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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.

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).ObjectiveTo identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM.DesignWe 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.ResultsMicroRNA 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.ConclusionTaken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer initiation. However, epidemiologic studies on the specific role of other bacteria in the development of gastric cancer 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 = 0.004–0.01) while Lactobacillus gasseri, Streptococcus mutans, S. parasanguinis, and S. sanguinis were under-represented (ORs = 0.66–0.76, P = 0.006–0.042) in cases. Species J. ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = 0.005 and 0.035, respectively), while S. mutans, S. parasanguinis, and S. sanguinis were under-represented (ORs = 0.61–0.75, P = 0.024–0.046), 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.

Although the intestinal microbiome has been increasingly implicated in autoimmune diseases, much is unknown about its roles in Multiple Sclerosis (MS). Our aim was to compare the microbiome between treatment-naïve MS subjects early in their disease course and controls, and between Caucasian (CA), Hispanic (HA), and African American (AA) MS subjects. From fecal samples, we performed 16S rRNA V4 sequencing and analysis from 45 MS subjects (15 CA, 16 HA, 14 AA) and 44 matched healthy controls, and whole metagenomic shotgun sequencing from 24 MS subjects (all newly diagnosed, treatment-naïve, and steroid-free) and 24 controls. In all three ethnic groups, there was an increased relative abundance of the same single genus, Clostridium, compared to ethnicity-matched controls. Analysis of microbiota networks showed significant changes in the network characteristics between combined MS cohorts and controls, suggesting global differences not restricted to individual taxa. Metagenomic analysis revealed significant enrichment of individual species within Clostridia as well as particular functional pathways in the MS subjects. The increased relative abundance of Clostridia in all three early MS cohorts compared to controls provides candidate taxa for further study as biomarkers or as etiologic agents in MS.

Background: The incidence of kidney stones is increasing in the US population. Oxalate, a major factor for stone formation, is degraded by gut bacteria reducing its intestinal absorption. Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. In the current study, we used a clinical trial of the eradication of Helicobacter pylori to assess the effects of an antibiotic course on O. formigenes colonization, urine electrolytes, and the composition of the intestinal microbiome. Methods: Of 69 healthy adult subjects recruited, 19 received antibiotics for H. pylori eradication, while 46 were followed as controls. Serial fecal samples were examined for O. formigenes presence and microbiota characteristics. Urine, collected serially fasting and following a standard meal, was tested for oxalate and electrolyte concentrations. Results: O. formigenes prevalence was 50%. Colonization was significantly and persistently suppressed in antibiotic-exposed subjects but remained stable in controls. Urinary pH increased after antibiotics, but urinary oxalate did not differ between the control and treatment groups. The O. formigenes-positive samples had higher alpha-diversity and significantly differed in Beta-diversity from the O. formigenes-negative samples. Specific taxa varied in abundance in relation to urinary oxalate levels.Conclusions: These studies identified significant antibiotic effects on O. formigenes colonization and urinary electrolytes and showed that overall microbiome structure differed in subjects according to O. formigenes presence. Identifying a consortium of bacterial taxa associated with urinary oxalate may provide clues for the primary prevention of kidney stones in healthy adults.

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.

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., 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 (β-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.

Important advances have been made since the last Mexican consensus on the diagnosis and treatment of Helicobacter pylori (H. pylori) infection was published in 2007. Therefore, the Asociacion Mexicana de Gastroenterologia summoned 20 experts to produce "The Fourth Mexican Consensus on Helicobacter pylori". From February to June 2017, 4 working groups were organized, a literature review was performed, and 3 voting rounds were carried out, resulting in the formulation of 32 statements for discussion and consensus. From the ensuing recommendations, it was striking that Mexico is a country with an intermediate-to-low risk for gastric cancer, despite having a high prevalence of H. pylori infection. It was also corroborated that peptic ulcer disease, premalignant lesions, and histories of gastric cancer and mucosa-associated lymphoid tissue lymphoma should be considered clear indications for eradication. The relation of H. pylori to dyspeptic symptoms continues to be controversial. Eradication triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor should no longer be considered first-line treatment, with the following 2 options proposed to take its place: quadruple therapy with bismuth (proton pump inhibitor, bismuth subcitrate, tetracycline, and metronidazole) and quadruple therapy without bismuth (proton pump inhibitor, amoxicillin, clarithromycin, and metronidazole). The need for antimicrobial sensitivity testing when 2 eradication treatments have failed was also established. Finally, the promotion of educational campaigns on the diagnosis and treatment of H. pylori for both primary care physicians and the general population were proposed.

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.

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.

Helicobacter pylori colonizes the human stomach of approximately 50% of the world's population, and increases the risk of several gastric diseases. The goal of this study is to compare the gastric microbiota in pediatric patients with and without H. pylori colonization.We studied 51 children who underwent gastric endoscopy because of dyspeptic symptoms (18 H. pylori positive and 33 negative). Gastric biopsies were obtained for rapid urease test, culture, histology and DNA extraction. H. pylori was quantified by quantitative polymerase chain reaction and the gastric microbiome studied by V4-16S ribosomal RNA gene high-throughput sequencing.Bacterial richness and diversity of H. pylori-positive specimens were lower than those of negative, and both groups were clearly separated according to beta diversity. Taxonomic analysis confirmed that H. pylori-positive subjects had a higher relative abundance of Helicobacter genus (66.3%) than H. pylori-negative subjects (0.45%). Four phyla (proteobacteria, bacteroidetes, firmicutes and actinobacteria) accounted for97% of all reads in both groups. Within proteobacteria, gamma- and betaproteobacteria were the most abundant for H. pylori-negative patients, whereas epsilonproteobacteria was for H. pylori positive. H. pylori-positive patients were associated with low body mass index. In the group of underweight patients (body mass index,18.5), there were 46.1% of H. pylori-positive patients compared with 24% in the nonunderweight group (P = 0.049). Patients with active superficial gastritis in H. pylori-positive patients had the lowest alpha diversity (P = 0.035).We characterized the gastric microbiota for the first time in children with and without H. pylori and observed that when H. pylori is present, it tends to dominate the microbial community. In the H. pylori-negative patients, there was more relative abundance of gammaproteobacteria, betaproteobacteria, bacteroidia and clostridia classes and a higher bacterial richness and diversity.

Helicobacter pylori remains one of the most common bacterial infections worldwide. Clarithromycin resistance is the most important cause of H. pylori eradication failures. Effective antibiotic therapies in H. pylori infection must be rapidly adapted to local resistance patterns. We investigated the prevalence of clarithromycin resistance due to mutations in positions 2142 and 2143 of 23SrRNA gene of H. pylori by fluorescence in situ hybridisation (FISH), and compared with culture and antimicrobial susceptibility testing in 234 adult patients with dyspepsia who were enrolled. Antrum and corpus biopsy specimens were obtained for rapid urease test, histopathology and culture. Epsilometer test was used to assess clarithromycin susceptibility. H. pylori presence and clarithromycin susceptibility were determined by FISH in paraffin-embedded biopsy specimens. We found that 164 (70.1%) patients were positive for H. pylori based on clinical criteria, 114 (69.5% CI 62.5-76.6%) were culture positive, and 137 (83.5% CI 77.8-89.2%) were FISH positive. Thus the sensitivity of FISH was significantly superior to that of culture. However specificity was not significantly different (91.4 versus 100.0%, respectively). The resistance rate to clarithromycin for both antrum and corpus was detected in H. pylori-positive patients; 20.2% by FISH and 28.0% by E-test.The concordance between E-test and FISH was only 89.5% due to the presence of point mutations different from A2143G, A2142G or A2142C. We conclude that FISH is significantly more sensitive than culture and the E-test for the detection of H. pylori and for rapid determinination of claritromycin susceptibility. The superior hybridisation efficiency of FISH is becoming an emerging molecular tool as a reliable, rapid and sensitive method for the detection and visualisation of H. pylori, especially when the management of H. pylori eradication therapy is necessary. This is particularly important for the treatment of patients with H. pylori eradication failure.

This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal-oral transmission and the use of well-water and other unpurified water. Finally, the long-term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection.

textabstractBackground Helicobacter pylori prevalence in Western countries has been declining simultaneously with increases in childhood asthma and allergic diseases; prior studies have linked these phenomena. Aims To examine the association between H. pylori colonisation in children and risk of asthma and related conditions at school age. We secondly examined additional effects of maternal H. pylori status by pairing with children's status. Methods This study was embedded in a multi-ethnic population-based cohort in Rotterdam, The Netherlands. We measured anti-H. pylori and anti-CagA antibodies in serum of children obtained at age 6 years, and of their mothers obtained during midpregnancy. Asthma or related conditions were reported for children at age 6 years. We used multivariate logistic regression analyses among 3797 subjects. Results In children, the H. pylori positivity rate was 8.7%, and 29.2% of these were CagA-positive. A child's colonisation with a CagA-negative-H. pylori strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60), but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. When taking into account maternal H. pylori status, only H. pylori-positive children with an H. pylori-negative mother had increased risk of asthma (2.42; 1.11-5.27), accounting for 3.4% of the asthma risk. Conclusions Colonisation of a European child with a CagA-negative-H. pylori strain at age 6 was associated with an increased prevalence of asthma, but there was no association for non-European children. The underlying mechanisms for the observed risk differences require further research.

Helicobacter pylori is considered the main etiological agent of gastritis, ulcers, and gastric carcinoma. It colonizes human gastric mucosa quite efficiently. Fifty % of the world population is actually infected. Since H. pylori discovery in 1982, it is well known the sensitivity of several H. pylori strains to a number of antibiotics when these are assayed in vitro. However, eradication therapies with a single antibacterial agent have failed. Recently, triple, quadruple, sequential, concomitant and hybrid therapies which include antibiotics and a proton pump inhibitor show improved eradication rate and low side effects. However, new problems have emerged. Antimicrobial resistance to the common antibiotics used has become a problem in both developed and developing countries. In particular, H. pylori clarithromycin- and metronidazole-resistant strains are a major problem in countries where H. pylori is highly prevalent. Thus, the widespread use of antibiotics is not economically feasible and might increase difficulties in the treatment of H. pylori. At present, there are no vaccines available in the market. As an alternative, effective non-antibiotic compounds should be highly desirable since their use may be safer and suitable to eradicate H. pylori. The first step in this direction has been to study the effect of medicinal herbs and natural products, such as green tea, ginseng, garlic, propolis, and probiotics, then identify their active components such as polyphenols, antioxidants, purify them, and finally test them using in vitro and in vivo H. pylori growth assays. Some of them have been quite effective. The topics related to alternative therapies for H. pylori infections and current status of their use will be discussed in the present review.

Gut microbiota are affected by antibiotics and may modulate host energy metabolism. Male and female C57BL/6J mice (n=5∼11/group) were exposed to low-dose penicillin (LDP) via maternal drinking water from birth to 4 weeks (w) of age, and chronic changes in energy balance were examined using metabolic cages. Through 8w of age (Chow), LDP and Control mice had comparable fat mass, but male and female LDP mice showed significantly increased O2 consumption rates without changes in food intake and activity (Figure). At 9w of age, mice were given a high-fat diet (HFD; 45% fat by calories), and they began gaining adiposity with female LDP mice showing ∼40% lower fat mass than Controls. After 8w of HFD, male LDP group showed significantly elevated O2 consumption rates compared to Controls. Male LDP mice also showed marked reductions in food intake and activity, but these effects were no longer observed after 12w of HFD. In contrast, female LDP group had reduced O2 consumption rates compared to Controls after 4 and 8w of HFD without changes in food intake and activity. In conclusion, these results indicate that early life exposure to penicillin modulates energy balance in young and mature mice, suggesting an important role of altered populations of gut microbiota in diet-induced obesity. Our findings also identify important gender-selective effects of early life antibiotic exposure on energy balance in mature mice. Disclosure H. Noh: None. S. Suk: None. R.H. Friedline: None. K. Inashima: None. D.A. Tran: None. A.M. Kim: None. S. Kim: None. S. Jeong: None. C. Uong: None. B.A. Ozkan: None. V. Kasina: None. K.P. Knowles: None. G. Perez-Perez: None. K. Lee: None. M.J. Blaser: None. J.K. Kim: None.

Patients commonly present to emergency departments with skin abscesses, and the incidence appears to be increasing [1]. While many factors contribute to the development of infection with community-acquired methicillin-resistant Staphylococcus aureus (MRSA), such as participation in contact sports, incarceration, injection drug use, and, for men, having sex with men, the strongest risk factors are having a household contact with MRSA infection and having a history of recent antibiotic use [2]. Systemic antibiotics, as well as topical agents, including antibacterial soaps and cleansers, can suppress or eliminate normal skin bacteria [3]; antibiotic use may alter the indigenous microbiota for several weeks or longer [3]. Among patients presenting to the emergency department with skin abscesses due to MRSA, antibiotic use within the prior month has been associated with an increased risk [2]. The composition of the normal cutaneous microbiota is complex; analysis of skin bacteria indicates multiple species, with particular compositions depending on body site [4–10]. The skin microbiome can be divided into dry, moist, and sebaceous sites [6]. As at other sites, the residential bacteria may play a role in defenses against pathogenic bacteria [3]. Our hypothesis is that the perturbation of the normal protective bacterial population predisposes individuals to contracting MRSA and developing skin abscesses. We tested this hypothesis by comparing the microbiota in patients with skin abscesses to the microbiota in control patients without abscesses. We hypothesized that, compared with controls, individuals who developed skin abscesses would have an abnormal microbiota, either at sites adjacent to the abscess, indicating a local diathesis, or more distantly, consistent with a more generally perturbed microbiota.

Objective Helicobacter pylori colonisation rates in childhood have declined in Western populations, but it is unknown whether this trend is similar in children of non-Western ethnic backgrounds, born in a Western country. We aimed to identify H. pylori status in children, and determine mother-to-child transmission and risk factors for colonisation. Design Antibodies against H. pylori and cytotoxin-associated gene A (CagA) were measured in children participating in a population-based prospective cohort study in Rotterdam, the Netherlands. Information on demographics and characteristics was collected using questionnaires. Results We analysed the serum of 4467 children (mean age 6.2 years±0.4 SD) and compared the results with the H. pylori status of their mothers (available for 3185 children). Overall, 438 (10%) children were H. pylori- positive, of whom 142 (32%) were CagA-positive. Independent risk factors for colonisation were: maternal H. pylori positivity (OR 2.12; 95% CI 1.62 to 2.77), non-Dutch ethnicity (OR 2.05; 95% CI 1.54 to 2.73), female gender (OR 1.47; 95% CI 1.20 to 1.80) and lower maternal education level (OR 1.38; 95% CI 1.06 to 1.79). Comparing mothers and children, we found an intergenerational decrease of 76% and 77% for Hp + CagA − and Hp + CagA + -strains, respectively, consistent across all nine ethnic groups studied. Male gender, higher maternal educational level and no older siblings, were independently associated with absence of H. pylori . Conclusions Although the highest H. pylori and CagA prevalence was found in children of non-Dutch ethnicities, the decreased colonisation rates were uniform across all ethnic groups, implying the importance of environmental factors in H. pylori transmission in modern cities, independent of ethnicity.

The isolation of Helicobacter pylori from the human stomach produced significant changes in how gastroenterologists, immunologists, epidemiologists, pathologists and microbiologists have approached gastro-duodenal diseases in the last half of the XX century. However, research of this organism has progressed greatly in the first decade of this century, evidence suggest that H. pylori is associated with disease only in humans older than 40 years, while, the lack of H. pylori colonization is associated with the emergence of new diseases, particularly in younger individuals. These differing effects of H. pylori colonization have created two contrasting concepts: the 'bad' and the 'good' Helicobacter. Following from renewed interest in the normal human microbiome, we need to reconsider our definitions and perhaps recognize that H. pylori might be a normal member of the human gastric microbiome in ancient humans that gradually, as results of the improvement in our environment, is disappearing.

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.

Microorganisms in humans form complex communities with important functions and differences in each part of the body. The stomach was considered to be a sterile organ until the discovery of Helicobacter pylori, but nowadays, it is possible to demonstrate that other microorganisms beyond H. pylori can colonize the gastric mucosa and that the diverse microbiota ecosystem of the stomach is different from the mouth and the esophagus, and also from the small intestine and large intestine. H. pylori seems to be the most important member of the gastric microbiota with the highest relative abundance when present, but when it is absent, the stomach has a diverse microbiota. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria are the most abundant phyla in both H. pylori-positive and H. pylori-negative patients. The gastric commensal flora may play some role in the H. pylori-associated carcinogenicity, and differences in the gastric microbiota composition of patients with gastric cancer, intestinal metaplasia, and chronic gastritis are described. The gastric microbiota changed gradually from non-atrophic gastritis to intestinal metaplasia, and to gastric cancer (type intestinal).

The persistence of Helicobacter pylori infection plays a fundamental role in the development of H. pylori-associated complications. Since the majority of infected persons acquire the bacteria during early childhood, an examination of the immunobiology of H. pylori infection in children compared with that of adults may help identify host factors that contribute to persistent infection. Therefore, we begin our review of the role of persistence in H. pylori disease with an assessment of the clinical features of H. pylori infection in children. We next review the bacterial factors that promote colonization and evasion of host defense mechanisms. We then focus our attention on the early host immunological factors that promote persistence of the infection and its complications in humans and mouse models. We also highlight topics in which further research is needed. An examination of how immunological factors cause divergent manifestations of H. pylori infection in children compared with adults may provide new insight for therapeutic modification or prevention of persistent H. pylori infection and its complications.

Background In developing countries, more than 50% of children have serological evidence of Helicobacter pylori infection. However, serological tests for H. pylori did not differentiate between active and past infection. The objectives of this study were to estimate the frequency of active and past H. pylori infection utilizing functional urea breath test (UBT) and serological tests and evaluate factors associated with the infection. Methods A total of 675 school children, 6–13 years of age, participated. UBT was performed to detect active H. pylori infection. Blood samples were obtained to determine iron status and Immunoglobulin G (IgG) responses to the H. pylori whole-cell and to Cag A antigens by antigen-specific enzyme-linked immunosorbent assays. Weight, height, and sociodemographic characteristics were recorded. Results A total of 37.9% (95% Confidence Intervals (CI): 34.2–41.6) of school children had active or past H. pylori infection; of them, 73.8% (CI95% 68.4−79.2) were carrying CagA-positive strain, 26.5% (CI95% 23.2–29.8) had active infection, and 11.4% (95%CI: 9.0–13.8) had evidence of past H. pylori infection. School children with iron deficiency and low height for age had higher risk of H. pylori infection: [OR to active or past infection was 2.30 (CI 95% 1.01–5.23) and to active infection it was 2.64 (CI 95% 1.09–6.44)] compared to school children with normal iron status and height for age or with normal iron status but low height for age or with iron deficiency and normal height for age. Conclusions The estimated prevalence of infection depends of the test utilized. Frequency of H. pylori infection and carrying CagA-positive strains was high in this population. Malnutrition was associated with active H. pylori infection.

textabstractBackground and Aim: At the same time that Helicobacter pylori prevalence is declining in Western countries, immigrants from developing countries with high H.pylori prevalence have settled in Western urban areas. Actual epidemiological data on H.pylori in a migrant community may help in realizing a more selective approach to assess H.pylori-related diseases. We aimed to define H.pylori prevalence as well as risk groups for H.pylori in a cohort of young women living in a multi-ethnic European city. Methods: We measured Immunoglobulin G (IgG) anti-H.pylori and CagA-antibodies in serum of pregnant women included in a population-based prospective cohort study, the Generation R study. Information on demographics and socioeconomic status was collected by questionnaires. Chi-square and logistic regression were used. Results: In total, 3146 (46%) of the 6837 tested women (mean age 29.7±5.3) were H.pylori-positive and 1110 (35%) of them were CagA-positive. The H.pylori prevalence in Dutch women was 24%, which was significantly lower than in non-Dutch women (64%; P

Diabetic foot ulcers are an important clinical problem, leading to infection and loss of limb [1]. Diabetic foot ulcers occur in 15% of patients with diabetes mellitus, with a yearly incidence of 1%–2% [2]. Diabetic patients have higher rates of hospitalization for skin and soft-tissue infections than patients without diabetes [3]. Most studies based on culture have shown that the infections are polymicrobial, with Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus species (especially Staphylococcus aureus) being the most prevalent isolates [4, 5]. Traditionally, the pathogenesis of these wounds has been attributed to factors such as neuropathy (a functional disturbance in peripheral nerves), repeated trauma, and peripheral vascular disease [6]. More recently, the roles of wound bioburden and functionally equivalent pathogroups in diabetic wound infections have been studied [7, 8]. Data on the composition of the cutaneous microbiota of diabetic patients is lacking. One of the few studies to address this question was performed in 1975, in the era prior to high-throughput 16S rRNA sequencing (HTS) technology [9]. No differences in culturable organisms between control and diabetic skin were found, but the study also did not examine the feet. Staphylococcus species account for 70% of the normal skin microbiome on the plantar aspect of the foot [10, 11]; most are coagulase-negative Staphylococcus species that are of low virulence and may compete with the more virulent S. aureus [12]. In contrast, on intact skin on the contralateral (opposite) limb of patients with unilateral diabetic ulcers, only 7% of the microbiota was represented by Staphylococcus species [13], suggesting a loss of these protective organisms or their replacement by other species. HTS identification based on deep sequencing is currently being used to better characterize the human microbiome [14, 15]. We sought to use HTS along with quantitative polymerase chain reaction (qPCR) to better characterize the microbiota of the diabetic foot. The aim of this study was to determine whether there are differences in surface microbiota of the arm and foot between nondiabetic men and diabetic men without a history of diabetic foot ulcer.

Background More than 50 years after the discovery of antibiotics, bacterial infections have decreased substantially; however, antibiotics also may have negative effects such as increasing susceptibility to pathogens. An intact microbiome is an important line of defense against pathogens. We sought to determine the effect of orally administered antibiotics both on susceptibility to pathogens and on impact to the microbiome. We studied Campylobacter jejuni, one of the most common causes of human diarrhea, and Acinetobacter baumannii, which causes wound infections. We examined the effects of antibiotic treatment on the susceptibility of mice to those pathogens as well as their influence on the mouse gut microbiome. Results In C57/BL6 mice models, we explored the effects of pathogen challenge, and antibiotic treatment on the intestinal microbiota. Mice were treated with either ciprofloxacin, penicillin, or water (control) for a 5-day period followed by a 5-day washout period prior to oral challenge with C. jejuni or A. baumannii to assess antibiotic effects on colonization susceptibility. Mice were successfully colonized with C. jejuni more than 118 days, but only transiently with A. baumannii. These challenges did not lead to any major effects on the composition of the gut microbiota. Although antibiotic pre-treatment did not modify pathogen colonization, it affected richness and community structure of the gut microbiome. However, the antibiotic dysbiosis was significantly reduced by pathogen challenge. Conclusions We conclude that despite gut microbiota disturbance, susceptibility to gut colonization by these pathogens was unchanged. The major gut microbiome disturbance produced by antibiotic treatment may be reduced by colonization with specific microbial taxa. Electronic supplementary material The online version of this article (doi:10.1186/s13099-016-0143-z) contains supplementary material, which is available to authorized users.

Early childhood is a critical stage for the foundation and development of both the microbiome and host. Early-life antibiotic exposures, cesarean section, and formula feeding could disrupt microbiome establishment and adversely affect health later in life. We profiled microbial development during the first two years of life in a cohort of 43 US infants, and identify multiple disturbances associated with antibiotic exposures, cesarean section, and diet. Antibiotics delayed microbiome development and suppressed Clostridiales, including Lachnospiraceae. Cesarean section led to depleted Bacteroidetes populations, altering establishment of maternal bacteria. Formula-feeding was associated with age-dependent diversity deviations. These findings illustrate the complexity of early-life microbiome development, and microbiota disturbances with antibiotic use, cesarean section, and formula feeding that may contribute to obesity, asthma, and other disorders.

The epidemiology of Helicobacter pylori (H. pylori) infection is related to human poverty with marked differences between developing and developed countries. Socioeconomic factors and living standards are the main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. The aim of this study was to assess the risk and sero-prevalence of H. pylori colonization among Orang Asli in Peninsula Malaysia. This cross-sectional study was conducted on Orang Asli subjects in seven isolated settlements spanning across all three major tribes (Negrito, Proto Malay and Senoi) in Malaysia. Socio-demographic characteristics of the subjects were obtained through interview. Subjects were tested for H. pylori colonization based on CagA and whole cell (WC) antigen serological assays. A total of 275 subjects participated in this study. Among these subjects, 115 (44.7%) were H. pylori sero-positive with highest sero-prevalence among Negrito (65.7%). Among subjects who were H. pylori sero-positive, CagA sero positivity was also significantly higher among Negrito. The highest proportion of respondents reported to be H. pylori sero-positive was from age group 30 years old and below (57.9%), males (56.2%), Negrito (48.6%) and live in bamboo house (92.3%). The highest proportion of respondents reported to be CagA sero-positive was from age group 30 years old and below (41.4%), males (35.6%) and Negrito (48.6%). The results of this study demonstrate that H. pylori colonization can be related to age, gender, tribes and house materials and CagA sero-positive stain closely associated with age, gender and tribes.

BackgroundAccumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome.MethodsAs part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18-30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline.ResultsWe compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000-170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders.ConclusionsOur preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.

UNLABELLED:We studied skin microbiota present in three skin sites (forearm, axilla, scalp) in men from six ethnic groups living in New York City. METHODS:Samples were obtained at baseline and after four days following use of neutral soap and stopping regular hygiene products, including shampoos and deodorants. DNA was extracted using the MoBio Power Lyzer kit and 16S rRNA gene sequences determined on the IIlumina MiSeq platform, using QIIME for analysis. RESULTS:Our analysis confirmed skin swabbing as a useful method for sampling different areas of the skin because DNA concentrations and number of sequences obtained across subject libraries were similar. We confirmed that skin location was the main factor determining the composition of bacterial communities. Alpha diversity, expressed as number of species observed, was greater in arm than on scalp or axilla in all studied groups. We observed an unexpected increase in α-diversity on arm, with similar tendency on scalp, in the South Asian group after subjects stopped using their regular shampoos and deodorants. Significant differences at phylum and genus levels were observed between subjects of the different ethnic origins at all skin sites. CONCLUSIONS:We conclude that ethnicity and particular soap and shampoo practices are secondary factors compared to the ecological zone of the human body in determining cutaneous microbiota composition.

textabstractBackground: The prevalence of Helicobacter pylori in Western populations has steadily decreased. This has been suggested as one of the factors involved in the recent increase of asthma and allergy. Some studies have reported a negative association between H. pylori and asthma and allergy, but data are inconsistent and there are a few studies in children. Aim: We investigated whether the prevalence of H. pylori was associated with asthma symptoms, allergic rhinitis, and atopic dermatitis in childhood. Methods: We determined IgG anti-H. pylori and CagA antibodies in serum of Dutch children, who took part in the PIAMA birth cohort study. Serum was collected from 545 children, aged 7-9years (Dutch ethnicity 91.5%). Symptoms of asthma and atopy were assessed by yearly questionnaires. Chi-square tests and logistic regression were used. Results: We found 9%H. pylori and 0.9% CagA seropositivity. Twelve (5.9%) children with reported wheezing ever were H. pylori positive, compared to 37 (10.9%) of the non-wheezers (p=.05). No significant differences in H. pylori prevalence were found between children with or without allergic rhinitis (8.5% vs 9.5%), atopic dermatitis (8.7% vs 9.2%), and physician-diagnosed asthma (7.1% vs 9.4%). Multivariate analysis showed no significant associations between H. pylori seropositivity and wheezing (OR 0.52; 95% CI 0.25-1.06), allergic rhinitis (OR 0.96; 95% CI 0.51-1.81), atopic dermatitis (OR 1.05; 95% CI 0.56-1.98) or physician-diagnosed asthma (OR 0.87; 95% CI 0.37-2.08). Conclusion: We found a borderline significantly lower H. pylori seropositivity in children with wheezing compared to non-wheezers, but no association between H. pylori serum-antibody status and allergic rhinitis, atopic dermatitis, or asthma.

Helicobacter pylori epidemiology in sub-Saharan Africa, particularly among children, has been little investigated. A secondary endpoint of our study was to examine for associations between the seroprevalence of H. pylori and the incidence of malaria. We explored H. pylori prevalence by measuring serum IgG antibodies to H. pylori whole cell and cytotoxin-associated gene A (CagA) antigens by ELISA in a longitudinal cohort of 200 Ugandan children, aged 1-10 years at enrollment, in whom malaria incidence was followed over 572 person-years. First-sample seroprevalence for H. pylori -specific IgG (63%) and for the H. pylori protein CagA (78.5%) were both high, and they were positively associated with advancing age (per each 1-year age increase, OR (95% CI): 1.60 (1.39-1.85), P

Background: Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. Materials and Methods: From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and b-(1,3)galT loci in 113 H. pylori strains. Results: Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le a and Le b ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). Conclusion: These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression.

textabstractBackground: The prevalence of Helicobacter pylori has declined over recent decades in developed countries. The increasing prevalence with age is largely because of a birth cohort effect. We previously observed a decline in H. pylori prevalence in 6- to 8-year-old Dutch children from 19% in 1978 to 9% in 1993. Knowledge about birth-cohort-related H. pylori prevalence is relevant as a predictor for the future incidence of H. pylori-associated conditions. Aim: The aim of this study was to investigate whether the birth cohort effect of H. pylori observed between 1978 and 1993 continued in subsequent years. Methods: Anti-H. pylori IgG antibodies and anti-CagA IgG antibodies were determined in serum samples obtained in 2005/2006 from 545 Dutch children aged 7-9years who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort. The H. pylori and CagA antibodies were determined by enzyme-linked immunosorbent assays that have been extensively validated in children, with a 94% sensitivity for H. pylori colonization and a 92.5% sensitivity for colonization with a cagA-positive strain. Results: Of the 545 children (M/F 300/245), most (91.5%) were of Dutch descent. The H. pylori positivity rate was 9% (95% CI 6.6-11.4%). The prevalence of CagA antibodies was 0.9% (95% CI 0.1-1.6%). No significant differences were demonstrated in H. pylori and cagA prevalence in relation to gender or ethnicity. Conclusion: The prevalence of H. pylori in childhood has remained stable in the Netherlands from 1993 to 2005, suggesting a stabilization of the previously decreasing trend in subsequent birth cohorts. This finding may reflect stabilization in determinants such as family size, housing, and hygienic conditions (or offset by day care). If confirmed in other populations in developed countries, it implies that colonization with H. pylori will remain common in the coming decades. Remarkably however, the rate of colonization with cagA+H. pylori strains has become very low, consistent with prior observations that cagA+strains are disappearing in Western countries.

The aims of this study were to assess the prevalence of Helicobacter pylori infection and to introduce a new algorithm to improve its diagnosis in Cuban symptomatic children. One hundred and thirty-three consecutive children with upper gastrointestinal symptoms were studied. Patients were endoscoped and antral biopsies were obtained for rapid urease test (RUT), culture and histology. Prevalence of H. pylori infection was 30.8%. No statistical differences were found concerning demographic, socio-economic factors or chief clinical complaints, between H. pylori-positive and negative children, except for haematemesis, which was significantly higher in infected children (p = 0.003). Histologically, there was statistical association between moderate chronic gastritis in infected children (p = 0.04). Culture and RUT had the highest specificity and sensitivity, respectively. The prevalence of H. pylori infection in Cuban symptomatic children is similar to the one observed in developed countries. Culture and RUT is a useful combination to diagnose H. pylori infection in paediatric patients.

The host immune response directed against Helicobacter pylori is ineffective in eliminating the organism and strains harboring the cag pathogenicity island augment disease risk. Because eosinophils are a prominent component of H. pylori-induced gastritis, we investigated microbial and host mechanisms through which H. pylori regulates eosinophil migration. Our results indicate that H. pylori increases production of the chemokines CCL2, CCL5, and granulocyte-macrophage colony-stimulating factor by gastric epithelial cells and that these molecules induce eosinophil migration. These events are mediated by the cag pathogenicity island and by mitogen-activated protein kinases, suggesting that eosinophil migration orchestrated by H. pylori is regulated by a virulence-related locus.

Clarithromycin is one of the antibiotics used for the treatment of Helicobacter pylori infections, and clarithromycin resistance is the most important factor when it comes to predicting eradication failure. The present study analyzed H. pylori isolates for the presence of 23S rRNA gene mutations and determined the risk factors associated with resistance among H. pylori isolates collected in Madrid, Spain, in 2008. We studied 118 H. pylori strains isolated from the same number of patients. A total of 76.3% of the patients were born in Spain, 52.7% were children, 20.3% had previously been treated, and 66.1% were female. Clarithromycin resistance was determined by Etest. H. pylori strains were considered resistant if the MIC was ≥1 mg/liter. DNA extraction was carried out by use of the NucliSens easyMAG platform with NucliSens magnetic extraction reagents (bioMérieux). The DNA sequences of the 23S rRNA genes of clarithromycin-resistant and -sensitive strains were determined to identify specific point mutations. The vacA genotype and cagA status were determined by PCR. We found that 42 (35.6%) strains were resistant to clarithromycin by Etest. Etest results were confirmed by detection of the presence of point mutations in 34 (88.1%) of these strains. Eight H. pylori strains were resistant to clarithromycin by Etest but did not have a point mutation in the 23S rRNA gene. Mutation at A2143G was found in 85.3% of the strains, mutation at A2142G in 8.8%, and mutation at T2182C in 5.9%. Dual mutations were found in 8.8% of the strains. H. pylori clarithromycin-resistant strains were strongly associated with pediatric patients, with patients born in Spain, and with patients who had previously been treated ( P ≤ 0.02). In addition, H. pylori strains resistant to clarithromycin more frequently presented the vacA s2 / m2 genotype and were more likely to be cagA negative than susceptible strains (39.1% and 11.2%, respectively; P value < 0.001). We concluded that, in the present study, H. pylori clarithromycin-resistant strains are more frequently found in children, in patients mostly born in Spain, and in individuals who were previously treated for H. pylori infection and that these individuals are more likely colonized with a less virulent H. pylori strain.

The purpose of this study was to assess the role of Helicobacter pylori and several genetic polymorphisms in relation to inflammatory bowel disease (IBD). We studied 44 unrelated patients with IBD and 75 subjects with no history of IBD as controls. Using pyrosequencing technology, we identified gene polymorphisms in IL-10, TNF-A, ILB-31, and TLR4. H. pylori status was determined by serology. Individuals homozygous for IL10-592 A or IL10-1082 A genotypes show significantly lower occurrence of IBD (P=0.03 and P

Background: Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved. Methods: We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Results: Gastric atrophy (PGI/PGII Conclusions: These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect. Impact: Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC. Cancer Epidemiol Biomarkers Prev; 19(8); 1966–75. ©2010 AACR.

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.

Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach.We sought to determine whether the presence of Helicobacter pylori affects gastric and systemic levels of leptin and ghrelin.We consecutively enrolled 256 patients referred for upper endoscopy at a Veterans Affairs outpatient endoscopy center.We obtained fasting serum, fundic and antral biopsies, and gastric juice. Based on histological, biochemical, and serological assays, patients were categorized as H. pylori+ or H. pylori-. Leptin and total ghrelin levels in serum, gastric biopsies, and gastric juice were determined by specific ELISAs.Of the 256 subjects, 120 were H. pylori+ and 96 were H. pylori-; 40 patients of indeterminate status were excluded. Serum and fundic leptin levels correlated with body mass index in the H. pylori+ (r = 0.35; P0.0001 and r = 0.35; P0.0001, respectively) and H. pylori- (r = 0.65; P0.0001 and r = 0.41; P0.0001, respectively) groups, but H. pylori+ subjects had significantly lower serum leptin levels [median 2.2 ng/ml (interquartile range 0.9-4.6) vs. 4.0 ng/ml (1.7-7.2); P = 0.0003]. Serum ghrelin levels were similar in the H. pylori+ and H. pylori- groups [median 1651 pg/ml (interquartile range 845-2247) vs. 1629 pg/ml (992-2886); P = 0.23]. H. pylori status did not significantly affect gastric biopsy leptin and ghrelin levels. Ghrelin levels in gastric juice varied over 4 log(10) (80-776,000 pg/ml) and correlated with gastric juice pH in the H. pylori+ group (r = 0.68; P0.0001).These findings provide evidence that H. pylori status affects leptin and ghrelin homeostasis, presumably via intragastric interactions.

The risk factors most strongly associated with gastric cancer are the gastric bacteria Helicobacter pylori and diet. Utilizing data from a case–control study among residents in Hawaii, we examined the association of diet, presence of H. pylori, and non-cardia gastric cancer risk. Serum taken at diagnosis for cases (n = 212) and at interview for controls (n = 336) was assayed for IgG antibodies to H. pylori group antigens and to a recombinant fragment of the cytotoxin-associated antigen A (CagA) protein, and subjects completed food frequency questionnaires. Risk measures were calculated using logistic regression. The likelihood ratio test was used to assess interactions. Inverse associations were found between gastric cancer risk and increasing intake of several micronutrients and vegetables among all individuals. For H. pylori/CagA-positive subjects, significant trends were present for total, green, and yellow vegetables, while a significant trend was present only for yellow vegetables among H. pylori/CagA-negative individuals. For intestinal gastric cancer, there was a suggestion that intake of vegetables, especially cruciferous vegetables, had a stronger protective effect for the H. pylori/CagA-positive group. Diet may play a greater role in the etiology of non-cardia gastric cancer among individuals with evidence of H. pylori infection than among those without.

Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet the effects of bacterial eradication on carcinogenesis remain unclear. Animal models provide important insights into factors that are involved in gastric carcinogenesis, and we previously utilized such a model to demonstrate that an in vivo-adapted H. pylori strain, 7.13, rapidly and reproducibly induces inflammation-mediated gastric carcinoma. In the current study, we used this bacterial strain as a prototype to define the role of targeted antimicrobial therapy in gastric carcinogenesis. Mongolian gerbils were infected with H. pylori for 4 or 8 weeks, treated with antimicrobial agents or vehicle, and then euthanized at 8 weeks after the completion of therapy. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals receiving antimicrobial therapy. Gastric dysplasia or cancer developed in >60% of the gerbils that remained persistently colonized with H. pylori, but in none of the animals treated with antibiotics following 4 weeks of infection. Infection with H. pylori for 8 weeks prior to therapy resulted in an attenuation, but not complete prevention, of pre-malignant and malignant lesions. Similarly, antibiotic therapy initiated at 4, but not 8, weeks after H. pylori challenge significantly reduced expression of the Th1 pro-inflammatory cytokine interferon-gamma within colonized gastric mucosa. These results indicate that treatment of H. pylori in this model decreases the incidence and severity of lesions with carcinogenic potential. The effectiveness of eradication is dependent upon the timing of intervention, providing insights into mechanisms that may regulate the development of malignancies arising within the context of inflammatory states.

The presence of Helicobacter pylori in pediatric population has been associated with recurrent abdominal pain (RAP) although this association is unclear. One of the major problems in studying the role of H. pylori in RAP is that methods used to detect the bacteria in children have poor sensitivity and specificity. The aims of the present study were to determine the prevalence of H. pylori in pediatric patients with RAP in northeastern Mexico and to assess the diagnostic utility of invasive tests and serology in this population. A total of 40 patients (mean age 7.9 years; range 2 - 16 years; F: M 0.81) who underwent an endoscopy procedure for RAP were studied. The presence of H. pylori was assessed using invasive diagnostic tests (culture rapid urease test polymerase chain reaction and histology) and one non-invasive test: determination of IgG antibodies. The prevalence of H. pylori in the present group and the diagnostic utility for each test were evaluated. The prevalence of H. pylori in the present pediatric group with RAP was 12.5 - 42.5% depending on the criteria of positivity used. The non-invasive methods (serology) had acceptable values in sensitivity and specificity in comparison with invasive tests. This is the first report on prevalence of H. pylori in pediatric patients with RAP from the northeastern region of Mexico. The prevalence of H. pylori was low compared with the adult population in the same geographic region. Serology had the best diagnostic utility. (authors)