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1.
Nat Commun ; 11(1): 5117, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037203

RESUMO

Exposure of gastric epithelial cells to the bacterial carcinogen Helicobacter pylori causes DNA double strand breaks. Here, we show that H. pylori-induced DNA damage occurs co-transcriptionally in S-phase cells that activate NF-κB signaling upon innate immune recognition of the lipopolysaccharide biosynthetic intermediate ß-ADP-heptose by the ALPK1/TIFA signaling pathway. DNA damage depends on the bi-functional RfaE enzyme and the Cag pathogenicity island of H. pylori, is accompanied by replication fork stalling and can be observed also in primary cells derived from gastric organoids. Importantly, H. pylori-induced replication stress and DNA damage depend on the presence of co-transcriptional RNA/DNA hybrids (R-loops) that form in infected cells during S-phase as a consequence of ß-ADP-heptose/ ALPK1/TIFA/NF-κB signaling. H. pylori resides in close proximity to S-phase cells in the gastric mucosa of gastritis patients. Taken together, our results link bacterial infection and NF-κB-driven innate immune responses to R-loop-dependent replication stress and DNA damage.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Helicobacter pylori/patogenicidade , NF-kappa B/metabolismo , Proteínas Quinases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular Tumoral , DNA/química , DNA/genética , Dano ao DNA , Replicação do DNA/efeitos dos fármacos , Floxuridina , Glicosiltransferases/metabolismo , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Lipopolissacarídeos/metabolismo , Mutação , NF-kappa B/genética , Proteínas Quinases/genética , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
2.
BMC Med Genet ; 21(1): 205, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066747

RESUMO

BACKGROUND: CpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa. METHODS: We determined the DNMT3A genotype and CpG methylation status of 4 genes (p14ARF, p16INK4a, DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/µL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis. RESULTS: The minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14ARF, p16INK4a, DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14ARF). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM. CONCLUSIONS: Our study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.


Assuntos
Ilhas de CpG/genética , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA , Mucosa Gástrica/metabolismo , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Antígenos CD/genética , Caderinas/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Proteínas Quinases Associadas com Morte Celular/genética , Feminino , Mucosa Gástrica/microbiologia , Frequência do Gene , Genótipo , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
3.
Anticancer Res ; 40(11): 6387-6398, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109577

RESUMO

BACKGROUND/AIM: Helicobacter pylori (Hp) infection affects a substantial proportion of the world population and is a major risk factor of gastric cancer (GC). The caveats of common Hp-tests can be evaded by a serological biomarker test (GastroPanel®, Biohit Oyj, Helsinki), the most comprehensive Hp-test on the market. The clinical validation of Helicobacter pylori IgG ELISA of the new-generation GastroPanel® test is reported. The aim of the study is to validate the clinical performance of the Helicobacter pylori IgG ELISA test in diagnosis of biopsy-confirmed Hp-infection in gastroscopy referral patients. PATIENTS AND METHODS: A cohort of 101 patients (mean age=50.1 years) referred for gastroscopy at the outpatient Department of Gastroenterology (SM Clinic, St. Petersburg) were examined by two test versions to validate the new-generation GastroPanel®. All patients were examined by gastroscopy and biopsies, which were stained with Giemsa for specific identification of Hp in the antrum (A) and corpus (C). RESULTS: Biopsy-confirmed Hp-infection was found in 64% of patients, most often confined to antrum. The overall agreement between Hp IgG ELISA and gastric biopsies in Hp-detection was 91% (95%CI=84.1-95.8%). Hp IgG ELISA diagnosed biopsy-confirmed Hp (A&C) with sensitivity (SE) of 92.3%, specificity (SP) of 88.6%, positive predictive value (PPV) of 93.8% and negative predictive value (NPV) of 86.1%, with AUC=0.904 (95%CI=0.842-0.967). In ROC analysis for Hp detection (A&C), Hp IgG ELISA shows AUC=0.978 (95%CI=0.956-1.000). CONCLUSION: The Hp IgG ELISA test successfully concludes the clinical validation process of the new-generation GastroPanel® test, which retains the unrivalled diagnostic performance of all its four biomarkers, extensively documented for the first-generation test in different clinical settings.


Assuntos
Anticorpos Antibacterianos/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Imunoglobulina G/isolamento & purificação , Adolescente , Adulto , Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/imunologia , Biópsia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Gastrinas/genética , Gastrinas/isolamento & purificação , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/genética , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastroscopia/métodos , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/genética , Pepsinogênio A/isolamento & purificação , Pepsinogênio C/genética , Pepsinogênio C/isolamento & purificação , Encaminhamento e Consulta , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Adulto Jovem
4.
PLoS One ; 15(9): e0238379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915799

RESUMO

BACKGROUND: The correlation between the infection of H. pylori and the occurrence of gastric MALT lymphoma (GML) has been well documented. However, the mechanism of how GML is caused by this bacterium is not well understood, although some immunologic mechanisms are thought to be involved. MATERIALS AND METHODS: In this study, we performed both transcriptomic and proteomic analyses on gastric cancer cells infected by H. pylori isolates from GML patients and the gastric ulcer strain 26695 to investigate the differentially expressed molecular signatures that were induced by GML isolates. RESULTS: Transcriptomic analyses revealed that the differentially expressed genes (DEGs) were mainly related to binding, catalytic activity, signal transducer activity, molecular transducer activity, nucleic acid binding transcription factor activity, and molecular function regulator. Fifteen pathways, including the Wnt signaling pathway, the mTOR signaling pathway, the NOD-like receptor signaling pathway and the Hippo signaling pathway, were revealed to be related to GML isolates. Proteomic analyses results showed that there were 116 differentially expressed proteins (DEPs). Most of these DEPs were associated with cancer, and 29 have been used as biomarkers for cancer diagnosis. We also found 63 upstream regulators that can inhibit or activate the expression of the DEPs. Combining the proteomic and transcriptomic analyses revealed 12 common pathways. This study provides novel insights into H. pylori-associated GML. The DEPs we found may be good candidates for GML diagnosis and treatment. CONCLUSIONS: This study revealed specific pathways related to GML and potential biomarkers for GML diagnosis.


Assuntos
Biomarcadores/análise , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Proteoma/análise , Neoplasias Gástricas/epidemiologia , Transcriptoma , China/epidemiologia , Perfilação da Expressão Gênica , Infecções por Helicobacter/microbiologia , Humanos , Incidência , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/microbiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Via de Sinalização Wnt
5.
PLoS One ; 15(9): e0237515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898138

RESUMO

BACKGROUND: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk. METHODS: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens). RESULTS: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy. CONCLUSIONS: The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia. IMPACT: The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/etiologia , Estômago/patologia , Adolescente , Adulto , Idoso , Atrofia/etiologia , Atrofia/microbiologia , Atrofia/patologia , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estômago/microbiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Adulto Jovem
6.
Croat Med J ; 61(4): 319-325, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881429

RESUMO

AIM: To assess the relationship between Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) and intestinal metaplasia (IM) development and to assess the rate of dysplasia or gastric cancer development in patients with AG and/or IM. METHODS: This retrospective endoscopic follow-up study enrolled 2214 patients. The patients were followed for at least five years between 2007 and 2017 at the Department of Endoscopy at Antalya Ataturk Government Hospital. The results of third-year and five-year surveillance biopsy were assessed. RESULTS: The mean follow-up time was 7.77 ± 2.78 years. H. pylori was histologically assessed in 1417 (64.6%) patients. Of 198 patients with severe H. pylori infection, 32 (16%) and 139 (70.3%) developed extensive AG and extensive IM, respectively. There was a significant relationship between H. pylori density and AG and IM degrees. High grade dysplasia, early gastric cancer, and advanced gastric cancer were diagnosed in 73 patients with median age 58.2 (28-80) years, and the incidence rate was 3.29% (73/2214). The annual incidence of gastric neoplastic lesions was 0.46% in total, 0.08% for early GC, and 0.02% for advanced gastric cancer. CONCLUSIONS: H. pylori infection has an important role in the development of AG and IM. H. pylori density is directly related to atrophy and metaplasia degree.


Assuntos
Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Endoscopia Gastrointestinal , Feminino , Seguimentos , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Humanos , Incidência , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Turquia/epidemiologia
7.
Medicine (Baltimore) ; 99(37): e21832, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925719

RESUMO

BACKGROUND: The existing evidence on the relationship between Helicobacter pylori infection and the risk of colorectal cancer is inconsistent. We conducted a systematic review with a meta-analysis to explore this relationship and to determine whether the relationship varies according to the study characteristics. METHODS: We searched the PubMed, OVID, EMBASE database, and the reference lists of pertinent articles published up to October 2019 by 2 researchers independently. Summary odds ratios (OR) with their 95% confidence intervals (CIs) were estimated using a random-effects model. RESULTS: Forty seven studies including 17,416 cases of colorectal cancer (CRC) and 55,811 cases of control were included. Overall, H. pylori infection was associated with an increased risk of CRC (OR = 1.70 95% CI 1.64-1.76, I = 97%), although there was significant heterogeneity among the studies. Subgroup analysis revealed that the positive correlation might vary by the design of study conducted. CONCLUSION: This meta-analysis demonstrates a positive association between H. pylori infection and the risk of colorectal cancer.


Assuntos
Neoplasias Colorretais/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Adulto , Idoso , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
8.
Medicine (Baltimore) ; 99(32): e20761, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769862

RESUMO

The regimens containing levofloxacin (LVX) have been recommended as an alternate to standard triple therapy to treat Helicobacter pylori infections and H pylori mixed infection always lead to H pylori chronic infection. Although the molecular mechanism of LVX resistance with gyrA gene mutation has been clearly understood in H pylori, other genes involved in antibiotic resistance remain unclear. Efflux pump plays an important role in clinically relevant multidrug resistance. Furthermore, the relationship between the strains with different LVX level-resistances from individuals is also unknown.Helicobacter pylori monoclonal strains were isolated from patients with eradication failure. E test was used to detect the minimal inhibitory concentration of LVX. One lower-level LVX-resistant clone and 2 higher-level LVX-resistant clones from the same patient were selected to sequence the complete genomes. Single-nucleotide variants (SNVs) and mutations were extracted and analyzed from gryA and resistance-nodulation-division family efflux genes.Two clones with higher-level resistance had the mutation pattern of Asn87Lys and one lower-level LVX-resistant clone had an Asp91Asn mutation. Compared to clones with higher-level resistance, the higher genetic variations were found in genes belonging to the resistance-nodulation-division family in H pylori strains with lower-level resistance to LVX. There were significantly more SNVs of Hp0970 (hefE) and Hp1329 (hefI) in the lower-level LVX-resistant clone than those in the higher-level LVX-resistant clones (P = .044).The mutation pattern of the Asn87Lys of the gyrA gene confers a higher resistance to LVX than that of the Asp91Asn in H pylori. Increase in the number of SNVs of the Hp0970 (hefE) and Hp1329 (hefI) genes change the resistance to LVX. Twelve mutations verified by Sanger sequencing in Hp0970 (hefE) and Hp1329 (hefI) may decrease resistant levels to LVX.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Levofloxacino/farmacologia , Mutação/genética , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
9.
Life Sci ; 259: 118200, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758621

RESUMO

AIMS: Diet is one of the factors affecting the pathogenicity of Helicobacter pylori (H. pylori) infection. Choline is a dietary component that is crucial for normal cellular function. However, choline intake imbalance can lead to liver injury, inflammation, and changes of the gut microbiota composition. The study aimed to explore the effects of choline supplementation on liver biology, gut microbiota, and inflammation in H. pylori-infected mice. MAIN METHODS: Liver function was detected by biochemical and histopathological analysis. Serum inflammatory markers were measured using ELISA. Fecal microbial profiles were determined via 16S rRNA sequencing. KEY FINDINGS: The results showed that choline supplementation decreased serum LDL level, while increased the activities of serum AST and ALT in normal BALB/c mice. Besides, choline also reduced hepatic SOD and GSH-Px activities, and elevated hepatic MDA level of H. pylori-infected mice. Moreover, choline markedly enhanced the concentrations of inflammatory factors including LPS, CRP, IL-6, TNF-α, and CXCL1 in H. pylori-infected mice. Meanwhile, choline and H. pylori cotreatment altered the richness and diversity of the mice gut microbiota, and increased the relative abundance of Escherichia_Shigella, which had a significant positive correlation with the levels of LPS, CRP, IL-6, TNF-α and CXCL1. SIGNIFICANCE: Our data suggest, for the first time, that choline can aggravate H. pylori-induced inflammation, which may be associated with the alterations of gut microbiota. This study may provide novel insights into the possible effects of food-derived choline on H. pylori infection-related diseases.


Assuntos
Colina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Fígado/efeitos dos fármacos , Animais , LDL-Colesterol/sangue , Dieta , Fezes/microbiologia , Feminino , Infecções por Helicobacter/patologia , Inflamação/sangue , Fígado/enzimologia , Fígado/patologia , Testes de Função Hepática , Camundongos , Camundongos Endogâmicos BALB C , RNA Ribossômico 16S/genética
10.
J Ayub Med Coll Abbottabad ; 32(2): 194-197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32583993

RESUMO

BACKGROUND: Despite many known variables affecting the outcome, little is known about the impact of histology on the location of tumour and outcomes. The objective of our study was to describe pattern of gastric cancer at single centre and association with H. Pylori and Signet ring cell variant with site of tumour in stomach. METHODS: This was a cross sectional study conducted at the Department of Surgery of Aga Khan University Hospital, Karachi, Pakistan. A total of 105 patients who underwent surgery for gastric adenocarcinoma were classified to have a proximal, distal or whole stomach cancer. An association was determined between the tumour histology and helicobacter pylori infection with the location of tumour in the stomach. RESULTS: Proximal gastric cancer was present in 27 (25.7%) patients and distal gastric cancer was present in 69 (65.7%) patients. There were 9 (8.6%) patients in whom tumour involved the whole stomach. Fifty-two patients (49.5%) had signet ring cell variant of gastric carcinoma and these patients were more like to have higher grade and advanced stage. Further analysis showed that that odds of proximal gastric tumour to have signet ring cell histopathology was 3.22 as compared to distal gastric tumour (p=0.017). Helicobacter Pylori infection status did not have any significant association with either grade of tumour or stage at the time of presentation. CONCLUSIONS: Despite limitations our data suggests that proximal gastric cancer may be biologically different from distal gastric cancers in terms of frequency of signet ring cell histology.


Assuntos
Carcinoma de Células em Anel de Sinete , Infecções por Helicobacter , Neoplasias Gástricas , Carcinoma de Células em Anel de Sinete/epidemiologia , Carcinoma de Células em Anel de Sinete/microbiologia , Carcinoma de Células em Anel de Sinete/patologia , Estudos Transversais , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Humanos , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
11.
Int J Infect Dis ; 97: 102-107, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32474200

RESUMO

OBJECTIVES: Bhutan suffers from a high prevalence of Helicobacter pylori (H. pylori) infection and gastric cancer-related mortality. In preparation for a countrywide H. pylori eradication program, the antibiotic resistance patterns of H. pylori infection were surveyed in different geographical regions. METHODS: Dyspeptic patients in 6 districts including Thimphu, Punakha, Wangdue, Trongsa, Bumthang, and Haa underwent upper gastrointestinal endoscopy during GASTROCAMP and were enrolled between December 2010 and April 2015. Gastric biopsies were obtained for rapid urease test, histopathology, and H. pylori culture. Antimicrobial susceptibility testing was later performed if the culture was positive. RESULTS: A total of 1178 patients were surveyed. The overall H. pylori infection in Bhutan was 66.2%. Punakha had the highest prevalence of H. pylori infection (85.6%). Thimphu and Punakha (city areas) had higher prevalence of H. pylori infection than rural districts (73.5% vs 63.3%, OR=1.61, 95% CI 1.22-2.13, p=0.0008). There were 357 patients (30.3%) with positive H. pylori culture completed antimicrobial susceptibility testing. The mean age was 40.5 years with female predominance (57.1%). No amoxicillin resistant strains were found. Metronidazole resistance was 81% followed by levofloxacin resistance (8.1%). Clarithromycin (2%) and tetracycline (0.6%) resistance was rare except in Thimphu, the capital city (10%) vs 0% in rural areas, p<0.001. The metronidazole resistance rate remained stable at approximately 80% during the past 5 years of study. Levofloxacin-resistant strains gradually rose from 5.3% in 2010 to 9.9% in 2015. CONCLUSIONS: Bhutan had a high prevalence of H. pylori infection. Metronidazole resistance was extremely high, whereas clarithromycin resistance was quite low in this specific area. Antibiotic resistance pattern could be good evidence for guiding a proper treatment regimen for H. pylori infection in Bhutan.


Assuntos
Farmacorresistência Bacteriana , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Adulto , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Butão/epidemiologia , Claritromicina/farmacologia , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Levofloxacino/farmacologia , Masculino , Metronidazol/farmacologia , Pessoa de Meia-Idade , Prevalência , Tetraciclina/farmacologia
12.
Eur J Clin Microbiol Infect Dis ; 39(10): 1821-1830, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32557327

RESUMO

Helicobacter pylori (H. pylori) infection is associated with some gastric diseases, such as gastritis, peptic ulcer, and gastric cancer. CagA and VacA are known virulence factors of H. pylori, which play a vital role in severe clinical outcomes. Additionally, the expression of outer membrane proteins (OMPs) helps H. pylori attach to gastric epithelial cells at the primary stage and increases the virulence of H. pylori. In this review, we have summarized the paralogs of H. pylori OMPs, their genomic loci, and the different receptors of OMPs identified so far. We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom. We highlight the coexpression of OMPs with other virulence factors and their relationship with clinical outcomes. In conclusion, OMPs are closely related to the pathogenic processes of adhesion, colonization, persistent infection, and severe clinical consequences. They are potential targets for the prevention and treatment of H. pylori-related diseases.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Fatores de Virulência/metabolismo , Células Epiteliais/microbiologia , Expressão Gênica , Humanos , Fatores de Virulência/genética
14.
PLoS One ; 15(6): e0234433, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511269

RESUMO

BACKGROUND: Several previous studies have suggested that Helicobacter pylori (H. pylori) infection affects the serum lipid profile. However, it remains controversial and the mechanism has not been elucidated. The purpose of this study is to use an epidemiological perspective to evaluate the association between H. pylori infection and the serum lipid profile. METHODS: Multivariate analysis was performed using the data of serum lipid profile, infection status of H. pylori, fitness/lifestyle habits, and various subjects' characteristics which were derived from the 15,679 generally healthy individuals in Japan. The average treatment effects (ATEs) of H. pylori infection on the serum lipid profile were estimated using augmented inverse probability weighting (AIPW). A meta-analysis was also performed using the 27 studies worldwide in which the status of H. pylori infection and at least one serum examination value (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), or triglyceride (TG)) were described. RESULTS: The ATEs determined with AIPW showed that H. pylori infection has significant positive effects on LDL-C and TC (ATE (95% confidence interval [95%CI]) = 3.4 (2.36-4.49) and 1.7 (0.58-2.88), respectively) but has significant negative effects on HDL-C and TG (ATE (95%CI) = -1.2 (-1.74 to -0.72) and -3.5 (-5.92 to -1.06), respectively). The meta-analysis to estimate the association between H. pylori infection and the serum lipid profile revealed that H. pylori infection is positively associated with LDL-C, TC, and TG (standardized mean difference [SMD] (95%CI) = 0.11 (0.09-0.12), 0.09 (0.07-0.10) and 0.06 (0.05-0.08), respectively) and negatively associated with HDL-C (SMD = -0.13 (-0.14 to -0.12)). CONCLUSION: Both our multivariate analyses and meta-analysis showed that H. pylori infection significantly affects the serum lipid profile, which might lead to various dyslipidemia-induced severe diseases like coronary thrombosis or cerebral infarction.


Assuntos
Dislipidemias/epidemiologia , Infecções por Helicobacter/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/etiologia , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Japão/epidemiologia , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Pontuação de Propensão , Fatores de Risco , Triglicerídeos/sangue , Adulto Jovem
15.
J Environ Pathol Toxicol Oncol ; 39(1): 77-88, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479014

RESUMO

Helicobacter pylori causes a Gram-negative bacterial infection that can increase the risk of gastric cancer. Consequently, meticulous prevention of an H. pylori infection is significant for averting gastric cancer in humans. Nobiletin, an important dietary polymethoxylated flavonoid in citrus fruits, possesses multidimensional pharmaceutical properties, including its ability to act as an anticancer, anti-inflammatory, antioxidative, cardiovascularly defensive, neuroprotective, and antimetabolic agent. Our study evaluates the role of nobiletin in inflammation-mediated gastric carcinogenic signaling of H. pylori-arbitrated coculture in the human gastric epithelial (GES)-1 cell line. Our results show that the culture system of H. pylori-tainted GES-1 cells demonstrates maximum fabrication of reactive oxygen species (ROS), mediating DNA injury and augmenting nuclear fragmentations. Treatment with nobiletin reduces ROS levels and apoptotic morphological changes by dual staining and decreases levels of lipid peroxides and glutathione content in H. pylori-infected GES-1 cells. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/phosphatase and tensin homolog signaling have been implicated to affect cell endurance, inflammation, proliferation, and carcinogenic activity in gastric GES-1 cells. We find that nobiletin strongly impedes tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, PI3K, AKT, and mitogen-activated protein kinase molecules, including p38, extracellular receptor kinase 1, and c-Jun amino-terminal expression in H. pylori-infected GES-1 cells. We conclude that nobiletin potentially impedes H. pylori infection and its related activation, likely preventing H. pylori infection-mediated gastric cancer.


Assuntos
Antioxidantes/farmacologia , Carcinogênese/efeitos dos fármacos , Flavonas/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular , Células Epiteliais , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Inflamação/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Gástricas/microbiologia
16.
Virchows Arch ; 477(4): 489-496, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32356024

RESUMO

Pyloric metaplasia (PM) and pseudopyloric metaplasia (PPM) are metaplastic changes resulting in pyloric-type glands in the gastric oxyntic mucosa that mainly occur in chronic gastritis caused by Helicobacter pylori (H. pylori) infection. Focusing on PM and PPM, we classified the histological changes in gastric mucosa according to the Updated Sydney System, using 314 biopsy specimens of gastric greater curvature of the middle body before H. pylori eradication (HPE). Next, the numbers of PM and PPM glands were counted in 47 specimens, and subjects were followed up over 10 years after HPE. PPM was recognized jointly with inflammation, activity, atrophy, and intestinal metaplasia, but PM was recognized more frequently than PPM as atrophy and intestinal metaplasia progressed. Both PM and PPM regressed significantly within 6 years after HPE. Additionally, we demonstrated that PM and PPM are not always coincident with spasmolytic polypeptide-expressing metaplasia (SPEM). In conclusion, PM and PPM are considered different modulations of the same line of differentiation, which are both reversible, with PM potentially emerging from PPM upon progression.


Assuntos
Mucosa Gástrica/patologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Biópsia , Diferenciação Celular , Doença Crônica , Mucosa Gástrica/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Metaplasia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
17.
Dig Dis ; 38(4): 261-268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396919

RESUMO

AIM: Helicobacter pylori infection has been established as a definite risk factor for gastric cancer. However, the consequence of H. pylori eradication on the progression of gastroesophageal reflux disease (GERD) remains controversial. The purpose of our study was to investigate the relationship between H. pylori eradication and the development of GERD. METHODS: A comprehensive, English literature search was performed from January 1990 to April 2019. Only randomized controlled trials (RCT) that evaluated the effect of H. pylori eradication on GERD were included. Meta-analysis of pooled OR was performed using Review Manger 5.1.7. RESULTS: Seventeen articles with 6,889 subjects (intention-to-treat) that fulfilled the inclusion criteria were finally included in the analysis. Of them, 8 RCTs have the similar study design and inclusion criterion, which included patients with H. pylori infection but without GERD at baseline. The OR for the development of erosive GERD after H. pylori eradication was 1.67 (95% CI 1.12-2.48, p = 0.01). The OR for the development of GERD-related symptoms after H. pylori eradication in eradication group compared with control group was 1.04 (95% CI 0.84-1.29, p = 0.71). In addition, 9 RCTs included patients with both baseline H. pylori infection and GERD. The OR for the healing rates and relapse rates after H. pylori eradication in the H. pylori eradication group vs. control group was 0.92 (95% CI 0.47-1.82, p = 0.82) and 1.12 (95% CI 0.60-2.09, p = 0.71), respectively. CONCLUSIONS: Our meta-analyses showed H. pylori eradication may lead to the development of new erosive GERD. However, eradication of H. pylori may affect neither the healing rates nor relapse rates of preexisting GERD.


Assuntos
Refluxo Gastroesofágico/complicações , Infecções por Helicobacter/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos de Casos e Controles , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Fatores de Risco
18.
Ann Intern Med ; 172(12): 795-802, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32365359

RESUMO

BACKGROUND: Although consensus supports eradication of Helicobacter pylori infections, antimicrobial resistance has substantially reduced eradication rates with most current therapies. OBJECTIVE: To assess the effectiveness of a novel rifabutin-based therapy (RHB-105) for H pylori eradication. DESIGN: Phase 3, double-blind trial (ERADICATE Hp2). (ClinicalTrials.gov: NCT03198507). SETTING: 55 clinical research sites in the United States. PARTICIPANTS: 455 treatment-naive adults with epigastric discomfort and confirmed H pylori infection. INTERVENTION: RHB-105 (amoxicillin, 3 g; omeprazole, 120 mg; and rifabutin, 150 mg) versus active comparator (amoxicillin, 3 g, and omeprazole, 120 mg), given as 4 capsules every 8 hours for 14 days. MEASUREMENTS: Between-group difference for H pylori eradication rate, demonstrated by 13C urea breath test 4 weeks after treatment, analyzed by using the χ2 test. RESULTS: In the intention-to-treat population, the eradication rate was higher with RHB-105 than with the active comparator (228 vs. 227 patients, respectively; 83.8% [95% CI, 78.4% to 88.0%] vs. 57.7% [95% CI, 51.2% to 64.0%]; P < 0.001). Eradication rates were unaffected by resistance to clarithromycin or metronidazole. No rifabutin resistance was detected. The most commonly reported adverse events (incidence ≥5%) were diarrhea (10.1% with RHB-105 vs. 7.9% with active comparator), headache (7.5% vs. 7.0%), and nausea (4.8% vs. 5.3%). LIMITATION: Persons of Asian descent were excluded because of their higher prevalence of poor cytochrome P450 2C19 metabolizers. CONCLUSION: These findings suggest potential for RHB-105 as first-line empirical H pylori therapy, addressing an unmet need in the current environment of increasing antibiotic resistance. PRIMARY FUNDING SOURCE: RedHill Biopharma Ltd.


Assuntos
Amoxicilina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Omeprazol/uso terapêutico , Rifabutina/uso terapêutico , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Adulto Jovem
19.
Am J Clin Pathol ; 154(2): 255-265, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32445464

RESUMO

OBJECTIVES: To assess the concordance and performance characteristics of Helicobacter pylori laboratory tests compared with histopathology and to propose algorithms for the diagnosis of H pylori that minimize diagnostic error. METHODS: H pylori diagnostics were reviewed from a 12-year period within a health system (2,560 cases). Analyses were performed to adjust diagnostic performance based on treatment and consensus histopathologic diagnoses among pathologists. Markers of access to care, including test cancellation frequency and turnaround time, were assessed. Costs and performance of candidate noninvasive testing algorithms were modeled as a function of disease prevalence. RESULTS: Serum H pylori IgG demonstrated a higher sensitivity (0.94) than urea breath and stool antigen tests (0.64 and 0.61, respectively). Evidence of an advantage in access to care for serology included a lower cancellation rate. Interobserver variability was higher (κ = 0.34) among pathologists for cases with a discordant laboratory test than concordant cases (κ = 0.56). A model testing algorithm utilizing serology for first-time diagnoses minimizes diagnostic error. CONCLUSIONS: Although H pylori serology has modestly lower specificity than other noninvasive tests, the superior sensitivity and negative predictive value in our population support its use as a noninvasive test to rule out H pylori infection. Reflexive testing with positive serology followed by either stool antigen or urea breath test may optimize diagnostic accuracy in low-prevalence populations.


Assuntos
Gastrite/diagnóstico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Adulto , Antígenos de Bactérias/análise , Testes Respiratórios , Feminino , Gastrite/sangue , Gastrite/microbiologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Sorológicos , Ureia/análise
20.
Immunity ; 52(4): 635-649.e4, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32240600

RESUMO

The intestinal microbiota shapes and directs immune development locally and systemically, but little is known about whether commensal microbes in the stomach can impact their immunological microenvironment. Here, we report that group 2 innate lymphoid cells (ILC2s) were the predominant ILC subset in the stomach and show that their homeostasis and effector functions were regulated by local commensal communities. Microbes elicited interleukin-7 (IL-7) and IL-33 production in the stomach, which in turn triggered the propagation and activation of ILC2. Stomach ILC2s were also rapidly induced following infection with Helicobacter pylori. ILC2-derived IL-5 resulted in the production of IgA, which coated stomach bacteria in both specific pathogen-free (SPF) and H. pylori-infected mice. Our study thus identifies ILC2-dependent IgA response that is regulated by the commensal microbiota, which is implicated in stomach protection by eliminating IgA-coated bacteria including pathogenic H. pylori.


Assuntos
Microbioma Gastrointestinal/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/patogenicidade , Imunoglobulina A/biossíntese , Interleucina-5/imunologia , Estômago/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Feminino , Regulação da Expressão Gênica , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/imunologia , Imunidade Humoral , Imunidade Inata , Interleucina-33/genética , Interleucina-33/imunologia , Interleucina-5/genética , Interleucina-7/genética , Interleucina-7/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Cultura Primária de Células , Transdução de Sinais , Estômago/microbiologia , Simbiose/imunologia , Subpopulações de Linfócitos T/classificação
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