Identificación y evaluación de lesiones gástricas premalignas asociadas a la infección por Helicobacter pylori / Identification and evaluation of premalignant gastric lesions associated with Helicobacter pylori infection

Introducción: La infección por Helicobacter pylori es la causa principal de enfermedades gastroduodenales (gastritis crónica, úlceras pépticas y cáncer gástrico). En Guatemala existen pocos estudios sobre la prevalencia de H. pylori y su relación con enfermedades gastrointestinales, particularmente con cáncer. Objetivos: Identificar la presencia de lesiones premalignas (atrofia gástrica, metaplasia intestinal y displasia) y su relación con la infección por H. pylori en pacientes de consulta externa en unidades de gastroenterología de dos hospitales nacionales de la ciudad de Guatemala. Métodos: El diagnóstico histopatológico y bacteriológico se realizó por medio de las tinciones de H & E y Giemsa, cultivo e identificación bioquímica, detección de anticuerpos específicos mediante la prueba ELISA, diagnóstico molecular por la amplificación del gen glmM y genotipificación por PCR para identificar los genes VacA y CagA. Se analizaron datos clínico-epidemiológicos de los pacientes, la prevalencia de la infección por H. pylori y la genotipificación de la bacteria. Resultados: En 293 de los pacientes estudiados (83 por ciento) se encontró algún tipo de lesión premaligna; las más frecuentes fueron la atrofia gástrica (70 por ciento), metaplasia intestinal (11 por ciento) y displasia gástrica (2 por ciento). El 17 por ciento de los pacientes no presentó lesiones premalignas. Se halló una prevalencia de infección por H. pylori del 58 por ciento, y el gen cagA se detectó en 118 (57 por ciento) de los pacientes infectados. Conclusiones: La mayoría de los pacientes presentó atrofia gástrica (70 por ciento) y el 43,5 por ciento estaba infectado por H. pylori, principalmente con cepas CagA positivo. Este hecho confirma la importancia del estudio de H. pylori y su relación con cáncer gástrico(AU)

Introduction: Helicobacter pylori infection is the main cause of gastroduodenal diseases (chronic gastritis, peptic ulcer and gastric cancer). In Guatemala few studies have been carried out on the prevalence of H. pylori and its relationship with gastrointestinal diseases, particularly with cancer. Objective: To identify the presence of premalignant lesions (gastric atrophy, intestinal metaplasia and dysplasia) and their relationship with H. pylori infection in outpatients in gastroenterology units in two national hospitals in Guatemala City. Methods: Histopathological and bacteriological diagnostic testings were performed by H & E and Giemsa stain, culture and biochemical identification, detection of specific antibodies by ELISA, molecular diagnosis by glmM gene amplification, and genotypification by PCR to identify vacA and cagA genes. Clinical and epidemiological data from patients, prevalence of H. pylori infection, and bacterium genotypification were analyzed. Results: Among the studied patients, 293 (83 percent) presented some type of premalignant lesion. The most prevalent were gastric atrophy (70 percent), intestinal metaplasia (11 percent), and gastric dysplasia (2 percent). Seventeen percent of the patients did not have any premalignant lesions. The prevalence of H. pylori infection was 58 percent, and cagA gene was identified in 118 (57 percent) of the infected patients. Conclusions: The majority of the patients presented gastric atrophy (70 percent), and 43.5 percent were infected by H. pylori, mainly with positive cagA strains. This finding confirms the importance of studying H. pylori and its relationship with gastric cancer(AU)

Oral and gastric microbiome in relation to gastric intestinal metaplasia.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

A 500-year tale of co-evolution, adaptation, and virulence: Helicobacter pylori in the Americas.

Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region.

A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis.

BACKGROUND: There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD). METHODS: By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS. RESULTS: A single PAT course early-in-life exacerbated later DSS-induced colitis by both perturbing the microbial community and altering mucosal immune cell composition. By conventionalizing germ-free mice with either antibiotic-perturbed or control microbiota obtained 40 days after the challenge ended, we showed the transferrable and direct effect of the still-perturbed microbiota on colitis severity in the DSS model. CONCLUSIONS: The findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.

Validación de una prueba serológica para detectar la infección por Helicobacter pylori en Costa Rica

Introduction: Helicobacter pylori is a Gram-negative bacterium capable to survive and multiply in the gastric mucosa. It is the most prominent factor in the development of chronic atrophic gastritis, peptic ulcer, adenocarcinoma and MALT lymphoma. It is estimated that half the world population is infected. The economic cost and impact on the quality of life caused by H. pylori are important. There are several methods to detect the bacteria, but some are invasive, expensive, or both. Objective: We compare an inexpensive serological test based on ELISA for the detection of IgG, using the urea breath test (PYtest) as the reference method. Methods: The area under the ROC curve, sensitivity, specificity and predictive values were calculated. A subset of 45 samples was used for validation of the ELISA test, while the assay was evaluated with 185 additional samples. Results: The cut-off point to discriminate between positive and negative infection status by H. pylori was 0.75, using the optical density ratio of each serum and a positive control. With a higher value of the ratio, the probability of being infected increased. Using this criterion, the test showed a sensitivity of 91.4 % and specificity of 93.7 %. All diagnostic values improved when a gray zone was considered. Conclusion: The serological test developed here is equivalent to the urea breath test. However, the serological test is more accessible to the general population because of its lower cost. This serological test could be used in large-scale clinical research.

Introducción: Helicobacter pylori es una bacteria Gram negativa capaz de sobrevivir y multiplicarse en la mucosa gástrica humana. Es el factor más importante en el desarrollo de gastritis atrófica crónica, úlcera péptica, linfoma MALT y adenocarcinoma. Se estima que la mitad de la población mundial está infectada con esta bacteria. La baja en calidad de vida y el costo económico causados por la infección por H. pylori son importantes. Existen varios métodos para su diagnóstico, pero algunos son invasivos, de alto costo o ambos. Objetivo: Comparar una prueba serológica de bajo costo basada en la técnica de ELISA para detección de IgG, usando la prueba de urea en aliento (PYtest) como método de referencia. Métodos: Se calculó el área bajo la curva ROC, sensibilidad, especificidad y valores predictivos. Se utilizaron 45 muestras de suero para validar la prueba de ELISA, mientras que para su evaluación se usaron otras 185 muestras de suero. Resultados: El punto de corte para discriminar entre positivos y negativos para la infección por H. pylori fue de 0.75 en la razón de densidad óptica entre los sueros de las muestras y el control positivo. A mayor valor de la razón, más probabilidad de ser positivo para la infección. Usando este criterio, la prueba tuvo una sensibilidad del 91.4 % y una especificidad del 93.7 %. Todos los valores diagnósticos mejoran al considerar una zona gris. Conclusiones: En la población estudiada, la prueba serológica se comporta de forma equivalente a la prueba de urea en aliento. Tiene la ventaja de que es más asequible a la población general por su bajo costo. La prueba podría ser usada en investigación clínica a gran escala.

Ongoing Challenges Faced in the Global Control of COVID-19 Pandemic.

The recent pandemic caused by SARS-CoV-2 has now spread worldwide and caused more than 51,000 deaths, by April 2nd 2020. As predicted, there are several obstacles for medical and governmental authorities to efficiently manage this respiratory illness. In spite of appropriated supplies, most hospitals are suffering from a scarcity of free beds, protective masks, sanitizing liquids and even ECMO machines for patients with severe cases. Defeating this pandemic is impossible without united and coordinated international attempts shaped by all countries of the world. We believe that an international scaled-determination is required to diminish the complex impacts of pandemic. The most important priorities are supposed to be i) The development of potential vaccine candidates to provide protection and interrupt the transmission of SARS-CoV-2, ii) To ensure enough supplies for hospitals and their homogeneous distribution among the countries with the worst number of severe cases, iii) There is a need for more studies to identify potential treatments that are effective for the control of this viral infection and iv) It is imperative to provide easy access to diagnostic kits for all countries affected by this pandemic. In the light of these suggestions, it would be recommendable to at least temporarily abandon the political checkouts in both national and international levels; therefore, all partners will be potentially able to efficiently enforce their strategies for the elimination of this unique threat to the human populations.

MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer.

The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM). OBJECTIVE: To identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM. DESIGN: We performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+ and SLFN4- cells from Helicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b. RESULTS: MicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth. CONCLUSION: Taken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.

Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection.

Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (ß-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens.IMPORTANCE The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility.

Development and Assessment of a Helicobacter pylori Medication Adherence and Stomach Cancer Prevention Curriculum for a Chinese American Immigrant Population.

Chinese American immigrants are at increased risk for Helicobacter pylori infection and stomach cancer. Despite their increased risk, very few prevention strategies exist which target this vulnerable population. The purpose of this article is to present the stakeholder engaged development, review, assessment, refinement, and finalization of a H. pylori treatment adherence and stomach cancer prevention curriculum specifically designed to engage vulnerable, limited English proficient Chinese Americans in New York City.

Is There a Role for the Non-Helicobacter pylori Bacteria in the Risk of Developing Gastric Cancer?

Helicobacter pylori is the most abundant bacterium in the gastric epithelium, and its presence has been associated with the risk of developing gastric cancer. As of 15 years ago, no other bacteria were associated with gastric epithelial colonization; but thanks to new methodologies, many other non-H. pylori bacteria have been identified. It is possible that non-H. pylori may have a significant role in the development of gastric cancer. Here, we discuss the specific role of H. pylori as a potential trigger for events that may be conducive to gastric cancer, and consider whether or not the rest of the gastric microbiota represent an additional risk in the development of this disease.

Helicobacter pylori the Latent Human Pathogen or an Ancestral Commensal Organism.

We dedicated this review to discuss Helicobacter pylori as one of the latest identified bacterial pathogens in humans and whether its role is mainly as a pathogen or a commensal. Diseases associated with this bacterium were highly prevalent during the 19th century and gradually have declined. Most diseases associated with H. pylori occurred in individuals older than 40 years of age. However, acquisition of H. pylori occurs mainly in young children inside the family setting. Prevalence and incidence of H. pylori has had a dramatic change in the last part of the 20th century and beginning of the 21th century. In developed countries there is a clear interruption of transmission and the lowest prevalence is observed in children younger than 10 years in these countries. A similar decline is observed but not at the same level in developing countries. Here we discuss the impact of the presence or absence of H. pylori in the health status of humans. We also discuss whether it is necessary or not to establish H. pylori eradication programs on light of the current decline in H. pylori prevalence.

When is Helicobacter pylori acquired in populations in developing countries? A birth-cohort study in Bangladeshi children.

Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.

Infección por Helicobacter pylori: mecanismos de contagio y prevención / Helicopabter pylori: infection and prevention mechanisms

H. pylori infection is a fascinating history, which combines the roles as one of the most prevalent commensal and a a pathogen responsible for severe diseases, some of them unimaginable until the end of last century, such as gastric cancer. In this review we present the available evidence that might help to identify the main mode of transmission of H. pylori and we discuss which could be the potential approaches to prevent the transmission of this bacterium in countries with high and low prevalence.

La infección por Helicobacter pylori es una historia fascinante, en donde se combinan el papel de un comensal con el de un patógeno humano que produce enfermedades graves, algunas inimaginables hasta hace menos de 30 años, como es el caso de cáncer gástrico. En esta revisión discutimos las evidencias disponibles en función de la prevalencia e incidencia de H. pylori tanto en países económicamente desarrollados como en proceso de desarrollo y tratamos de establecer cuál es el principal modo de transmisión de este organismo. Finalmente, se discuten cuáles pueden ser las mejores medidas de prevención, tanto en países con baja prevalencia como en aquellos con una alta prevalencia.

Gut Microbiome and Antibiotics.

Despite that the human gastrointestinal tract is the most populated ecological niche by bacteria in the human body, much is still unknown about its characteristics. This site is highly susceptible to the effects of many external factors that may affect in the quality and the quantity of the microbiome. Specific factors such as diet, personal hygiene, pharmacological drugs and the use of antibiotics can produce a significant impact on the gut microbiota. The effect of these factors is more relevant early in life, when the gut microbiota has not yet fully established. In this review, we discussed the effect of type and doses of the antibiotics on the gut microbiota and what the major consequences in the use and abuse of these antimicrobial agents.

A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity.

Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased.High or multiple doses of macrolide antibiotics, when given early in life, can perturb the metabolic and immunological development of lab mice. Here, Ruiz et al. show that even a single macrolide course, given early in life, leads to long-lasting changes in the gut microbiota and immune system of mice.