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BACKGROUND: Helicobacter pylori (H. pylori) infects over 50% of the global population and is a significant risk factor for gastric cancer. The pathogenicity of H. pylori is primarily attributed to virulence factors such as vacA. Timely and accurate identification, along with genotyping of H. pylori virulence genes, are essential for effective clinical management and controlling its prevalence. METHODS: In this study, we developed a dual-target RAA-LFD assay for the rapid, visual detection of H. pylori genes (16s rRNA, ureA, vacA m1/m2), using recombinase aided amplification (RAA) combined with lateral flow dipstick (LFD) methods. Both 16s rRNA and ureA were selected as identification genes to ensure reliable detection accuracy. RESULTS: A RAA-LFD assay was developed to achieve dual-target amplification at a stable 37 °C within 20 min, followed by visualization using the lateral flow dipstick (LFD). The whole process, from amplification to results, took less than 30 min. The 95 % limit of detection (LOD) for 16 s rRNA and ureA, vacA m1, vacA m2 were determined as 3.8 × 10-2 ng/µL, 5.8 × 10-2 ng/µL and 1.4 × 10-2 ng/µL, respectively. No cross-reaction was observed in the detection of common pathogens including Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis, showing the assay's high specificity. In the evaluation of the clinical performance of the RAA-LFD assay. A total of 44 gastric juice samples were analyzed, immunofluorescence staining (IFS) and quantitative polymerase chain reaction (qPCR) were used as reference methods. The RAA-LFD results for the 16s rRNA and ureA genes showed complete agreement with qPCR findings, accurately identifying H. pylori infection as confirmed by IFS in 10 out of the 44 patients. Furthermore, the assay successfully genotyped vacA m1/m2 among the positive samples, showing complete agreement with qPCR results and achieving a kappa (κ) value of 1.00. CONCLUSION: The dual-target RAA-LFD assay developed in this study provides a rapid and reliable method for detecting and genotyping H. pylori within 30 min, minimizing dependency on sophisticated laboratory equipment and specialized personnel. Clinical validation confirms its efficacy as a promising tool for effectively control of its prevalence and aiding in the precise treatment of H. pylori-associated diseases.
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Proteínas Bacterianas , Helicobacter pylori , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Proteínas Bacterianas/genética , Humanos , ARN Ribosómico 16S/genética , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Técnicas de Amplificación de Ácido Nucleico/métodosRESUMEN
BACKGROUND: European and North-American guidelines on management of H. pylori infection in children provide the option not to treat even if the infection is endoscopically confirmed. We used data from the EuroPedHp Registry to identify factors associated with therapy decisions. METHODS: We included treatment-naïve patients reported between 2017 and 2020 from 30 centers in 17 European countries. Multivariable logistic regression identified factors including comorbidities within and outside the gastrointestinal (GI) tract influencing the decision for or against therapy. RESULTS: Of 1165 patients (52% females, median age 12.8), 28% (321/1165) reported any alarm symptom, 26% (307/1165) comorbidities, and 16% (192/1165) did not receive eradication treatment. Therapy was initiated less often in children having any GI comorbidity (57%, n = 181), particularly in those with eosinophilic esophagitis (60%, n = 35), inflammatory bowel disease (54%, n = 28), and celiac disease (43%, n = 58), compared to those with non-GI (86%, n = 126) or no comorbidity (89%, n = 858), despite similar frequencies of alarm and non-alarm symptoms, ulcers, erosions, and nodular gastritis. Patients with GI and without comorbidities remained more likely untreated in high versus low H. pylori prevalence countries (p < 0.0001). In children without comorbidities, factors favoring therapy included older age, being overweight, having symptoms, erosions, antral nodularity, and available antibiotic susceptibility results. CONCLUSION: In this cohort, H. pylori-infected children with GI comorbidities compared to no comorbidity showed 75% reduced chance of receiving eradication therapy. We found no evidence supporting different management strategies in infected patients with GI comorbidities compared to all pediatric patients with endoscopically proven H. pylori infection.
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Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Sistema de Registros , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Niño , Femenino , Masculino , Helicobacter pylori/efectos de los fármacos , Adolescente , Antibacterianos/uso terapéutico , Europa (Continente)/epidemiología , Preescolar , Comorbilidad , LactanteRESUMEN
BACKGROUND: We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS: This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS: A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS: VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Helicobacter pylori/efectos de los fármacos , Bismuto/uso terapéutico , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , China , Resultado del Tratamiento , Claritromicina/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Metronidazol/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto Joven , Esomeprazol/uso terapéutico , Esomeprazol/administración & dosificaciónRESUMEN
A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.
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Enfermedades Autoinmunes , Bibliometría , Mucosa Gástrica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/epidemiología , Humanos , Gastritis/inmunología , Gastritis/microbiología , Gastritis/epidemiología , Gastritis/patología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Lesiones Precancerosas/epidemiología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/epidemiología , Mucosa Gástrica/patología , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Metaplasia , Factores de Riesgo , Estómago/patología , Estómago/inmunología , Estómago/microbiología , Microbioma Gastrointestinal/inmunología , RatonesRESUMEN
Infections from Helicobacter pylori (Hp) are endangering Public Health safety worldwide, due to the associated high risk of developing severe diseases, such as peptic ulcer, gastric cancer, diabetes, and cardiovascular diseases. Current therapies are becoming less effective due to the rise of (multi)drug-resistant phenotypes and an urgent need for new antibacterial agents with innovative mechanisms of action is pressing. Among the most promising pharmacological targets, Carbonic Anhydrases (EC: 4.2.1.1) from Hp, namely HpαCA and HpßCA, emerged for their high druggability and crucial role in the survival of the pathogen in the host. Thereby, in the last decades, the two isoenzymes were isolated and characterized offering the opportunity to profile their kinetics and test different series of inhibitors.
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Antibacterianos , Inhibidores de Anhidrasa Carbónica , Infecciones por Helicobacter , Helicobacter pylori , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/enzimología , Humanos , Inhibidores de Anhidrasa Carbónica/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Anhidrasas Carbónicas/metabolismo , Isoenzimas/antagonistas & inhibidoresRESUMEN
BACKGROUND: Metronidazole is a first-line antibiotic to treat Helicobacter pylori infections. However, the Clinical Laboratory Standards Institute guidelines recommend against using antimicrobial susceptibility test (AST) to test metronidazole resistance, due to the unreliable predictive power which can result in treatment failure. OBJECTIVES: The aim of this study was to establish an 8-h, metabolic-phenotype based AST for H. pylori metronidazole susceptibility using D2O-probed Raman microspectroscopy. METHODS: Minimal inhibitory concentration (MIC) measured by conventional AST (E-test) were compared with expedited MIC via metabolic activity (eMIC-MA) for 10 H. pylori isolates. Raman barcodes of cellular-response to stress (RBCS) incorporating protein and carbohydrate Raman bands, were utilized to identify a biomarker to distinguish metronidazole susceptibility. RESULTS: Specifically, eMIC-MA produces metronidazole susceptibility results showing 100% agreement with E-test, and determines the bactericidal dosage for both high- and low-level resistant H. pylori strains. In addition, RBCS not just reliably distinguish between metronidazole-susceptible and -resistant strains, but reveal their distinct mechanisms in bacterial responses to metronidazole. CONCLUSION: The speed, accuracy, low cost, and rich information content that reveals the mode-of-action of drugs suggest the method's value in guiding metronidazole prescriptions for H. pylori eradication and in rapid screening based on drug-resistance mechanism.
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Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Metronidazol , Pruebas de Sensibilidad Microbiana , Espectrometría Raman , Helicobacter pylori/efectos de los fármacos , Metronidazol/farmacología , Espectrometría Raman/métodos , Pruebas de Sensibilidad Microbiana/métodos , Humanos , Antibacterianos/farmacología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/diagnóstico , Análisis de la Célula Individual/métodos , Farmacorresistencia BacterianaRESUMEN
Helicobacter pylori is a bacterium that may colonise and proliferate in human stomachs, leading invariably to chronic inflammation and, to a lesser extent, to peptic ulcers and cancer. The main objective of this study is to describe the epidemiology surrounding H. pylori in Nunavik's Inuit population using the 2004 and 2017 Health Surveys. Estimated prevalences were 70.9% for bacterial colonisation using a stool antigens test (SAT), 72.5% for anti-H. pylori antibodies, 12.7% for faecal occult blood in participants aged ≥ 50 and respectively of 28.4%, 11.2% and 2.4% for a prior diagnosis of colonisation, gastritis and peptic ulcer in the medical charts, with under five cases of gastric cancer reported. Variables associated with higher SAT+ prevalence were the number of household members (prevalence ratio [PR] = 1.03) and age (quadratic relationship), whereas mainly drinking municipal (PR = 0.84) and natural water (PR = 0.72) compared to bottled water, and increasing alcohol consumption (PR = 0.96) were associated with reduced prevalence. Despite current regional guidelines targeting high risk individuals in the context of high prevalence, Nunavik's health authorities must remain vigilant by following gastric cancer incidence and the rapid evolution of guidelines, while considering local realities.
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Infecciones por Helicobacter , Helicobacter pylori , Inuk , Humanos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/etnología , Helicobacter pylori/aislamiento & purificación , Femenino , Persona de Mediana Edad , Adulto , Masculino , Estudios Transversales , Prevalencia , Quebec/epidemiología , Adulto Joven , Adolescente , Anciano , Regiones Árticas/epidemiología , Encuestas Epidemiológicas , Niño , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/microbiología , Gastritis/microbiología , Gastritis/epidemiología , Gastritis/etnologíaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection. DESIGN: Through searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. RESULTS: The RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety. CONCLUSION: Compared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.
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Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Metaanálisis en Red , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Helicobacter pylori/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To compare the sex differences of Helicobacter pylori (HP) infection rate and 1-year recurrence rate. METHODS: A cross-sectional study was conducted on the prevalence of HP infection in 81,754 people who underwent physical examination in physical examination centers and outpatient clinics of the Affiliated Hospital of Gansu University of Traditional Chinese Medicine, the Second People's Hospital of Zhangye City, Tianshui City Hospital of Integrated Chinese and Western Medicine, the First and Second Department of The First Hospital of Lanzhou University Physical Examination Center, from March 2010 to December 2019. Among them, 53,771 (65.77%) were males (18-91 years old) and 27,983 (34.23%) were females (18-94 years old). According to age, they were divided into young group, middle-aged group and old group. 1448 asymptomatic infected patients were selected and treated with bismuth-containing quadruple drug eradication therapy for 2 weeks. The eradication rate and recurrence rate after 1 year were compared between males and females. RESULTS: The overall infection rate was 49.59%, including 49.74% in males and 49.3% in females. The risk of infection in young women was lower than that in men (OR = 0.908, 95%CI: 0.868-0.95, P < 0.01), the risk of infection in older women was higher than that in men (OR = 1.137, 95%CI: 1.041-1.243, P < 0.01). The female infection rate was positively correlated with age from 18 to 60, and Spearman's correlation coefficient was 0.825 (P < 0.01). The overall eradication rate was 84.67% in intention-to-treat analysis (ITT) and 88.46% in protocol analysis (PP). The eradication rates of ITT and PP in the older group were 78.38% and 82.27%, respectively, which were lower than 87.25% and 89.39% in the male group (P < 0.05). The 1-year overall recurrence rate was 3.86%, including 2.82% in males and 5.44% in females (P < 0.05), female was a risk factor for recurrence after eradication after controlling for age (OR = 2.177, 95%CI 1.166-4.066, P < 0.05). There were no obvious adverse reactions during the treatment. CONCLUSION: There is a positive linear correlation between HP infection rate and age increase in women. Older women have the characteristics of high HP infection rate, low eradication rate and high recurrence rate.
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Infecciones por Helicobacter , Helicobacter pylori , Recurrencia , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Adulto , Anciano , Adolescente , Adulto Joven , Anciano de 80 o más Años , China/epidemiología , Factores Sexuales , Antibacterianos/uso terapéutico , Prevalencia , Quimioterapia Combinada , Factores de EdadRESUMEN
Introduction: The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate. Method: A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome. Results: Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with. Discussion: Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.
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Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Secuenciación de Nucleótidos de Alto Rendimiento , Medicina de Precisión , Humanos , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Medicina de Precisión/métodos , Inhibidores de la Bomba de Protones/uso terapéutico , Claritromicina/farmacología , Claritromicina/uso terapéutico , Masculino , Farmacorresistencia Bacteriana/genética , Persona de Mediana Edad , Femenino , Adulto , Quimioterapia Combinada , Metronidazol/farmacología , Metronidazol/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/farmacología , Citocromo P-450 CYP2C19/genética , Pruebas de Sensibilidad Microbiana , Levofloxacino/farmacología , Levofloxacino/uso terapéutico , Tetraciclina/farmacología , Tetraciclina/uso terapéutico , Resultado del TratamientoRESUMEN
Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, where it can cause a variety of diseases. H. pylori uses a cluster of sheathed flagella for motility, which is required for host colonization in animal models. The flagellar sheath is continuous with the outer membrane and is found in most Helicobacter species identified to date. HP0018 is a predicted lipoprotein of unknown function that is conserved in Helicobacter species that have flagellar sheaths but is absent in Helicobacter species that have sheath-less flagella. Deletion of hp0018 in H. pylori B128 resulted in the formation of long chains of outer membrane vesicles, which were most evident in an aflagellated variant of the Δhp0018 mutant that had a frameshift mutation in fliP. Flagellated cells of the Δhp0018 mutant possessed what appeared to be a normal flagellar sheath, suggesting that HP0018 is not required for sheath formation. Cells of the Δhp0018 mutant were also less helical in shape compared to wild-type cells. A HP0018-superfolder green fluorescent fusion protein expressed in the H. pylori Δhp0018 mutant formed fluorescent foci at the cell poles and lateral sites. Co-immunoprecipitation assays with HP0018 identified two enzymes involved in the modification of the cell wall peptidoglycan, AmiA and MltD, as potential HP0018 interaction partners. HP0018 may modulate the activity of AmiA or MltD, and in the absence of HP0018, the unregulated activity of these enzymes may alter the peptidoglycan layer in a manner that results in an altered cell shape and hypervesiculation.
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Flagelos , Helicobacter pylori , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Helicobacter pylori/fisiología , Flagelos/metabolismo , Membrana Celular/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Humanos , Lipoproteínas/metabolismo , Lipoproteínas/genéticaRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) is a gastric Gram-negative, spiral-shaped microaerophilic pathogen. H. pylori may play a potential pathogenic role in extra-intestinal diseases such as hepatobiliary, respiratory, and dermatological disorders. The latter included chronic urticaria, psoriasis and rosacea. The first report in literature on the relationship between H. pylori and acne vulgaris (AV), found association between severe AV and H. pylori infection. There are very limited data in AV patients addressing the impact of H. pylori infection on various severities. In this context, the aim of the present work was to determine the association of H. Pylori infection among AV patients and correlate it with the disease severity. METHODS: This case-control study included 45 Patients with AV and 45 age and sex matched healthy volunteers as a control group. H. pylori antigen in stool and serum H. pylori antibody IgG using commercially available ELISA kits was tested in all included subjects. RESULTS: The percentage of participants with a positive H. pylori antigen in stool and positive H. pylori antibody in serum in the whole study population was 35/90 (38. 9%) and 41/90 (45. 6%). On comparing between the percentages of positive H. pylori antigen in stool and positive H. pylori antibody in serum between the patients with AV and healthy controls, a highly statistically significant difference was found between the two groups (P < 0.001, P = 0.006). On comparing between the percentages of positive H. pylori antigen in stool and positive H. pylori antibody in serum in the patients with different grades of acne severity and healthy controls, the rate of positive H. pylori antigen in stool and positive H. pylori Ab in serum was significantly associated with severity of acne comparing with healthy controls (p < 0. 001). CONCLUSION: The rate of H. pylori infection in patients with AV is high so it may influence the pathogenesis of this skin disease. Patients with severe AV had higher rates of H. pylori antigen in stool and H. pylori antibody in serum as compared to the patients with mild AV and healthy controls.
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Acné Vulgar , Anticuerpos Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Índice de Severidad de la Enfermedad , Humanos , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/inmunología , Acné Vulgar/microbiología , Acné Vulgar/inmunología , Masculino , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/complicaciones , Femenino , Estudios de Casos y Controles , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Adulto Joven , Heces/microbiología , Adolescente , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/sangre , Persona de Mediana EdadRESUMEN
Aim: This study aims to evaluate the efficacy of Lacticaseibacillus rhamnosus LRa05 supplementation in enhancing Helicobacter pylori (H. pylori) eradication rate and alleviating the gastrointestinal side effects associated with bismuth quadruple therapy. Methods: H. pylori-positive patients were randomized to receive levofloxacin-based bismuth quadruple therapy combined either probiotic LRa05 or a placebo for two weeks, followed by LRa05 (1 × 1010 CFU) or maltodextrin for the next two weeks. H. pylori infection was detected by 13C breath test pre- and post-treatment. Blood and stool samples were collected at week 0 and week 4 for routine and biochemical analysis, and serum inflammatory markers. Gastrointestinal symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS). Intestinal microbiota was analyzed using 16S rRNA sequencing. The research was listed under the Chinese Clinical Trial Registry (ChiCTR2300072220), and written informed consent was obtained from all participants. Results: The LRa05 group exhibited a trend toward higher H. pylori eradication rates (86.11%) compared to the placebo group (82.86%), though the difference was not statistically significant. Significant reductions in neutrophil count, alanine aminotransferase, aspartate aminotransferase, pepsinogen I, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) (p < 0.05) suggest that LRa05 supplementation may mitigate inflammation, enhance liver function, and potential aid in early cancer prevention. GSRS symptom scores showed that LRa05 alleviated abdominal pain, acid reflux, bloating, and diarrhea, enhancing patient compliance. Furthermore, 16S rRNA sequencing showed that LRa05 countered the antibiotic-induced disruption of gut microbiota diversity, primarily by increasing beneficial bacteria. Conclusion: Although LRa05 did not significantly improve the success rate of H. pylori eradication therapy, it has the potential to improve liver function and reduced levels of inflammatory markers such as IL-6 and TNF-α in the body, regulating the inflammatory response. In addition, it played a positive role in alleviating the adverse symptoms and gut microbiota disturbances caused by eradication therapy, providing a possible way to improve the overall health of patients and demonstrating promising clinical potential. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2300072220.
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Infecciones por Helicobacter , Helicobacter pylori , Lacticaseibacillus rhamnosus , Probióticos , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Masculino , Femenino , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Persona de Mediana Edad , Método Doble Ciego , Adulto , Resultado del Tratamiento , Microbioma Gastrointestinal/efectos de los fármacos , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Quimioterapia CombinadaRESUMEN
The oral cavity may play a role as a reservoir and in the transmission and colonization of Helicobacter pylori. The route of transmission for H. pylori is not fully understood. The prevalence of this pathogen varies globally, affecting half of the world's population, predominantly in developing countries. Here, we review the prevalence of H. pylori in the oral cavity, the characteristics that facilitate its colonization and dynamics in the oral microbiome, the heterogeneity and diversity of virulence of among strains, and noninvasive techniques for H. pylori detection in oral samples. The prevalence of H. pylori in the oral cavity varies greatly, being influenced by the characteristics of the population, regions where samples are collected in the oral cavity, and variations in detection methods. Although there is no direct association between the presence of H. pylori in oral samples and stomach infection, positive cases for gastric H. pylori frequently exhibit a higher prevalence of the bacterium in the oral cavity, suggesting that the stomach may not be the sole reservoir of H. pylori. In the oral cavity, H. pylori can cause microbiome imbalance and remodeling of the oral ecosystem. Detection of H. pylori in the oral cavity by a noninvasive method may provide a more accessible diagnostic tool as well as help prevent transmission and gastric re-colonization. Further research into this bacterium in the oral cavity will offer insights into the treatment of H. pylori infection, potentially developing new clinical approaches.
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Infecciones por Helicobacter , Helicobacter pylori , Boca , Humanos , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Boca/microbiología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/transmisión , Prevalencia , Microbiota , VirulenciaRESUMEN
Introduction: Helicobacter pylori (H. pylori) infection is endemic in Africa. It is a major aetiological factor in the development of peptic ulcer disease and distal gastric cancers. Existing data shows that clinical outcomes are dependent on the virulence of the infecting strain, host´s susceptibility, and environmental factors. In Ghana, a previous study showed that the majority of symptomatic individuals harboured cagA and vacA virulent strains. The main objective of this study was to characterize and assess the significance of other virulence factors, specifically iceA and babA2 in Ghana. Methods: H. pylori iceA and babA2 genes were investigated in dyspeptic patients at the Korle Bu Teaching Hospital (KBTH), Accra, Ghana. The study employed a cross-sectional design consecutively recruiting patients with upper gastrointestinal symptoms for endoscopy. Nucleic acid was extracted from gastric biopsies using a commercial kit (QIAGEN DNeasy tissue kit). H. pylori babA2 and iceA genes were amplified using extracted deoxyribonucleic acid (DNA) and primers by polymerase chain reaction (PCR). Results: majority, (71.1%), of the study participants, were H. pylori positive when tested with urease-campylobacter-like organism (CLO). In total, 46 H. pylori urease CLO-positive samples were randomly analyzed by PCR for iceA, of which, 12 (26%) and 7 (15%) were found to have iceA1 and iceA2 respectively. Of the CLO-positive samples, 9 were randomly analysed for babA2 by PCR. Three samples were babA2 positive and 6 were babA2 negative. Conclusion: in Ghana, although H. pylori is endemic, iceA prevalence is rather low and probably exerts a limited effect on bacterial virulence. Further evaluation would be required, not only to determine association with other virulence factors but more importantly, inter-relationships with wider host and environmental factors that impact on disease pathogenesis.
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Adhesinas Bacterianas , Dispepsia , Infecciones por Helicobacter , Helicobacter pylori , Reacción en Cadena de la Polimerasa , Factores de Virulencia , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Adhesinas Bacterianas/genética , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas , Estudios Transversales , Dispepsia/microbiología , Ghana , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Hospitales de Enseñanza , Virulencia/genética , Factores de Virulencia/genéticaRESUMEN
OBJECTIVE: To determine the presence of microplastics in the stomach, and the relationship between pathological changes in stomach tissue and microplastics. STUDY DESIGN: An analytical study. Place and Duration of the Study: Department of Internal Medicine, Sorgun State Hospital, Yozgat, Turkiye, from December 2022 to November 2023. METHODOLOGY: Fasting gastric fluid sampling and endoscopic sampling including mucosal and submucosal layers from the antrum were performed. The pH values of the gastric fluids were recorded. Samples were analysed gradually by adding iron solution, hydrogen peroxide, and sodium chloride (NaCl) in a beaker at 75 degrees for 30 minutes. Biopsy materials obtained from antrum were examined histopathologically and reported according to the Sydney classification. The relationship between gastric biopsy results and the presence of microplastic was evaluated using Chi-square test. The significance level was taken as p <0.005. RESULTS: The study included 61 individuals. The presence of microplastics was detected in 17 (27.86%) gastric fluid samples obtained from the individuals. A significant correlation was found between increased activity and inflammation in antrum biopsy and the presence of microplastic (χ2 = 8.55 p = 0.014; χ2 = 25.75, p = 0.001). The relationship between atrophy, metaplasia, and Helicobacter pylori in gastric tissue and the presence of microplastic was statistically insignificant (p >0.05). CONCLUSION: Microplastics were detected in gastric fasting fluid. These materials can cause histopathologic changes and inflammation in the gastric antrum. KEY WORDS: H. pylori, Intestinal metaplasia, Inflammation, Microplastic, Plastic, Sydney classification.
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Ayuno , Microplásticos , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Microplásticos/análisis , Jugo Gástrico/química , Mucosa Gástrica/patología , Biopsia , Estómago/patología , Helicobacter pylori/aislamiento & purificación , Antro Pilórico/patología , Metaplasia/patología , Turquía , AncianoRESUMEN
BACKGROUND: Helicobacter pylori colonizes the human stomach and may affect the inflammatory response, hormone production related to energy regulation, and gastrointestinal microbiota composition. Previous studies have explored a potential association between H. pylori infection and pediatric obesity with varying results. Considering the immunomodulatory effects of early-life infection with H. pylori that can confer beneficial effects, we hypothesized that we would find an inverse relationship between H. pylori seropositivity and obesity among Danish children and adolescents. METHODS: We assessed H. pylori seroprevalence in 713 subjects from an obesity clinic cohort and 990 subjects from a population-based cohort, aged 6 to 19 years, and examined its association with obesity and other cardiometabolic risk factors. RESULTS: No association was found between H. pylori and body mass index standard deviation score (BMI SDS). H. pylori seropositivity was, however, significantly associated with higher fasting plasma glucose levels and the prevalence of hyperglycemia. CONCLUSION: While we did not find an association between H. pylori seropositivity and BMI SDS, we observed a significant association with higher fasting plasma glucose levels and increased prevalence of hyperglycemia, suggesting that H. pylori infection may contribute to impaired glucose regulation in Danish children and adolescents.
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Infecciones por Helicobacter , Helicobacter pylori , Hiperglucemia , Humanos , Adolescente , Niño , Dinamarca/epidemiología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/sangre , Masculino , Femenino , Hiperglucemia/epidemiología , Hiperglucemia/sangre , Estudios Seroepidemiológicos , Adulto Joven , Obesidad Infantil/epidemiología , Obesidad Infantil/sangre , Obesidad Infantil/microbiología , Estudios de Cohortes , Índice de Masa Corporal , Prevalencia , Glucemia/análisisRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease. METHODS: The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model. RESULTS: Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC. CONCLUSIONS: CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong.
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Antígenos Bacterianos , Proteínas Bacterianas , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/genética , Humanos , Proteínas Bacterianas/genética , Masculino , Persona de Mediana Edad , Femenino , Infecciones por Helicobacter/microbiología , Antígenos Bacterianos/genética , Polimorfismo Genético , Adulto , China/epidemiología , Genotipo , Anciano , Virulencia/genética , Factores de Virulencia/genéticaRESUMEN
BACKGROUND: Helicobacter pylori infects the stomach and/or small intestines in more than half of the human population. Infection with H. pylori is the most common cause of chronic gastritis, which can lead to more severe gastroduodenal pathologies such as peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. H. pylori infection is particularly concerning in Colombia in South America, where > 80% of the population is estimated to be infected with H. pylori and the rate of stomach cancer is one of the highest in the continent. RESULTS: We compared the antimicrobial susceptibility profiles and short-read genome sequences of five H. pylori isolates obtained from patients diagnosed with gastritis of varying severity (chronic gastritis, antral erosive gastritis, superficial gastritis) in Pereira, Colombia sampled in 2015. Antimicrobial susceptibility tests revealed the isolates to be resistant to at least one of the five antimicrobials tested: four isolates were resistant to metronidazole, two to clarithromycin, two to levofloxacin, and one to rifampin. All isolates were susceptible to tetracycline and amoxicillin. Comparative genome analyses revealed the presence of genes associated with efflux pump, restriction modification systems, phages and insertion sequences, and virulence genes including the cytotoxin genes cagA and vacA. The five genomes represent three novel sequence types. In the context of the Colombian and global populations, the five H. pylori isolates from Pereira were phylogenetically distant to each other but were closely related to other lineages circulating in the country. CONCLUSIONS: H. pylori from gastritis of different severity varied in their antimicrobial susceptibility profiles and genome content. This knowledge will be useful in implementing appropriate eradication treatment regimens for specific types of gastritis. Understanding the genetic and phenotypic heterogeneity in H. pylori across the geographical landscape is critical in informing health policies for effective disease prevention and management that is most effective at local and country-wide scales. This is especially important in Colombia and other South American countries that are poorly represented in global genomic surveillance studies of bacterial pathogens.
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Antibacterianos , Farmacorresistencia Bacteriana , Gastritis , Genoma Bacteriano , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/genética , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/patogenicidad , Helicobacter pylori/aislamiento & purificación , Gastritis/microbiología , Colombia , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Virulencia/genética , Farmacorresistencia Bacteriana/genética , Genómica , Pruebas de Sensibilidad Microbiana , Filogenia , Persona de Mediana Edad , Masculino , FemeninoRESUMEN
The mucus serves as a protective barrier in the gastrointestinal tract against microbial attacks. While its role extends beyond merely being a physical barrier, the extent of its active bactericidal properties remains unclear, and the mechanisms regulating these properties are not yet understood. We propose that inflammation induces epithelial cells to secrete antimicrobial peptides, transforming mucus into an active bactericidal agent. To investigate the properties of mucus, we previously developed mucosoid culture models that mimic the healthy human stomach epithelium. Similar to organoids, mucosoids are stem cell-driven cultures; however, the cells are cultivated on transwells at air-liquid interface. The epithelial cells of mucosoids form a polarized monolayer, allowing differentiation into all stomach lineages, including mucus-secreting cells. This setup facilitates the secretion and accumulation of mucus on the apical side of the mucosoids, enabling analysis of its bactericidal effects and protein composition, including antimicrobial peptides. Our findings show that TNFα, IL1ß, and IFNγ induce the secretion of antimicrobials such as lactotransferrin, lipocalin2, complement component 3, and CXCL9 into the mucus. This antimicrobial-enriched mucus can partially eliminate Helicobacter pylori, a key stomach pathogen. The bactericidal activity depends on the concentration of each antimicrobial and their gene expression is higher in patients with inflammation and H.pylori-associated chronic gastritis. However, we also find that H. pylori infection can reduce the expression of antimicrobial encoding genes promoted by inflammation. These findings suggest that controlling antimicrobial secretion in the mucus is a critical component of epithelial immunity. However, pathogens like H. pylori can overcome these defenses and survive in the mucosa.