Search

The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface cells with histopathologic changes like foveolar hyperplasia. Deeper, usually chronic, injury/inflammation, most frequently induced by the carcinogenic bacteria Helicobacter pylori, elicits glandular histopathologic alterations, initially manifesting as pyloric (also known as pseudopyloric) metaplasia. In this pyloric metaplasia, corpus glands become antrum (pylorus)-like with loss of acid-secreting parietal cells (atrophic gastritis), expansion of foveolar cells, and reprogramming of digestive enzyme-secreting chief cells into deep antral gland-like mucous cells. After acute parietal cell loss, chief cells can reprogram through an orderly stepwise progression (paligenosis) initiated by interleukin-13-secreting innate lymphoid cells (ILC2s). First, massive lysosomal activation helps mitigate reactive oxygen species and remove damaged organelles. Second, mucus and wound-healing proteins (eg, TFF2) and other transcriptional alterations are induced, at which point the reprogrammed chief cells are recognized as mucus-secreting spasmolytic polypeptide-expressing metaplasia cells. In chronic severe injury, glands with pyloric metaplasia can harbor both actively proliferating spasmolytic polypeptide-expressing metaplasia cells and eventually intestine-like cells. Gastric glands with such lineage confusion (mixed incomplete intestinal metaplasia and proliferative spasmolytic polypeptide-expressing metaplasia) may be at particular risk for progression to dysplasia and cancer. A pyloric-like pattern of metaplasia after injury also occurs in other gastrointestinal organs including esophagus, pancreas, and intestines, and the paligenosis program itself seems broadly conserved across tissues and species. Here we discuss aspects of metaplasia in stomach, incorporating data derived from animal models and work on human cells and tissues in correlation with diagnostic and clinical implications., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Autophagy is a cellular degradation mechanism, which is triggered by the bacterium Helicobacter pylori . A single nucleotide polymorphism (SNP) in the autophagy gene ATG16L1 (rs2241880, G-allele) has been shown to dysregulate autophagy and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate the role of this SNP in H. pylori -mediated gastric carcinogenesis and its molecular pathways. ATG16L1 rs2241880 was genotyped in subjects from different ethnic cohorts (Dutch and Australian) presenting with gastric (pre)malignant lesions of various severity. Expression of GRP78 (a marker for ER stress) was assessed in gastric tissues. The effect of ATG16L1 rs2241880 on H. pylori -mediated ER stress and pro-inflammatory cytokine induction was investigated in organoids and CRISPR/Cas9 modified cell lines. Development of gastric cancer was associated with the ATG16L1 rs2241880 G-allele. Intestinal metaplastic cells in gastric tissue of patients showed increased levels of ER-stress. In vitro models showed that H. pylori increases autophagy while reducing ER stress, which appeared partly mediated by the ATG16L1 rs2241880 genotype. H. pylori -induced IL-8 production was increased while TNF-α production was decreased, in cells homozygous for the G-allele. The ATG16L1 rs2241880 G-allele is associated with progression of gastric premalignant lesions and cancer. Modulation of H. pylori -induced ER stress pathways and pro-inflammatory mediators by ATG16L1 rs2441880 may underlie this increased risk.

Multiple theories have been proposed describing the pathogenic mechanisms of Helicobacter pylori ( H. pylori )-associated gastric motility disorders. We assessed ex vivo pyloric activity in H. pylori -infected rats, and tried to explore the associated ghrelin hormone alteration and pyloric fibrogenesis. In addition, miR-1 was assessed in pyloric tissue samples, being recently accused of having a role in smooth muscle dysfunction. Ninety adult male Wistar albino rats were assigned into nine groups: 1 ) control group, 2 ) sterile broth (vehicle group), 3 ) amoxicillin control, 4 ) omeperazole control, 5 ) clarithromycin control, 6 ) triple therapy control, 7 ) H. pylori - group, 8 ) H. pylori -clarithromycin group, and 9 ) H. pylori -triple therapy group. Urease enzyme activity was applied as an indicator of H. pylori infection. Ex vivo pyloric contractility was evaluated. Serum ghrelin was assessed, and histological tissue evaluation was performed. Besides, pyloric muscle miR-1 expression was measured. The immunological epithelial to mesenchymal transition (EMT) markers; transforming growth factor β (TGFβ), α-smooth muscle actin (α-SMA), and E-cadherin-3 were also evaluated. By H. pylori infection, a significant ( P < 0.001) reduced pyloric contractility index was recorded. The miR-1 expression was decreased ( P < 0.001) in the H. pylori- infected group, associated with reduced serum ghrelin, elevated TGFβ, and α-SMA levels and reduced E-cadherin levels. Decreased miR-1 and disturbed molecular pattern were improved by treatment. In conclusion, H. pylori infection was associated with reduced miR-1, epithelial to mesenchymal transition, and pyloric hypomotility. The miR-1 may be a target for further studies to assess its possible involvement in H. pylori -associated pyloric dysfunction, which might help in the management of human H. pylori manifestations and complications. NEW & NOTEWORTHY This work is investigating functional, histopathological, and molecular changes underlying Helicobacter pylori hypomotility and is correlating these with miR-1, whose disturbance is supposed to be involved in smooth muscle dysfunction and cell proliferation according to literature. Epithelial to mesenchymal transition and reduced ghrelin hormone may contribute to H. pylori infection-associated hypomotility. H. pylori infection was associated with reduced pyloric miR-1 expression. Targeting miR-1 could be valuable in the clinical management of pyloric hypofunction.

Background: During autophagy defense against invading microbes, certain lipid types are indispensable for generating specialized membrane-bound organelles. The lipid composition of autophagosomes remains obscure, as does the issue of how specific lipids and lipid-associated enzymes participate in autophagosome formation and maturation. Helicobacter pylori is auxotrophic for cholesterol and converts cholesterol to cholesteryl glucoside derivatives, including cholesteryl 6'-O-acyl-α-D-glucoside (CAG). We investigated how CAG and its biosynthetic acyltransferase assist H. pylori to escape host-cell autophagy., Methods: We applied a metabolite-tagging method to obtain fluorophore-containing cholesteryl glucosides that were utilized to understand their intracellular locations. H. pylori 26695 and a cholesteryl glucosyltransferase (CGT)-deletion mutant (ΔCGT) were used as the standard strain and the negative control that contains no cholesterol-derived metabolites, respectively. Bacterial internalization and several autophagy-related assays were conducted to unravel the possible mechanism that H. pylori develops to hijack the host-cell autophagy response. Subcellular fractions of H. pylori-infected AGS cells were obtained and measured for the acyltransferase activity., Results: The imaging studies of fluorophore-labeled cholesteryl glucosides pinpointed their intracellular localization in AGS cells. The result indicated that CAG enhances the internalization of H. pylori in AGS cells. Particularly, CAG, instead of CG and CPG, is able to augment the autophagy response induced by H. pylori. How CAG participates in the autophagy process is multifaceted. CAG was found to intervene in the degradation of autophagosomes and reduce lysosomal biogenesis, supporting the idea that intracellular H. pylori is harbored by autophago-lysosomes in favor of the bacterial survival. Furthermore, we performed the enzyme activity assay of subcellular fractions of H. pylori-infected AGS cells. The analysis showed that the acyltransferase is mainly distributed in autophago-lysosomal compartments., Conclusions: Our results support the idea that the acyltransferase is mainly distributed in the subcellular compartment consisting of autophagosomes, late endosomes, and lysosomes, in which the acidic environment is beneficial for the maximal acyltransferase activity. The resulting elevated level of CAG can facilitate bacterial internalization, interfere with the autophagy flux, and causes reduced lysosomal biogenesis., (© 2021. The Author(s).)

Chronic Helicobacter pylori infection is a critical risk factor for gastric cancer (GC). However, only 1-3 % of people with H. pylori develop GC. In gastric carcinogenesis, non-H. pylori bacteria in the stomach might interact with H. pylori. Bacterial dysbiosis in the stomach can strengthen gastric neoplasia development via generating tumor-promoting metabolites, DNA damaging, suppressing antitumor immunity, and activating oncogenic signaling pathways. Other bacterial species may generate short-chain fatty acids like butyrate that may inhibit carcinogenesis and inflammation in the human stomach. The present article aimed at providing a comprehensive overview of the effects of gut microbiota and H. pylori on the development of GC. Next, the potential mechanisms of intestinal microbiota were discussed in gastric carcinogenesis. We also disserted the complicated interactions between H. pylori, intestinal microbiota, and host in gastric carcinogenesis, thus helping us to design new strategies for preventing, diagnosing, and treating GC., (© 2021. The Author(s).)

Background: Helicobacter pylori ( Hp ) colonizes the human stomach and can induce gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Clinical observations suggest a role for the Hp virulence factor cytotoxin-associated gene A (CagA) in pathogenesis. The pathogenic activity of CagA is partly regulated by tyrosine phosphorylation of C-terminal Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in host cells. However, CagA differs considerably in EPIYA motifs, whose functions have been well characterized in epithelial cells. Since CagA is fragmented in immune cells, different CagA variants may exhibit undetected functions in B cells., Methods: B cells were infected with Hp isolates and isogenic mutants expressing different CagA EPIYA variants. CagA translocation and tyrosine phosphorylation were investigated by Western blotting. Apoptosis was analyzed by flow cytometry and metabolic activity was detected by an MTT assay., Results: Isogenic CagA EPIYA variants are equally well translocated into B cells, followed by tyrosine phosphorylation and cleavage. B cell apoptosis was induced in a CagA-independent manner. However, variants containing at least one EPIYA-C motif affected metabolic activity independently of phosphorylation or multiplication of EPIYA-C motifs., Conclusions: The diverse structure of CagA regulates B cell physiology, whereas B cell survival is independent of CagA.

Background: Helicobacter pylori (H pylori) infection is a common health problem, which is closely related to peptic ulcers, gastric cancer, and extragastric diseases. Drugs can successfully eradicate it. However, the recurrence of H pylori often occurs after initial eradication. To confirm the global incidence of H pylori reinfection and systematically evaluate its risk factors., Methods: We will search for the relevant literature through Chinese and English databases, with the retrieval deadline being November 2021. Databases include PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, and China Biomedical Literature Database. Stata14.0 will be used to conduct this systematic review. The preferred reporting items for systematic reviews and meta-analysis protocols statements are followed in this protocol, and the PRISMA statement will be followed in the completed systematic review., Results: The results will be published in a peer-reviewed journal., Conclusions: This systematic review will provide evidence regarding the rate of H pylori reinfection and its risk factors after successful eradication. It can guide the management of patients with H pylori infection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The localization of bacterial components and/or metabolites in the central nervous system may elicit neuroinflammation and/or neurodegeneration. Helicobacter pylori (a non-commensal symbiotic gastrointestinal pathogen) infection and its related metabolic syndrome have been implicated in the pathogenesis of gastrointestinal tract and central nervous system disorders, thus medications affecting the nervous system - gastrointestinal tract may shape the potential of Helicobacter pylori infection to trigger these pathologies. Helicobacter pylori associated metabolic syndrome, by impairing gut motility and promoting bacterial overgrowth and translocation, might lead to brain pathologies. Trimebutine maleate is a prokinetic drug that hastens gastric emptying, by inducing the release of gastrointestinal agents such as motilin and gastrin. Likewise, it appears to protect against inflammatory signal pathways, involved in inflammatory disorders including brain pathologies. Trimebutine maleate also acts as an antimicrobial agent and exerts opioid agonist effect. This study aimed to investigate a hypothesis regarding the recent advances in exploring the potential role of gastrointestinal tract microbiota dysbiosis-related metabolic syndrome and Helicobacter pylori in the pathogenesis of gastrointestinal tract and brain diseases. We hereby proposed a possible neuroprotective role for trimebutine maleate by altering the dynamics of the gut-brain axis interaction, thus suggesting an additional effect of trimebutine maleate on Helicobacter pylori eradication regimens against these pathologies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Colonization of the stomach by Helicobacter pylori is the trigger for a series of gastric mucosal changes that culminate in gastric cancer. Infection with this bacterium is considered the major risk factor for this malignancy. The introduction of high-throughput sequencing technologies coupled to advanced computational pipelines offered an improved understanding of the microbiome, and it is now currently accepted that, besides H. pylori, the stomach harbours a complex microbial community. While it is well established that H. pylori plays a central role in gastric carcinogenesis, the significance of the non-H. pylori microbiota is yet to be clarified. This review will address the state of the art on the relationship between the gastric microbiota and gastric cancer development, and identify areas where additional research is needed before translating microbiome research into preventive and therapeutic strategies to reduce gastric cancer burden., Competing Interests: Declaration of competing interest R.M.F., J.C.M. and C.F. own patent WO/2018/169,423 on microbiome markers for gastric cancer. J.P.-M. declares no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The lining of the stomach is a tight monolayer of epithelial cells performing functions in digestion and a protective barrier against gastric acid, toxic metabolites and infectious agents, including Helicobacter pylori. The response of the epithelial barrier to infections underlies gastric pathologies, including gastric cancer. H. pylori has the unique capacity to colonise the gastric mucosa while evading the immune system. The colonised mucosa initiates an inflammatory response to fight the infection and a strong regenerative program to avoid barrier failure and ulceration. This response changes the morphology and cell composition of the gastric epithelium and in parallel it might contribute to the accumulation of somatic mutations leading to cellular transformation. Genetically modified mice, cell lines and human-derived organoids are the main biological models to study the gastric epithelial barrier. With these models it is possible to dissect the stepwise process of tissue adaptation to infection that places the epithelium at risk of malignant transformation., Competing Interests: Declaration of competing interest No conflict of interest has been declared by the authors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although the type 4 secretion system of the integrating and conjugative elements (tfs ICE) is common in Helicobacter pylori, its clinical association with the cag pathogenicity island (cagPAI) have not yet been well-investigated. In this study, Vietnamese patient H. pylori samples (46 duodenal ulcer (DU), 51 non-cardia gastric cancer (NCGC), 39 chronic gastritis (CG)) were fully sequenced using next-generation sequencing and assembled into contigs. tfs3, tfs4, and cagPAI genes were compared with the public database. Most (94%) H. pylori strains possessed a complete cagPAI, which was the greatest risk factor for clinical outcomes, while the prevalences of tfs3 and tfs4 were 45% and 77%, respectively. Complete tfs3 and tfs4 were found in 18.3% and 17.6% of strains, respectively. The prevalence of H. pylori strains with complete tfs3 ICE in DU patients was significantly higher than that in NCGC patients (30.4% vs 11.7%, P < 0.05). In addition, the prevalence of strains with complete tfs3 ICE and cagPAI was significantly higher in DU patients than that in NCGC (28.4% vs 9.8%, P = 0.038) and CG patients (28.2% vs 7.7%, P = 0.024). cagPAI and complete tfs3 increased the risk of DU compared to NCGC (OR = 3.56, 95%CI: 1.1-14.1, P = 0.038) and CG (OR = 4.64, 95%CI: 1.1-27.6, P = 0.024). A complete cluster of tfs3 ICE was associated with gastroduodenal diseases in Vietnam. However, there was a low prevalence of the dupA/complete dupA cluster (15.4%) in the Vietnam strains. The prevalence of cagPAI in Vietnam strains was significantly higher than in US (P = 0.01) and Indonesia (P < 0.0001); the prevalence of the dupA cluster was also higher in the Vietnam strains than in the Indonesian strains (P < 0.05). In addition, the prevalence of ctkA, an accessory gene of tfs3, was significantly different between Vietnam and US strains (28% vs 2%, P = 0.0002). In summary, the acquisition of tfs3/4 ICE was common in H. pylori strains in patients with gastroduodenal disease in Vietnam, and the complete cluster of tfs3 ICE was a reliable marker for the severity of disease in the H. pylori infected population.

Oral levothyroxine sodium is absorbed in the small intestine, mainly in the jejunum and the ileum being lower the absorption rate at duodenal level. The time interval between the ingestion of oral thyroxine and its appearance in the plasma renders unlike a gastric absorption of the hormone. However, several evidence confirm the key role of the stomach as a prerequisite for an efficient absorption of oral levothyroxine. In the stomach, in fact, occur key steps leading to the dissolution of thyroxine from the solid form, the process bringing the active ingredient from the pharmaceutical preparation to the aqueous solution. In particular, gastric juice pH, volume, viscosity, as well as gastric emptying time seem to be the most important limiting factors. These hypotheses are confirmed by the detection of an increased need for levothyroxine in patients with Helicobacter pylori infection, chronic atrophic gastritis, gastroparesis, or in simultaneous treatment with drugs interfering with gastric acidic output. The aim of the present article is to focus on the knowledge of pathophysiologic events that determine the absorptive fate of traditional (tablet) and alternative thyroxine preparations (softgel capsule and liquid solution) in patients bearing gastric disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Virili, Brusca, Capriello and Centanni.)

Background: Helicobacter pylori infection and hyperplastic polyp are known to have strong connections, but there are not enough randomized controlled trial data., Aims: To evaluate the effect of H. pylori eradication on gastric hyperplastic polyp., Method: This is an open-labeled, single-center, randomized controlled trial. Patients with hyperplastic polyp and current infection of H. pylori were randomly assigned to eradication or non-eradication groups. All participants underwent follow-up endoscopy to investigate the regression of gastric polyps. Gastric polyp regression was defined as the disappearance of polyps or a reduction of more than 50% in size., Results: Thirty-two patients were randomized to eradication (n = 17) and non-eradication groups (n = 15). Final included patients were 14 in eradication group and 13 in non-eradication group. All patients showed polyp regression in eradication group, whereas no regression was observed in non-eradication group (P < 0.001). Disappearance of polyp (n = 7) and decrease in size (n = 7) were observed in eradication group. In non-eradication group, no change (n = 5), increase of size (n = 5), and increase of number (n = 3) were observed. Mean regression time was 6.8 months, and disappearance time was 9.8 months. In non-eradication group, hyperglycemia was noted in 50% of progression group but not noted in no change group (P = 0.057)., Conclusions: H. pylori eradication induced regression of hyperplastic polyp, and persistent H. pylori infection was related to progression of gastric polyp., Clinical Trial Registration: ClinicalTrials.gov ID: NCT03065868.

Background and Aims: It has been reported that Helicobacter pylori (HP) infection was more prevalent in infertile populations. HP infection could lead to decreased sperm parameters, and treating the HP infection could improve the quality of sperm. However, studies investigating the relationship between infertility and HP infection are still limited, and more evidence is required. Therefore, we performed the present study to investigate the impact of HP infection on sperm quality in males and on ovarian reserve in females., Methods: A total of 16,522 patients who visited the Second Hospital of Zhejiang University from January 2016 to June 2019 due to abdominal discomfort and underwent a 13/14 C-urea breath HP test were included in this retrospective cross-sectional study. Among them, 565 had performed sperm analysis or ovarian reserve tests in the past three months and were involved for further analyses. Sperm parameters were examined with a computer-assisted sperm analysis system, and serum anti-Müllerian hormone (AMH) and sex hormones were tested with an electrochemiluminescence method., Results: Among 363 patients who underwent the sperm test, 136 (37.47%) had HP infection. Among 202 patients who underwent the AMH test, 55 (27.23%) had HP infection. There was no difference in sperm concentration and motility between the HP+ and HP- groups (P > 0.05). Further subgroup analyses stratified into 5-year age groups confirmed that there was no significant difference in sperm parameters (P > 0.05). When pooled with previously published data, no significant difference in sperm concentration or motility was found (P > 0.05). Meanwhile, this study found that the serum AMH level was similar between the HP+ and HP- groups (P > 0.05). Further subgroup analyses confirmed that there was no significant difference in serum AMH level (P > 0.05)., Conclusions: There were no differences in sperm parameters and AMH levels based on history of HP infection among Chinese patients.

Helicobacter pylori ( H. pylori ) infection is the strongest known risk factor for the development of gastric cancer. DNA damage response (DDR) and autophagy play key roles in tumorigenic transformation. However, it remains unclear how H. pylori modulate DDR and autophagy in gastric carcinogenesis. Here we report that H. pylori infection promotes DNA damage via suppression of Rad51 expression through inhibition of autophagy and accumulation of p62 in gastric carcinogenesis. We find that H. pylori activated DNA damage pathway in concert with downregulation of repair protein Rad51 in gastric cells, C57BL/6 mice and Mongolian gerbils. In addition, autophagy was increased early and then decreased gradually during the duration of H. pylori infection in vitro in a CagA-dependent manner. Moreover, loss of autophagy led to promotion of DNA damage in H. pylori -infected cells. Furthermore, knockdown of autophagic substrate p62 upregulated Rad51 expression, and p62 promoted Rad51 ubiquitination via the direct interaction of its UBA domain. Finally, H. pylori infection was associated with elevated levels of p62 in gastric intestinal metaplasia and decreased levels of Rad51 in dysplasia compared to their H. pylori- counterparts. Our findings provide a novel mechanism into the linkage of H. pylori infection, autophagy, DNA damage and gastric tumorigenesis.

Introduction: This study aimed to identify the Helicobacter pylori cagA+ genotype prevalent in a region of north-eastern Brazil and find possible associations between this genotype and socioeconomic variables., Methods: This cross-sectional study included 751 patients with dyspepsia from a public endoscopy clinic. Genotyping was carried out on 98 samples from gastric tissue with positive urease test for H. pylori using polymerase chain reaction (PCR). Socioeconomic variables were collected via forms. Pearson's χ 2 test was used to analyze associations between variables and odds ratios were obtained to compare effects. Statistical significance was defined as p < 0.05 for univariate and multivariate analyses., Results: H. pylori infection was present in 52.7% of the patients and associated with low income and consumption of untreated drinking water. The prevalence of the cagA+ genotype was 25.5%. Low income was inversely related to the presence of cagA+ genotype, even after adjustment. Untreated drinking water consumption was associated with the presence of the cagA+ genotype in both the univariate ( p = 0.03; OR = 2.55; 95% CI: 1.008-6.48) and multivariate ( p = 0.03; OR = 2.89; 95% CI: 1.08-7.67) analyses., Conclusion: The findings of this study suggest that water can be an important vehicle for the transmission of pathogenic H. pylori strains and may be a public health challenge, especially in less developed regions with precarious water and sanitary conditions.

Introduction Helicobacter pylori causes, via the influence of several virulence factors, persistent infection of the stomach, which leads to severe complications. Vacuolating cytotoxin A (VacA) is observed in almost all clinical strains of H. pylori ; however, only some strains produce the toxigenic and pathogenic VacA, which is influenced by the gene sequence variations. VacA exerts its action by causing cell vacuolation and apoptosis. We performed a PubMed search to review the latest literatures published in English language. Areas covered Articles regarding H. pylori VacA and its genotypes, architecture, internalization, and role in gastric infection and pathogenicity are reviewed. We included the search for recently published literature until January 2020. Expert opinion H. pylori VacA plays a crucial role in severe gastric pathogenicity. In addition, VacA mediated in vivo bacterial survival leads to persistent infection and an enhanced bacterial evasion from the action of antibiotics and the innate host defense system, which leads to drug evasion. VacA as a co-stimulator for the CagA phosphorylation may exert a synergistic effect playing an important role in the CagA-mediated pathogenicity.

Background and Aims: Patients that have failed therapy for Helicobacter pylori (H. pylori) infection are incompletely characterized. The aim of this study was to characterize a H. pylori treatment resistant cohort compared to the cohorts of newly diagnosed, earlier eradicated and non-infected., Material and Methods: Patients were selected from routine referrals to the Endoscopy units at three different Norwegian hospitals. In all four cohorts, gastric biopsies were scored according to the Sydney classification, and symptoms according to the Gastrointestinal Symptom Rating Scale score, including sub-scores for upper gastrointestinal symptoms and functional bowel symptoms. Patients in the H. pylori resistant group were treated with a triple therapy regimen that consisted of levofloxacin, amoxicillin and a proton pump inhibitor., Results: We included 185 patients, 42 H. pylori treatment resistant, 50 newly diagnosed, 61 previously H. pylori eradicated and 32 never infected. The treatment-resistant cohort had higher scores for upper gastrointestinal symptoms and functional bowel symptoms compared to the other groups except for the group being never H. pylori infected. The H. pylori resistant patients had lower Sydney scores than patients with newly diagnosed H. pylori infection. The triple combination showed a high efficacy of 91% to eradicate H. pylori., Conclusions: Patients with treatment-resistant H. pylori infection had more gastrointestinal symptoms, but a lower Sydney score than patients with newly diagnosed infection. A treatment regimen including levofloxacin showed a high efficacy in eradicating H. pylori in patients that previously had failed eradication treatment., Competing Interests: No authors have competing interests

Helicobacter pylori is the most prevalent infection worldwide, while non-alcoholic fatty liver disease emerged as the most frequent liver disease. The common occurrence can be either by chance or due to certain pathogenetic factors. Epidemiologic studies revealed that the risk of non-alcoholic liver disease is increased in patients infected with Helicobacter pylori. DNA fragments of Helicobacter pylori were rarely identified in human samples of liver carcinoma and fatty liver. Helicobacter pylori could influence the development of non-alcoholic fatty liver either by hormonal (ghrelin? gastrin? insulin?), or by effect of pro-inflammatory cytokines (interleukin 1 and 8, tumor necrosis factor ɑ, interferon ɣ) and by changes of gut microbiome as well. Probiotic supplementation could improve some clinical parameters of non-alcoholic fatty liver disease and eradication rates of Helicobacter pylori. Regimens used for eradication can be safely administered, although non-alcoholic fatty liver increases the risk of drug-induced liver damage. Controlled studies of the effect of eradication on the development and progression of non-alcoholic fatty liver are warranted.

Phosphate binder pill (PBP) burden is a significant problem in dialysis patients. Phosphate absorption through the paracellular pathway increases in relatively acidic pH. In this study, we evaluated the effect of factors contributing to duodenal pH-Helicobacter pylori (HP), proton pump inhibitors (PPIs), and NaHCO 3 capsules-on PBP burden. We evaluated 255 dialysis patients with gastric biopsies and excluded patients with low Kt/V, gastrectomy, and parathyroidectomy. Patients were divided into groups and subgroups regarding HP existence, use of PPI, or NaHCO 3 capsules. HP+ group had significantly higher PBP burden and PBP equivalent doses (P < 0.001; both). HP+ subgroup not using daily PPIs or NaHCO 3 capsules had the highest PBP burden and PBP equivalent doses (P < 0.001; both). HP- subgroups had similar PBP and PBP equivalent doses (P = 0.446 and P = 0.382; respectively). HP colonization might affect the PBP burden in dialysis patients due to a decrease of duodenal pH., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background Epidemiological studies have suggested an association between Helicobacter pylori ( H pylori ) infection and atherosclerosis through undefined mechanisms. Endothelial dysfunction is critical to the development of atherosclerosis and related cardiovascular diseases. The present study was designed to test the hypothesis that H pylori infection impaires endothelial function through exosome-mediated mechanisms. Methods and Results Young male and female patients (18-35 years old) with and without H pylori infection were recruited to minimize the chance of potential risk factors for endothelial dysfunction for the study. Endothelium-dependent flow-mediated vasodilatation of the brachial artery was evaluated in the patients and control subjects. Mouse infection models with CagA + H pylori from a gastric ulcer patient were created to determine if H pylori infection-induced endothelial dysfunction could be reproduced in animal models. H pylori infection significantly decreased endothelium-dependent flow-mediated vasodilatation in young patients and significantly attenuated acetylcholine-induced endothelium-dependent aortic relaxation without change in nitroglycerin-induced endothelium-independent vascular relaxation in mice. H pylori eradication significantly improved endothelium-dependent vasodilation in both patients and mice with H pylori infection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA + H pylori or serum exosomes from patients and mice with H pylori infection significantly decreased endothelial functions with decreased migration, tube formation, and proliferation in vitro. Inhibition of exosome secretion with GW4869 effectively preserved endothelial function in mice with H pylori infection. Conclusions H pylori infection impaired endothelial function in patients and mice through exosome-medicated mechanisms. The findings indicated that H pylori infection might be a novel risk factor for cardiovascular diseases.

Background and Aim: Helicobacter pylori infection is very common worldwide, and it is associated with an important gastric pathology. Treatment of this infection is difficult and consists of the combination of two or three antibiotics. However, the rate of resistance to treatment is high. Antimicrobial resistance of Helicobacter pylori is based on its cultivation in the laboratory and testing of phenotypic susceptibility, a time-consuming, laborious method. This study aimed to detect the genetic resistance to antibiotics of Helicobacter pylori in the south-eastern region of Romania., Methods: Ninety patients with positive rapid urease test gastric biopsy samples were tested. Genetic resistance to antibiotics (fluoroquinolone and clarithromycin) was tested by GenoType HelicoDR kit (Hain Lifescience GmbH, Germany)., Results: Clarithromycin resistance mutations were detected in 20% of patients, the commonest mutation in our study beeing A2147G (associated with high level of clarithromycin resistance and lower cure rates). Fluoroquinolones resistance mutations were detected in 30% of patients, and the most common mutations were D91N, D91G, and N87K. There was no correlation with patients gender or age, with the exception of fluoroquinolone resistance, which was detected more frequently in females.   Conclusions. Clarithromycin and fluoroquinolone resistance of Helicobacter pylori is moderately high in our study. There is a need for monitoring Helicobacter resistance patterns in Romania to provide data that can guide empirical treatment. This is the first published study on the genetic resistance of Helicobacter pylori in Romania.

Helicobacter pylori (H. pylori) has been shown to be one of the leading causes of peptic ulcer diseases (PUDs) and gastritis. T helper-22 (Th22) cells and its most important cytokine, interleukin-22 (IL-22) are importantly active in inflammation and inflammatory tissues. Since inflammation is one of the main attributes of infection caused by H. pylori and resulting complications (gastritis and gastrointestinal ulcer), this study was designed to evaluate the Th22 cells count and the IL-22 protein expression in people suffering from PUD and gastritis. The present study was conducted on 55 patients with gastritis, 47 patients with PUD and 48 uninfected subjects. After preparation of section and extraction of protein from antral biopsies, immunohistochemistry and western blot methods were used to evaluate the Th22 cells and IL-22 protein expression level, respectively. According to findings, the Th22 cells count and the IL-22 protein expression level in the infected subjects were siginficantly more than in the uninfected subjects. It should be noted that the Th22 cells count and the IL-22 protein expression level in the infected subjects with PUD were significantly greater than those in the infected subjects with gastritis. In addition, the Th22 cells count had positive correlation with the density of H. pylori, chronic inflammation score and acute inflammatory score in the infected subjects with PUD. The Th22 cells count had positive correlation with the Th17 cells count and inverse correlation with the Treg cells count in the infected subjects with PUD and gastritis. Our data demonstrated that abnormal hyper-activation of Th22 cells as well as its correlation with the Th17 cells during infection caused by H. pylori might damage tissues through immunopathological responses.

Helicobacter pylori ( H. pylori ) is a common problem and a significant cause of chronic gastric inflammation. H. pylori , ongoing gastric inflammation and its severity are the most critical component of precursors of gastric cancer. Hypothetically, every chronic tissue injury activates platelets, and the mean platelet volume (MPV) reflects this action well. The potential relationship between H. pylori and platelet count has been shown before. However, there are few and conflicting papers about the relationship between MPV and H. pylori related chronic gastric inflammation and its severity. The study aimed to assess any potential relationship between MPV and presence of H. pylori , as well as the severity of chronic gastric inflammation. A total of 6890 endoscopic reports were initially evaluated, and a total of 218 dyspeptic patients having undergone upper endoscopy were included. Of these, 118 (54.2%) were H. pylori positive and 100 (45.8%) were H. pylori negative. At least four gastric biopsies were obtained and evaluated according to Sydney classification. Age, gender, hemoglobin, mean corpuscular volume, ferritin, serum iron and C-reactive protein, as well as endoscopic findings were also recorded. A p<0.05 was accepted as significant. The MPV and platelet count did not differ between H. pylori positive and H. pylori negative groups of patients (p>0.05). There were no differences and correlation between MPV and gastric inflammation severity according to Sydney classification (p>0.05). When stratifying MPV as <9.15 fL and >9.15 fL, there was no difference between H. pylori positive and H. pylori negative groups either (p>0.05). In this study, we found no relationship between MPV and presence of H. pylori or severity of gastric inflammation. Although there are still conflicting publications on this issue, in our opinion and according to the results of this study, MPV is not a suitable marker for evaluation of gastric inflammation severity, being H. pylori either positive or negative.

In this review, we shall focus on the last year progression understanding the pathogenesis of Helicobacter pylori infection in the light of recent data related to adaptation of H pylori to the harsh acidic environment in the stomach, colonization of gastric mucosa via interaction with mucin 5 (MUC5AC) and other host cell receptors, the ability to form biofilm, interference with the host metabolic pathways, and induction of neuroimmune cross-talk as well as downregulation of gastric barrier homeostasis and its consequences for the disease development. The role of the membrane vesicles of these bacteria has been emphasized as an important source of virulence factors. Furthermore, we shall describe molecular and functional studies on new aspects of VacA and CagA virulence, including the role of urease in the upregulation of VacA toxicity, an epithelial-mesenchymal transition mediated by CagA, and the role of interaction of HopQ adhesin with carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in CagA translocation into the host cells by the type IV secretion system (T4SS). The role of molecular mimicry between a common sequence (ATVLA) of H pylori heat shock protein (Hsp) B and human Hsp60 in the induction of potentially autoreactive antibodies is discussed. All these new data illustrate further progress in understanding H pylori pathogenicity and facilitate the search for new therapeutic targets as well as development of immunoprophylaxis methods based on new chimeric UreB and HpA proteins., (© 2019 John Wiley & Sons Ltd.)

Background: Chronic systemic inflammation is an important causative factor in the pathogenesis of atherosclerosis. However, the effect of chronic Helicobacter pylori (Hp) infection on arterial stiffness, a predictor of cardiovascular events, remains unclear. We evaluated the association between Hp infection and arterial stiffness in asymptomatic healthy individuals., Methods: Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). We included subjects who underwent CAVI and anti-Hp IgG antibody evaluations, simultaneously, between March 2013 and July 2017. Demographic characteristics and metabolic and cardiovascular parameters were compared with respect to anti-Hp IgG antibody status. Multivariable logistic regression analyses were performed to determine the effect of Hp-seropositivity and conventional cardiovascular risk factors on arterial stiffness., Results: Of 2,251 subjects, 1,326 (58.9%) were included in the Hp-seropositive group. Median age (P < 0.001) and systolic blood pressure (P = 0.027) were significantly higher in the Hp-seropositive than in the Hp-seronegative group. Levels of LDL-cholesterol were significantly higher in the Hp-seropositive than in the Hp-seronegative group (P = 0.016). Other serum metabolic parameters were not significantly different between the two groups. The median CAVI value and the proportion of subjects with a CAVI ≥ 8 were significantly higher in the Hp-seropositive than in the Hp-seronegative group (both P < 0.001). On multivariable logistic regression analyses, Hp-seropositivity, age, body mass index, waist circumference, smoking, hypertension, diabetes mellitus, and dyslipidemia were significantly associated with high CAVI values. In the subgroup analysis conducted according to age group, a tendency towards an increased association between Hp-seropositivity and CAVI was observed with increasing age, even though the difference did not reach the statistical significance., Conclusions: Hp-seropositivity was significantly associated with arterial stiffness. Hp infection may contribute to the development of cardiovascular diseases., Competing Interests: The authors have declared that no competing interests exist.

Objective To demonstrate HpaA can intensify the inflammatory response and gastric mucosa injury by IL-21 from induced T cell. Methods Biopsy specimens were taken from gastric mucosa of 56 patients with H.pylori infection before and after H.pylori radical elimination by endoscope. The levels of IL-21, matrix metalloproteinase-2 (MMP2) and MMP9 from the biopsy were detected by reverse transcription PCR and Western blot analysis. Meanwhile, the recombinant HpaA was cloned, expressed and purified to stimulate the magnetic cell sorting CD3 + T cells from healthy donors' peripheral blood mononuclear cells (PBMCs), and the level of IL-21 in the supernatant fluid was detected by ELISA. Thereafter, AGS cells were cultured and Western blot analysis was performed to detect the levels of MMP2 and MMP9 in the AGS cells with human IL-21 and anti-IL-21 antibody treatment for 24 hours. Results The protein levels of IL-21 and MMP2 and MMP9 in gastric mucosa infected with H. pylori was significantly higher than that in gastric mucosa after radical treatment of H. pylori. Meanwhile, the recombinant HpaA promoted IL-21 secretion by induced CD3 + T cells in vitro. IL-21 stimulated the expression of MMP2 and MMP9 in AGS cells. When IL-21 was blocked by the antibody, the levels of MMP2 and MMP9 in AGS cells decreased significantly. Conclusion HpaA plays a significant role in the gastric mucosa injury caused by H.pylori infection through IL-21 from induced T cells.

There is an association between Helicobacter pylori infection and immune thrombocytopenia (ITP), and few studies have suggested that eradicative treatment of H. pylori infection may improve platelet counts in patients with ITP. Conventional treatments for ITP include immunosuppressive agents, and more recently thrombopoietic agents. However, based on clinical reports of association between H. pylori and ITP, several medical societies increasingly suggest detection and eradication of H. pylori as a treatment for ITP. In this article, we reappraise recent medical literature to determine the effectiveness of platelet response after treatment of H. pylori infection in patients with ITP. We searched two online databases (MEDLINE and Google Scholar) for full articles published between January 2008 and May 2018, and found a total of 11 studies that presented data and outcomes of treatment of H. pylori infection in ITP patients. All the studies administered triple therapy (amoxicillin 500 mg, clarithromycin 250 mg and a proton-pump inhibitor each given twice daily for either 7- or 14-day course) for eradication of H. pylori . Median overall platelet response ranged from 27 to 69.2% with a complete response rate ranging from 0 to 65.4% and a partial response rate ranging from 0 to 29.4%. Although there is variability in the effectiveness between different populations, it appears to be of benefit to ITP patients with concomitant H. pylori infection when treated with triple therapy. However, further studies to understand the pathogenesis of H. pylori -associated ITP is necessary for the development of new therapeutic approaches for ITP., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Helicobacter pylori (HP) is a gram-negative flagellated pathogen acid-resistant bacterium; it belongs to the order Campylobacterales that is wide spread all over the world, infecting more than 50% of the world population. HP infection is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and with 3 to 6-fold increased relative risk for developing gastric adenocarcinoma and mucosa-associated lymphoid tissue (MA LT) lymphoma. For this reason HP is recognized by the World Health Organization as a Class I human carcinogen. In the last years a lot of studies clarified the role of this pathogen in nutrition and metabolism; particularly, it has been shown that it is able to induce malabsorption of several nutrients like iron, cobalamin, vitamin C and vitamin E, with strong consequences on nutritional status. Interesting, this bacterium is able to produce different biological effects on hormones like ghrelin and leptin controlling both appetite and growth, mostly depending on the time of acquisition of the infection and of its treatment. In this review, the authors focused their attention on nutritional effects of HP infection and particularly on the role that diet, food, plants and specific nutrients can play in its treatment, considering that HP eradication rates, with standard triple-therapy, have fallen to a low level in the last years.

Background: The prevalence of Helicobacter pylori varies geographically by age, race, and socioeconomic status (SES). However, the impact of ethnicity on endoscopic outcomes in infected individuals is not well known., Objectives: To assess the impact of ethnicity among Israelis with biopsy-proven H. pylori infection., Methods: A retrospective study, including patients who underwent gastroscopy and were diagnosed histologically with H. pylori infection, was conducted. Information on demographics, SES, medications, and co-morbidities were extracted from medical records. Univariate (Student's t-test, chi-square test) and multivariate (multinomial and logistic) regression analysis were conducted to examine the predictors of the clinical outcome., Results: The study included 100 Israeli Jews and 100 Israeli Arabs diagnosed with biopsy-proven H. pylori infection. At univariate analysis, the number of households was higher among Arabs (P < 0.001), whose family income and parental education were lower than among Jews (P < 0.001 for both variables). The response to amoxicillin and clarithromycin differed between the two groups, being higher among Jews (P < 0.001).In clinical outcomes (gastritis severity, gastric and duodenal ulcer, intestinal metaplasia, atrophic gastritis, and MALT), no statistically significant differences could be detected between Jews and Arabs. Concerning intestinal metaplasia, lack of consumption of nonsteroidal anti-inflammatory drugs resulted a statistically significant protective factor (odds ratio 0.128, 95% confidence interval 0.024-0.685, P = 0.016)., Conclusions: Although in the literature ethnicity seems to be a risk factor for H. pylori colonization, no statistical significance was detected in various endoscopic and histological findings related to H. Pylori infection between Israeli Arabs and Jews.

Background: Helicobacter pylori ( H. pylori ) eradication therapy may improve gastric atrophy and intestinal metaplasia, but the results of previous studies have not always been consistent. The aim of this study was to compare the histological changes of intestinal metaplasia and gastric atrophy among the use of acid-suppressing drugs after H. pylori eradication., Methods: A cohort of 242 patients who underwent successful eradication therapy for H . pylori gastritis and surveillance endoscopy examination from 1996 to 2015 was analyzed. Changes in the histological scores of intestinal metaplasia and atrophy according to drug use (proton-pump inhibitors (PPIs), H 2 receptor antagonists (H2RAs), and non-acid suppressant use) were evaluated in biopsies of the antrum and corpus using a generalized linear mixed model in all patients., Results: The mean follow-up period and number of biopsies were 5.48 ± 4.69 years and 2.62 ± 1.67 times, respectively. Improvement in the atrophy scores of both the antrum ( p = 0.042) and corpus ( p = 0.020) were significantly superior in patients with non-acid suppressant drug use compared with those of PPI and H2RA use. Metaplasia scores in both the antrum and corpus did not improve in all groups, and no significant differences were observed among groups in the antrum ( p = 0.271) and corpus ( p = 0.077)., Conclusions: Prolonged acid suppression by PPIs or H2RAs may limit the recovery of gastric atrophy following H. pylori eradication.

This study was undertaken to further investigate the CD177 expression in Helicobacter pylori- (Hp-) infected wild-type and CD177 -/- C57BL/6 mice, which may be helpful to elucidate the relationship between CD177 and Hp-related gastritis. 20 WT mice were randomly assigned into the Hpss1 WT group ( n = 10) and Hp49503 WT group ( n = 10); 20 KO mice were randomly assigned into the Hpss1 KO group ( n = 10) and Hp49503 KO group ( n = 10). The remaining mice served as controls. Mice in the HpSS1 groups and Hp49503 groups were independently infected with corresponding strains. Results showed that the Hp colonization score was related to the grade of mucosal inflammation ( P < 0.05). The inflammation grade was comparable between the HpSS1 group and Hp49503 group as well as between the WT group and KO group. In addition, the Hp colonization score was related to the CD177 expression score ( P < 0.05). The CD177 expression in the Hp colonization group was higher than that in the non-Hp colonization group ( P < 0.05). CD177 expression was positively related to the inflammation grade ( P < 0.01). In conclusion, CD177 expression was similar between HP49503- and HPss1-infected WT C57BL/6 mice, and CD177 expression was undetectable in CD177 -/- mice. CD177 expression in the gastric mucosa increases with the elevation of inflammation grade. In Hp-infected mice, the inflammation grade had no relationship with the type of Hp strain and the CD177 expression, but the mucosal inflammation score in Hp-infected mice was higher than that in non-Hp infected mice.

The gastric bacterium Helicobacter pylori causes a persistent infection that is directly responsible for gastric ulcers and gastric cancer in some patients and protective against allergic and other immunological disorders in others. The two outcomes of the Helicobacter -host interaction can be modeled in mice that are infected as immunocompetent adults and as neonates, respectively. Here, we have investigated the contribution of the Helicobacter immunomodulator VacA to H. pylori -specific local and systemic immune responses in both models. We found that neonatally infected mice are colonized at higher levels than mice infected as adults and fail to generate effector T-cell responses to the bacteria; rather, T-cell responses in neonatally infected mice are skewed toward Foxp3-positive (Foxp3 + ) regulatory T cells that are neuropilin negative and express RORγt. We found these peripherally induced regulatory T cells (pTregs) to be enriched, in a VacA-dependent manner, not only in the gastric mucosa but also in the lungs of infected mice. Pulmonary pTreg accumulation was observed in mice that have been infected neonatally with wild-type H. pylori but not in mice that have been infected as adults or mice infected with a VacA null mutant. Finally, we traced VacA to gastric lamina propria myeloid cells and show that it suppressed interleukin-23 (IL-23) expression by dendritic cells and induced IL-10 and TGF-β expression in macrophages. Taken together, the results are consistent with the idea that H. pylori creates a tolerogenic environment through its immunomodulator VacA, which skews T-cell responses toward Tregs, favors H. pylori persistence, and affects immunity at distant sites. IMPORTANCE Helicobacter pylori has coexisted with humans for at least 60.000 years and has evolved persistence strategies that allow it to evade host immunity and colonize its host for life. The VacA protein is expressed by all H. pylori strains and is required for high-level persistent infection in experimental mouse models. Here, we show that VacA targets myeloid cells in the gastric mucosa to create a tolerogenic environment that facilitates regulatory T-cell differentiation, while suppressing effector T-cell priming and functionality. Tregs that are induced in the periphery during H. pylori infection can be found not only in the stomach but also in the lungs of infected mice, where they are likely to affect immune responses to allergens., (Copyright © 2019 Altobelli et al.)

Evidence suggests that Helicobacter pylori (H. pylori) is not only the main cause of gastric cancer (GC), but is also closely associated with its metastasis. One of the major virulence factors in H. pylori is the cytotoxin‑associated gene A (CagA). With the growing proportion of amoxicillin‑resistant H. pylori strains, the present study aimed to explore the effects of CagA‑ and penicillin‑binding protein 1A (PBP1A) mutation‑positive H. pylori (H. pyloriCagA+/P+) on GC cells, and its clinical significance. The clinical significance of H. pyloriCagA+/P+ infection was analyzed in patients with GC. In vitro, GC cells were infected with H. pyloriCagA+/P+ to investigate whether it was involved in the epithelial‑mesenchymal transition (EMT) of SGC‑7901 cells using immunofluorescence and western blot analysis. The results of clinical analysis demonstrated that, although CagA‑negative H. pylori infection had no significant association with the characteristics of patients with GC, H. pyloriCagA+/P+ infection was significantly associated with various clinicopathological parameters, including invasion depth, lymphatic metastasis and distant metastasis. In vitro, the results indicated that H. pyloriCagA+/P+ promoted proliferation, invasion and EMT of SGC‑7901 cells. MicroRNA (miR)‑134 was downregulated in H. pyloriCagA+/P+ infected tissues compared with in those with H. pyloriCagA+/P‑ infection. miR‑134 overexpression significantly reversed H. pyloriCagA+/P+ infection‑associated cell proliferation, invasion and EMT. Furthermore, the results revealed that Forkhead box protein M1 (FoxM1) was a direct target of miR‑134, and FoxM1 knockdown impeded H. pyloriCagA+/P+‑induced EMT. In conclusion, the present study demonstrated that miR‑134 may suppress the proliferation, invasion and EMT of SGC‑7901 cells by targeting FoxM1, and may serve a protective role in the process of H. pyloriCagA+/P+‑induced GC. These findings may lead to an improved understanding of H. pyloriCagA+/P+‑associated poor clinical characteristics in patients with GC.

Epidemiological studies have shown that Helicobacter pylori (HP) infection is a risk factor for gastric cancer (GC). HP infection may induce the release of pro-inflammatory mediators, and abnormally increase the level of reactive oxygen species (ROS), nitric oxide (NO), and cytokines in mucosal epithelial cells of the stomach. However, the specific mechanism underlying the pathogenesis of HP-associated GC is still poorly understood. Recent studies have revealed that abnormal microRNA expression may affect the proliferation, differentiation, and apoptosis of mucosal epithelial cells of the stomach to further influence GC occurrence, development, and metastasis. Herein, we summarize the role of abnormal microRNAs in the regulation of HP-associated GC progression. Abnormal microRNA expression in HP-positive GC may be a biomarker for GC diagnosis, occurrence, and development as well as its targeted treatment and prognosis.

Background: Concomitant quadruple (CQT) or bismuth-containing quadruple therapy (BQT) is recommended as first-line treatment for Helicobacter pylori infection depending on antibiotic resistance., Aim: To compare the efficacy, safety, and compliance of CQT and BQT as first-line therapy for H. pylori eradication in real clinical practice in an area of high resistance to clarithromycin., Methods: A prospective, open, comparative cross-sectional study including dyspeptic patients >18 years with H. pylori infection and with no previous eradication treatment was performed. CQT (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + metronidazole 500 mg, all given twice daily, for 14 days) or BQT (omeprazole 20 mg twice daily + 3 capsules of Pylera® 4 times a day, for 10 days) was prescribed at the discretion of the prescribing physician. Eradication was tested by 13 C-urea breath test. Efficacy was assessed by intention-to-treat (ITT) and per-protocol (PP) analyses., Results: One hundred and four consecutive patients were included (64.4% female, age 52.9 years). Fifty patients received CQT and 54 BQT. Eradication rate was similar with both therapies at the PP (CQT 97.9%, 95% CI: 93.9-100 vs BQT 96.2%, 95% CI: 90.9-100, P = 0.605) and ITT analyses (CQT 98.0%, 95% CI: 94-100 vs BQT 94.4%, 95% CI: 88.1-100, P = 0.346). The rate of adverse events was also similar with CQT (56%) and BQT (46.3%). One patient in each group discontinued the treatment due to significant adverse events., Conclusion: The use of CQT and BQT as first-line treatment against H. pylori is similarly effective and safe strategy in an area of high clarithromycin resistance., (© 2018 John Wiley & Sons Ltd.)

Background: Inflammatory bowel diseases (IBD), are chronic, relapsing-remitting diseases of the gastrointestinal tract, including Crohn's disease (CD), Ulcerative colitis (UC) and Unclassified IBD (IBDU). Their pathogenesis involves genes and environment as cofactors in inducing autoimmunity; particularly the interactions between enteric pathogens and immunity is being studied. Helicobacter pylori (HP) is common pathogen causing gastric inflammation. Studies found an inverse prevalence association between HP and IBD, suggesting a potential protecting role of HP from IBD., Methods: A literature search of the PubMed database was performed using the key words ''helicobacter pylori'', ''inflammatory bowel disease'', ''crohn disease'', "ulcerative colitis". Embase, Medline (OvidSP), Web of Science, Scopus, PubMed publisher, Cochrane and Google Scholar were also searched. Prevalence rate-ratios among HP in IBD patients, HP in CD patients, HP in UC patients, HP in IBDU patients were extracted, each group was compared with controls, to verify the inverse association between HP and IBD prevalence., Results: In all groups the dispersion of data suggested an inverse association between IBD group and controls, even when the comparison was carried out separately between each group of newly diagnosed patients and controls, to rule out the possible bias of ongoing pharmacologic therapy., Conclusions: The results of this review show a striking inverse association between HP infection and the prevalence of IBD, independently from the type of IBD considered across distinct geographic regions. Anyway, data should be interpreted cautiously, as wider, prospective and more homogeneous research on this topic are awaited, which could open new scenarios about environmental etiology of IBD.

Objective: Helicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease., Design: Whole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed., Results: A total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034)., Conclusion: These results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The aim is to determine whether there is an independent association between Hp infection and carotid intima-media thickness (CIMT) in a cross-section observational study. Among of 14588 routine health check-up participants, 13770 subjects underwent the 13 C-urea breath test ( 13 C-UBT) and ultrasound measurement of CIMT. Traditional atherosclerotic risk factors were also recorded. The ratio of increased CIMT in Hp positive group (28.6%) was not significant difference compared with Hp negative group (29.7%) (p = 0.164). The HP infection rates was no significant difference between increased CIMT (38.4%) and non- increased CIMT (39.7%) patients. However, all the traditional atherosclerotic risk factors including age, gender, BMI, waistline, total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, free fatty acid, homocysteine, systolic and diastolic blood pressure, fasting plasma glucose and C reactive protein were different between increased CIMT and non- increased CIMT participants. The odds of Hp infection for CIMT risk (OR 0.948; 95% CI 0.879-1.022; P = 0.164) was not higher in binary logistic regression analysis even after adjustment for traditional risk factors (OR 1.118; 95% CI 0.958-1.306; P = 0.157). Our study found no evidence of association between CIMT and HP infection.

Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.

Gastro-oesophageal reflux disease (GORD) is a common comorbidity in bronchiectasis, and is often associated with poorer outcomes. The cause and effect relationship between GORD and bronchiectasis has not yet been fully elucidated and a greater understanding of the pathophysiology of the interaction and potential therapies is required. This review explores the underlying pathophysiology of GORD, its clinical presentation, risk factors, commonly applied diagnostic tools, and a detailed synthesis of original articles evaluating the prevalence of GORD, its influence on disease severity and current management strategies within the context of bronchiectasis. The prevalence of GORD in bronchiectasis ranges from 26% to 75%. Patients with co-existing bronchiectasis and GORD were found to have an increased mortality and increased bronchiectasis severity, manifest by increased symptoms, exacerbations, hospitalisations, radiological extent and chronic infection, with reduced pulmonary function and quality of life. The pathogenic role of Helicobacter pylori infection in bronchiectasis, perhaps via aspiration of gastric contents, also warrants further investigation. Our index of suspicion for GORD should remain high across the spectrum of disease severity in bronchiectasis. Identifying GORD in bronchiectasis patients may have important therapeutic and prognostic implications, although clinical trial evidence that treatment targeted at GORD can improve outcomes in bronchiectasis is currently lacking., (Copyright © 2018. Published by Elsevier Ltd.)

Helicobacter pylori ( H. pylori ) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.

BACKGROUND The effects of Helicobacter pylori (H. pylori) infection on gastroesophageal reflux disease (GERD) remain unclear. The aim of this study was to compare the results of clinical esophageal function tests and the effect of H. pylori infection on GERD. MATERIAL AND METHODS A prospective clinical study included 124 patients diagnosed with GERD (four grades). H. pylori infection was determined by gastroscopy and a rapid urease test (RUT) to divide patients into an HP-positive and an HP-negative group. Esophageal function tests included high-resolution manometry (HRM), peristalsis break (PB), and 24-hour pH monitoring (composite pH DeMeester score). Different grades of GERD, with and without H. pylori infection, esophageal function test results were analyzed. RESULTS The HP-positive group, compared with the HP-negative group with GERD, showed a significantly reduced median PB value (3.41±3.65 vs. 6.18±5.27), reduced PBs >5 cm per ten swallows (2.23±3.05 vs. 4.04±3.70) indicating that that H. pylori infection improved esophageal peristalsis. During 24-hour esophageal pH monitoring, the HP-positive group showed a significantly reduced percentage of time for esophageal pH <4.0, number of reflux events >5 min, and number of reflux episodes in 24 hours, compared with the HP-negative group. The DeMeester score was significantly increased in the HP-negative group, indicating a higher esophageal acid exposure (9.11±8.15 vs. 24.30±30.27). CONCLUSIONS H. pylori infection improved esophageal peristalsis, enhanced lower esophageal sphincter (LES) pressure, and reduced esophageal acid exposure, which might be protective factors for GERD.

Background: Helicobacter pylori is a major cause of gastric diseases including gastric cancer. This study was aimed to explore whether hydrotalcite can inhibit H. pylori infection of gastric epithelial cells., Methods: the gastric epithelial cell line GES-1 and the gastric cancer cell line BGC823 were infected with H. pylori at multiplicities of infections (MOIs) of 50:1 and 100:1. Hydrotalcite was added to cell cultures. Cell apoptosis and cell cycle analysis were performed to measure the situation of cell growth. The main changes of cell ultrastructure were observed by transmission electron microscopy. H. pylori cell adhesion was observed by scanning electron microscopy., Results: hydrotalcite could significantly inhibit cell apoptosis of GES-1 and cell proliferation of BGC823 induced by H. pylori infection at an MOI of 50:1. Hydrotalcite treatment protected gastric cells from H. pylori infection, and H. pylori adhesion to gastric cells was reduced. However, hydrotalcite could not reverse damage induced by H. pylori infection at an MOI of 100:1., Conclusion: hydrotalcite can protect gastric cells from H. pylori infection when cell damage is not serious. It can weaken the damage of cells induced by H. pylori and decrease H. pylori adhesion to gastric cells.

Background: Lynch syndrome (LS) patients have a high risk of developing various tumors. This study aimed to clarify the characteristics of tumors developing in LS patients., Methods: This is a retrospective review of 55 LS patients treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital., Results: The median age at the diagnosis of the first malignant tumor and first LS-related tumor was 44 (range, 19-65) and 44 (range, 24-66) years, respectively. Of the 55 LS patients with developing malignant tumors, 45 (93.8%) developed an LS-related tumor as the first malignant tumor. Colorectal cancer (CRC) developed in 47 patients (85.4%), followed by endometrial cancer (n = 13, 56.5%) in females and gastric cancer (n = 10, 18.1%). In 6 gastric cancer patients, Helicobacter pylori was detected in resected specimens. Twenty-nine patients (52.7%) developed CRC and extra-colonic tumors; of these, 15 patients (48.3%) had mutations in MLH1, 10 (58.8%) in MSH2, and 4 (57.1%) in MSH6. At the age of 50, the cumulative incidence was 50.9% [95% confidence interval (CI), 36.9-63.3%] for CRC, 17.4% (95% CI, 5.2-35.6%) for endometrial cancer, and 5.5% (95% CI, 1.4-13.8%) for gastric cancer. Eight gastric cancer, one breast cancer patient, five bladder cancer patients, and one prostate cancer patient demonstrated loss of expression of the mismatch repair (MMR) protein; patients with thyroid cancer, spindle cell sarcoma, and giant cell tumors did not demonstrate this., Conclusion: Gastric cancer incidence was high in Japanese patients with LS and associated with H. pylori infection. MMR protein deficiency caused the development of malignant tumors in LS patients.

Non-variceal upper gastrointestinal bleeding (NVUGIB) is bleeding that develops in the oesophagus, stomach or proximal duodenum. Peptic ulcers, caused by Helicobacter pylori infection or use of NSAIDs and low-dose aspirin (LDA), are the most common cause. Although the incidence and mortality associated with NVUGIB have been decreasing owing to considerable advances in the prevention and management of NVUGIB over the past 20 years, it remains a common clinical problem with an annual incidence of ∼67 per 100,000 individuals in the United States in 2012. NVUGIB is a medical emergency, and mortality is in the range ∼1-5%. After resuscitation and initial assessment, early (within 24 hours) diagnostic and therapeutic endoscopy together with intragastric pH control with proton pump inhibitors (PPIs) form the basis of treatment. With a growing ageing population treated with antiplatelet and/or anticoagulant medications, the clinical management of NVUGIB is complex as the risk between gastrointestinal bleeding events and adverse cardiovascular events needs to be balanced. The best clinical approach includes identification of risk factors and prevention of bleeding; available strategies include continuous treatment with PPIs or H. pylori eradication in those at increased risk of developing NVUGIB. Treatment with PPIs and/or use of cyclooxygenase-2-selective NSAIDs should be implemented in those patients at risk of NVUGIB who need NSAIDs and/or LDA.

Background: Helicobacter pylori are gram-negative spiral shaped bacteria, with sheathed flagella. H. pylori infection is one of the most common chronic infections in humans. Infection is usually acquired during childhood, and becomes a lifelong infection in most people unless treated. The aim of this study was to evaluate serum levels of oxidative stress indices in children with H. pylori infection., Material and Methods: The present study was carried out on 60 children infected with H. pylori including 28 males, 32 females with their age ranging from 7-10 years and mean age value of 8.5 ± 1.65 ( Group I). This study included also 60 children as a control group including 26 males, 34 females with their age ranging from 7-11 and mean age value of 8.99 ± 1.63 (Group II). For all children in groups I the following were done: Diagnosis of H. pylori infection through H. pylori stool antigen testing using enzyme immunoassay kit and gastric antrum mucosal biopsies which were tested for urease activity using Campylobacter like organism test (CLO test). Measurements of serum oxidative stress markers including Superoxide dismutase (SOD), Malondialdhyde, Glutathione, Catalase and Nitric oxide were done in patients and controls., Results: Serum nitric oxide and reduced glutathione were significantly lower in patients compared to controls while serum MDA, Serum catalase and Serum SOD were significantly higher in patients compared to controls (nitric oxide was 91.111 ±6.366 in patients versus 107.211±2.121 in controls with p value of 0.001, reduced glutathione in patients was 2.457± 0.081 versus 2.889±0.491 in controls with p value of 0.001, serum MDA in patients was 140.22±5.18 versus 116.22±2.98 in controls with p value of 0.001, catalase was 401.645± 4.344 versus 278.221±71.712 in controls with p value of 0.001 and SOD in patients was 16.936±9.145 versus 5.578±0.231 in controls with p value of 0.001)., Conclusion: H. pylori infection is associated with oxidative stress with significantly lower serum nitric oxide and reduced glutathione and significantly higher serum MDA, catalase and SOD in patients compared to controls., Recommendations: Antioxidants may be beneficial adjuvant treatment in H. pylori infection as H. pylori infection is associated with oxidative stress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In the annual meeting of the Japan Gastroenterological Association (JGA), the scientific organizing committee selected the serial topics for the core symposium. One of the core symposia held during 2015-2017 was entitled "New medical approach to functional dyspepsia (FD)." In 2015, the subtitle of this symposium was "Helicobacter pylori gastritis and FD." In 2016, the subtitle of this symposium was "overlap with other functional GI disorders." In 2017, the subtitle was "therapeutic approach to FD." During these 3 years, a total of 24 presentations were included in Core Symposium 3 and deep and intensive discussions were carried out., (© 2018 S. Karger AG, Basel.)

In 2001, it was observed that the cardia region of the lumen of the stomach remained highly acidic after a meal and escaped the buffering effect of the food. This phenomenon was termed the acid pocket and is thought to explain why reflux symptoms occur after meals despite the buffering effect of food. This review describes the discovery of the acid pocket and our progress in understanding the intragastric physiology producing it, its exaggeration in hiatus hernia and role in reflux disease. The recent discovery that the acid pocket is attenuated in the Helicobacter pylori-infected population and the significance of this to the negative association between H. pylori and reflux disease and its complications is also addressed. Finally, the role of the acid pocket in providing protection from potentially pathogenic ingested microorganisms is discussed.