RESUMEN

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.

Asunto(s)

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 , Femenino

RESUMEN

Gastric cancer is an aggressive and multifactorial disease. Helicobacter pylori (H. pylori) is identified as a significant etiological factor in gastric cancer. Although only a fraction of patients infected with H. pylori progresses to gastric cancer, bacterial infection is critical in the pathology and development of this malignancy. The pathogenic mechanisms of this bacterium involve the disruption of the gastric epithelial barrier and the induction of chronic inflammation, oxidative stress, angiogenesis and metastasis. Adherence molecules, virulence (CagA and VacA) and colonization (urease) factors are important in its pathogenicity. On the other hand, resveratrol is a natural polyphenol with anti-inflammatory and antioxidant properties. Resveratrol also inhibits cancer cell proliferation and angiogenesis, suggesting a role as a potential therapeutic agent against cancer. This review explores resveratrol as an alternative cancer treatment, particularly against H. pylori-induced gastric cancer, due to its ability to mitigate the pathogenic effects induced by bacterial infection. Resveratrol has shown efficacy in reducing the proliferation of gastric cancer cells in vitro and in vivo. Moreover, the synergistic effects of resveratrol with chemotherapy and radiotherapy underline its therapeutic potential. However, further research is needed to fully describe its efficacy and safety in treating gastric cancer.

Asunto(s)

Infecciones por Helicobacter , Helicobacter pylori , Resveratrol , Neoplasias Gástricas , Resveratrol/farmacología , Resveratrol/uso terapéutico , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/tratamiento farmacológico , Humanos , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/patogenicidad , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Proliferación Celular/efectos de los fármacos , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico

RESUMEN

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

Asunto(s)

Antígenos Bacterianos , Proteínas Bacterianas , Infecciones por Helicobacter , Helicobacter pylori , MicroARNs , Neoplasias Gástricas , Humanos , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/genética , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , MicroARNs/genética , MicroARNs/análisis , Femenino , Masculino , Infecciones por Helicobacter/microbiología , Persona de Mediana Edad , Adulto , Anciano , Gastritis/microbiología

RESUMEN

Helicobacter pylori is a major cause of gastrointestinal disorders such as chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. It is estimated that around half of the world's population is infected with this pathogen, with underdeveloped countries reporting the highest frequencies. The genes cagA, cagM, vacA, and oipA are some of the most important virulence factors of H. pylori; however, there are no recent studies from Recife-PE demonstrating their frequency, and their relationship with severe gastric modifications. This work aims to use qualitative PCR to detect the virulence genes cagA, cagM, vacA, and oipA in H. pylori isolates obtained from patients in a public hospital in Recife (PE). We collected samples from the stomach's body and antrum of 147 patients, from which 71 (48%) tested positive for H. pylori. Among positive samples, the most frequently infected gender was female (44/71, 62%), and the most frequently infected age group was those above the age of 46 (31/71, 44%). Histological examination of H. pylori-positive samples revealed alterations other than chronic gastritis, including metaplasia and atrophy. The frequency of cagA, cagM, and oipA genes were identified in 84%, 56%, and 69% of the samples tested, respectively, as well as the vacA-s1m1 allelic combination (77%). However, there was no statistically significant variation in the occurrence of these genes, therefore they cannot be considered unique markers of severity in our setting. New research with larger samples and investigations of other genetic markers can aid uncover local risk factors and lead to a better understanding of H. pylori's pathogenesis.

Asunto(s)

Antígenos Bacterianos , Proteínas Bacterianas , Infecciones por Helicobacter , Helicobacter pylori , Factores de Virulencia , Humanos , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/patogenicidad , Helicobacter pylori/clasificación , Proteínas Bacterianas/genética , Femenino , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/epidemiología , Masculino , Persona de Mediana Edad , Adulto , Brasil/epidemiología , Factores de Virulencia/genética , Antígenos Bacterianos/genética , Anciano , Adulto Joven , Prevalencia , Adolescente , Anciano de 80 o más Años , Proteínas de la Membrana Bacteriana Externa

RESUMEN

Helicobacter pylori is the most common cause of gastroduodenal diseases. The concept that cagA-positive H. pylori is a risk factor for gastric cancer appears to be true only for H. pylori strains from Western countries. Other virulent genes may have a synergistic interaction with cagA during pathogenesis. This study aims to investigate H. pylori cagA, vacA, and iceA prevalence, genotypes, and their association to clinical outcomes in Vietnamese patients. The cagA status and vacA and iceA genotypes were determined using the PCR technique on DNA extracted from gastric biopsies of 141 patients with gastroduodenal diseases. After performing molecular analysis for cagA, vacA, and iceA genes, samples with mixed H. pylori strains, positivity, or negativity for both cagA and cagPAI-empty site, or unidentified genotypes were excluded. Finally, 107 samples were examined. The presence of the cagA, vacA, and iceA genes were detected in 77.6%, 100%, and 80.4% of cases, respectively. Notably, cagA( +) with EPIYA-ABD, vacA s1i1m1, vacA s1i1m2, iceA1, and iceA2 accounted for 73.8%, 44.9%, 33.6%, 48.6%, and 31.8% of cases, respectively. Four iceA2 subtypes (24-aa, 59-aa, 94-aa, and 129-aa variants) were found, with the 59-aa variant the most prevalent (70.6%). The cagA( +)/vacAs1i1m1/iceA1 and cagA( +)/vacAs1i1m2/iceA1 combinations were found in 26.2% and 25.1% of cases, respectively. A multivariable logistic regression analysis was performed, after adjusting for age and gender, with the gastritis group was used as a reference control. Statistically significant associations were found between the vacA s1i1m2 genotype, the iceA1 variant, and the cagA( +)/vacAs1i1m2/iceA1 combination and gastric cancer; the adjusted ORs were estimated as 18.02 (95% CI: 3.39-95.81), 4.09 (95% CI: 1.1-15.08), and 16.19 (95% CI: 3.42-76.66), respectively. Interestingly, for the first time, our study found that vacA s1i1m2, but not vacA s1i1m1, was a risk factor for gastric cancer. This study illustrates the genetic diversity of the H. pylori cagA, vacA, and iceA genes across geographical regions and contributes to understanding the importance of these genotypes for clinical outcomes.

Asunto(s)

Antígenos Bacterianos , Proteínas Bacterianas , Genotipo , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Proteínas Bacterianas/genética , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/clasificación , Helicobacter pylori/patogenicidad , Vietnam/epidemiología , Antígenos Bacterianos/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/epidemiología , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Adulto , Proteínas de la Membrana Bacteriana Externa/genética , Anciano , Adulto Joven , Prevalencia , Factores de Virulencia/genética

RESUMEN

Helicobacter pylori é uma bactéria Gram-negativa que acomete cerca de 50% da população mundial. A infecção causada por H. pyloriestá associada com algumas enfermidades gástricas. Entretanto, estudos mais recentes têm demonstrado a etiologia do microrganismo em doenças extra gástricas, como doenças metabólicas. O trabalho teve como objetivo realizar uma pesquisa na literatura de artigos que avaliaram a associação da infecção por H. pyloricom doenças metabólicas, com foco em diabetes. Foram utilizadas as seguintes bases de dados, PubMed, Medline, LILACS e SciELO. Termos combinados juntamente com o operador booleano "AND" em português e em inglês foram empregados. O resultado do levantamento bibliográfico totalizou 31 artigos. A infecção por H. pyloripossivelmente está relacionada com a síndrome metabólica. A relação pode ser decorrente da inflamação crônica, redução dos movimentos gastrointestinais, falta de secreção de ácido gástrico e interferência na produção ou secreção de alguns hormônios. Apesar dos estudos demonstrarem que entre os indivíduos infectados por H.pyloria prevalência da síndrome metabólica é maior e que a erradicação do microrganismo favorece a melhora dos índices glicêmicos, mais pesquisas são requeridas. A compreensão da etiologia da infecção porH. pyloriem doenças metabólicas, pode auxiliar em políticas públicas de erradicação da bactéria.

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Helicobacter pylori is a Gram-negative bacterium that affects about 50% of the world's population. Infection caused by H. pylori is associated with some gastric diseases. However, more recent studies have demonstrated the etiology of the microorganism in extra gastric diseases, such as metabolic diseases. The objective of this study was to carry out a literature search for articles that evaluated the association ofH. pyloriinfection with metabolic diseases, focusing on diabetes. The following databases were used, PubMed, Medline, LILACS and SciELO. Combined terms together with the Boolean operator "AND" in Portuguese and English were used. The result of the bibliographic survey totaled 31 articles.H. pyloriinfection is possibly related to the metabolic syndrome. The relationship may be due to chronic inflammation, reduced gastrointestinal movements, lack of gastric acid secretion and interference in the production or secretion of some hormones. Despite studies demonstrating that infected individuals had a higher prevalence of metabolic syndrome and that the eradication of the microorganism favors the improvement of glycemic indexes, more research is required. Understanding the etiology of H. pyloriinfection in metabolic diseases can help in public policies to eradicate the bacterium.

Asunto(s)

Humanos , Helicobacter pylori , Helicobacter pylori/patogenicidad , Síndrome Metabólico/fisiopatología , Diabetes Mellitus/fisiopatología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Síndrome Metabólico/complicaciones , Inflamación

RESUMEN

Helicobacter pylori is the etiological agent of chronic gastritis, peptic ulcer, and gastric cancer. The duodenal ulcer-promoting gene dupA, which is located in the plasticity region of the H. pylori genome, is homologous to the virB gene which encodes a type IV secretion protein in Agrobacterium tumefaciens. Studies have shown associations between H. pylori dupA-positive strains and gastroduodenal diseases. However, whether dupA acts as a risk factor or protective factor in these diseases remains unclear. Therefore, in this study, we aimed to verify the presence of the dupA gene in infectious H. pylori strains in the Brazilian mid-west and to investigate its association with the clinical outcomes of patients with dyspepsia. Additionally, the phylogenetic origin of the strains was determined. Gastric biopsies from 117 patients with dyspepsia were analyzed using histological and molecular techniques. The hpx gene (16S rRNA) was used to screen for H. pylori infection, and positive samples were then subjected to dupA gene detection and sequencing. The estimated prevalence of H. pylori infection was 64.1%, with the dupA gene being detected in a high proportion of infectious strains (70.7%). Furthermore, a risk analysis revealed that for women, a dupA-positive H. pylori infection increased the chance of developing gastritis by twofold. The partial dupA sequences from isolated infectious strains in this work are similar to those of strains isolated in westerns countries. This study provides useful insights for understanding the role of the H. pylori dupA gene in disease development.

Asunto(s)

Proteínas Bacterianas , Infecciones por Helicobacter , Helicobacter pylori , Factores de Virulencia , Proteínas Bacterianas/genética , Brasil/epidemiología , Dispepsia/complicaciones , Dispepsia/epidemiología , Dispepsia/microbiología , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/clasificación , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Masculino , Filogenia , Factores Protectores , ARN Ribosómico 16S/genética , Factores de Riesgo , Factores de Virulencia/genética

RESUMEN

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

Asunto(s)

Vesículas Extracelulares/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Gastropatías/metabolismo , Membrana Externa Bacteriana/metabolismo , Progresión de la Enfermedad , Vesículas Extracelulares/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Humanos , Gastropatías/microbiología , Gastropatías/patología

RESUMEN

RESUMEN Introducción: la infección por Helicobacter pylori es la enfermedad bacteriana crónica que afecta con mayor prevalencia al ser humano. Objetivo: identificar la frecuencia de infección por Helicobacter pylori y su relación con variables consideradas factores de riesgo de esta infección. Materiales y métodos: estudio de corte transversal realizado en el Policlínico Docente Camilo Cienfuegos, del municipio Habana del Este, durante el año 2018, en un universo de 42 pacientes con 18 años y más de edad, con sospecha clínica y hallazgo endoscópico de úlcera duodenal e informe del resultado de estudio histológico para el diagnóstico de la infección. Se confeccionó una planilla de recolección de datos que incluyó variables como hacinamiento, agua de consumo, lugar de nacimiento, estancia en una institución, contacto con animales y antecedentes familiares. Se determinó relación entre variables con la prueba de chi cuadrado (c2) con significación estadística ɒ = 0,05, y se identificaron variables cuyos coeficientes fueron significativamente diferentes de 0 (p < 0,05). La fuerza de asociación se determinó mediante odds ratio. Resultados: la prevalencia fue de 59,5 %. Se encontró asociación estadística y constituyeron factores de riesgo de infección por Helicobacter pylori, el hacinamiento (c2 = 4,37; OR = 3,89), el agua de consumo (c2 = 4,92; OR = 3,43), el contacto con animales (c2 = 7,41; OR = 6,17) y los antecedentes familiares (c2 = 13,18; OR = 13). Conclusiones: el estudio permitió determinar la prevalencia de infección por Helicobacter pylori y las principales variables asociadas, coincidiendo con otros estudios revisados que tratan el tema (AU).

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ABSTRACT Introduction: the infection by Helicobacter pylori is the chronic bacterial disease that affects the human being with greater prevalence. Objective: to identify the frequency of the infection by Helicobacter pylori and its relationship with variables considered risk factors for this infection. Materials and methods: a cross-sectional study was carried out in the teaching Polyclinic Camilo Cienfuegos, municipality Habana del Este, during 2018. In a universe of 42 patients aged 18 years and over, with clinical suspicion and endoscopic diagnosis of duodenal ulcer and histological study report for the diagnosis of the infection. A data collection form was made, which included variables such as: overcrowding, consumption water, place of birth, staying in an institution, contact with animals, and family history. The relationship within variables was found using the chi-square test (c2) with statistical significance ɒ = 0.05, and there were identified variables significantly different from 0 (p < 0.05). The association strength was determined through odds ratio. Results: the prevalence was 59.5%. Statistical association was found and overcrowding (c2 = 4.37, OR = 3.89), consumption water (c2 = 4.92; OR = 3.43), contact with animals (c2 = 7.41, OR = 6.17) and family history (c2 = 13.18, OR = 13) were found risk factors for Helicobacter pylori infection. Conclusions: the study allowed to determine the prevalence of Helicobacter pylori infection and the main associated variables, coinciding with other reviewed studies dealing with the subject (AU).

Asunto(s)

Humanos , Masculino , Femenino , Helicobacter pylori/virología , Úlcera Duodenal/diagnóstico , Signos y Síntomas , Prevalencia , Factores de Riesgo , Helicobacter pylori/patogenicidad , Factores de Virulencia/fisiología

RESUMEN

Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. H. pylori remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-H. pylori microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the H. pylori protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, Helicobacter and Prevotella figured in the "top 6" genera of every group. Helicobacter was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while Prevotella was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk.

Asunto(s)

Microbioma Gastrointestinal/genética , Neoplasias Gástricas/microbiología , Biología Computacional , Mucosa Gástrica/microbiología , Microbioma Gastrointestinal/fisiología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Redes y Vías Metabólicas , Metagenoma , Prevotella/genética , Prevotella/patogenicidad

RESUMEN

Se determinó la respuesta inmunológica a proteínas recombinantes de Helicobacter pylori en pacientes dis-pépticos (adultos y niños), pacientes con cáncer gástrico y sus familiares asintomáticos adultos viviendo con ellos. Se utilizó la prueba recomLine® Helicobacter IgG e IgA, y con base en el reconocimiento de los factores de virulencia VacA y CagA se determinó si la cepa de H. pylori era de tipo I o II. El análisis de los datos fue descriptivo y analítico y se estimaron los intervalos de confianza de 95%, con un nivel de error de 0.05 y Odds ratio. El 58.7% (121/206) de los pacientes presentó la bacteria en tinción histológica de biopsia, positividad que disminuyó con la edad y daño histológico. La frecuencia de la respuesta a los anticuerpos IgG fue mayor que IgA, en ambos casos ésta fue menor en los niños. Las proteínas del H. pylori más reconocidas tanto por IgA como IgG fueron VacA y CagA, y la respuesta a las otras proteínas investigadas fue mayor al aumentar el daño histológi-co. La cepa tipo I fue la que predominó en la población en estudio con 66% (136/206). Se deben continuar con los estudios de prevalencia de la cepa tipo I del H. pylori y del reconocimiento de sus antígenos en la población guatemalteca a fin de determinar su utilidad en el diagnóstico y pronóstico de la infección.

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The immune response to recombinant Helicobacter pylori proteins was determined in dyspeptic patients (adults and children), patients with gastric cancer and their asymptomatic adults' relatives living with them. The recomLine® Helicobacter IgG and IgA test was used and based on the recognition of the virulence factors VacA and CagA, it was determined whether the H. pylori strain was type I or II. The data analysis was descriptive and analytic, and 95% confidence intervals were estimated, with an error level of 0.05, and Odds ratio. The patients that presented the bacterium in histological biopsy were 58.7% (121/206), positivity that decreased with age and histological damage. The frecuency of response to IgG antibodies was higher than IgA, in both cases it was lower in children. VacA and CagA were the H. pylori proteins most recognized by both IgA and IgG and it was observed that the number of recognized proteins was greater with increasing histological damage. The type I strain was the one that predominated in the study population 66% (136/206). Prevalence studies of the type I strain of H. pylori ant the recognition of its antigens in the Guatemalan population should continue in order to determine its usefulness in the diagnosis and prognosis of infection.

Asunto(s)

Humanos , Niño , Adulto , Neoplasias Gástricas/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Helicobacter pylori/inmunología , Dispepsia/inmunología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Biopsia , Proteínas Recombinantes/análisis , Proteínas Recombinantes/inmunología , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/patogenicidad , Dispepsia/microbiología , Dispepsia/patología , Guatemala

RESUMEN

Antecedentes: Las recomendaciones de esquemas para erradicar Helicobacter pylori se encuentran ampliamente dis- ponibles. Este es un patógeno de alta prioridad para búsqueda y desarrollo de nuevos y efectivos tratamientos. Objetivo: Descri- bir la respuesta terapéutica con terapia de rescate para infección por H. pylori, Hospital Escuela, Tegucigalpa, diciembre 2016-abril 2017. Métodos: Estudio descriptivo longitudinal retrospectivo en pacientes consecutivos con sintomatología gastrointestinal e in- fección conirmada por H. pylori. Mediante el registro del Servi- cio de Gastroenterología, Departamento de Medicina Interna, se identiicaron pacientes positivos por H. pylori. Se registraron datos sociodemográicos, clínicos y diagnósticos. El tratamiento de res- cate brindado fue, vía oral por 10 días: levoloxacina 500 mg/día, esomeprazol 40 mg dos veces/día, amoxicilina 1 gr dos veces/ día. La conirmación de la erradicación fue realizada 4-8 semanas postratamiento. Se registró información sobre la adherencia al tra- tamiento y los efectos secundarios. Resultados: Se analizaron 30 casos; 56.7% (17) pacientes nuevos y 43.3% (13) pacientes con al menos un fracaso. En el 16.0% (5) no hubo conirmación de erra- dicación; se obtuvo una tasa de erradicación del 72.0% (18/25), IC95% 50.6-87.9; siendo 78.5% (11/14) en pacientes nuevos ver- sus 63.6% (7/11) en fracasos previos, IC95% -9.6-54.0, p=0.318. Discusión: La tasa de erradicación en este grupo de pacientes no fue satisfactoria. Actualmente el tratamiento con levoloxacina es recomendado como terapia de segunda línea o de rescate en regiones con baja o alta resistencia a la claritromicina, aunque la resistencia a quinolonas ha aumentado en los últimos años en va- rios países...(AU)

Asunto(s)

Humanos , Adulto , Helicobacter pylori/patogenicidad , Enfermedades Gastrointestinales/complicaciones , Levofloxacino/uso terapéutico , Amoxicilina/uso terapéutico

RESUMEN

RESUMEN Introducción: la infección por Helicobacter pylori es una de las más prevalentes en el planeta. Supone una carga significativa para los sistemas sanitarios, debido a la elevada resistencia a antibióticos que presenta para su erradicación. Objetivo: determinar las características clínico epidemiológicas de infección por Helicobacter pylori de pacientes atendidos en Consulta Provincial de Gastroenterología. Materiales y métodos: se realizó un estudio observacional descriptivo. El universo estuvo conformado por los 167 pacientes con determinación de Helicobacter pylori positivo, por test de ureasa. Las variables a considerar fueron: la edad, el sexo, diagnóstico histológico, síntomas clínicos y la evolución clínica posterior al tratamiento específico para Helicobacter pylori. Se utilizó la técnica estadística de análisis de distribución de frecuencias. Resultados: un 59,6 % de los pacientes resultó con Helicobacter pylori positivo con predominio del sexo masculino. Fue la gastritis crónica la alteración gástrica que más se asoció a la infección. La epigastralgia y distensión abdominal resultaron los síntomas más frecuentes. Evolucionaron de forma satisfactoria el 49 % de los casos y solo un 17 % presentaron una mala respuesta al tratamiento. Conclusiones: se obtuvo un alto porcentaje de infección por Helicobacter pylori y una buena respuesta al tratamiento utilizado (AU).

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ABSTRACT Introduction: the infection for Helicobacter pylori is one of the more prevalent in the world; it supposes a significant burden for the sanitary systems, due to the high resistance to antibiotics that it presents for its eradication. Objective: to determine the clinical epidemiological characteristics of the infection due to Helicobacter pylori in patients treated in the provincial consultation of Gastroenterología. Materials and methods: an observational, descriptive study was carried out in a universe formed by 167 patients with positive Helicobacter pylori determined by urease test. The variables to consider were age, sex, histologic diagnosis, clinical symptoms and clinical evolution after the specific treatment for Helicobacter pylori. The statistical technique of analysis of frequencies distribution was used. Results: 59, 6% of the patients was Helicobacter pylori positive with prevalence of the male sex; chronic gastritis was the gastric alteration more associated to the infection. Epigastralgia and abdominal distension were the most frequent symptoms. 49% of the cases evolved in a satisfactory way and only 17% answered bad to the treatment. Conclusions: a high percent of infection by Helicobacter pylori was found and also a good answer to the used treatment (AU).

Asunto(s)

Humanos , Masculino , Femenino , Helicobacter pylori/patogenicidad , Gastroenterología/métodos , Pacientes , Condiciones Patológicas, Signos y Síntomas , Gastritis/complicaciones , Infecciones/complicaciones , Infecciones/parasitología , Antibacterianos

RESUMEN

Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.

Asunto(s)

Mucosa Gástrica/patología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Lesiones Precancerosas/microbiología , Neoplasias Gástricas/epidemiología , Adulto , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Biopsia , Colombia/epidemiología , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Femenino , Mucosa Gástrica/microbiología , Gastritis/microbiología , Gastritis/patología , Marcadores Genéticos , Genoma Bacteriano/genética , Islas Genómicas , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/patogenicidad , Humanos , Masculino , Metaplasia/microbiología , Metaplasia/patología , México/epidemiología , Persona de Mediana Edad , Polimorfismo Genético , Lesiones Precancerosas/patología , Medición de Riesgo/métodos , Factores de Riesgo , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Secuenciación Completa del Genoma

RESUMEN

BACKGROUND: Helicobacter pylori is a chronic pathogenic bacteria that causes gastric mucosal damage through various host-related and pathogen-related factors. Thus, a single gene research cannot fully explain its pathogenicity. PURPOSE OF STUDY: It is necessary to establish a Helicobacter pylori pathogenic gene transcription factor regulatory network (TFRN) and study its central nodes. RESULTS: The expression data of Helicobacter pylori pathogenic genes were obtained through GEO Datasets of NCBI. The genes were screened using linear model-empirical Bayesian statistics in R language Limma package combined with the conventional t-test; the results identified 1231 differentially expressed genes. The functional analysis (gene ontology-analysis) and signal pathway analysis (pathway-analysis) of differentially expressed genes were performed using the DAVID and KEGG databases, respectively. The pathogenic gene regulatory network was constructed by integrating transcriptional regulatory element database (TRED); the disease-related analysis of the pathogenic genes was conducted using the DAVID annotation tool. Five pathogenic genes (Nos2, Il5, Colla1, Tnf, and Nfkb1) and their transcription factors (Jun, Cebpa, Egrl, Ppara, and Il6) were found to suppress the host immune function and enhance the pathogenicity of Helicobacter pylori by regulating the host immune system. CONCLUSIONS: This effect was largely mediated via three signaling pathways: Tnf pathway, PI3K Akt pathway, and Jak­STAT pathway. The pathogenicity of Helicobacter pylori is closely related to the body's immune and inflammatory system. A better understanding of the correlation of the pathogenic factors with the host immune and inflammatory factors may help to determine the precise pathogenic mechanism of H. pylori infection.

Asunto(s)

Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Biología Computacional , Factores de Transcripción , Citocinas , Factores de Virulencia , Gastritis/inmunología , Gastritis/microbiología , Genes Bacterianos , Sistema Inmunológico , Inflamación

RESUMEN

Helicobacter pylori (H. pylori) is one of the main causes of gastric gancer. TNF-related apoptosis-inducing ligand (TRAIL) is a protein able to promote apoptosis in cancer cells, however not in gastric cancer, which presents resistance to apoptosis via TRAIL. It is believed that MicroRNA-106b-5p might be involved in this resistance, although its role in Gastric Cancer is unclear. We aimed to determine the expression of microRNA-106b-5p and TRAIL in patients with gastric diseases, infected by H. pylori, and understand the relationship between these genes and their role in apoptosis and the gastric cancer pathways. H. pylori was detected by PCR, gene expression analysis was performed by real-time-qPCR, and bioinformatics analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cytoscape software. A total of 244 patients were divided into groups (Control, Gastritis, and Cancer); H. pylori was detected in 42.2% of the samples. The cancer group had a poor expression of TRAIL (p < 0.0001) and overexpression of microRNA-106b-5p (p=0.0005), however, our results confirmed that these genes are not directly related to each other although both are apoptosis-related regulators. Our results also indicated that H. pylori decreases microRNA-106b-5p expression and that this is a carcinogenic bacterium responsible for gastric diseases.

Asunto(s)

Infecciones por Helicobacter/genética , MicroARNs/genética , Neoplasias Gástricas/genética , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Apoptosis/genética , Femenino , Gastritis/genética , Gastritis/microbiología , Gastritis/patología , Regulación Neoplásica de la Expresión Génica/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Transducción de Señal/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología

RESUMEN

Peptic ulcer disease (PUD) is a multifactorial and complex disease caused by an imbalance of protective and aggressive factors (endogenous and exogenous). Despite advances in recent years, it is still responsible for substantial mortality and triggering clinical problems. Over the last decades, the understanding of PUD has changed a lot with the discovery of Helicobacter pylori infection. However, this disease continues to be a challenge due to side-effects, incidence of relapse from use of various anti-ulcer medicines, and the rapid appearance of antimicrobial resistance with current H. pylori therapies. Consequently, there is the need to identify more effective and safe anti-ulcer agents. The search for new therapies with natural products is a viable alternative and has been encouraged. The literature reports the importance of monoterpenes based on the extensive pharmacological action of this class, including wound healing and anti-ulcerogenic agents. In the present study, 20 monoterpenes with anti-ulcerogenic properties were evaluated by assessing recent in vitro and in vivo studies. Here, we review the anti-ulcer effects of monoterpenes against ulcerogenic factors such as ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori, highlighting challenges in the field.

Asunto(s)

Monoterpenos/farmacología , Úlcera Péptica/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/patogenicidad , Humanos , Monoterpenos/metabolismo , Úlcera Péptica/epidemiología , Úlcera Péptica/etiología , Factores de Riesgo

RESUMEN

BACKGROUND AND AIMS: Nodular gastropathy (NG) is an inflammatory condition of the gastric mucosa characterized by the endoscopic detection of multiple millimeter protrusions. A strong association between NG and Helicobacter pylori and a possible role of NG as a risk factor for undifferentiated gastric cancer have been described. The aim of this study was to characterize the pathogenic and inflammatory profile of patients with NG. METHODS: Adult patients referred for upper gastrointestinal endoscopy were prospectively enrolled in this study. H. pylori infection status was determined by rapid urease test. Biopsies were stained with hematoxylin-eosin. Sydney and OLGA scores were used to assess gastritis characteristics and gastric cancer risk. PCR analysis was performed to determine bacterial load and virulence factors CagA (and its EPIYA motifs) and VacA alleles. Finally, gastric mucosa cytokine gene expression (IL-8, IL-1ß, and TNF-α) was determined by real-time RT-PCR. RESULTS: Forty-eight patients, mean age of 36 years, were recruited. All NG patients were infected by H. pylori. OLGA score was similar in both groups (NG patients and non-NG patients). NG patients had higher bacterial load in the gastric corpus (p = 0.01) and significantly less pro-inflammatory cytokine levels than non-NG infected patients (p = 0.01). CONCLUSIONS: In our study, NG is not associated with preneoplastic lesions. An increase in bacterial load without a concomitant increase in mucosal inflammatory cytokine responses in H. pylori-infected subjects with NG may represent a general dampening of immune responses or an additional mechanism of H. pylori active immune evasion.

Asunto(s)

Carga Bacteriana , Citocinas/genética , Mucosa Gástrica/microbiología , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Adulto , Antígenos Bacterianos , Proteínas Bacterianas , Estudios de Casos y Controles , Citocinas/metabolismo , Endoscopía del Sistema Digestivo , Endosonografía , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastritis/genética , Gastritis/metabolismo , Gastritis/patología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Adulto Joven

RESUMEN

BACKGROUND & AIMS: Gastric carcinoma is related mostly to CagA+-Helicobacter pylori infection, which disrupts the gastric mucosa turnover and elicits an epithelial-mesenchymal transition (EMT) and preneoplastic transdifferentiation. The tumor suppressor Hippo pathway controls stem cell homeostasis; its core, constituted by the large tumor suppressor 2 (LATS2) kinase and its substrate Yes-associated protein 1 (YAP1), was investigated in this context. METHODS: Hippo, EMT, and intestinal metaplasia marker expression were investigated by transcriptomic and immunostaining analyses in human gastric AGS and MKN74 and nongastric immortalized RPE1 and HMLE epithelial cell lines challenged by H pylori, and on gastric tissues of infected patients and mice. LATS2 and YAP1 were silenced using small interfering RNAs. A transcriptional enhanced associated domain (TEAD) reporter assay was used. Cell proliferation and invasion were evaluated. RESULTS: LATS2 and YAP1 appear co-overexpressed in the infected mucosa, especially in gastritis and intestinal metaplasia. H pylori via CagA stimulates LATS2 and YAP1 in a coordinated biphasic pattern, characterized by an early transient YAP1 nuclear accumulation and stimulated YAP1/TEAD transcription, followed by nuclear LATS2 up-regulation leading to YAP1 phosphorylation and targeting for degradation. LATS2 and YAP1 reciprocally positively regulate each other's expression. Loss-of-function experiments showed that LATS2 restricts H pylori-induced EMT marker expression, invasion, and intestinal metaplasia, supporting a role of LATS2 in maintaining the epithelial phenotype of gastric cells and constraining H pylori-induced preneoplastic changes. CONCLUSIONS: H pylori infection engages a number of signaling cascades that alienate mucosa homeostasis, including the Hippo LATS2/YAP1/TEAD pathway. In the host-pathogen conflict, which generates an inflammatory environment and perturbations of the epithelial turnover and differentiation, Hippo signaling appears as a protective pathway, limiting the loss of gastric epithelial cell identity that precedes gastric carcinoma development.

Asunto(s)

Transición Epitelial-Mesenquimal/inmunología , Mucosa Gástrica/patología , Infecciones por Helicobacter/patología , Lesiones Precancerosas/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Animales , Proteínas de Ciclo Celular/metabolismo , Femenino , Mucosa Gástrica/microbiología , Regulación Neoplásica de la Expresión Génica/inmunología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Interacciones Huésped-Patógeno/genética , Humanos , Masculino , Metaplasia/genética , Metaplasia/microbiología , Metaplasia/patología , Ratones , Lesiones Precancerosas/genética , Lesiones Precancerosas/inmunología , Factores Protectores , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/genética , Transducción de Señal/inmunología , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Señalizadoras YAP

RESUMEN

Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. However, its prevalence varies among different geographic areas, and is influenced by several factors. The infection can be acquired by means of oral-oral or fecal-oral transmission, and the pathogen possesses various mechanisms that improve its capacity of mobility, adherence and manipulation of the gastric microenvironment, making possible the colonization of an organ with a highly acidic lumen. In addition, H. pylori presents a large variety of virulence factors that improve its pathogenicity, of which we highlight cytotoxin associated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and gamma-glutamyl transpeptidase. The host immune system, mainly by means of a Th1-polarized response, also plays a crucial role in the infection course. Although most H. pylori-positive individuals remain asymptomatic, the infection predisposes the development of various clinical conditions as peptic ulcers, gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas. Invasive and non-invasive diagnostic methods, each of them with their related advantages and limitations, have been applied in H. pylori detection. Moreover, bacterial resistance to antimicrobial therapy is a major challenge in the treatment of this infection, and new therapy alternatives are being tested to improve H. pylori eradication. Last but not least, the development of effective vaccines against H. pylori infection have been the aim of several research studies.

Asunto(s)

Mucosa Gástrica/microbiología , Infecciones por Helicobacter/terapia , Helicobacter pylori/patogenicidad , Gastropatías/terapia , Antiácidos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Vacunas Bacterianas/uso terapéutico , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/transmisión , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/inmunología , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Probióticos/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Gastropatías/diagnóstico , Gastropatías/microbiología , Resultado del Tratamiento , Factores de Virulencia/metabolismo