ; 29(1): e13048, 2024.
Article En | MEDLINE | ID: mdl-38716864

Current global variations exist in Helicobacter pylori (H. pylori) eradication regimens. Triple therapy (TT), bismuth quadruple therapy (BQT), and high-dose dual therapy (HDDT) currently represent the predominant regimens. These regimens diverge in terms of treatment duration, the utilization of susceptibility testing, acid-inhibiting drug administration, and patient education. We conducted a comprehensive systematic literature review on these H. pylori treatment regimens. Our review aims to provide standardized treatment recommendations for H. pylori, reducing the risk of amalgamating findings from diverse eradication regimens. Recent research suggests that the optimal treatment duration for TT and BQT may be 14 and 10 days, respectively. Selecting the appropriate treatment duration for HDDT should rely on regional research evidence, and 14 days may be the optimal duration. The incorporation of susceptibility testing in TT is of paramount importance. In the case of BQT, the absence of susceptibility testing may be considered as an option, contingent upon cost and availability, and should be determined based on local antibiotic resistance patterns and the efficacy of empirical regimens. The type and dosage of acid-inhibiting drug would affect the efficacy of these regimens. Acid-inhibiting drugs should be selected and applied reasonably according to the population and therapies. Adequate patient education plays a pivotal role in the eradication of H. pylori. In regions with accessible local research evidence, the 10-day empirical BQT regimen may be considered a preferred choice for H. pylori eradication.


Anti-Bacterial Agents , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Humans , Helicobacter pylori/drug effects , Anti-Bacterial Agents/therapeutic use , Bismuth/therapeutic use , Proton Pump Inhibitors/therapeutic use
7.
Helicobacter ; 29(3): e13081, 2024.
Article En | MEDLINE | ID: mdl-38717008

BACKGROUND: The main antibiotics used against Helicobacter pylori have been chosen empirically over time, with few preclinical studies to provide support. The rise in resistance to some of these antibiotics is prompting a reassessment of their use. This work aimed to evaluate the in vitro efficacy of 2 × 2 combinations of the most widely used antibiotics against H. pylori. MATERIALS AND METHODS: J99 reference strains and 19 clinical isolates of H. pylori with various antibiotic resistance phenotypes were used. Minimum inhibitory concentrations were carried out using the microdilution method in 96-well plates. The activity of 15 possible combinations of two antibiotics including amoxicillin, clarithromycin (CLA), levofloxacin, rifampicin, tetracycline, and metronidazole was determined for all strains by the checkerboard method. A mean fractional inhibitory concentration index (FICmean) was calculated for each combination and strain and the type of pharmacodynamic interaction was considered as synergic if FICmean ≤ 0.5, additive if 0.5 < FICmean ≤ 1, indifferent if 1 < FICmean < 4 or antagonistic if FICmean ≥ 4. RESULTS: Most of the 285 pharmacodynamic interactions tested with clinical strains were close to additivity (average FICmean = 0.89 [0.38-1.28]). No interaction was found to be antagonistic. When two antibiotics to which a strain was resistant were combined, the concentrations required to inhibit bacterial growth were higher than their respective breakpoints. CONCLUSION: The present results have shown that in vitro, the different antibiotics used in therapeutics have additive effects. The addition of the effects of two antibiotics to which a strain was resistant was not sufficient to inhibit bacterial growth. In probabilistic treatment, the choice of antibiotics to combine should therefore be based on the local epidemiology of resistance, and on susceptibility testing in the case of CLA therapy, so that at least one antibiotic to which the strain is susceptible is used.


Anti-Bacterial Agents , Helicobacter Infections , Helicobacter pylori , Microbial Sensitivity Tests , Helicobacter pylori/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Drug Resistance, Bacterial , Drug Therapy, Combination , Drug Synergism
8.
Helicobacter ; 29(3): e13084, 2024.
Article En | MEDLINE | ID: mdl-38717034

BACKGROUND: Recently, a simple tailored therapy based on clarithromycin resistance has been implemented as Helicobacter pylori (H. pylori) eradication therapy. Nonetheless, despite the tailored therapy and frequent adverse events, studies on treatment period are lacking. This study aimed to compare the H. pylori eradication rates of 7-day and 14-day tailored therapy regimens according to clarithromycin resistance. MATERIALS AND METHODS: This multicenter, prospective, randomized, noninferiority trial enrolled H. pylori-positive patients who were randomly assigned to 7-day and 14-day regimen groups, depending on the presence or absence of clarithromycin resistance by 23S rRNA gene point mutations. Standard triple therapy (STT) (20 mg rabeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily) or bismuth quadruple therapy (BQT) (20 mg rabeprazole twice daily, 500 mg metronidazole thrice daily, 120 mg bismuth four times daily, and 500 mg tetracycline four times daily) was assigned by clarithromycin resistance. Eradication rates and adverse events were evaluated. RESULTS: A total of 314 and 278 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively; however, 31 patients were lost to follow-up, whereas five patients violated the protocol. Both the 7-day and 14-day regimens showed similar eradication rates in the ITT (7-day vs. 14-day: 78.3% vs. 78.3%, p > 0.99) and PP (87.9% vs. 89.1%, p = 0.851) analyses. Non-inferiority was confirmed (p < 0.025). A subgroup analysis according to clarithromycin resistance (clarithromycin resistance rate: 28.7%) revealed no significant difference in eradication rates between the 7-day and 14-day STT (90.0% vs. 90.1%, p > 0.99) and BQT (82.5% vs. 86.5%, p = 0.757). Furthermore, adverse events did not significantly differ between the two groups. CONCLUSIONS: The 7-day triple and quadruple therapy according to clarithromycin resistance showed similar eradication rates, as compared to the 14-day therapy.


Anti-Bacterial Agents , Clarithromycin , Drug Resistance, Bacterial , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Clarithromycin/therapeutic use , Clarithromycin/pharmacology , Helicobacter pylori/drug effects , Helicobacter pylori/genetics , Male , Female , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Middle Aged , Adult , Prospective Studies , Drug Therapy, Combination , Aged , Treatment Outcome , Rabeprazole/therapeutic use , Rabeprazole/administration & dosage , Bismuth/therapeutic use , Bismuth/administration & dosage , RNA, Ribosomal, 23S/genetics
9.
Sci Rep ; 14(1): 10069, 2024 05 02.
Article En | MEDLINE | ID: mdl-38697990

Helicobacter pylori infection, a worldwide health issue, is typically treated with standard antibiotic therapies. However, these treatments often face resistance and non-compliance due to side effects. In this umbrella review, we aimed to comprehensively assess the impact of probiotics supplementation in different preparations on Helicobacter pylori standard treatment. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials in the Cochrane Library from inception to June 1, 2023, to identify systematic reviews with meta-analyses that focused on eradication rates, total side effects and other outcomes of interest. The most comprehensive meta-analysis was selected for data extraction. AMSTAR 2 was used to assess quality of meta-analyses. Overall, 28 unique meta-analyses based on 534 RCTs were included. The results suggests that probiotics supplementation with pooled probiotic strains was significantly associated with improved eradication rates (RR 1.10, 95% CI 1.06-1.14) and reduced risk of total side effects (RR 0.54, 95% CI 0.42-0.70) compared with standard therapy alone. Single-strained or multi-strained preparation of probiotics supplementation showed similar results. Despite Bifidobacterium spp. showing the highest potential for eradication, the study quality was critically low for most meta-analyses, necessitating further high-quality research to explore the optimal probiotic strains or their combinations for Helicobacter pylori treatment.aq_start?>Kindly check and confirm the edit made in article title.


Helicobacter Infections , Helicobacter pylori , Probiotics , Systematic Reviews as Topic , Probiotics/therapeutic use , Helicobacter pylori/drug effects , Helicobacter Infections/drug therapy , Helicobacter Infections/therapy , Helicobacter Infections/microbiology , Humans , Meta-Analysis as Topic , Dietary Supplements , Anti-Bacterial Agents/therapeutic use , Treatment Outcome
10.
Gut Microbes ; 16(1): 2347025, 2024.
Article En | MEDLINE | ID: mdl-38693666

Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. The host immune response evoked by H. pylori infection is complicated and can influence the development and progression of diseases. We have reported that the Group 2 innate lymphocytes (ILC2) were promoted and took part in building type-2 immunity in H. pylori infection-related gastric diseases. Therefore, in the present study, we aim to clarify how H. pylori infection induces the activation of ILC2. It was found that macrophages were necessary for activating ILC2 in H. pylori infection. Mechanistically, H. pylori infection up-regulated the expression of indoleamine 2,3-dioxygenase (IDO) in macrophages to induce M2 polarization, and the latter secreted the alarmin cytokine Thymic Stromal Lymphopoietin (TSLP) to arouse ILC2.


Cytokines , Helicobacter Infections , Helicobacter pylori , Immunity, Innate , Macrophages , Helicobacter pylori/immunology , Macrophages/immunology , Macrophages/microbiology , Helicobacter Infections/immunology , Helicobacter Infections/microbiology , Animals , Mice , Cytokines/metabolism , Mice, Inbred C57BL , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Thymic Stromal Lymphopoietin , Lymphocytes/immunology , Humans
11.
J Int Med Res ; 52(5): 3000605241253454, 2024 May.
Article En | MEDLINE | ID: mdl-38759213

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.


Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter pylori/isolation & purification , Helicobacter pylori/immunology , Helicobacter pylori/pathogenicity , Male , Female , China/epidemiology , Helicobacter Infections/microbiology , Helicobacter Infections/epidemiology , Helicobacter Infections/diagnosis , Middle Aged , Risk Factors , Cross-Sectional Studies , Adult , Bacterial Proteins , Prevalence , Antigens, Bacterial/immunology , Peptic Ulcer/microbiology , Peptic Ulcer/epidemiology , Aged , Breath Tests , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology
12.
J Cell Mol Med ; 28(9): e18358, 2024 May.
Article En | MEDLINE | ID: mdl-38693868

Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each year. However, the major challenge to fight against H. pylori and its associated gastric cancer due to drug resistance. This research gap had led our research team to investigate a potential drug candidate targeting the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein. In this study, a total of 45 daidzein derivatives were investigated and the best 10 molecules were comprehensively investigated using in silico approaches for drug development, namely pass prediction, quantum calculations, molecular docking, molecular dynamics simulations, Lipinski rule evaluation, and prediction of pharmacokinetics. The molecular docking study was performed to evaluate the binding affinity between the target protein and the ligands. In addition, the stability of ligand-protein complexes was investigated by molecular dynamics simulations. Various parameters were analysed, including root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM). The results has confirmed that the ligand-protein complex CID: 129661094 (07) and 129664277 (08) formed stable interactions with the target protein. It was also found that CID: 129661094 (07) has greater hydrogen bond occupancy and stability, while the ligand-protein complex CID 129664277 (08) has greater conformational flexibility. Principal component analysis revealed that the ligand-protein complex CID: 129661094 (07) is more compact and stable. Hydrogen bond analysis revealed favourable interactions with the reported amino acid residues. Overall, this study suggests that daidzein derivatives in particular show promise as potential inhibitors of H. pylori.


Helicobacter pylori , Isoflavones , Molecular Docking Simulation , Molecular Dynamics Simulation , Helicobacter pylori/drug effects , Helicobacter pylori/metabolism , Isoflavones/pharmacology , Isoflavones/chemistry , Isoflavones/metabolism , Humans , Hydrogen Bonding , Ligands , Protein Binding , Principal Component Analysis , Helicobacter Infections/microbiology , Helicobacter Infections/drug therapy , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/antagonists & inhibitors , Stomach Neoplasms/microbiology , Stomach Neoplasms/drug therapy
13.
Helicobacter ; 29(3): e13093, 2024.
Article En | MEDLINE | ID: mdl-38757432

BACKGROUND: The purpose of this analysis is to evaluate the antimicrobial susceptibility of eight drugs effective against Helicobacter pylori (H. pylori) strains and the genetic diversity of H. pylori virulence genes to foresee clinical outcomes in North India. MATERIALS AND METHODS: Fifty-eight H. pylori strains isolated from patients suffering from various gastrointestinal (GI) diseases were included in the study. MICs of various antibiotics were determined by the agar dilution method. The chi-squared test and Fisher exact test were used to determine the p-value, which was considered significant at p-value ≤ 0.05. RStudio 4.0 was used to for the data visualization. RESULTS: The prevalence of drug resistance was found to be: cefixime (CFM) (41.3%), furazolidone (FZD) (34.4%), amoxicillin (AMX) (20.7%), levofloxacin (LVFX) (70.7%), metronidazole (MTZ) (39.6%), tetracycline (TET) (20.7%), clarithromycin (CLA) (17.2%), and rifabutin (RIF) (17.2%). Out of 58 H. pylori strains, 3 were pan susceptible. There were H. pylori strains with single-drug resistance (21.8%, 12/55), dual resistance (30.9%, 17/55), triple resistance (20%, 11/55), and multidrug resistance (27.3%, 15/55). The resistance rate in MTZ, CLA and RIF were found to be significantly higher in females as compared to males (p = 0.005, p = 0.002, and p = 0.02), respectively. The resistance to TET exhibited significantly higher levels in gastritis compared to GERD, DU, and other disease groups (p = 0.04) respectively. CONCLUSION: TET, AMX, CLA, and RIF were found to be more effective antibiotics against H. pylori infections, whereas more studies are required to provide evidence on increasing resistance rate of LVFX.


Anti-Bacterial Agents , Helicobacter Infections , Helicobacter pylori , Microbial Sensitivity Tests , Helicobacter pylori/drug effects , Helicobacter pylori/genetics , Helicobacter pylori/isolation & purification , Humans , Anti-Bacterial Agents/pharmacology , India/epidemiology , Female , Male , Helicobacter Infections/microbiology , Helicobacter Infections/drug therapy , Adult , Middle Aged , Young Adult , Aged , Adolescent , Drug Resistance, Bacterial
14.
J Med Microbiol ; 73(5)2024 May.
Article En | MEDLINE | ID: mdl-38712922

Introduction. Resistance towards amoxicillin in Helicobacter pylori causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard H. pylori treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy.Hypothesis/Gap Statement. The high eradication rate with amoxicillin-based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently.Aim. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of H. pylori, correlating with amoxicillin resistance in the Malaysian population.Methodology. The full-length pbp1A gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of H. pylori-positive treatment-naïve Malaysian patients. The sequences were then compared with reference H. pylori strain ATCC 26695 for mutation and variant detection. A phylogenetic analysis of 50 sequences along with 43 additional sequences from the NCBI database was performed. These additional sequences included both amoxicillin-resistant strains (n=20) and amoxicillin-sensitive strains (n=23).Results. There was a total of 21 variants of amino acids, with three of them located in or near the PBP-motif (SKN402-404). The percentages of these three variants are as follows: K403X, 2%; S405I, 2% and E406K, 16%. Based on the genetic markers identified, the resistance rate for amoxicillin in our sample remained at 0%. The phylogenetic examination suggested that H. pylori might exhibit unique conserved pbp1A sequences within the Malaysian context.Conclusions. Overall, the molecular analysis of PBP1A supported the therapeutic superiority of amoxicillin-based regimens. Therefore, it is crucial to continue monitoring the amoxicillin resistance background of H. pylori with a larger sample size to ensure the sustained effectiveness of amoxicillin-based treatments in Malaysia.


Amoxicillin , Anti-Bacterial Agents , Drug Resistance, Bacterial , Genetic Variation , Helicobacter Infections , Helicobacter pylori , Penicillin-Binding Proteins , Amoxicillin/pharmacology , Humans , Helicobacter pylori/genetics , Helicobacter pylori/drug effects , Malaysia , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Penicillin-Binding Proteins/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Phylogeny , Mutation , Male , Adult , Microbial Sensitivity Tests , Proton Pump Inhibitors/therapeutic use , Female , Middle Aged , Drug Therapy, Combination , Bacterial Proteins/genetics
15.
Sci Rep ; 14(1): 9998, 2024 05 01.
Article En | MEDLINE | ID: mdl-38693196

It is estimated that more than half of the world population has been infected with Helicobacter pylori. Most newly acquired H. pylori infections occur in children before 10 years of age. We hypothesized that early life H. pylori infection could influence the composition of the microbiome at mucosal sites distant to the stomach. To test this hypothesis, we utilized the infant rhesus macaque monkey as an animal model of natural H. pylori colonization to determine the impact of infection on the lung and oral microbiome during a window of postnatal development. From a cohort of 4-7 month-old monkeys, gastric biopsy cultures identified 44% of animals infected by H. pylori. 16S ribosomal RNA gene sequencing of lung washes and buccal swabs from animals showed distinct profiles for the lung and oral microbiome, independent of H. pylori infection. In order of relative abundance, the lung microbiome was dominated by the phyla Proteobacteria, Firmicutes, Bacteroidota, Fusobacteriota, Campilobacterota and Actinobacteriota while the oral microbiome was dominated by Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota. In comparison to the oral cavity, the lung was composed of more genera and species that significantly differed by H. pylori status, with a total of 6 genera and species that were increased in H. pylori negative infant monkey lungs. Lung, but not plasma IL-8 concentration was also associated with gastric H. pylori load and lung microbial composition. We found the infant rhesus macaque monkey lung harbors a microbiome signature that is distinct from that of the oral cavity during postnatal development. Gastric H. pylori colonization and IL-8 protein were linked to the composition of microbial communities in the lung and oral cavity. Collectively, these findings provide insight into how H. pylori infection might contribute to the gut-lung axis during early childhood and modulate future respiratory health.


Helicobacter Infections , Helicobacter pylori , Lung , Macaca mulatta , Microbiota , Mouth , RNA, Ribosomal, 16S , Animals , Macaca mulatta/microbiology , Lung/microbiology , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Mouth/microbiology , RNA, Ribosomal, 16S/genetics , Male , Disease Models, Animal
16.
Cell Commun Signal ; 22(1): 250, 2024 May 02.
Article En | MEDLINE | ID: mdl-38698410

Single nucleotide polymorphisms (SNPs) account for significant genomic variability in microbes, including the highly diverse gastric pathogen Helicobacter pylori. However, data on the effects of specific SNPs in pathogen-host interactions are scarce. Recent functional studies unravelled how a serine/leucine polymorphism in serine protease HtrA affects the formation of proteolytically active trimers and modulates cleavage of host cell-to-cell junction proteins during infection. A similar serine/leucine mutation in the carbohydrate binding domain of the adhesin BabA controls binding of ABO blood group antigens, enabling binding of either only the short Lewis b/H antigens of blood group O or also the larger antigens of blood groups A and B. Here we summarize the functional importance of these two remarkable bacterial SNPs and their effect on the outcome of pathogen-host interactions.


Adhesins, Bacterial , Helicobacter pylori , Leucine , Serine , Helicobacter pylori/genetics , Adhesins, Bacterial/genetics , Adhesins, Bacterial/metabolism , Humans , Serine/genetics , Serine/metabolism , Leucine/genetics , Leucine/metabolism , Polymorphism, Single Nucleotide/genetics , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Helicobacter Infections/microbiology , Helicobacter Infections/genetics , Animals
17.
Helicobacter ; 29(2): e13060, 2024.
Article En | MEDLINE | ID: mdl-38581134

BACKGROUND: Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador. METHODS: A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied. RESULTS: All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin-amoxicillin was 43.4%, to tetracycline-metronidazole 30.3%, to amoxicillin-levofloxacin 27.6%, and to clarithromycin-metronidazole 59.2%. CONCLUSIONS: In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.


Anti-Infective Agents , Helicobacter Infections , Helicobacter pylori , Humans , Clarithromycin/pharmacology , Clarithromycin/therapeutic use , Metronidazole/pharmacology , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Levofloxacin/pharmacology , Ecuador , Anti-Bacterial Agents/pharmacology , Amoxicillin/pharmacology , Tetracycline/therapeutic use , Tetracycline/pharmacology , Drug Therapy, Combination
18.
PLoS One ; 19(4): e0300696, 2024.
Article En | MEDLINE | ID: mdl-38603679

The primary treatment method for eradicating Helicobacter pylori (H. pylori) infection involves the use of antibiotic-based therapies. Due to the growing antibiotic resistance of H. pylori, there has been a surge of interest in exploring alternative therapies. Cetylpyridinium chloride (CPC) is a water-soluble and nonvolatile quaternary ammonium compound with exceptional broad-spectrum antibacterial properties. To date, there is no documented or described specific antibacterial action of CPC against H. pylori. Therefore, this study aimed to explore the in vitro activity of CPC against H. pylori and its potential antibacterial mechanism. CPC exhibited significant in vitro activity against H. pylori, with MICs ranging from 0.16 to 0.62 µg/mL and MBCs ranging from 0.31 to 1.24 µg/mL. CPC could result in morphological and physiological modifications in H. pylori, leading to the suppression of virulence and adherence genes expression, including flaA, flaB, babB, alpA, alpB, ureE, and ureF, and inhibition of urease activity. CPC has demonstrated in vitro activity against H. pylori by inhibiting its growth, inducing damage to the bacterial structure, reducing virulence and adherence factors expression, and inhibiting urease activity.


Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter pylori/genetics , Cetylpyridinium/pharmacology , Urease/genetics , Helicobacter Infections/microbiology , Anti-Bacterial Agents/pharmacology
19.
Curr Microbiol ; 81(5): 125, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38558085

More than half of the world's population is infected with Helicobacter pylori (H. pylori), which may lead to chronic gastritis, peptic ulcers, and stomach cancer. LeoA, a conserved antigen of H. pylori, aids in preventing this infection by triggering specific CD3+ T-cell responses. In this study, recombinant plasmids containing the LeoA gene of H. pylori are created and conjugated with chitosan nanoparticle (CSNP) to immunize BALB/c mice against the H. pylori infection. We used the online Vaxign tool to analyze the genomes of five distinct strains of H. pylori, and we chose the outer membrane as a prospective vaccine candidate. Afterward, the proteins' immunogenicity was evaluated. The DNA vaccine was constructed and then encapsulated in CSNPs. The effectiveness of the vaccine's immunoprotective effects was evaluated in BALB/c mice. Purified activated splenic CD3+ T cells are used to test the anticancer effects in vitro. Nanovaccines had apparent spherical forms, were small (mean size, 150-250 nm), and positively charged (41.3 ± 3.11 mV). A consistently delayed release pattern and an entrapment efficiency (73.35 ± 3.48%) could be established. Compared to the non-encapsulated DNA vaccine, vaccinated BALB/c mice produced higher amounts of LeoA-specific IgG in plasma and TNF-α in splenocyte lysate. Moreover, BALB/c mice inoculated with nanovaccine demonstrated considerable immunity (87.5%) against the H. pylori challenge and reduced stomach injury and bacterial burdens in the stomach. The immunological state in individuals with GC with chronic infection with H. pylori is mimicked by the H. pylori DNA nanovaccines by inducing a shift from Th1 to Th2 in the response. In vitro human GC cell development is inhibited by activated CD3+ T lymphocytes. According to our findings, the H. pylori vaccine-activated CD3+ has potential immunotherapeutic benefits.


Chitosan , Helicobacter Infections , Helicobacter pylori , Nanoparticles , Vaccines, DNA , Humans , Animals , Mice , Helicobacter pylori/genetics , Vaccines, DNA/genetics , DNA , Vaccination , Helicobacter Infections/prevention & control , Helicobacter Infections/microbiology , Bacterial Vaccines/genetics , Mice, Inbred BALB C , Antibodies, Bacterial
20.
Helicobacter ; 29(2): e13075, 2024.
Article En | MEDLINE | ID: mdl-38627919

BACKGROUND: The current standard treatment for Helicobacter pylori infection, which involves a combination of two broad-spectrum antibiotics, faces significant challenges due to its detrimental impact on the gut microbiota and the emergence of drug-resistant strains. This underscores the urgent requirement for the development of novel anti-H. pylori drugs. Zoliflodacin, a novel bacterial gyrase inhibitor, is currently undergoing global phase III clinical trials for treating uncomplicated Neisseria gonorrhoeae. However, there is no available data regarding its activity against H. pylori. MATERIALS AND METHODS: We evaluated the in vitro activity of zoliflodacin against H. pylori clinical isolates (n = 123) with diverse multidrug resistance. We performed DNA gyrase supercoiling and microscale thermophoresis assays to identify the target of zoliflodacin in H. pylori. We analyzed 2262 H. pylori whole genome sequences to identify Asp424Asn and Lys445Asn mutations in DNA gyrase subunit B (GyrB) that are associated with zoliflodacin resistance. RESULTS: Zoliflodacin exhibits potent activity against all tested isolates, with minimal inhibitory concentration (MIC) values ranging from 0.008 to 1 µg/mL (MIC50: 0.125 µg/mL; MIC90: 0.25 µg/mL). Importantly, there was no evidence of cross-resistance to any of the four first-line antibiotics commonly used against H. pylori. We identified GyrB as the primary target of zoliflodacin, with Asp424Asn or Lys445Asn substitutions conferring resistance. Screening of 2262 available H. pylori genomes for the two mutations revealed only one clinical isolate carrying Asp424Asn substitution. CONCLUSION: These findings support the potential of zoliflodacin as a promising candidate for H. pylori treatment, warranting further development and evaluation.


Barbiturates , Helicobacter Infections , Helicobacter pylori , Isoxazoles , Morpholines , Oxazolidinones , Spiro Compounds , Humans , Anti-Bacterial Agents/pharmacology , DNA Gyrase/genetics , Drug Resistance, Bacterial , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Microbial Sensitivity Tests , Clinical Trials, Phase III as Topic
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