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Sample records for helicobacter pylori induces

  1. HELICOBACTER PYLORI

    EPA Science Inventory

    Helicobacter pylori is a pathogenic bacteria which inhabits the human stomach and upper gastrointestinal tract. This encyclopedic entry summarizes the potential role of this organism as a waterborne pathogen. Information is provided on the physiology and morphology of this bacter...

  2. Helicobacter pylori.

    PubMed Central

    Dunn, B E; Cohen, H; Blaser, M J

    1997-01-01

    Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori has been found in the stomachs of humans in all parts of the world. In developing countries, 70 to 90% of the population carries H. pylori. In developed countries, the prevalence of infection is lower. There appears to be no substantial reservoir of H. pylori aside from the human stomach. Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes. H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen. All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium. A variety of tests to diagnose H. pylori infection are now available. Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy. In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy. In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection. PMID:9336670

  3. Helicobacter Pylori Infections

    MedlinePlus

    Helicobacter pylori (H. pylori) is a type of bacteria that causes infection in the stomach. It is found in about two- ... breath or stool to see if it contains H. pylori. The best treatment is a combination of ...

  4. Probiotic BIFICO cocktail ameliorates Helicobacter pylori induced gastritis

    PubMed Central

    Yu, Hong-Jing; Liu, Wei; Chang, Zhen; Shen, Hui; He, Li-Juan; Wang, Sha-Sha; Liu, Lu; Jiang, Yuan-Ying; Xu, Guo-Tong; An, Mao-Mao; Zhang, Jun-Dong

    2015-01-01

    AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. METHODS: Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. RESULTS: We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1β, IL-10, IL-6, G-CSF and MIP-2 (P < 0.05). These results led us to hypothesize that BIFICO treatment would diminish the H. pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-κB and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-κB subunit p65 and in the phosphorylation of IκB-α, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-α, G-CSF and GM-CSF (P < 0.05), and the increased expression of TLR2, TLR4 and MyD88 induced by H. pylori in the stomach was also significantly reduced following BIFICO treatment (P < 0.05). CONCLUSION: Our

  5. Screening Helicobacter pylori genes induced during infection of mouse stomachs

    PubMed Central

    Singh, Aparna; Hodgson, Nathaniel; Yan, Ming; Joo, Jungsoo; Gu, Lei; Sang, Hong; Gregory-Bryson, Emmalena; Wood, William G; Ni, Yisheng; Smith, Kimberly; Jackson, Sharon H; Coleman, William G

    2012-01-01

    AIM: To investigate the effect of in vivo environment on gene expression in Helicobacter pylori (H. pylori) as it relates to its survival in the host. METHODS: In vivo expression technology (IVET) systems are used to identify microbial virulence genes. We modified the IVET-transcriptional fusion vector, pIVET8, which uses antibiotic resistance as the basis for selection of candidate genes in host tissues to develop two unique IVET-promoter-screening vectors, pIVET11 and pIVET12. Our novel IVET systems were developed by the fusion of random Sau3A DNA fragments of H. pylori and a tandem-reporter system of chloramphenicol acetyltransferase and beta-galactosidase. Additionally, each vector contains a kanamycin resistance gene. We used a mouse macrophage cell line, RAW 264.7 and mice, as selective media to identify specific genes that H. pylori expresses in vivo. Gene expression studies were conducted by infecting RAW 264.7 cells with H. pylori. This was followed by real time polymerase chain reaction (PCR) analysis to determine the relative expression levels of in vivo induced genes. RESULTS: In this study, we have identified 31 in vivo induced (ivi) genes in the initial screens. These 31 genes belong to several functional gene families, including several well-known virulence factors that are expressed by the bacterium in infected mouse stomachs. Virulence factors, vacA and cagA, were found in this screen and are known to play important roles in H. pylori infection, colonization and pathogenesis. Their detection validates the efficacy of these screening systems. Some of the identified ivi genes have already been implicated to play an important role in the pathogenesis of H. pylori and other bacterial pathogens such as Escherichia coli and Vibrio cholerae. Transcription profiles of all ivi genes were confirmed by real time PCR analysis of H. pylori RNA isolated from H. pylori infected RAW 264.7 macrophages. We compared the expression profile of H. pylori and RAW 264

  6. Helicobacter pylori: Helicobacter pylori gastritis--a novel distinct disease entity.

    PubMed

    Suzuki, Hidekazu; Mori, Hideki

    2015-10-01

    A global consensus report on Helicobacter pylori gastritis has been developed. Topics discussed include whether dyspepsia caused by H. pylori infection is separate from functional dyspepsia or not, the evaluation method for H. pylori-induced gastritis, eradication therapy for H. pylori gastritis to prevent gastric carcinogenesis and management after H. pylori eradication. PMID:26369312

  7. Probiotics in Helicobacter pylori-induced peptic ulcer disease.

    PubMed

    Boltin, Doron

    2016-02-01

    The ideal treatment regimen for the eradication Helicobacter pylori infection has yet to be identified. Probiotics, particularly Lactobacillus, Bifidobacterium and Saccharomyces, have been suggested as adjuncts to antibiotics for the treatment of H. pylori. There is in vitro evidence that probiotics dampen the Th1 response triggered by H. pylori, attenuate H. pylori associated hypochlorhydria and secrete bacteriocidal metabolites. Probiotics interact with the innate host immune system through adherence to the gastric epithelium and secretion of bacterial adhesins. In prospective human studies, probiotic monotherapy effectively decrease H. pylori density (expired (13)CO2) by 2.0%-64.0%. Probiotic monotherapy has also been shown to eradicate H. pylori in up to 32.5%, although subsequent recrudescence is likely. Eleven meta-analyses have evaluated the efficacy of probiotics as adjuvants to antibiotics for the eradication of H. pylori. The addition of a probiotic increased treatment efficacy, OR 1.12-2.07. This benefit is probably strain-specific and may only be significant with relatively ineffective antibiotic regimens. The pooled prevalence of adverse effects was 12.9%-31.5% among subjects receiving adjuvant probiotics, compared with 24.3%-45.9% among controls. Diarrhea in particular was significantly reduced in subjects receiving adjuvant probiotics, compared with controls (OR 0.16-0.47). A reduction in adverse events other than diarrhea is variable. Despite the apparent benefit on efficacy and side effects conferred by probiotics, the optimal probiotic species, dose and treatment duration has yet to be determined. Further studies are needed to identify the probiotic, antibiotic and patient factors which might predict benefit from probiotic supplementation. PMID:27048901

  8. Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Chronic infection by Helicobacter pylori (H. pylori) is the most common cause of gastric cancer. H. pylori induced oxidative stress and zinc deficiency results in increased sensitivity to the stress. In Ecuador, the prevalence of gastric cancer and zinc deficiency is high. We hypothesize...

  9. Effect of Rumex Aquaticus Herba Extract Against Helicobacter pylori-Induced Inflammation in Gastric Epithelial Cells.

    PubMed

    Han, Jeong Hoon; Khin, Phyu Phyu; Sohn, Uy Dong

    2016-01-01

    The purposes of this study were to examine the characteristics of Helicobacter pylori and the effect of Rumex Aquaticus Herba extract on the expression of cytokines in H. pylori-infected gastric epithelial cells. Cultured human adenocarcinoma gastric cells (AGS) were infected by H. pylori in RPMI 1640 media. Cell growth was measured by trypan blue assay. Western blot analysis was performed to investigate effect of extract containing Quercetin-3-O-β-d-glucuronopyranoside (ECQ) on the expression of inflammatory factors and the inhibition on cell growth. Furthermore, we compared the inhibitory effects with various combinations of clarithromycin, amoxicillin, omeprazole, and ECQ. The urease test with Christensen's Urea Agar was performed to identify the urease activity of H. pylori and the effect ECQ has on urease activity. When the cells were exposed to H. pylori, the trypan blue assay revealed a decrease in the rate of cell growth. Western blot analysis showed that H. pylori-infected cells had increased levels of degraded IκB-α and inflammatory factors. Pretreatment with ECQ inhibited interleukin expression induced by H. pylori in a dose-dependent manner. A combination of ECQ and antibiotics inhibited cytokine expression more effectively than other treatments. H. pylori displayed significant urease activity. ECQ did not significantly inhibit urease activity. These data suggest that H. pylori infection has cytotoxic effects against AGS cells, and ECQ may inhibit the production of proinflammatory cytokines in H. pylori-infected AGS cells. PMID:26580421

  10. AMP-activated protein kinase activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis.

    PubMed

    Lv, Guoqiang; Zhu, Huanhuan; Zhou, Feng; Lin, Zhou; Lin, Gang; Li, Chenwan

    2014-10-10

    Helicobacter pylori (H pylori), infecting half of the world's population, causes gastritis, duodenal and gastric ulcer, and gastric cancers. AMP-activated protein kinase (AMPK) is a highly conserved regulator of cellular energy and metabolism. Recent studies indicated an important role for AMPK in promoting cell survival. In this study, we discovered that H Pylori induced AMPK activation in transformed (GEC-1 line) and primary human gastric epithelial cells (GECs). Inhibition of H Pylori-stimulated AMPK kinase activity by AMPK inhibitor compound C exacerbated apoptosis in transformed and primary GECs. Meanwhile, downregulation of AMPK expression by targeted shRNAs promoted apoptosis in H pylori-infected GECs. In contrast, A-769662 and resveratrol, two known AMPK activators, or AMPKα1 over-expression, enhanced H Pylori-induced AMPK activation, and inhibited GEC apoptosis. Our data suggested that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) could be the upstream kinase for AMPK activation by H pylori. Partial depletion of TAK1 by shRNAs not only inhibited AMPK activation, but also suppressed survival of H pylori-infected GECs. Taken together, these results suggest that TAK1-dependent AMPK activation protects GECs from H pylori-Induced apoptosis. PMID:25229685

  11. Helicobacter pylori γ-Glutamyltranspeptidase Induces Tolerogenic Human Dendritic Cells by Activation of Glutamate Receptors.

    PubMed

    Käbisch, Romy; Semper, Raphaela P; Wüstner, Stefanie; Gerhard, Markus; Mejías-Luque, Raquel

    2016-05-15

    Helicobacter pylori infection is characterized by chronic persistence of the bacterium. Different virulence factors, including H. pylori γ-glutamyltranspeptidase (gGT), have been reported to induce tolerogenicity by reprogramming dendritic cells (DCs). gGT is present in all bacterial isolates, indicating an important role for gGT in the course of infection. In the current study, we have analyzed the effect of H. pylori gGT on human DCs and the subsequent adaptive immune response. We show that glutamate produced due to H. pylori gGT enzymatic activity tolerizes DCs by inhibiting cAMP signaling and dampening IL-6 secretion in response to the infection. Together, our results provide a novel molecular mechanism by which H. pylori manipulates the host's immune response to persist within its host. PMID:27183641

  12. ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis

    PubMed Central

    Luo, Bin; Wang, Minggang; Hou, Nengyi; Hu, Xiao; Jia, Guiqing; Qin, Xianpeng; Zuo, Xiaofei; Liu, Yang; Luo, Kun; Song, Wei; Wang, Kang; Pang, Minghui

    2016-01-01

    Helicobacter pylori infection is the strongest risk factor for development of gastric cancer. Host cellular stress responses, including inflammatory and immune responses, have been reported highly linked to H. pylori-induced carcinogenesis. However, whether mitochondrial regulation and metabolic reprogramming, which are potently associated with various cancers, play a role in H. pylori-induced gastric carcinogenesis is largely unknown. Here we revealed that Lon protease (Lonp1), which is a key inductive of mitochondrial unfolded protein response (UPRmt) and is required to maintain the mitochondrial quality, was greatly induced in H. pylori infected gastric epithelial cells. Importantly, we uncovered that knockdown of Lonp1 expression significantly diminished the metabolic switch to glycolysis and gastric cell proliferation associated with low multiplicity of H. pylori infection. In addition, Lonp1 overexpression in gastric epithelial cells also promoted glycolytic switch and cell overgrowth, suggesting H. pylori effect is Lonp1 dependent. We further demonstrated that H. pylori induced Lonp1 expression and cell overgrowth, at least partially, via HIF-1α regulation. Collectively, our results concluded the relevance of Lonp1 for cell proliferation and identified Lonp1 as a key regulator of metabolic reprogramming in H. pylori-induced gastric carcinogenesis. PMID:27108387

  13. [Helicobacter pylori and Arteriosclerosis].

    PubMed

    Matsui, Teruaki

    2011-03-01

    Helicobacter pylori (H. pylori) infection-related diseases are known to include gastritis, gastric and duodenal ulcer, gastric cancer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, iron-deficient anemia, urticaria, reflux esophagitis, and some lifestyle-related diseases. It is indicated that homocysteine involved with arteriosclerosis induces lifestyle-related diseases. Homocysteine is decomposed to methionine and cysteine (useful substances) in the liver, through the involvement of vitamin B₁₂ (VB₁₂) and folic acid. However, deficiency of VB₁₂ and folic acid induces an increase in unmetabolized homocysteine stimulating active oxygen and promoting arteriosclerosis. VB₁₂ and folic acid are activated by the intrinsic factors of gastric parietal cells and gastric acid. The question of whether homocysteine, as a trigger of arteriosclerosis, was influenced by H. pylori infection was investigated. H. pylori infection induces atrophy of the gastric mucosa, and the function of parietal cells decreases with the atrophy to inactivate its intrinsic factor. The inactivation of the intrinsic factor causes a deficiency of VB₁₂ and folic acid to increase homocysteine's chances of triggering arteriosclerosis. The significance and usefulness of H. pylori eradication therapy was evaluated for its ability to prevent arteriosclerosis that induces lifestyle-related diseases. Persons with positive and negative results of H. pylori infection were divided into a group of those aged 65 years or more (early and late elderly) and a group of those under 65 years of age, and assessed for gastric juice. For twenty-five persons from each group who underwent gastrointestinal endoscopy, the degree of atrophy of the gastric mucosa was observed. Blood homocysteine was measured as a novel index of arteriosclerosis, as well as VB₁₂ and folic acid that affect the metabolism of homocysteine, and then activated by gastric acid and intrinsic factors. Their

  14. Helicobacter pylori induces IL-1β protein through the inflammasome activation in differentiated macrophagic cells.

    PubMed

    Kameoka, Shoichiro; Kameyama, Takeshi; Hayashi, Takaya; Sato, Seiichi; Ohnishi, Naomi; Hayashi, Takeru; Murata-Kamiya, Naoko; Higashi, Hideaki; Hatakeyama, Masanori; Takaoka, Akinori

    2016-01-01

    More than 50% of people in the world are infected with Helicobacter pylori (H. pylori), which induces various gastric diseases. Especially, epidemiological studies have shown that H. pylori infection is a major risk factor for gastric cancer. It has been reported that the levels of interleukin (IL)-1β are upregulated in gastric tissues of patients with H. pylori infection. In this study, we investigated the induction mechanism of IL-1β during H. pylori infection. We found that IL-1βmRNA and protein were induced in phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells after H. pylori infection. This IL-1β production was inhibited by a caspase-1 inhibitor and a ROS inhibitor. Furthermore, K(+) efflux and Ca(2+) signaling were also involved in this process. These data suggest that NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3) and its complex, known as NLRP3 inflammasome, are involved in IL-1β production during H. pylori infection because it is reported that NLRP3 inflammasome is activated by ROS, K(+) efflux and/or Ca(2+) signaling. These findings may provide therapeutic strategy for the control of gastric cancer in H. pylori-infected patients. PMID:26912137

  15. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

    PubMed Central

    Crabtree, Jean E.; Jeremy, Anthony H.T.; Duval, Cedric; Dixon, Michael F.; Danjo, Kazuma; Carr, Ian M.; Pritchard, D. Mark; Robinson, Philip A.

    2013-01-01

    Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR) and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H. pylori- induced gastric adenocarcinoma. PMID:25437333

  16. Expression of inflammatory mediators in the otitis media induced by Helicobacter pylori antigen in mice.

    PubMed

    Kariya, S; Okano, M; Fukushima, K; Nomiya, S; Kataoka, Y; Nomiya, R; Akagi, H; Nishizaki, K

    2008-10-01

    Helicobacter pylori is a Gram-negative bacterium that is recognized as one of the key factors in gastric diseases such as gastritis, peptic ulcer and gastric cancer. Recent studies have shown relationships between H. pylori and extra-digestive diseases, and the presence of H. pylori in the middle ear and upper respiratory tract has been reported. However, the role of H. pylori in middle ear disease remains unclear. The present study demonstrated that H. pylori whole-cell protein directly induces macrophage migration inhibitory factor, macrophage inflammatory protein 2, interleukin 1 beta and tumor necrosis factor alpha in middle ear epithelium in mice, and severe proliferation of inflammatory cells was observed in middle ear cavity inoculated with H. pylori whole-cell protein. In addition, trans-tympanic injection of macrophage migration inhibitory factor up-regulated expression of macrophage inflammatory protein 2 in the middle ear. These findings indicate that H. pylori infection causes immunological inflammation in middle ear epithelium, and H. pylori may play a significant role in otitis media. PMID:18727622

  17. [Dyspepsia and Helicobacter pylori].

    PubMed

    Carella, A M; Bianco, G; D'Alessandro, V; Villella, M; D'Amico, G; Mazzoccoli, G; Sperandeo, M; Annese, M A; Sabella, G

    1999-01-01

    Since Helicobacter pylori (Hp) was first isolated in 1983, much work has been carried out on the pathogenic effects of this organism. Hp infection is common in humans and currently is the most important etiologic agent in the development of chronic active gastritis, gastric and duodenal ulcers, carcinoma and Malt-lymphoma of the stomach. Moreover Hp infection has also been associated with various extradigestive diseases. At present, a role of Hp infection in dyspepsia is discussed. Dyspepsia is defined by persistence of pain, burning or discomfort localised to the upper abdomen; some authors include in dyspepsia symptoms such as belching, bloating, alitosis, nausea, postprandial repletion, vomiting and regurgitation. In absence of any underlying pathologies, such as peptic ulcer, gastroesophageal reflux, pancreatitis, biliary tract disease or others, dyspepsia is defined as functional or idiopathic dyspepsia. Functional dyspepsia may be distinct in ulcer, reflux or dysmotility-like dyspepsia and unspecified dyspepsia. Hp infection is common in dyspeptic patients and a role of this bacterium has been postulated mostly in ulcer-like dyspepsia. Mechanisms by when Hp induces dyspeptic symptoms are uncertain; bacterial cytotoxins, phlogosis mediators, activity of chronic gastritis Helicobacter-related and host immune response probably play an important role in pathogenesis of functional dyspepsia. However, dyspepsia is not present only in infected patients; therefore other pathogenic factors may be implicated in expression of dyspeptic symptoms in uninfected subjects, such as gastric dysmotility, modifications of gastric output or altered visceral sensibility, psychological factors, gastroesophageal reflux and irritable bowel. PMID:10367546

  18. Vaccinating against Helicobacter pylori infection.

    PubMed

    Czinn, Steven J; Blanchard, Thomas

    2011-03-01

    Helicobacter pylori infection of the gastric mucosa remains a cause of significant morbidity and mortality almost 30 years after its discovery. H. pylori infection can lead to several gastric maladies, including gastric cancer, and although antimicrobial therapies for the infection exist, the cost of treatment for gastric cancer and the prognosis of individuals who present with this disease make vaccine development a cost effective alternative to bacterial eradication. Experimental mucosal and systemic H. pylori vaccines in mice significantly reduce bacterial load and sometimes provide sterilizing immunity. Clinical trials of oral vaccines consisting of H. pylori proteins with bacterial exotoxin adjuvants or live attenuated bacterial vectors expressing H. pylori proteins induce adaptive immune mechanisms but fail to consistently reduce bacterial load. Clinical trials and murine studies demonstrate that where H. pylori is killed, either spontaneously or following vaccination, the host demonstrated cellular immunity. Improved efficacy of vaccines may be achieved in new trials of vaccine formulations that include multiple antigens and use methods to optimize cellular immunity. Unfortunately, the industrial sponsors that served as the primary engine for much of the previous animal and human research have withdrawn their support. A renewed or expanded commitment from the biotechnology or pharmaceutical industry that could exploit recent advances in our understanding of the host immune response to H. pylori is necessary for the advancement of an H. pylori vaccine. PMID:21304478

  19. Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

    PubMed Central

    Santos, António M.; Lopes, Teresa; Oleastro, Mónica; Gato, Inês Vale; Floch, Pauline; Benejat, Lucie; Chaves, Paula; Pereira, Teresa; Seixas, Elsa; Machado, Jorge; Guerreiro, António S.

    2015-01-01

    Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available. PMID:25569625

  20. Curcumin inhibits gastric inflammation induced by Helicobacter pylori infection in a mouse model.

    PubMed

    Santos, António M; Lopes, Teresa; Oleastro, Mónica; Gato, Inês Vale; Floch, Pauline; Benejat, Lucie; Chaves, Paula; Pereira, Teresa; Seixas, Elsa; Machado, Jorge; Guerreiro, António S

    2015-01-01

    Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available. PMID:25569625

  1. CD44 Plays a Functional Role in Helicobacter pylori-induced Epithelial Cell Proliferation

    PubMed Central

    Bertaux-Skeirik, Nina; Feng, Rui; Schumacher, Michael A.; Li, Jing; Mahe, Maxime M.; Engevik, Amy C.; Javier, Jose E.; Peek Jr, Richard M.; Ottemann, Karen; Orian-Rousseau, Veronique; Boivin, Gregory P.; Helmrath, Michael A.; Zavros, Yana

    2015-01-01

    The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat). Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylorithat was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique approach to study H

  2. Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk

    PubMed Central

    Rafiei, Alireza; Hosseini, Vahid; Janbabai, Ghasem; Fazli, Bahman; Ajami, Abulghasem; Hosseini-khah, Zahra; Gilbreath, Jeremy; Merrell, D Scott

    2012-01-01

    AIM: To investigate the association of the inducible nitric oxide synthetase (iNOS) C150T polymorphism with Helicobacter pylori (H. pylori) infection and gastric cancer (GC) risk in Iran. METHODS: In order to determine whether there was a correlation between iNOS genotype and GC in Iran, we conducted a case-control study using samples from 329 individuals. For each sample, the C150T iNOS polymorphism was genotyped by polymerase chain reaction (PCR) and restriction digestion. Patients were grouped by cancer presence, demographic and behavior characteristics, and H. pylori infection status. Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population. RESULTS: In this population, we found that smoking, hot beverage consumption, a familial history of GC and H. pylori infection status were significantly associated with GC development (P = 0.015, P < 0.001, P = 0.0034, and P < 0.015, respectively). The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone, but was impacted by H. pylori infection status. When compared to the non-H. pylori infected group, cancer patients who had a heterozygous CT genotype and were also infected with H. pylori were 2.1 times more at risk of developing GC [odds ratio (OR) = 2.1, P = 0.03] while those with a homozygous TT genotype and infected with H. pylori were 5.0 times more at risk of developing GC (OR = 5.0, P = 0.029). In contrast, this association was not seen in patients in the control group. CONCLUSION: A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility. PMID:23002365

  3. Helicobacter pylori in children.

    PubMed

    Sustmann, Andrea; Okuda, Masumi; Koletzko, Sibylle

    2016-09-01

    Helicobacter pylori infection in early childhood may differ in many aspects compared to infection in adulthood: the immune response in the gut, the type and prevalence of complications within and outside the stomach, and the impact on long-term health. In high prevalence countries, transient infections seem to be common in infants and toddlers, and the consequences of this phenomenon on the short- and long-term immune response are still unclear. Other controversial issues are related to the question of which H. pylori-infected children benefit from treatment and which is the best regimen to eradicate the infection in the presence of a worldwide increasing antibiotic resistance. The first large-scale randomized placebo-controlled vaccination trial in schoolchildren indicates that prevention of the infection may be possible. PMID:27531540

  4. Coccoid and spiral Helicobacter pylori differ in their abilities to adhere to gastric epithelial cells and induce interleukin-8 secretion.

    PubMed Central

    Cole, S P; Cirillo, D; Kagnoff, M F; Guiney, D G; Eckmann, L

    1997-01-01

    Helicobacter pylori exists as an actively dividing spiral form and a nonculturable, but viable, metabolizing coccoid form. Both forms are present in the stomach, but their relative pathophysiologic significances are unknown. Here we show that the coccoid form of H. pylori, in contrast to the spiral form, binds poorly to gastric epithelial cells and induces little, if any, interleukin-8 secretion by these cells. PMID:9009355

  5. Helicobacter pylori infection in Japan

    PubMed Central

    Shiota, Seiji; Murakawi, Kazunari; Suzuki, Rumiko; Fujioka, Toshio; Yamaoka, Yoshio

    2013-01-01

    The prevalence of Helicobacter pylori infection is gradually decreasing in Japan. On the main island of Japan, nearly all H. pylori isolates possess cagA and vacA with strong virulence. However, less virulent H. pylori strains are frequently found in Okinawa where cases of gastric cancer are the lowest in Japan. Eradication therapy for peptic ulcer, idiopathic thrombocytopenic purpura, gastric mucosa-associated lymphoid tissue lymphoma and early gastric cancer after endoscopic resection has been approved by the Japanese national health insurance system. However, the Japanese Society for Helicobacter Research recently stated that all ‘H. pylori infection’ was considered as the indication for eradication irrespective of the background diseases. To eliminate H. pylori in Japan, the Japanese health insurance system should approve the eradication of all H. pylori infections. PMID:23265147

  6. Paradoxical role of Helicobacter pylori infection: protective effect against ethanol-induced gastric mucosal injury in Mongolian gerbils.

    PubMed

    Sugiyama, A; Ikeno, T; Ishida, K; Maruta, F; Murakami, M; Sato, T; Saito, H; Ishizone, S; Kawasaki, S; Ota, H; Katsuyama, T

    2001-11-01

    We investigated the effect of ethanol (a representative necrotizing agent) on gastritis induced by Helicobacter pylori infection in Mongolian gerbils. Seventy-eight gerbils were used. Four and 12 weeks after H. pylori inoculation, 30% ethanol was administered into the stomach. The stomachs were removed after 30 min, the intramucosal prostaglandin (PG) E2 concentration was measured, and histopathology was recorded. H. pylori infection caused chronic active gastritis, gastric erosion, hypersecretion of mucin from gland mucus cells, and a rise in the activity of intramucosal PGE2. After ethanol administration, gastric erosion was significantly less in animals infected with H. pylori than in uninfected animals. In conclusion, in the early stage of H. pylori infection, accentuation of intramucosal PGE2 and hypersecretion of mucin from gland mucus cells have a protective effect against gastric mucosal injury induced by necrotizing agents. PMID:11713948

  7. [Helicobacter pylori - 2012].

    PubMed

    Buzás, György Miklós

    2012-09-01

    The author overviews some aspects of literature data of the past 2 years. Genetic research has identified polymorphisms of Helicobacter pylori virulence factors and the host which could play a role in the clinical outcome of the infection (peptic ulcer or gastric cancer). So far they have been performed in research centers but with a decrease of costs, they will take their place in diagnosing the diseases and tailoring the treatment. Antibiotic resistance is still growing in Southern European countries and is decreasing in Belgium and Scandinavia. Currently, the clarithromycin resistance rate is of 17-33% in Budapest and levofloxacin resistance achieved 27%. With careful assessment of former antibiotic use the resistance to certain antibiotics can be avoided and the rates of eradication improved. Immigration is a growing problem worldwide: according to Australian, Canadian and Texan studies, the prevalence of Helicobacter pylori is much higher in the immigrant groups than in the local population. An Italian study showed that the eradication rate of triple therapy is significantly lower in the Eastern European immigrants than in the Italians. A recent research has suggested a link between female/male infertility, habitual abortion and Helicobacter pylori infection. However, there are no published data or personal experience to show whether successful eradication of the virus in these cases is followed by successful pregnancies or not. The author overviews the Maastricht process and analyzes the provisions of the Maastricht IV/Florence consensus, in which the new diagnostic algorithms and indications of eradication therapy are reformulated according to the latest levels of evidence and recommendation grading. According to the "test and treat" strategy, either the urea breath test or the stool monoclonal antigen test are recommended as a non-invasive diagnostic method in primary care. Endoscopy is still recommended in case of alarm symptoms, complicated ulcer, or if

  8. BET Inhibition Attenuates Helicobacter pylori-Induced Inflammatory Response by Suppressing Inflammatory Gene Transcription and Enhancer Activation.

    PubMed

    Chen, Jinjing; Wang, Zhen; Hu, Xiangming; Chen, Ruichuan; Romero-Gallo, Judith; Peek, Richard M; Chen, Lin-Feng

    2016-05-15

    Helicobacter pylori infection causes chronic gastritis and peptic ulceration. H. pylori-initiated chronic gastritis is characterized by enhanced expression of many NF-κB-regulated inflammatory cytokines. Brd4 has emerged as an important NF-κB regulator and regulates the expression of many NF-κB-dependent inflammatory genes. In this study, we demonstrated that Brd4 was not only actively involved in H. pylori-induced inflammatory gene mRNA transcription but also H. pylori-induced inflammatory gene enhancer RNA (eRNA) synthesis. Suppression of H. pylori-induced eRNA synthesis impaired H. pylori-induced mRNA synthesis. Furthermore, H. pylori stimulated NF-κB-dependent recruitment of Brd4 to the promoters and enhancers of inflammatory genes to facilitate the RNA polymerase II-mediated eRNA and mRNA synthesis. Inhibition of Brd4 by JQ1 attenuated H. pylori-induced eRNA and mRNA synthesis for a subset of NF-κB-dependent inflammatory genes. JQ1 also inhibited H. pylori-induced interaction between Brd4 and RelA and the recruitment of Brd4 and RNA polymerase II to the promoters and enhancers of inflammatory genes. Finally, we demonstrated that JQ1 suppressed inflammatory gene expression, inflammation, and cell proliferation in H. pylori-infected mice. These studies highlight the importance of Brd4 in H. pylori-induced inflammatory gene expression and suggest that Brd4 could be a potential therapeutic target for the treatment of H. pylori-triggered inflammatory diseases and cancer. PMID:27084101

  9. A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis

    PubMed Central

    Betten, Åsa; Bylund, Johan; Cristophe, Thierry; Boulay, François; Romero, Ana; Hellstrand, Kristoffer; Dahlgren, Claes

    2001-01-01

    Infection with Helicobacter pylori causes chronic gastritis, which is characterized by a dense mucosal infiltration by inflammatory cells such as monocytes/macrophages. H. pylori–induced inflammation is a risk factor for the development of gastric adenocarcinoma, but the mechanisms involved in H. pylori–associated carcinogenesis are poorly understood. A cecropin-like H. pylori peptide, Hp(2-20), was found to be a monocyte chemoattractant and activated the monocyte NADPH-oxidase to produce oxygen radicals. The receptors mediating monocyte activation were identified as FPRL1 and the monocyte-specific orphan receptor FPRL2. Hp(2-20)–activated monocytes inhibited lymphocytes with antitumor properties, such as CD56+ natural killer (NK) cells and CD3ε+ T cells. The changes observed in NK cells and T cells — a reduced antitumor cytotoxicity, downregulation of CD3ζ expression, and apoptosis — were mediated by Hp(2-20)–induced oxygen radicals. Histamine, a gastric mucosal constituent, rescued NK cells and T cells from inhibition and apoptosis by suppressing Hp(2-20)–induced oxygen radical formation. We conclude that H. pylori expression of this monocyte-activating peptide contributes to its ability to attract and activate monocytes and reduces the function and viability of antineoplastic lymphocytes. These novel mechanisms may be subject to local, histaminergic regulation in the gastric mucosa. PMID:11602630

  10. Prevention of Helicobacter pylori-induced gastric cancers in gerbils by a DNA demethylating agent.

    PubMed

    Niwa, Tohru; Toyoda, Takeshi; Tsukamoto, Tetsuya; Mori, Akiko; Tatematsu, Masae; Ushijima, Toshikazu

    2013-04-01

    Suppression of aberrant DNA methylation is a novel approach to cancer prevention, but, so far, the efficacy of the strategy has not been evaluated in cancers associated with chronic inflammation. Gastric cancers induced by Helicobacter pylori infection are known to involve aberrant DNA methylation and associated with severe chronic inflammation in their early stages. Here, we aimed to clarify whether suppression of aberrant DNA methylation can prevent H. pylori-induced gastric cancers using a Mongolian gerbil model. Administration of a DNA demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC), to gerbils (0.125 mg/kg for 50-55 weeks) decreased the incidence of gastric cancers induced by H. pylori infection and N-methyl-N-nitrosourea (MNU) treatment from 55.2% to 23.3% (P < 0.05). In gastric epithelial cells, DNA methylation levels of six CpG islands (HE6, HG2, SB1, SB5, SF12, and SH6) decreased to 46% to 68% (P < 0.05) of gerbils without 5-aza-dC treatment. Also, the global DNA methylation level decreased from 83.0% ± 4.5% to 80.3% ± 4.4% (mean ± SD) by 5-aza-dC treatment (P < 0.05). By 5-aza-dC treatment, Il1b and Nos2 were downregulated (42% and 58% of gerbils without, respectively) but Tnf was upregulated (187%), suggesting that 5-aza-dC treatment induced dysregulation of inflammatory responses. No obvious adverse effect of 5-aza-dC treatment was observed, besides testicular atrophy. These results showed that 5-aza-dC treatment can prevent H. pylori-induced gastric cancers and suggested that removal of induced DNA methylation and/or suppression of DNA methylation induction can become a target for prevention of chronic inflammation-associated cancers. PMID:23559452

  11. Helicobacter pylori Infection in Pediatrics.

    PubMed

    Roma, Eleftheria; Miele, Erasmo

    2015-09-01

    This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality. PMID:26372825

  12. [Helicobacter pylori-related diseases].

    PubMed

    Gisbert, Javier P

    2013-10-01

    This article summarizes the main conclusions drawn from the presentations on Helicobacter pylori at Digestive Disease Week 2013. Knowledge of this infection among the general population continues to be extremely limited. H. pylori is the main cause of "aging" of the human stomach. In developed countries, the prevalence of H. pylori infection has decreased but continues to be considerable. In most countries, clarithromycin and metronidazole resistance rates are markedly high. H. pylori eradication improves the symptoms of functional dyspepsia, but only in a minority of patients. The frequency of idiopathic peptic ulcers seems to be rising and their prognosis is worse. Most patients with gastric cancer have, or have had, prior H. pylori infection. The risk of developing preneoplastic lesions depends on the type (strain) of the microorganism. To prevent the development of gastric cancer, eradication therapy should be administered early (before the development of intestinal metaplasia). Among H. pylori-infected patients, those who receive long-term treatment with proton pump inhibitors more frequently develop preneoplastic lesions. In patients who undergo endoscopic resection of early gastric cancer, H. pylori eradication reduces the incidence of metachronous tumors. Eradication therapy induces regression of MALT lymphoma in most patients and tumoral recurrence in the long term is exceptional; eradication is a reasonable option even when H. pylori infection has not been identified in patients with MALT lymphoma. Several diagnostic innovations were presented, such as some polymerase chain reaction techniques for use in gastric biopsy specimens or gastric juice. The efficacy of triple standard therapy is clearly inadequate. The superiority of "sequential" therapy over standard triple therapy has not been definitively established. "Concomitant" therapy is more effective and is simpler than "sequential" therapy. After failure of standard triple therapy, second

  13. DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

    SciTech Connect

    Kuzuhara, T. Suganuma, M.; Oka, K.; Fujiki, H.

    2007-11-03

    Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggests a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.

  14. Pathogenesis of Helicobacter pylori infection.

    PubMed

    Backert, Steffen; Neddermann, Matthias; Maubach, Gunter; Naumann, Michael

    2016-09-01

    Helicobacter pylori is estimated to infect more than half of the worlds human population and represents a major risk factor for chronic gastritis, peptic ulcer disease, MALT lymphoma, and gastric adenocarcinoma. H. pylori infection and clinical consequences are controlled by highly complex interactions between the host, colonizing bacteria, and environmental parameters. Important bacterial determinants linked with gastric disease development include the cag pathogenicity island encoding a type IV secretion system (T4SS), the translocated effector protein CagA, vacuolating cytotoxin VacA, adhesin BabA, urease, serine protease HtrA, secreted outer membrane vesicles, and many others. The high quantity of these factors and allelic changes in the corresponding genes reveals a sophisticated picture and problems in evaluating the impact of each distinct component. Extensive work has been performed to pinpoint molecular processes related to H. pylori-triggered pathogenesis using Mongolian gerbils, mice, primary tissues, as well as novel in vitro model systems such as gastroids. The manipulation of host signaling cascades by the bacterium appears to be crucial for inducing pathogenic downstream activities and gastric disease progression. Here, we review the most recent advances in this important research area. PMID:27531534

  15. Diagnosis of Helicobacter pylori Infection.

    PubMed

    Tongtawee, Taweesak; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

    2016-01-01

    Helicobacter pylori infection plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease and gastric malignancy. A diagnosis of infection is thus an important part of a treatment strategy of many gastrointestinal tract diseases. Many diagnostic tests are available but all have some limitations in different clinical situations and laboratory settings. A single gold standard cannot available, but be used for diagnosis of Helicobacter pylori infection in daily clinical practice in all areas, so several techniques have been developed to give reliable results, especially focusing on real time endoscopic features. The narrow band imaging system (NBI) and high resolution endoscopy are imaging techniques for enhanced visualization of infected mucosa and premalignant gastric lesions. The aim of this article is to review the current diagnostic options and possible future developments detection of Helicobacter pylori infection. PMID:27221831

  16. Helicobacter pylori Test

    MedlinePlus

    ... pylori stool antigen test; H. pylori breath test; Urea breath test; CLO test; Rapid urease test (RUT) ... of H. pylori antigen in a stool sample Urea breath test A person drinks a liquid containing ...

  17. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    2016-01-01

    Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer. PMID:27573782

  18. Immune responses to Helicobacter pylori infection

    PubMed Central

    Moyat, Mati; Velin, Dominique

    2014-01-01

    Helicobacter pylori (H. pylori) infection is one of the most common infections in human beings worldwide. H. pylori express lipopolysaccharides and flagellin that do not activate efficiently Toll-like receptors and express dedicated effectors, such as γ-glutamyl transpeptidase, vacuolating cytotoxin (vacA), arginase, that actively induce tolerogenic signals. In this perspective, H. pylori can be considered as a commensal bacteria belonging to the stomach microbiota. However, when present in the stomach, H. pylori reduce the overall diversity of the gastric microbiota and promote gastric inflammation by inducing Nod1-dependent pro-inflammatory program and by activating neutrophils through the production of a neutrophil activating protein. The maintenance of a chronic inflammation in the gastric mucosa and the direct action of virulence factors (vacA and cytotoxin-associated gene A) confer pro-carcinogenic activities to H. pylori. Hence, H. pylori cannot be considered as symbiotic bacteria but rather as part of the pathobiont. The development of a H. pylori vaccine will bring health benefits for individuals infected with antibiotic resistant H. pylori strains and population of underdeveloped countries. PMID:24914318

  19. Detection of Helicobacter pylori in Nasal Polyps.

    PubMed

    Bansal, Divya; Sharma, Sonal; Agarwal, Sarla; Saha, Rumpa; Gupta, Neelima

    2016-09-01

    To detect the presence of Helicobacter pylori in nasal polyps. A case-control study was conducted enrolling 35 patients with nasal polyps (cases) and patients undergoing septoplasty (controls). Fresh tissue samples were used for urea broth test and imprint cytology, while formalin fixed tissue sections were used for morphology, special stains and immunohistochemistry for H. pylori. Fresh stool samples from both groups were tested to correlate the gastrointestinal status. H. pylori was detected in 40.0 % (14/35) of cases and 8.5 % of controls (3/35) (p = 0.004) by immunohistochemistry. Amongst cases, eight were positive with urea broth test, six with imprint cytology (Giemsa stain), three with H & E, and nine with modified McMullen's stain. Hyperplasia of the lining epithelium and lymphoid aggregates were significantly noticed in nasal polyps positive for H. pylori. Stool antigen test was positive in subjects who were positive for H. pylori in the nasal mucosa. There appears to be an association between H. pylori and nasal polyps. Immunohistochemistry is more sensitive and specific method to detect H. pylori. H. pylori induced inflammatory tissue reaction pattern indicates a possible causal association. Further studies are needed to prove the causal relationship between H. pylori and nasal polyps. PMID:26830396

  20. Delineation of a Carcinogenic Helicobacter pylori Proteome*

    PubMed Central

    Franco, Aime T.; Friedman, David B.; Nagy, Toni A.; Romero-Gallo, Judith; Krishna, Uma; Kendall, Amy; Israel, Dawn A.; Tegtmeyer, Nicole; Washington, M. Kay; Peek, Richard M.

    2009-01-01

    Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons ever develop cancer. The extensive genetic diversity inherent to this pathogen has precluded comprehensive analyses of constituents that mediate carcinogenesis. We previously reported that in vivo adaptation of a non-carcinogenic H. pylori strain endowed the output derivative with the ability to induce adenocarcinoma, providing a unique opportunity to identify proteins selectively expressed by an oncogenic H. pylori strain. Using a global proteomics DIGE/MS approach, a novel missense mutation of the flagellar protein FlaA was identified that affects structure and function of this virulence-related organelle. Among 25 additional differentially abundant proteins, this approach also identified new proteins previously unassociated with gastric cancer, generating a profile of H. pylori proteins to use in vaccine development and for screening persons infected with strains most likely to induce severe disease. PMID:19470446

  1. [Helicobacter pylori and gastric ulcer].

    PubMed

    Maaroos, H I

    1994-01-01

    In connection with longitudinal ulcer studies and the demonstration of Helicobacter pylori as the main cause of chronic gastritis, new aspects of gastric ulcer recurrences and healing become evident. This extends the possibilities to prognosticate the course of gastric ulcer and to use more effective treatment. PMID:7937016

  2. Cell-Associated Hemolysis Induced by Helicobacter pylori Is Mediated by Phospholipases with Mitogen-Activated Protein Kinase-Activating Properties

    PubMed Central

    Sitaraman, Ramakrishnan; Israel, Dawn A.; Romero-Gallo, Judith

    2012-01-01

    Pathogenic Helicobacter pylori strains can selectively activate epithelial mitogen-activated protein kinase (MAPK) signaling pathways linked with disease. We now demonstrate that H. pylori-induced hemolysis is strain specific and is mediated by phospholipases PldA1 and PldD. Inactivation of PldD inhibited activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), indicating that H. pylori hemolytic phospholipases also harbor MAPK-activating properties. PMID:22205825

  3. Cell-associated hemolysis induced by Helicobacter pylori is mediated by phospholipases with mitogen-activated protein kinase-activating properties.

    PubMed

    Sitaraman, Ramakrishnan; Israel, Dawn A; Romero-Gallo, Judith; Peek, Richard M

    2012-03-01

    Pathogenic Helicobacter pylori strains can selectively activate epithelial mitogen-activated protein kinase (MAPK) signaling pathways linked with disease. We now demonstrate that H. pylori-induced hemolysis is strain specific and is mediated by phospholipases PldA1 and PldD. Inactivation of PldD inhibited activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), indicating that H. pylori hemolytic phospholipases also harbor MAPK-activating properties. PMID:22205825

  4. Toxicosis in Helicobacter Pylori infection - a hypothesis

    PubMed Central

    BELASCU, MIHAI

    2013-01-01

    Background and aim We present a new clinical entity in relation to the Helicobacter pylori infection characterized by complex and varied clinical extra-digestive manifestations. Clinical findings such as asthenia, adynamia, sleep disorders, hair and nails modifications, digestive symptoms and heart rhythm disorders describe the clinical aspect of toxicosis associated with Helicobacter pylori infection. Methods The clinical presentation and therapy of patients with Helicobacter pylori infection were analyzed. Results Combined drug therapy: antibiotics + proton pump inhibitors + colloidal bismuth compound determinate remission of the symptoms in the first 3 to 5 days. The characteristic of the relation between Helicobacter pylori and the mucus-epithelial cell complex, the properties of the bacterial cell components, and the inflammatory and immunological response targeting other organs describe the immuno-pathological outbreak of Helicobacter pylori. Conclusion We support the term of toxicosis associated with Helicobacter pylori infection in selected cases. PMID:26527950

  5. Diagnostic of Helicobacter pylori infection.

    PubMed

    Mégraud, Francis; Floch, Pauline; Labenz, Joachim; Lehours, Philippe

    2016-09-01

    There is progress in endoscopy techniques. While it is not yet possible to detect Helicobacter pylori directly in the stomach, it becomes easier to detect the mucosal changes induced by the bacteria. Some small changes can also increase the sensitivity of the invasive tests, for example culture or histology, but the wide use of proton-pump inhibitors has a negative impact on these tests. Only molecular methods are able to detect a limited load of bacteria, especially by using real-time PCR but also with new methods, for example dual-priming oligonucleotide-based PCR, loop-medicated isothermal amplification, droplet-digital PCR or a multiple genetic analysis system. Among the noninvasive tests, urea breath test remains a test of major interest, while there are attempts to develop an ammonia breath test and other nanosensor devices. A new antigen stool test, a chemoluminescence immunoassay using the LIAISON apparatus has also been tested for the first time with success. Despite its limitations, serology remains the most popular test to detect H. pylori antibodies. It also allows pepsinogen dosage which is of interest for detecting atrophy. PMID:27531532

  6. Natural Killer Cells and Helicobacter pylori Infection: Bacterial Antigens and Interleukin-12 Act Synergistically To Induce Gamma Interferon Production

    PubMed Central

    Yun, Cheol H.; Lundgren, Anna; Azem, Josef; Sjöling, Åsa; Holmgren, Jan; Svennerholm, Ann-Mari; Lundin, B. Samuel

    2005-01-01

    Helicobacter pylori is known to induce a local immune response, which is characterized by activation of lymphocytes and the production of IFN-γ in the stomach mucosa. Since not only T cells, but also natural killer (NK) cells, are potent producers of gamma interferon (IFN-γ), we investigated whether NK cells play a role in the immune response to H. pylori infection. Our results showed that NK cells were present in both the gastric and duodenal mucosae but that H. pylori infection did not affect the infiltration of NK cells into the gastrointestinal area. Furthermore, we could show that NK cells could be activated directly by H. pylori antigens, as H. pylori bacteria, as well as lysate from H. pylori, induced the secretion of IFN-γ by NK cells. NK cells were also activated without direct contact when separated from the bacteria by an epithelial cell layer, indicating that the activation of NK cells by H. pylori can also occur in vivo, in the infected stomach mucosa. Moreover, the production of IFN-γ by NK cells was greatly enhanced when a small amount of interleukin-12 (IL-12) was added, and this synergistic effect was associated with increased expression of the IL-12 receptor β2. It was further evident that bacterial lysate alone was sufficient to induce the activation of cytotoxicity-related molecules. In conclusion, we demonstrated that NK cells are present in the gastroduodenal mucosa of humans and that NK cells produce high levels of IFN-γ when stimulated with a combination of H. pylori antigen and IL-12. We propose that NK cells play an active role in the local immune response to H. pylori infection. PMID:15731046

  7. ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.

    PubMed

    Das, Lopamudra; Kokate, Shrikant Babanrao; Rath, Suvasmita; Rout, Niranjan; Singh, Shivaram Prasad; Crowe, Sheila Eileen; Mukhopadhyay, Asish K; Bhattacharyya, Asima

    2016-06-01

    Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose. PMID:27048589

  8. ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2

    PubMed Central

    Das, Lopamudra; Kokate, Shrikant Babanrao; Rath, Suvasmita; Rout, Niranjan; Singh, Shivaram Prasad; Crowe, Sheila Eileen; Mukhopadhyay, Asish K.; Bhattacharyya, Asima

    2016-01-01

    Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose. PMID:27048589

  9. Helicobacter pylori and skin autoimmune diseases.

    PubMed

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-02-14

    Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori (H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins (HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Behçet's disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review. PMID:24587626

  10. Inactivation of Helicobacter pylori by Chloramination

    EPA Science Inventory

    Three strains of Helicobacter pylori (H. pylori) were studied to determine their resistance to chloramination. H. pylori is an organism listed on the U.S. Environmental Protection Agency’s (USEPA) Contaminant Control List (CCL). H. pylori was exposed to 2ppm of pre-formed monoc...

  11. Helicobacter pylori in oral ulcerations.

    PubMed

    Shimoyama, T; Horie, N; Kato, T; Kaneko, T; Komiyama, K

    2000-12-01

    Helicobacter pylori is an important pathogen involved in the development of gastrointestinal ulcers, but its involvement in oral ulcerous lesions is unclear. As culture is generally recognized as the gold standard for diagnosis of H. pylori infection, we employed this approach to assess the association of H. pylori with oral mucosal ulcerations. Samples were collected from patients with oral mucosal ulcerative disorders: 12 cases of recurrent aphthous stomatitis (RAS), 7 cases of herpes simplex virus (HSV) stomatitis, and 3 cases of erosive lichen planus (LP). Serum IgG antibodies against H. pylori were examined in all cases. All of the RAS and erosive LP cases were culture-negative for H. pylori, while two cases of HSV stomatitis were positive. The two culture-positive cases were also seropositve for the H. pylori antigen. It is suggested that H. pylori might not have a direct association with oral ulcerations. However, H. pylori in the oral cavity might exist in a non-culturable coccoid state without productive infection, and might form colonies only under special conditions such as HSV infection. PMID:11269381

  12. Halitosis and Helicobacter pylori infection.

    PubMed

    Tangerman, A; Winkel, E G; de Laat, L; van Oijen, A H; de Boer, W A

    2012-03-01

    There is disagreement about a possible relationship between Helicobacter pylori (H. pylori) infection and objective halitosis, as established by volatile sulfur compounds (VSCs) in the breath. Many studies related to H. pylori used self-reported halitosis, a subjective and unreliable method to detect halitosis. In this study a possible relation between H. pylori and halitosis was evaluated, using an objective method (gas chromatography, GC) to detect the VSCs, responsible for the halitosis. The levels of the VSCs hydrogen sulfide (H(2)S), methyl mercaptan (MM) and dimethyl sulfide (DMS) were measured in mouth breath and in stomach air of 11 H. pylori positive patients and of 38 H. pylori negative patients, all with gastric pathology. Halitosis was also established by organoleptic scoring (OLS) of mouth-breath. The levels of H(2)S, MM and DMS in the mouth-breath and stomach air of the H. pylori positive patients did not differ significantly from those of the H. pylori negative patients. OLS of the mouth-breath resulted in 9 patients with halitosis, 1 out of the H. pylori positive group and 8 out of the H. pylori negative group, which is not statistically different. The concentrations of the VSCs in stomach air were in nearly all cases below the thresholds of objectionability of the various VSCs, indicating that halitosis does not originate in the stomach. The patients with gastric pathology were also compared with control patients without gastric pathology and with normal volunteers. No significant differences in VSCs in mouth breath were observed between these groups. Thus, in this study no association between halitosis and H. pylori infection was found. Halitosis, as established by GC and OLS, nearly always originates within the oral cavity and seldom or never within the stomach. PMID:22368251

  13. Arginase II Restricts Host Defense to Helicobacter pylori by Attenuating Inducible Nitric Oxide Synthase Translation in Macrophages

    PubMed Central

    Lewis, Nuruddeen D.; Asim, Mohammad; Barry, Daniel P.; Singh, Kshipra; de Sablet, Thibaut; Boucher, Jean-Luc; Gobert, Alain P.; Chaturvedi, Rupesh; Wilson, Keith T.

    2010-01-01

    Helicobacter pylori infection of the stomach causes peptic ulcer disease and gastric cancer. Despite eliciting a vigorous immune response, the bacterium persists for the life of the host. An important antimicrobial mechanism is the production of NO derived from inducible NO synthase (iNOS). We have reported that macrophages can kill H. pylori in vitro by an NO-dependent mechanism, but supraphysiologic levels of the iNOS substrate L-arginine are required. Because H. pylori induces arginase activity in macrophages, we determined if this restricts NO generation by reducing L-arginine availability. Inhibition of arginase with S-(2-boronoethyl)-L-cysteine (BEC) significantly enhanced NO generation in H. pylori-stimulated RAW 264.7 macrophages by enhancing iNOS protein translation but not iNOS mRNA levels. This effect resulted in increased killing of H. pylori that was attenuated with an NO scavenger. In contrast, inhibition of arginase in macrophages activated by the colitis-inducing bacterium Citrobacter rodentium increased NO without affecting iNOS levels. H. pylori upregulated levels of arginase II (Arg2) mRNA and protein, which localized to mitochondria, whereas arginase I was not induced. Increased iNOS protein and NO levels were also demonstrated by small interfering RNA knockdown of Arg2 and in peritoneal macrophages from C57BL/6 Arg2−/− mice. In H. pylori-infected mice, treatment with BEC or deletion of Arg2 increased iNOS protein levels and NO generation in gastric macrophages, but treatment of Arg2−/− mice with BEC had no additional effect. These studies implicate Arg2 in the immune evasion of H. pylori by causing intracellular depletion of L-arginine and thus reduction of NO-dependent bactericidal activity. PMID:20097867

  14. [Helicobacter pylori infection in childhood].

    PubMed

    Okuda, Masumi; Fukuda, Yoshihiro

    2009-12-01

    Helicobacter pylori (H. pylori) infection is mainly acquired in the first 2 or 3 years and the risk of infection declines rapidly after 5 years of age. In developing countries, acquisition age of the infection is probably lower than in developed countries. In Japan, main transmission route is intrafamilial and mother to children infection is most important. But in developing countries, some reports suggest that extrafamilial infection is more important. The famous paper revealed that H. pylori can be cultivated from vomitus, saliva and cathartic stools and the possibility of source of H. pylori infection. Bed sharing, large number of family members, delayed weaning from a feeding bottle, regurgitated gastric juice in the mother's mouth are reported as risk factors of the infection. PMID:19999106

  15. Helicobacter pylori infection and gastric cancer.

    PubMed

    Sugiyama, Toshiro; Asaka, Masahiro

    2004-09-01

    Helicobacter pylori infection has an association with histological gastritis, gastric atrophy, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma in the stomach. Gastric cancer occurs in only a minority of infected individuals, however. Such clinical diversities are caused by variations of H. pylori pathogenicity, host susceptibility, environmental factors, and interactions of these factors. By three prospective epidemiological studies, the International Agency for Research on Cancer, World Health Organization (IARC/WHO) concluded in 1994 that H. pylori had a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. In addition, the Mongolian gerbil model with or without low-dose chemical carcinogens demonstrated that H. pylori infection could develop into gastric cancer. The experimental studies have elucidated that virulence factors of H. pylori have an interaction with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster and codes the type IV secretion machinery system, forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird morphology, growth factor-like effect. The other gene products are probably translocated into target cells and accelerate cellular proliferation and apoptosis. Understanding the molecular mechanism of the interaction between H. pylori and gastric epithelial cells will provide us with a new strategy for effective prevention of the development of gastric cancer induced by H. pylori infection. PMID:15449106

  16. [Association of chronic urticaria with Helicobacter pylori-induced antrum gastritis].

    PubMed

    Bohmeyer, J; Heller, A; Hartig, C; Wetenberger-Treumann, M; Huchzermeyer, H; Otte, H G; Stadler, R

    1996-02-01

    In spite of its high incidence, not much is known about the etiology of chronic urticaria. We performed gastroscopic evaluation of 10 patients in whom no cause for chronic urticaria had been found. In 8 of these 10 patients, Helicobacter pylori was identified in the gastric mucosa. The chronic urticarial lesions disappeared within a few days after starting therapy with amoxicillin and omeprazol. PMID:8868453

  17. Mucosal Inducible NO Synthase-Producing IgA+ Plasma Cells in Helicobacter pylori-Infected Patients.

    PubMed

    Neumann, Laura; Mueller, Mattea; Moos, Verena; Heller, Frank; Meyer, Thomas F; Loddenkemper, Christoph; Bojarski, Christian; Fehlings, Michael; Doerner, Thomas; Allers, Kristina; Aebischer, Toni; Ignatius, Ralf; Schneider, Thomas

    2016-09-01

    The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)-dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori-infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS(+) cell population in H. pylori-infected patients and confirmed intracellular NO production. Because we did not detect iNOS(+) PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS(+) PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA(+) PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS(+) PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection. PMID:27456483

  18. Characterization of an Acidic-pH-Inducible Stress Protein (hsp70), a Putative Sulfatide Binding Adhesin, from Helicobacter pylori

    PubMed Central

    Huesca, Mario; Goodwin, Avery; Bhagwansingh, Arianna; Hoffman, Paul; Lingwood, Clifford A.

    1998-01-01

    The in vitro glycolipid binding specificity of the gastric pathogen Helicobacter pylori is altered to include sulfated glycolipids (sulfatides) following brief exposure of the organism to acid pH typical of the stomach. This change is prevented by anti-hsp70 antibodies, suggesting that hsp70 may be a stress-induced surface adhesin, mediating sulfatide recognition. To facilitate investigation of the role of hsp70 in attachment, we have cloned and sequenced the H. pylori hsp70 gene (dnaK). The hsp70 gene was identified by probing a cosmid DNA library made from H. pylori 439 with a PCR amplicon generated with oligonucleotides synthesized to highly conserved regions of dnaK. The 1.9-kb H. pylori hsp70 gene encodes a product of 616 amino acids. Primer extension analysis revealed a single transcription start site, while Northern blot analysis established that hsp70 was preferentially induced by low pH rather than by heat shock. The ability of H. pylori to alter its glycolipid binding specificity following exposure to low pH by upregulating hsp70 and by expressing hsp70 on the bacterial surface may provide a survival advantage during periods of high acid stress. PMID:9712748

  19. Helicobacter pylori in gastric carcinogenesis

    PubMed Central

    Ahn, Hyo Jun; Lee, Dong Soo

    2015-01-01

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981

  20. Helicobacter pylori in gastric carcinogenesis.

    PubMed

    Ahn, Hyo Jun; Lee, Dong Soo

    2015-12-15

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981

  1. Laryngopharyngeal reflux and Helicobacter pylori

    PubMed Central

    Yılmaz, Taner; Bajin, Münir Demir; Günaydın, Rıza Önder; Özer, Serdar; Sözen, Tevfik

    2014-01-01

    Laryngopharyngeal reflux (LPR) occurs when gastric contents pass the upper esophageal sphincter, causing symptoms such as hoarseness, sore throat, coughing, excess throat mucus, and globus. The pattern of reflux is different in LPR and gastroesophageal reflux. LPR usually occurs during the daytime in the upright position whereas gastroesophageal reflux disease more often occurs in the supine position at night-time or during sleep. Ambulatory 24-h double pH-probe monitoring is the gold standard diagnostic tool for LPR. Acid suppression with proton pump inhibitor on a long-term basis is the mainstay of treatment. Helicobacter pylori (H. pylori) is found in many sites including laryngeal mucosa and interarytenoid region. In this paper, we aim to present the relationship between LPR and H. pylori and review the current literature. PMID:25083069

  2. Enterohepatic Helicobacter other than Helicobacter pylori.

    PubMed

    Mateos-Muñoz, Beatriz; Pérez-de-la-Serna, Julio; Ruiz-de-León, Antonio; Serrano-Falcón, Blanca; Casabona-Francés, Sergio; Velasco-Cerrudo, Aurelio; Rey-Díaz-Rubio, Enrique

    2013-09-01

    The Helicobacter genus includes Gram negative bacteria which were originally considered to belong to the Campylobacter genus. They have been classified in a separate genus since 1989 because they have different biochemical characteristics, with more than 24 species having been identified and more still being studied.H. pylori is the best known. It has an important etiopathogenic role in peptic ulcer disease and gastric cancer. Enterohepatic Helicobacters (EHH) other than H. pylori colonize the bowel, biliary tree and liver of animals and human beings with pathogenic potential. The difficulties existing to correctly isolate these microorganisms limit the description of their true prevalence and of the diseases they cause. Many studies have tried to discover the different clinical implications of EHH. Diseases like chronic liver disease, autoimmune hepatitis, hepatocarcinoma, autoimmune hepatobiliary disease, biliary lithiasis, cholangiocarcinoma and gallbladder cancer, Meckel´s diverticulum, acute appendicitis and inflammatory bowel disease have been related with different EHH species with different results, although their prevalence is greater than in healthy subjects. However, these data are currently not sufficient to draw definitive conclusions. Finally, the best known role of EHH in bowel disease is production of acute and chronic diarrhea pictures initially referred to as Campylobacter. H. pullorum has been identified in patients with acute gastroenteritis. The correct identification of EHH as producers of infectious gastroenteritis is found in its antibiotic susceptibility. It is generally macrolide-susceptible and quinolone-resistant. PMID:24274445

  3. Green Synthesis of Silver Nanoparticles: Structural Features and In Vivo and In Vitro Therapeutic Effects against Helicobacter pylori Induced Gastritis

    PubMed Central

    Hameed, Sadaf; Ali, Asghar; Anwar, Farooq; Shahid, Shaukat Ali; Shakir, Imran; Yaqoob, Aqdas; Hasan, Sara; Khan, Safyan Akram; Sajjad-ur-Rahman

    2014-01-01

    This study evaluates in vivo and in vitro anti-Helicobacter pylori (H. pylori) efficacy of silver nanoparticles (Ag-NPs) prepared via a cost-effective green chemistry route wherein Peganum harmala L. seeds extract was used as a reducing and capping agent. The structural features, as elucidated by surface plasmon resonance spectrophotometry, transmission electron microscopy, and powder X-ray diffraction spectroscopy, revealed the Ag-NPs synthesized to be polydispersed in nature and spherical in shape with 5–40 nm size. A typical Ag-NPs suspension (S5), with size being 15 nm, when tested in vitro against forty-two local isolates and two reference strains, showed a considerable anti-H. pylori activity. In case of in vivo trial against H. pylori induced gastritis, after oral administration of 16 mg/kg body weight of S5 for seven days, a complete clearance was recorded in male albino rates. In comparative time-killing kinetics, S5 exhibited dose- and time-dependent anti-H. pylori activity that was almost similar to tetracycline and clarithromycin, less than amoxicillin, but higher than metronidazole. Furthermore, S5 was found to be an equally effective anti-H. pylori agent at low (≤4) and high pH with no drug resistance observed even up to 10 repeated exposures while a significant drug resistance was recorded for most of the standard drugs employed. The present results revealed the potential of the synthesized Ag-NPs as safer bactericidal agents for the treatment of H. pylori induced gastritis. PMID:25214825

  4. Accumulation of abasic sites induces genomic instability in normal human gastric epithelial cells during Helicobacter pylori infection.

    PubMed

    Kidane, D; Murphy, D L; Sweasy, J B

    2014-01-01

    Helicobacter pylori infection of the human stomach is associated with inflammation that leads to the release of reactive oxygen and nitrogen species (RONs), eliciting DNA damage in host cells. Unrepaired DNA damage leads to genomic instability that is associated with cancer. Base excision repair (BER) is critical to maintain genomic stability during RONs-induced DNA damage, but little is known about its role in processing DNA damage associated with H. pylori infection of normal gastric epithelial cells. Here, we show that upon H. pylori infection, abasic (AP) sites accumulate and lead to increased levels of double-stranded DNA breaks (DSBs). In contrast, downregulation of the OGG1 DNA glycosylase decreases the levels of both AP sites and DSBs during H. pylori infection. Processing of AP sites during different phases of the cell cycle leads to an elevation in the levels of DSBs. Therefore, the induction of oxidative DNA damage by H. pylori and subsequent processing by BER in normal gastric epithelial cells has the potential to lead to genomic instability that may have a role in the development of gastric cancer. Our results are consistent with the interpretation that precise coordination of BER processing of DNA damage is critical for the maintenance of genomic stability. PMID:25417725

  5. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis

    PubMed Central

    Valenzuela, Manuel A; Canales, Jimena; Corvalán, Alejandro H; Quest, Andrew FG

    2015-01-01

    The sequence of events associated with the development of gastric cancer has been described as “the gastric precancerous cascade”. This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context. PMID:26668499

  6. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis.

    PubMed

    Valenzuela, Manuel A; Canales, Jimena; Corvalán, Alejandro H; Quest, Andrew F G

    2015-12-01

    The sequence of events associated with the development of gastric cancer has been described as "the gastric precancerous cascade". This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context. PMID:26668499

  7. [Role of ammonia-monochloramine system in Helicobacter pylori--induced gastric mucosal injury].

    PubMed

    Suzuki, M; Miura, S

    1993-12-01

    Monochloramine is a reactive oxidant which is yielded by the reaction of neutrophil-derived hypochlorous acid and ammonia. Luminol-dependent chemiluminescence assay reveals that H. pylori directly elicits a respiratory burst of neutrophils. This activation is also observed by adding the bacterial supernatant of cultured or sonicated H. pylori, suggesting that H. pylori-derived soluble factor may be responsible for the release of chlorinated oxidants. In vitro cytotoxicity assay indicates that cultured rabbit gastric mucosal cells are significantly damaged by neutrophils which are stimulated by H. pylori. This injury is attenuated by urease inhibitor, antioxidants, and taurine (monochloramine scavenger). These data support the concept that ammonia-monochloramine system plays an important role in H. pylori-associated gastric mucosal injury. Omeprazole and rebamipide significantly inhibit not only H. pylori-induced respiratory burst of neutrophils but also H. pylori-associated urease activity. This evidence emphasizes the advantageous effect of these anti-ulcer compounds on H. pylori-positive gastric lesion and postulates a new strategy for anti-H. pylori treatment. PMID:8283624

  8. Epidemiology of Helicobacter pylori infection.

    PubMed

    Leja, Mārcis; Axon, Anthony; Brenner, Hermann

    2016-09-01

    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. PMID:27531531

  9. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    SciTech Connect

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  10. The Mongolian Gerbil: A Robust Model of Helicobacter pylori-Induced Gastric Inflammation and Cancer.

    PubMed

    Noto, Jennifer M; Romero-Gallo, Judith; Piazuelo, M Blanca; Peek, Richard M

    2016-01-01

    The Mongolian gerbil is an efficient, robust, and cost-effective rodent model that recapitulates many features of H. pylori-induced gastric inflammation and carcinogenesis in humans, allowing for targeted investigation of the bacterial determinants and environmental factors and, to a lesser degree, host constituents that govern H. pylori-mediated disease. This chapter discusses means through which the Mongolian gerbil model has been used to define mechanisms of H. pylori-inflammation and cancer as well as the current materials and methods for utilizing this model of microbially induced disease. PMID:27246040

  11. Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45.

    PubMed Central

    Aihara, M; Tsuchimoto, D; Takizawa, H; Azuma, A; Wakebe, H; Ohmoto, Y; Imagawa, K; Kikuchi, M; Mukaida, N; Matsushima, K

    1997-01-01

    Accumulating evidence suggests an important role of interleukin-8 (IL-8) in Helicobacter pylori infection-associated chronic atrophic gastritis and peptic ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori but not with killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by a permeable membrane, indicating that IL-8 production requires a direct contact between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori-induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA expression in MKN45 cells and an increase in luciferase activity in cells which were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8 production occurred at the transcriptional level. This region contain three cis elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of the NF-kappaB binding site abrogated completely the induction of luciferase activity, whereas that of the AP-1 site partially reduced the induction. However, mutation of the NF-IL6 binding site resulted in no decrease in the induction of luciferase activity. Moreover, specific NF-kappaB complexes were detected in the nuclear proteins extracted from MKN45 cells which were infected with H. pylori. Collectively, these results suggest that H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription. PMID:9234778

  12. Non-pharmacological treatment of Helicobacter pylori

    PubMed Central

    Shmuely, Haim; Domniz, Noam; Yahav, Jacob

    2016-01-01

    Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532

  13. Non-pharmacological treatment of Helicobacter pylori.

    PubMed

    Shmuely, Haim; Domniz, Noam; Yahav, Jacob

    2016-05-01

    Many food and plant extracts have shown in vitro anti-Helicobacter pylori (H. pylori) activity, but are less effective in vivo. The anti-H. pylori effects of these extracts are mainly permeabilitization of the membrane, anti-adhesion, inhibition of bacterial enzymes and bacterial grown. We, herein, review treatment effects of cranberry, garlic, curcumin, ginger and pistacia gum against H. pylori in both in vitro, animal studies and in vivo studies. PMID:27158532

  14. Consequences of Helicobacter pylori infection in children

    PubMed Central

    Pacifico, Lucia; Anania, Caterina; Osborn, John F; Ferraro, Flavia; Chiesa, Claudio

    2010-01-01

    Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the human stomach for many decades without adverse consequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent abdominal pain, chronic idiopathic thrombocytopenia, and poor growth. There is evidence of the role of H. pylori in childhood iron deficiency anemia, but the results are not conclusive. The possibility of an inverse relationship between H. pylori and gastroesophageal reflux disease, as well as childhood asthma, remains a controversial question. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. PMID:21049552

  15. Eradication of Helicobacter pylori Infection.

    PubMed

    Marcus, Elizabeth A; Sachs, George; Scott, David R

    2016-07-01

    Helicobacter pylori infects about 50 % of the world's population, causing at a minimum chronic gastritis. A subset of infected patients will ultimately develop gastric or duodenal ulcer disease, gastric adenocarcinoma, or MALT (mucosa-associated lymphoid tissue) lymphoma. Eradication of H. pylori requires complex regimens that include acid suppression and multiple antibiotics. The efficacy of treatment using what were once considered standard regimens have declined in recent years, mainly due to widespread development of antibiotic resistance. Addition of bismuth to standard triple therapy regimens, use of alternate antibiotics, or development of alternative regimens using known therapies in novel combinations have improved treatment efficacy in specific populations, but overall success of eradication remains less than ideal. Novel regimens under investigation either in vivo or in vitro, involving increased acid suppression ideally with fewer antibiotics or development of non-antibiotic treatment targets, show promise for future therapy. PMID:27177639

  16. Helicobacter pylori and extragastric diseases.

    PubMed

    Goni, Elisabetta; Franceschi, Francesco

    2016-09-01

    During the past year, many articles were published on the extragastric diseases related to Helicobacter pylori infection. This supports the theory that some microorganisms may cause diseases even far from the primary site of infection by interfering with different biologic processes. The role of H. pylori on idiopathic thrombocytopenic purpura, sideropenica anemia, and vitamin B12 deficiency is well known. On the other hand, there is a growing interest in the bacterium's association with cardiovascular, neurologic, hematologic, dermatologic, head and neck, and uro-gynecologic diseases, as well as diabetes mellitus and metabolic syndrome, with very promising results. This review has been aimed at summarizing the results of the most relevant studies published over the last year on this fascinating topic. PMID:27531539

  17. Effect of Di(2-ethylhexyl)phthalate on Helicobacter pylori-Induced Apoptosis in AGS Cells

    PubMed Central

    Wu, Chien-Yi; Kou, Hwang-Shang; Chen, Chiao-Yun; Huang, Meng-Chuan; Hu, Huang-Ming; Wu, Meng-Chieh; Lu, Chien-Yu; Wu, Deng-Chyang; Wu, Ming-Tsang; Kuo, Fu-Chen

    2013-01-01

    Plastic products are wildly used in human life. Di(2-ethylhexyl)phthalate (DEHP) is an essential additive in plastic manufacturing and is used as plasticizer for many products including plastic food packaging. DEHP is a teratogenic compound and can cause potent reproductive toxicity. DEHP can also cause liver damage, peroxisome proliferation, and carcinogenesis. DEHP is also strongly associated with peptic ulcers and gastric cancer; however, the underlying effect and mechanism of DEHP on the gastrointestinal tract are not entirely clear. The oral infection route of H. pylori parallels the major ingestion route of DEHP into the human body. Therefore, we wanted to study the effect of DEHP and H. pylori exposure on the human gastric epithelial cell line, AGS (gastric adenocarcinoma). The viability of the AGS cell line was significantly lower in 80 μM-DEHP and H. pylori (MOI = 100 : 1) coexposure than DEHP or H. pylori alone. DEHP and H. pylori coexposure also induced caspase-3 activation, and increased Bax/Bcl-2 ratio and DNA fragmentation in AGS cells. These results indicate that DEHP can enhance H. pylori cytotoxicity and induce gastric epithelial cell apoptosis. Therefore, it is possible that DEHP and H. pylori coexposure might enhance the disruption of the gastric mucosa integrity and potentially promote the pathogenesis of gastric carcinogenesis. PMID:24454344

  18. Effect of Di(2-ethylhexyl)phthalate on Helicobacter pylori-Induced Apoptosis in AGS Cells.

    PubMed

    Lin, Chuang-Hao; Wu, Chien-Yi; Kou, Hwang-Shang; Chen, Chiao-Yun; Huang, Meng-Chuan; Hu, Huang-Ming; Wu, Meng-Chieh; Lu, Chien-Yu; Wu, Deng-Chyang; Wu, Ming-Tsang; Kuo, Fu-Chen

    2013-01-01

    Plastic products are wildly used in human life. Di(2-ethylhexyl)phthalate (DEHP) is an essential additive in plastic manufacturing and is used as plasticizer for many products including plastic food packaging. DEHP is a teratogenic compound and can cause potent reproductive toxicity. DEHP can also cause liver damage, peroxisome proliferation, and carcinogenesis. DEHP is also strongly associated with peptic ulcers and gastric cancer; however, the underlying effect and mechanism of DEHP on the gastrointestinal tract are not entirely clear. The oral infection route of H. pylori parallels the major ingestion route of DEHP into the human body. Therefore, we wanted to study the effect of DEHP and H. pylori exposure on the human gastric epithelial cell line, AGS (gastric adenocarcinoma). The viability of the AGS cell line was significantly lower in 80  μ M-DEHP and H. pylori (MOI = 100 : 1) coexposure than DEHP or H. pylori alone. DEHP and H. pylori coexposure also induced caspase-3 activation, and increased Bax/Bcl-2 ratio and DNA fragmentation in AGS cells. These results indicate that DEHP can enhance H. pylori cytotoxicity and induce gastric epithelial cell apoptosis. Therefore, it is possible that DEHP and H. pylori coexposure might enhance the disruption of the gastric mucosa integrity and potentially promote the pathogenesis of gastric carcinogenesis. PMID:24454344

  19. Helicobacter pylori infection in pediatrics.

    PubMed

    Iwańczak, Barbara; Francavailla, Ruggiero

    2014-09-01

    This review concerns important pediatric studies published from April 2013 to March 2014. New data on pathogenesis have demonstrated that Th1 type cytokine secretion at the gastric level is less intense in children compared with adults. They have also shown that the most significant risk factor for Helicobacter pylori infection is the parents' origin and frequency of childcare in settings with a high prevalence of infection. A new hypothesis on the positive relationship between childhood H. pylori infection and the risk of gastric cancer in adults has been suggested which calls for an implementation of preventive programs to reduce the burden of childhood H. pylori infection in endemic areas. Several studies have investigated the role of H. pylori infection in iron-deficiency anemia, and results support the role of the bacterium in this condition. Antibiotic resistance is an area of intense research with data confirming an increase in antibiotic resistance, and the effect of CYP2C19 genetic polymorphism on proton-pump inhibitor metabolism should be further investigated as cure rates are lower in extensive metabolizers. Studies confirmed that probiotic supplementation may have beneficial effects on eradication and therapy-related side effects, particularly diarrhea in children. PMID:25167945

  20. Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role.

    PubMed

    Ricci, Vittorio; Giannouli, Maria; Romano, Marco; Zarrilli, Raffaele

    2014-01-21

    Helicobacter pylori (H. pylori) gamma-glutamyl transpeptidase (GGT) is a bacterial virulence factor that converts glutamine into glutamate and ammonia, and converts glutathione into glutamate and cysteinylglycine. H. pylori GGT causes glutamine and glutathione consumption in the host cells, ammonia production and reactive oxygen species generation. These products induce cell-cycle arrest, apoptosis, and necrosis in gastric epithelial cells. H. pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2, epidermal growth factor-related peptides, inducible nitric oxide synthase and interleukin-8. H. pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation. The effect of GGT on H. pylori colonization and gastric persistence are also discussed. PMID:24574736

  1. Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role

    PubMed Central

    Ricci, Vittorio; Giannouli, Maria; Romano, Marco; Zarrilli, Raffaele

    2014-01-01

    Helicobacter pylori (H. pylori) gamma-glutamyl transpeptidase (GGT) is a bacterial virulence factor that converts glutamine into glutamate and ammonia, and converts glutathione into glutamate and cysteinylglycine. H. pylori GGT causes glutamine and glutathione consumption in the host cells, ammonia production and reactive oxygen species generation. These products induce cell-cycle arrest, apoptosis, and necrosis in gastric epithelial cells. H. pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2, epidermal growth factor-related peptides, inducible nitric oxide synthase and interleukin-8. H. pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation. The effect of GGT on H. pylori colonization and gastric persistence are also discussed. PMID:24574736

  2. Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori.

    PubMed

    Watanabe, Tatsuro; Takahashi, Atsushi; Suzuki, Kaori; Kurusu-Kanno, Miki; Yamaguchi, Kensei; Fujiki, Hirota; Suganuma, Masami

    2014-05-15

    Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. Tipα acts as a homodimer with 38-kDa protein, whereas del-Tipα is an inactive monomer. H. pylori isolated from gastric cancer patients secreted large amounts of Tipα, which are incorporated into gastric cancer cells by directly binding to nucleolin on the cell surface, which is a receptor of Tipα. The binding complex induces expression of TNF-α and chemokine genes, and activates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). To understand the mechanisms of Tipα in tumor progression, we looked at numerous effects of Tipα on human gastric cancer cell lines. Induction of cell migration and elongation was found to be mediated through the binding to surface nucleolin, which was inhibited by the nucleolin-targeted siRNAs. Tipα induced formation of filopodia in MKN-1 cells, suggesting invasive morphological changes. Tipα enhanced the phosphorylation of 11 cancer-related proteins in serine, threonine and tyrosine, indicating activation of MEK-ERK signal cascade. Although the downregulation of E-cadherin was not shown in MKN-1 cells, Tipα induced the expression of vimentin, a significant marker of the epithelial-mesenchymal transition (EMT). It is of great importance to note that Tipα reduced the Young's modulus of MKN-1 cells determined by atomic force microscopy: This shows lower cell stiffness and increased cell motility. The morphological changes induced in human gastric cancer cells by Tipα are significant phenotypes of EMT. This is the first report that Tipα is a new inducer of EMT, probably associated with tumor progression in human gastric carcinogenesis. PMID:24249671

  3. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis.

    PubMed

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-08-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK-HO-1 signaling. PMID:26022128

  4. Inactivation of Helicobacter pylori by chlorination.

    PubMed Central

    Johnson, C H; Rice, E W; Reasoner, D J

    1997-01-01

    Three strains of Helicobacter pylori were studied to determine their resistance to chlorination. The organisms were readily inactivated by free chlorine and should therefore be controlled by disinfection practices normally employed in the treatment of drinking water. PMID:9406419

  5. Helicobacter pylori γ-glutamyl transpeptidase-induced Ca(2+) release via PLC-IP3 receptors in AGS cells.

    PubMed

    Park, Eun-Hee; Kim, Jung-Min; Kim, Kyung-Mi; Kang, Dawon; Cho, Young-Ah; Choi, Jun-Young; Song, Jea-Young; Kang, Hyung-Lyun; Lee, Woo-Kon; Cho, Myung-Je; Rhee, Kwang-Ho; Seo, Ji-Hyun; Youn, Hee-Shang; Baik, Seung-Chul

    2014-12-01

    In our previous study, γ-glutamyl transpeptidase (GGT) isolated from Helicobacter pylori induced apoptosis of AGS cells. Here, we investigate Ca(2+) effects on GGT-induced apoptosis. The GGT transiently and significantly increased intracellular Ca(2+) concentration ([Ca(2+)]i) in AGS cells in a dose-dependent manner (P < 0.05). The GGT-induced Ca(2+) increase resulted from Ca(2+) influx and release through the phospholipase C - inositol 1,4,5-trisphosphate (PLC-IP3) pathway. The GGT-induced apoptosis was significantly reduced by treatment with U73122 (a PLC inhibitor) and xestospongin (an IP3 receptor antagonist) (P < 0.05). These results indicate that GGT could induce apoptosis of AGS cells by high levels of [Ca(2+)]i. PMID:25409842

  6. Effect of resveratrol on Helicobacter pylori-induced interleukin-8 secretion, reactive oxygen species generation and morphological changes in human gastric epithelial cells.

    PubMed

    Zaidi, Syed Faisal Haider; Ahmed, Kanwal; Yamamoto, Takeshi; Kondo, Takashi; Usmanghani, Khan; Kadowaki, Makoto; Sugiyama, Toshiro

    2009-11-01

    Inflammatory cytokine interleukin-8 (IL-8) and reactive oxygen species (ROS) overexpressed in the gastric mucosa when exposed to Helicobacter pylori, defined as a class I carcinogen. Moreover, infection with H. pylori leads to morphological changes in co-cultured cells known as hummingbird phenomenon along with increased motility. Resveratrol, a highly abundant polyphenol in red grapes, has shown anti-inflammatory, anti-cancer, cardioprotective and neuroprotective activities. However, the effect of resveratrol in H. pylori-infected cells has not been investigated. The present study was, therefore, aimed to evaluate the effect of resveratrol on the induction of IL-8, ROS and hummingbird morphology in H. pylori-infected gastric epithelial cells. The non-toxic concentration of resveratrol for both H. pylori and epithelial cells was determined by brucella broth dilution method and DNA fragmentation assay. The non-toxic resveratrol (< or =100 microM) treatment did not demonstrate any inhibitory effect against H. pylori adhesion to gastric epithelial cells. However, preincubation of the cells with 75 and 100 muM of resveratrol significantly (p<0.05 and p<0.01 respectively) inhibited the secretion of IL-8 from H. pylori-infected cells. In addition, resveratrol pretreatment at 1-100 muM suppressed H. pylori-induced ROS generation in a concentration dependent manner. Moreover, H. pylori-initiated morphological changes were markedly blocked by resveratrol. Hence, resveratrol can be considered as a potential candidate against various H. pylori related gastric pathogenic processes. PMID:19881312

  7. Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis

    PubMed Central

    Santos, Juliana Carvalho; Ribeiro, Marcelo Lima

    2015-01-01

    Although thousands of DNA damaging events occur in each cell every day, efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoiding the maintenance of mutations. The DNA repair enzymes continuously monitor the chromosomes to correct any damage that is caused by exogenous and endogenous mutagens. If DNA damage in proliferating cells is not repaired because of an inadequate expression of DNA repair genes, it might increase the risk of cancer. In addition to mutations, which can be either inherited or somatically acquired, epigenetic silencing of DNA repair genes has been associated with carcinogenesis. Gastric cancer represents the second highest cause of cancer mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes during the lifetime. Among the risk factors, Helicobacter pylori (H. pylori) infection is considered the main driving factor to gastric cancer development. Thus, in this review, we summarize the current knowledge of the role of H. pylori infection on the epigenetic regulation of DNA repair machinery in gastric carcinogenesis. PMID:26290630

  8. Soluble extracts from Helicobacter pylori induce dome formation in polarized intestinal epithelial monolayers in a laminin-dependent manner.

    PubMed

    Terrés, A M; Windle, H J; Ardini, E; Kelleher, D P

    2003-07-01

    Helicobacter pylori colonizes the stomach at the interface between the mucus layer and the apical pole of gastric epithelial cells. A number of secreted and shed products from the bacteria, such as proteins and lipopolysaccharide, are likely to have a role in the pathogenesis at the epithelial level. To determine the physiological response of transporting polarized epithelia to released soluble factors from the bacterium, we used the T84 cell line. Monolayers of T84 cells were exposed to soluble extracts from H. pylori. The extracts induced rapid "dome" formation as well as an immediate decrease in transepithelial electrical resistance. Domes are fluid-filled blister-like structures unique to polarized epithelia. Their formation has been linked to sodium-transporting events as well as to diminished adherence of the cells to the substrate. H. pylori-induced dome formation in T84 monolayers was exacerbated by amiloride and inhibited by ouabain. Furthermore, it was associated with changes in the expression of the laminin binding alpha 6 beta 4 integrin and the 67-kDa laminin receptor. Domes formed primarily on laminin-coated filters, rather than on fibronectin or collagen matrices, and their formation was inhibited by preincubating the bacterial extract with soluble laminin. This effect was specific to H. pylori and independent of the urease, vacA, cagA, and Lewis phenotype of the strains. These data indicate that released elements from H. pylori can alter the physiological balance and integrity of the epithelium in the absence of an underlying immune response. PMID:12819097

  9. Helicobacter pylori: a role in schizophrenia?

    PubMed

    Yilmaz, Yusuf; Gul, Cuma Bulent; Arabul, Mahmut; Eren, Mehmet Ali

    2008-07-01

    Schizophrenia is a devastating psychiatric disorder that affects approximately one percent of the world's adult population. Despite substantial investigative efforts over the last decades, the exact mechanisms and pathogenesis of this condition are not yet fully understood. Published data support certain infectious agents as potential risk factors for schizophrenia. Since its discovery, Helicobacter pylori has been implicated in a variety of extra-digestive diseases, but its potential role in the pathogenesis of psychiatric disorders has thus far been neglected. It is hypothesized here that infection with H. pylori occurring in early childhood may induce persisting systemic biochemical aberrations, including dopaminergic dysfunction, decreased levels of essential polyunsaturated fatty acids, subtle inflammation, and homocysteine alterations, that may play a crucial role in the development of schizophrenia in genetically predisposed individuals. Evidence in favor of this hypothesis is provided and possible therapeutic implications are discussed. PMID:18591925

  10. Biofilm formation by Helicobacter pylori.

    PubMed

    Stark, R M; Gerwig, G J; Pitman, R S; Potts, L F; Williams, N A; Greenman, J; Weinzweig, I P; Hirst, T R; Millar, M R

    1999-02-01

    Helicobacter pylori NCTC 11637 produces a water-insoluble biofilm when grown under defined conditions with a high carbon:nitrogen ratio in continuous culture and in 10% strength Brucella broth supplemented with 3 g l-1 glucose. Biofilm accumulated at the air/liquid interface of the culture. Light microscopy of frozen sections of the biofilm material showed few bacterial cells in the mass of the biofilm. The material stained with periodic acid Schiff's reagent. Fucose, glucose, galactose, and glycero-manno-heptose, N-acetylglucosamine and N-acetylmuramic acid were identified in partially purified and in crude material, using gas chromatography and mass spectrometry. The sugar composition strongly indicates the presence of a polysaccharide as a component of the biofilm material. Antibodies (IgG) to partially purified material were found in both sero-positive and sero-negative individuals. Treatment of the biofilm material with periodic acid reduced or abolished immunoreactivity. Treatment with 5 mol l-1 urea at 100 degrees C and with phenol did not remove antigenic recognition by patient sera. The production of a water-insoluble biofilm by H. pylori may be important in enhancing resistance to host defence factors and antibiotics, and in microenvironmental pH homeostasis facilitating the growth and survival of H. pylori in vivo. PMID:10063642

  11. Helicobacter pylori and Gastrointestinal Malignancies.

    PubMed

    Venerito, Marino; Vasapolli, Riccardo; Rokkas, Theodoros; Malfertheiner, Peter

    2015-09-01

    Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population

  12. [Helicobacter pylori-associated diseases].

    PubMed

    Gisbert, Javier P

    2015-09-01

    This article summarizes the main conclusions of the studies presented at Digestive Disease Week this year (2015) related to Helicobacter pylori infection. Despite the undeniable widespread reduction in the prevalence of H. pylori infection, developing countries continue to have substantial infection rates. The prevalence of clarithromycin, metronidazole and quinolone resistance is markedly higher in most countries and continues to rise. Although H. pylori eradication reduces the incidence of gastric adenocarcinoma, it does not completely prevent its development; the presence of precancerous lesions--intestinal atrophy and metaplasia--is associated with a higher risk of developing this neoplasm, despite H. pylori eradication. The use of molecular diagnostic methods (polymerase chain reaction) in faecal samples could allow non-invasive evaluation of the antibiotic susceptibility of H. pylori. The effectiveness of standard triple therapy is clearly insufficient and continues to decrease. The effectiveness of sequential therapy in recent studies is lower than initially described and consequently this treatment cannot be recommended in clinical practice. Concomitant therapy is more effective and simpler than sequential therapy. In penicillin-allergic patients, quadruple therapy with bismuth is the treatment of choice in our environment. After the failure of standard triple therapy, second-line therapy with levofloxacin is effective and, moreover, is simpler and better tolerated than quadruple therapy with bismuth. Quadruple therapy with a proton pump inhibitor, bismuth, levofloxacin and amoxicillin is an effective (≥ 90% eradication), simple and safe second-line therapy if triple or quadruple therapy without bismuth (sequential or concomitant) fails to eradicate the infection. The new-generation quinolones, such as moxifloxacin or sitafloxacin, could be useful in second- or third-line rescue eradication therapy. Even after the failure of 3 eradication treatments, a

  13. Changes in gastric microbiota induced by Helicobacter pylori infection and preventive effects of Lactobacillus plantarum ZDY 2013 against such infection.

    PubMed

    Pan, Mingfang; Wan, Cuixiang; Xie, Qiong; Huang, Renhui; Tao, Xueying; Shah, Nagendra P; Wei, Hua

    2016-02-01

    Helicobacter pylori is a gram-negative pathogen linked to gastric ulcers and stomach cancer. Gastric microbiota might play an essential role in the pathogenesis of these stomach diseases. In this study, we investigated the preventive effect of a probiotic candidate Lactobacillus plantarum ZDY 2013 as a protective agent against the gastric mucosal inflammation and alteration of gastric microbiota induced by H. pylori infection in a mouse model. Prior to infection, mice were pretreated with or without 400 µL of L. plantarum ZDY 2013 at a concentration of 10(9) cfu/mL per mouse. At 6 wk postinfection, gastric mucosal immune response and alteration in gastric microbiota mice were examined by quantitative real-time PCR and high-throughput 16S rRNA gene amplicon sequencing, respectively. The results showed that L. plantarum ZDY 2013 pretreatment prevented increase in inflammatory cytokines (e.g., IL-1β and IFN-γ) and inflammatory cell infiltration in gastric lamina propria induced by H. pylori infection. Weighted UniFrac principal coordinate analysis showed that L. plantarum ZDY 2013 pretreatment prevented the alteration in gastric microbiota post-H. pylori infection. Linear discriminant analysis coupled with effect size identified 22 bacterial taxa (e.g., Pasteurellaceae, Erysipelotrichaceae, Halomonadaceae, Helicobacteraceae, and Spirochaetaceae) that overgrew in the gastric microbiota of H. pylori-infected mice, and most of them belonged to the Proteobacteria phylum. Lactobacillus plantarum ZDY 2013 pretreatment prevented this alteration; only 6 taxa (e.g., Lachnospiraceae, Ruminococcaceae, and Clostridiaceae), mainly from the taxa of Firmicutes and Bacteroidetes, were dominant in the gastric microbiota of the L. plantarum ZDY 2013 pretreated mice. Administration of L. plantarum ZDY 2013 for 3 wk led to increase in several bacterial taxa (e.g., Rikenella, Staphylococcus, Bifidobacterium), although a nonsignificant alteration was found in the gastric microbiota

  14. Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype.

    PubMed Central

    Crabtree, J E; Covacci, A; Farmery, S M; Xiang, Z; Tompkins, D S; Perry, S; Lindley, I J; Rappuoli, R

    1995-01-01

    AIMS--To use a range of natural phenotypically variant strains of Helicobacter pylori with disparate CagA and VacA (vacuolating cytotoxin) expression to determine which bacterial factors are more closely associated with epithelial interleukin-8 (IL-8) induction. METHODS--Gastric epithelial cells (AGS and KATO-3) were co-cultured with five H pylori strains which were variously shown to express the cagA gene/CagA protein, VacA and/or to exhibit biological cytotoxicity. Secreted IL-8 was assayed by enzyme leaked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) was assayed using a reverse transcription polymerase chain reaction based technique (RT-PCR). RESULTS--Strains expressing CagA, including a variant strain (D931) which is non-cytotoxic and does not express the VacA protein, were found to upregulate epithelial IL-8 secretion and gene expression. In contrast, strains with no CagA expression, even in the presence of VacA and/or biological cytotoxicity, (G104, BA142), failed to induce IL-8 protein or mRNA above control values. CONCLUSIONS--These results strongly support a role for H pylori CagA or coexpressed factors other than the cytotoxin in upregulation of gastric epithelial IL-8. Increased epithelial IL-8 secretion and concomitant neutrophil chemotaxis and activation in addition to direct cytotoxicity may be an important factor in tissue damage and ulceration. Images PMID:7706517

  15. Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments.

    PubMed Central

    Papini, E; de Bernard, M; Milia, E; Bugnoli, M; Zerial, M; Rappuoli, R; Montecucco, C

    1994-01-01

    Pathogenic strains of Helicobacter pylori cause progressive vacuolation and death of epithelial cells. To identify the nature of vacuoles, the distribution of markers of various membrane traffic compartments was studied. Vacuoles derive from the endocytic pathway since they include the fluid-phase marker Lucifer yellow. Early endosome markers such as rab5, transferrin, and transferrin receptor, as well as the lysosomal hydrolase cathepsin D, are excluded from these structures. In contrast, the vacuolar membrane is specifically stained by affinity-purified antibodies against rab7, a small GTPase, localized to late endosomal compartments. The labeling of rab7 on vacuolar membranes increases as vacuolation progresses, without a concomitant increase of cellular rab7. Cell vacuolation is inhibited by the microtubule-depolymerizing agents nocodazole and colchicine. Taken together, these findings indicate that the vacuoles specifically originate from late endosomal compartments. Images PMID:7937879

  16. Helicobacter pylori-infected MSCs acquire a pro-inflammatory phenotype and induce human gastric cancer migration by promoting EMT in gastric cancer cells

    PubMed Central

    ZHANG, QIANG; DING, JUAN; LIU, JINJUN; WANG, WEI; ZHANG, FENG; WANG, JUNHE; LI, YUYUN

    2016-01-01

    Accumulating clinical and experimental evidence has suggested that Helicobacter pylori (H. pylori) infection-associated gastric cancer (GC) is associated with high rates of mortality and serious health effects. The majority of patients succumb to H. pylori infection-associated GC due to metastasis. Mesenchymal stem cells (MSCs), which have multipotent differentiation potential, may be recruited into the tumor-associated stroma. MSCs are crucial components of the H. pylori infection-associated GC microenvironment, and may be critical for GC cell migration. In this study, an MSCs/H. pylori co-culture model was designed, and the effect of H. pylori-infected MSCs on the migration of GC cells was evaluated using a Transwell migration assay. H. pylori-infected MSC cytokine expression was evaluated using Luminex/ELISA. The expression of epithelial-mesenchymal transition (EMT) markers in the GC cells treated with supernatants from H. pylori-infected MSCs were detected by western blot analysis. The results demonstrated that the interaction between MSCs and H. pylori may induce GC cell migration, through secretion of a combination of cytokines that promote EMT in GC cells. The expression of phosphorylated forms of nuclear factor-κB (NF-κB) was observed to be increased in MSCs by H. pylori. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate blocked the effects of H. pylori-infected MSCs on SGC-7901 human stomach adenocarcinoma cell migration. Overall, the results of the present study suggest that H. pylori-infected MSCs acquire a pro-inflammatory phenotype through secretion of a combination of multiple cytokines, a number of which are NF-κB-dependent. These cytokines enhance H. pylori infection-associated GC cell migration by promoting EMT in GC cells. The results of the present study provide novel evidence for the modulatory effect of MSCs in the tumor microenvironment and provide insight into the significance of stromal cell involvement in GC progression

  17. Effect of Byrsonima crassa and Phenolic Constituents on Helicobacter pylori-Induced Neutrophils Oxidative Burst

    PubMed Central

    Bonacorsi, Cibele; Raddi, Maria Stella G.; da Fonseca, Luiz Marcos; Sannomiya, Miriam; Vilegas, Wagner

    2012-01-01

    Byrsonima crassa Niedenzu (Malpighiaceae) is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In a previous study, our group described the gastric protective effect of the methanolic extract from the leaves of B. crassa. The present study was carried out to investigate the effects of methanolic extract and its phenolic compounds on the respiratory burst of neutrophils stimulated by H. pylori using a luminol-based chemiluminescence assay as well as their anti-H. pylori activity. The suppressive activity on oxidative burst of H. pylori-stimulated neutrophils was in the order of methyl gallate > (+)-catechin > methanol extract > quercetin 3-O-α-l-arabinopyranoside > quercetin 3-O-β-d-galactopyranoside > amentoflavone. Methyl gallate, compound that induced the highest suppressive activity with IC50 value of 3.4 μg/mL, did not show anti-H. pylori activity. B. crassa could be considered as a potential source of natural antioxidant in gastric ulcers by attenuating the effects on the damage to gastric mucosa caused by neutrophil generated reactive oxygen species, even when H. pylori displays its evasion mechanisms. PMID:22312243

  18. (-)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells.

    PubMed

    Xie, Jianhui; Lin, Zhixiu; Xian, Yanfang; Kong, Songzhi; Lai, Zhengquan; Ip, Siupo; Chen, Haiming; Guo, Huizhen; Su, Zuqing; Yang, Xiaobo; Xu, Yang; Su, Ziren

    2016-06-01

    (-)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions. PMID:27017292

  19. Medicinal plant activity on Helicobacter pylori related diseases

    PubMed Central

    Wang, Yuan-Chuen

    2014-01-01

    More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori

  20. Helicobacter pylori in dental plaque of Pakistanis.

    PubMed

    Butt, A K; Khan, A A; Bedi, R

    1999-07-01

    Helicobacter pylori is now generally accepted to play a key role in acid related and neoplastic pathology of gastroduodenal diseases. Recent reports have concluded that dental plaque is not an important reservoir for Helicobacter pylori, however, these studies did not consider the ethnic background of their subjects nor the amounts of dental plaque present. The aim of this study was to explore the association of Helicobacter pylori dental plaque colonisation in 125 males and 53 females (group I) attending a dental clinic in Pakistan. A simultaneous sample of 30 healthy volunteers with good orodental hygiene consisting of 17 males and 13 females was included as a control group (group II). Six dental plaque specimens were obtained from each subject with a sickle scaler; two were inoculated into CLO test gel and the remaining four were used to prepare cytology slides stained with Giemsa's stain. CLO test was positive in all specimens from group I, while cytology for Helicobacter pylori was positive in 173 cases in this group. One hundred and forty two cases had heavy plaque deposits and all of them were positive on cytology. In group II CLO test was positive in 20 and dental plaque cytology was positive in 7 cases. In conclusion, it is important that future studies into the prevalence of Helicobacter pylori in the oral cavity should take into account the levels of oral cleanliness and the ethnic background of the subjects. PMID:10833287

  1. Acid, protons and Helicobacter pylori.

    PubMed Central

    Sachs, G.; Meyer-Rosberg, K.; Scott, D. R.; Melchers, K.

    1996-01-01

    The anti-ulcer drugs that act as covalent inhibitors of the gastric acid pump are targeted to the gastric H+/K+ ATPase by virtue of accumulation in acid and conversion to the active sulfenamide. This results in extremely effective inhibition of acid secretion. Appropriate dosage is able to optimize acid control therapy for reflux and peptic ulcer disease as compared to H2 receptor antagonists. However, clinical data on recurrence show that Helicobacter pylori eradication should accompany treatment of the lesion. These drugs have been found to synergize with many antibiotics for eradication. The survival of aerobes depends on their ability to maintain a driving force for protons across their inner membrane, the sum of a pH and potential difference gradient, the protonmotive force (pmf). The transmembrane flux of protons across the F1F0 ATPase, driven by the pmf, is coupled to the synthesis of ATP. The internal pH of H. pylori was measured using the fluorescent dye probe, BCECF, and the membrane potential defined by the uptake of the carbocyanine dye, DiSC3 [5] at different pHs to mimic the gastric environment. The protonmotive force at pH 7.0 was composed of a delta pH of 1.4 (-84mV) and a delta potential difference of -131mV, to give a pmf of -215 mV. The effect of variations in external pH on survival of the bacteria in the absence of urea correlated with the effect of external pH on the ability of the bacteria to maintain a pmf. The effect of the addition of 5 mM urea on the pmf was measured at different medium pH values. Urea restored the pmf at pH 3.0 or 3.5, but abolished the pmf at pH 7.0 or higher, due the production of the alkalinizing cation, NH3. Hence H. pylori is an acid-tolerant neutrophile due to urease activity, but urease activity also limits its survival to an acidic environment. These data help explain the occupation of the stomach by the organism and its distribution between fundus and antrum. This distribution and its alteration by proton pump

  2. Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells

    PubMed Central

    Byun, Eunyoung; Park, Bohye; Lim, Joo Weon

    2016-01-01

    Purpose In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. Materials and Methods Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. Results H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. Conclusion H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells. PMID:26996564

  3. Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates DSS-induced colitis

    PubMed Central

    Luther, Jay; Owyang, Stephanie Y.; Takeuchi, Tomomi; Cole, Tyler; Zhang, Min; Liu, Maochang; Erb-Downward, John; Rubenstein, Joel H.; Kao, John Y.

    2012-01-01

    Background & Aims Recently there has been emerging epidemiological data to suggest Helicobacter pylori (H. pylori) may protect against certain chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, the mechanism for the observed inverse association between H. pylori and IBD has not been described. Methods The frequency of immunoregulatory (IRS) to immunostimulatory (ISS) sequences within the genome of various bacteria was calculated using MacVector software. The induction of type I IFN and IL-12 responses by DNA-pulsed murine bone marrow–derived dendritic cells (BMDC) and human plasmacytoid dendritic cells (pDC) was analyzed by cytokine production. The effect of H. pylori DNA on E. coli DNA production of type I IFN and IL-12 was assessed. The in vivo significance of H. pylori DNA suppression was assessed in a DSS-model of colitis. The systemic levels of type I IFN were assessed in H. pylori-colonized and non-colonized patients. Results We showed that H. pylori DNA has a significantly elevated IRS:ISS ratio. In vitro experiments revealed the inability of H. pylori DNA to stimulate type I IFN or IL-12 production from mouse BMDCs or human pDCs. Additionally, H. pylori DNA was able to suppress E. coli-DNA production of type I IFN and IL-12. Administration of H. pylori DNA prior to the induction of DSS colitis significantly ameliorated the severity of colitis as compared to E. coli DNA or vehicle control in both an acute and chronic model. Finally, the systemic levels of type I IFN were found to be lower in H. pylori-colonized patients versus non-colonized controls. Conclusions Overall, our study indicates that H pylori DNA has the ability to down-regulate pro-inflammatory responses from DCs and this may in part explain the inverse association between H. pylori and IBD. PMID:21471567

  4. Immunization with Heat Shock Protein A and γ-Glutamyl Transpeptidase Induces Reduction on the Helicobacter pylori Colonization in Mice.

    PubMed

    Zhang, Xiaoli; Zhang, Jinyong; Yang, Feng; Wu, Weiru; Sun, Heqiang; Xie, Qinghua; Si, Weike; Zou, Quanming; Yang, Zhong

    2015-01-01

    The human gastric pathogen Helicobacter pylori (H. pylori) is a successful colonizer of the stomach. H. pylori infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing H. pylori infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and H. pylori γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against H. pylori infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in Escherichia coli and purified. Mice were then immunized intranasally with these proteins, with or without adjuvant. Immunized mice exhibited reduced bacterial colonization in stomach. The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response, as well as a balanced Th1/Th2 cytokine response. In addition, immunofluorescence microscopy confirmed that rHspA-GGT specific rabbit antibodies were able to directly bind H. pylori in vitro. These results suggest antibodies are essential to the protective immunity associated with rHspA-GGT immunization. In summary, our results suggest HspA and GGT are promising vaccine candidates for protection against H. pylori infection. PMID:26102080

  5. Variant of Helicobacter pylori CagA proteins induce different magnitude of morphological changes in gastric epithelial cells.

    PubMed

    Alfizah, Hanafiah; Ramelah, Mohamed

    2012-06-01

    Infection with Helicobacter pylori cagA-positive strains is associated with gastroduodenal diseases. The CagA protein is injected into gastric epithelial cells and supposedly induces morphological changes termed the 'hummingbird phenotype', which is associated with scattering and increased cell motility. The molecular mechanisms leading to the CagA-dependent morphological changes are only partially known. The present study was carried out to investigate the effect of CagA variants on the magnitude of gastric epithelial cell morphological changes. Recombinant 3' terminal domains of cagA were cloned and expressed in a gastric epithelial cell line and the hummingbird phenotype was quantified by microscopy. The 3' region of the cagA gene of Malaysian H. pylori isolates showed six sub-genotypes that differed in the structural organization of the EPIYA repeat sequences. The percentage of hummingbird cells induced by CagA increased with duration of transfection. The hummingbird phenotype was observed to be more pronounced when CagA with 4 EPIYA motifs rather than 3 or 2 EPIYA motifs was produced. The activity of different CagA variants in the induction of the hummingbird phenotype in gastric epithelial cells depends at least in part on EPIYA motif variability. The difference in CagA genotypes might influence the potential of individual CagAs to cause morphological changes in host cells. Depending on the relative exposure of cells to CagA genotypes, this may contribute to the various disease outcomes caused by H. pylori infection in different individuals. PMID:22870595

  6. Helicobacter pylori activation of PARP-1

    PubMed Central

    Nossa, Carlos W

    2010-01-01

    Chronic infection of the human stomach by Helicobacter pylori is an important risk factor for gastric cancer. H. pylori produces a cache of virulence factors that promote colonization and persistence, which, in turn, contributes to a robust inflammatory response at the host-pathogen interface. Recently, we reported that H. pylori activates the abundant nuclear regulator poly(ADP-ribose) polymerase (PARP)-1, resulting in the production of the catabolite poly(ADP-ribose) (PAR). PARP-1 is emerging as a key player in establishing homeostasis at the host-pathogen interface. In this article, we summarize the discovery of H. pylori-dependent PARP-1 activation, and discuss potential roles for PARP-1 in H. pylori-mediated gastric disease. In light of the remarkable successes that have reported for treating inflammatory disorders and cancers with PARP-1 inhibitors, we discuss the prospects of targeting PARP-1 for treatment of H. pylori-associated gastric disease. PMID:21468218

  7. Recurrent aphthous stomatitis and Helicobacter pylori

    PubMed Central

    Gomes, Carolina-Cavaliéri; Gomez, Ricardo-Santiago; Zina, Lívia-Guimarães

    2016-01-01

    Background Recurrent aphthous stomatitis (RAS) is a recurrent painful ulcerative disorder that commonly affects the oral mucosa. Local and systemic factors such as trauma, food sensitivity, nutritional deficiencies, systemic conditions, immunological disorders and genetic polymorphisms are associated with the development of the disease. Helicobacter pylori (H. pylori) is a gram-negative, microaerophile bacteria, that colonizes the gastric mucosa and it was previously suggested to be involved in RAS development. In the present paper we reviewed all previous studies that investigated the association between RAS and H. pylori. Material and Methods A search in Pubmed (MEDLINE) databases was made of articles published up until July 2015 using the following keywords: Helicobacter Pylori or H. pylori and RAS or Recurrent aphthous stomatitis. Results Fifteen experimental studies that addressed the relationship between infection with H. pylori and the presence of RAS and three reviews, including a systematic review and a meta-analysis were included in this review. The studies reviewed used different methods to assess this relationship, including PCR, nested PCR, culture, ELISA and urea breath test. A large variation in the number of patients included in each study, as well as inclusion criteria and laboratorial methods was observed. H. pylori can be detected in the oral mucosa or ulcerated lesion of some patients with RAS. The quality of the all studies included in this review was assessed using levels of evidence based on the University of Oxford’s Center for Evidence Based Medicine Criteria. Conclusions Although the eradication of the infection may affect the clinical course of the oral lesions by undetermined mechanisms, RAS ulcers are not associated with the presence of the bacteria in the oral cavity and there is no evidence that H. pylori infection drives RAS development. Key words:Campylobacter, elisa, h. pylori, Helicobacter Pylori, RAS, recurrent aphthous

  8. [Helicobacter pylori, the story so far].

    PubMed

    D'Elios, Mario Milco

    2007-01-01

    Helicobacter pylori is a bacterial pathogen infecting the gastric antrum of half the population worldwide. H. pylori has been discovered in 1982 by J. Robin Warren and Barry J. Marshall as the major cause of gastroduodenal pathologies, including gastric and duodenal ulcer, gastric cancer and gastric B-cell lymphoma of mucosa-associated lymphoid tissue. For this great discovery Warren and Marshall deserved the Nobel Prize for Medicine and Physiology in 2005. PMID:18450040

  9. Hyperhomocysteinaemia, Helicobacter pylori, and coronary heart disease.

    PubMed

    Sung, J J; Sanderson, J E

    1996-10-01

    Hyperhomocysteinaemia and Helicobacter pylori infection have recently been implicated in the pathogenesis of coronary artery disease. These two risk factors, though they seem unrelated, could be linked by a deficiency of vitamins and folate caused by chronic gastritis in H pylori infection. This nutritional defect could lead to failure of methylation by 5-methyl-tetrahydrofolic acid and thus exacerbate the accumulation of homocysteine in susceptible patients. Homocysteine is toxic to endothelial cells and results in coronary artery disease. PMID:8983673

  10. Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection.

    PubMed

    Liu, Wei; Tan, Zhoulin; Xue, Jinfeng; Luo, Wenjin; Song, Hui; Lv, Xiaobo; Zheng, Tianjing; Xi, Tao; Xing, Yingying

    2016-07-01

    The gastric bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans and plays a critical role in the development of gastritis, peptic ulceration and gastric adenocarcinoma. Consequently, the eradication of H. pylori might contribute to the prevention of H. pylori-associated gastric diseases. In this study, a multi-epitope vaccine CTB-UE (CUE) was displayed on the surface of non-genetically modified Lactococcus lactis particles (GEM) to enhance immunogenicity. This particulate vaccine CUE-GEM induced serum and mucosal specific antibody responses against native H. pylori urease and provided potent protection to eliminate H. pylori colonization and relieve gastritis in an H. pylori-infected BALB/c mouse model. The immuno-protective mechanisms are highly associated with CD4(+) Th cell-mediated and humoral immunity, especially local immunity. There might be two main aspects of this association. One aspect is related to the suppression of urease activity by promotion of the production of specific mucosal neutralizing antibody. The other aspect is correlated with alleviating gastritis by regulating the gastric pro-inflammatory cytokine profile, especially IFN-γ and IL-17. These results demonstrated that conjugating antigen vaccines with GEM particles could lead to promising oral therapeutic vaccine formulations against H. pylori infection. PMID:26846746

  11. RAD51 G135C genetic polymorphism and their potential role in gastric cancer induced by Helicobacter pylori infection in Bhutan.

    PubMed

    Trang, T T H; Nagashima, H; Uchida, T; Mahachai, V; Vilaichone, R-K; Tshering, L; Binh, T T; Yamaoka, Y

    2016-01-01

    In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan--a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients. PMID:26119522

  12. Identification of MyD88 as a novel target of miR-155, involved in negative regulation of Helicobacter pylori-induced inflammation.

    PubMed

    Tang, Bin; Xiao, Bin; Liu, Zhen; Li, Na; Zhu, En-Dong; Li, Bo-Sheng; Xie, Qing-Hua; Zhuang, Yuan; Zou, Quan-Ming; Mao, Xu-Hu

    2010-04-16

    MicroRNA-155 (miR-155) has been implicated as a central regulator of the immune system. We have previously reported that miR-155 negatively regulates Helicobacter pylori (H. pylori)-induced inflammation, but the molecular mechanism of miR-155 regulating the inflammation is not fully clear. Here, we identified myeloid differentiation protein 88 (MyD88) as a target gene of miR-155, and found that miR-155 decreased MyD88 expression at the protein but not the mRNA message level, suggesting that the miR-155-mediated inhibition is a post-transcriptional event. Furthermore, the overexpression of miR-155 led to significantly reduced IL-8 production induced by H. pylori infection. Thus, we have demonstrated that miR-155 can negatively regulate inflammation by targeting a key adaptor molecule MyD88 in inflammatory pathways. PMID:20219467

  13. Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and invasive growth of gastric epithelial cells

    PubMed Central

    2011-01-01

    Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of Helicobacter pylori (H. pylori) infected gastric epithelial cells leading to cell migration and invasive growth. Considering the cellular mechanisms, the type IV secretion system (T4SS) and the effector protein cytotoxin-associated gene A (CagA) of H. pylori are well-studied initiators of distinct signal transduction pathways in host cells targeting kinases, adaptor proteins, GTPases, actin binding and other proteins involved in the regulation of the actin lattice. In this review, we summarize recent findings of how H. pylori functionally interacts with the complex signaling network that controls the actin cytoskeleton of motile and invasive gastric epithelial cells. PMID:22044652

  14. Jak1/Stat3 is an upstream signaling of NF-κB activation in Helicobacter pylori-induced IL-8 production in gastric epithelial AGS cells.

    PubMed

    Cha, Boram; Lim, Joo Weon; Kim, Hyeyoung

    2015-05-01

    Helicobacter pylori (H. pylori) induces the activation of nuclear factor-kB (NF-κB) and cytokine expression in gastric epithelial cells. The Janus kinase/signal transducers and activators of transcription (Jak/Stat) cascade is the inflammatory signaling in various cells. The purpose of the present study is to determine whether H. pylori-induced activation of NF-κB and the expression of interleukin-8 (IL-8) are mediated by the activation of Jak1/Stat3 in gastric epithelial (AGS) cells. Thus, gastric epithelial AGS cells were infected with H. pylori in Korean isolates (HP99) at bacterium/cell ratio of 300:1, and the level of IL-8 in the medium was determined by enzyme-linked immonosorbent assay. Phospho-specific and total forms of Jak1/Stat3 and IκBα were assessed by Western blot analysis, and NF-κB activation was determined by electrophoretic mobility shift assay. The results showed that H. pylori induced the activation of Jak1/Stat3 and IL-8 production, which was inhibited by a Jak/Stat3 specific inhibitor AG490 in AGS cells in a dose-dependent manner. H. pylori-induced activation of NF-κB, determined by phosphorylation of IκBα and NF-κB-DNA binding activity, were inhibited by AG490. In conclusion, Jak1/Stat3 activation may mediate the activation of NF-κB and the expression of IL-8 in H. pylori-infected AGS cells. Inhibition of Jak1/Stat3 may be beneficial for the treatment of H. pylori-induced gastric inflammation, since the activation of NF-κB is inhibited and inflammatory cytokine expression is suppressed. PMID:25837197

  15. Jak1/Stat3 Is an Upstream Signaling of NF-κB Activation in Helicobacter pylori-Induced IL-8 Production in Gastric Epithelial AGS Cells

    PubMed Central

    Cha, Boram; Lim, Joo Weon

    2015-01-01

    Helicobacter pylori (H. pylori) induces the activation of nuclear factor-kB (NF-κB) and cytokine expression in gastric epithelial cells. The Janus kinase/signal transducers and activators of transcription (Jak/Stat) cascade is the inflammatory signaling in various cells. The purpose of the present study is to determine whether H. pylori-induced activation of NF-κB and the expression of interleukin-8 (IL-8) are mediated by the activation of Jak1/Stat3 in gastric epithelial (AGS) cells. Thus, gastric epithelial AGS cells were infected with H. pylori in Korean isolates (HP99) at bacterium/cell ratio of 300:1, and the level of IL-8 in the medium was determined by enzyme-linked immonosorbent assay. Phospho-specific and total forms of Jak1/Stat3 and IκBα were assessed by Western blot analysis, and NF-κB activation was determined by electrophoretic mobility shift assay. The results showed that H. pylori induced the activation of Jak1/Stat3 and IL-8 production, which was inhibited by a Jak/Stat3 specific inhibitor AG490 in AGS cells in a dose-dependent manner. H. pylori-induced activation of NF-κB, determined by phosphorylation of IκBα and NF-κB-DNA binding activity, were inhibited by AG490. In conclusion, Jak1/Stat3 activation may mediate the activation of NF-κB and the expression of IL-8 in H. pylori-infected AGS cells. Inhibition of Jak1/Stat3 may be beneficial for the treatment of H. pylori-induced gastric inflammation, since the activation of NF-κB is inhibited and inflammatory cytokine expression is suppressed. PMID:25837197

  16. Iron deficiency anaemia and Helicobacter pylori infection.

    PubMed

    Annibale, B; Capurso, G; Martino, G; Grossi, C; Delle Fave, G

    2000-12-01

    Iron deficiency anaemia (IDA) is the most common form of anaemia world-wide. IDA is the simple result of an imbalance between iron loss and absorption. Gastric function with hydrochloric and ascorbic acid is essential for iron absorption. Some strains of Helicobacter pylori are able to acquire iron, competing with the host. A large percentage of patients with atrophic body gastritis (ABG) develop IDA and 61% of them are H. pylori positive. Recent evidence suggests that H. pylori infection could cause IDA in the absence of peptic ulcer or other upper gastrointestinal (GI) tract bleeding lesions. Gastritis extending to the corpus and a high bacterial load are features of these patients. About 70% of IDA patients with ABG or H. pylori gastritis are premenopausal women. Both ABG and H. pylori gastritis should be considered when evaluating the GI tract of patients with iron deficiency anaemia. PMID:11118871

  17. Withaferin A Inhibits Helicobacter pylori-induced Production of IL-1β in Dendritic Cells by Regulating NF-κB and NLRP3 Inflammasome Activation

    PubMed Central

    Kim, Jae-Eun; Lee, Jun-Young; Kang, Min-Jung; Jeong, Yu-Jin; Choi, Jin-A; Oh, Sang-Muk

    2015-01-01

    Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. There is evidence that IL-1β is associated with the development of gastric cancer. Therefore, downregulation of H. pylori-mediated IL-1β production may be a way to prevent gastric cancer. Withaferin A (WA), a withanolide purified from Withania somnifera, is known to exert anti-inflammatory and anti-tumor effects. In the present study, we explored the inhibitory activity of WA on H. pylori-induced production of IL-1β in murine bone marrow-derived dendritic cells (BMDCs) and the underlying cellular mechanism. Co-treatment with WA decreased IL-1β production by H. pylori in BMDCs in a dose-dependent manner. H. pylori-induced gene expression of IL-1β and NLRP3 (NOD-like receptor family, pyrin domain containing 3) were also suppressed by WA treatment. Moreover, IκB-α phosphorylation by H. pylori infection was suppressed by WA in BMDCs. Western blot analysis revealed that H. pylori induced cleavage of caspase-1 and IL-1β, as well as increased procaspase-1 and pro IL-1β protein levels, and that both were suppressed by co-treatment with WA. Finally, we determined whether WA can directly inhibit ac tivation of the NLRP3 inflammasome. NLRP3 activators induced IL-1β secretion in LPS-primed macrophages, which was inhibited by WA in a dose-dependent manner, whereas IL-6 production was not affected by WA. Moreover, cleavage of IL-1β and caspase-1 by NLRP3 activators was also dose-dependently inhibited by WA. These findings suggest that WA can inhibit IL-1β production by H. pylori in dendritic cells and can be used as a new preventive and therapeutic agent for gastric cancer. PMID:26770181

  18. Withaferin A Inhibits Helicobacter pylori-induced Production of IL-1β in Dendritic Cells by Regulating NF-κB and NLRP3 Inflammasome Activation.

    PubMed

    Kim, Jae-Eun; Lee, Jun-Young; Kang, Min-Jung; Jeong, Yu-Jin; Choi, Jin-A; Oh, Sang-Muk; Lee, Kyung-Bok; Park, Jong-Hwan

    2015-12-01

    Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. There is evidence that IL-1β is associated with the development of gastric cancer. Therefore, downregulation of H. pylori-mediated IL-1β production may be a way to prevent gastric cancer. Withaferin A (WA), a withanolide purified from Withania somnifera, is known to exert anti-inflammatory and anti-tumor effects. In the present study, we explored the inhibitory activity of WA on H. pylori-induced production of IL-1β in murine bone marrow-derived dendritic cells (BMDCs) and the underlying cellular mechanism. Co-treatment with WA decreased IL-1β production by H. pylori in BMDCs in a dose-dependent manner. H. pylori-induced gene expression of IL-1β and NLRP3 (NOD-like receptor family, pyrin domain containing 3) were also suppressed by WA treatment. Moreover, IκB-α phosphorylation by H. pylori infection was suppressed by WA in BMDCs. Western blot analysis revealed that H. pylori induced cleavage of caspase-1 and IL-1β, as well as increased procaspase-1 and pro IL-1β protein levels, and that both were suppressed by co-treatment with WA. Finally, we determined whether WA can directly inhibit ac tivation of the NLRP3 inflammasome. NLRP3 activators induced IL-1β secretion in LPS-primed macrophages, which was inhibited by WA in a dose-dependent manner, whereas IL-6 production was not affected by WA. Moreover, cleavage of IL-1β and caspase-1 by NLRP3 activators was also dose-dependently inhibited by WA. These findings suggest that WA can inhibit IL-1β production by H. pylori in dendritic cells and can be used as a new preventive and therapeutic agent for gastric cancer. PMID:26770181

  19. New immunological investigations on Helicobacter pylori-induced gastric ulcer in patients.

    PubMed

    Rahimi, Hamid Reza; Rasouli, Manoochehr; Jamshidzadeh, Akram; Farshad, Shohreh; Firoozi, Mehdi Saberi; Taghavi, Ali Reza; Kiany, Simin

    2013-06-01

    Although Helicobacter pylori (Hp) plays an important role in the pathogenesis of chronic gastritis and gastric ulcer, little is known about the probable mechanisms of these types of gastrointestinal damage. To determine the precise mechanisms involved in ulcer formation, immune responses in patients with gastric ulcer (GUP) caused by Hp infection (Hp(+)) were compared with those of other gastritis patients (GP). The sensitivity and proliferation of peripheral blood mononuclear cells (PBMNCs) obtained from patients were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against exposure with complex Hp crude antigen (HPCA) and mitogen (phytohemagglutinin, PHA). Production of inflammatory cytokines, including interleukin (IL)-1β and IL-8, in serum and supernatants of PBMNCs were then measured by ELISA. It was found that, after stimulation with PHA, both IL-8 and IL-1β concentrations in sera and supernatants as well as proliferation and sensitivity were statistically greater in GUP Hp(+) than GP Hp(-) . Furthermore, HPCA inhibited the proliferation of PBMNCs dose-dependently; however, it stimulated IL-8 and IL-1β production in supernatants of mononuclear cells. Therefore, the up-regulated concentrations of IL-8 and IL-1β may have been caused by increase in the size of mononuclear cell subpopulations or in their cytokine secretory activity, indicating the greatest cell responsiveness in GUP Hp(+) patients. These results suggest that tissue damage and ulcers occur in patients who produce more IL-8 and IL-1β than patients who do not develop ulcers; the former consequently have more activated immune cells at the site of infection. Therefore, both host responses and Hp virulence factors may be involved in the development of gastric ulcers. PMID:23773024

  20. Helicobacter pylori infection and drugs malabsorption

    PubMed Central

    Lahner, Edith; Virili, Camilla; Santaguida, Maria Giulia; Annibale, Bruno; Centanni, Marco

    2014-01-01

    Drug absorption represents an important factor affecting the efficacy of oral drug treatment. Gastric secretion and motility seem to be critical for drug absorption. A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori (H. pylori) infection has been proposed. Associations have been reported between poor bioavailability of l-thyroxine and l-dopa and H. pylori infection. According to the Maastricht Florence Consensus Report on the management of H. pylori infection, H. pylori treatment improves the bioavailability of both these drugs, whereas the direct clinical benefits to patients still await to be established. Less strong seems the association between H. pylori infection and other drugs malabsorption, such as delavirdine and ketoconazole. The exact mechanisms forming the basis of the relationship between H. pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated. H. pylori infection may trigger a chronic inflammation of the gastric mucosa, and impaired gastric acid secretion often follows. The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption. This minireview focuses on the evidence of H. pylori infection associated with impaired drug absorption. PMID:25132749

  1. Helicobacter pylori and allergy: Update of research

    PubMed Central

    Daugule, Ilva; Zavoronkova, Jelizaveta; Santare, Daiga

    2015-01-01

    Recently a lot of literature has been published about the possible preventive action of Helicobacter pylori (H. pylori) against allergy. The present review summarizes research data about the association between H. pylori and allergic diseases, as well as discusses possible hypotheses about the preventive action of H. pylori against atopy. There is evidence from observational studies to support a weak inverse association between prevalence of H. pylori infection and allergy. However, confounders like some unidentified socioeconomic factors, antibiotic use and others could bias the association. Although data from cohort studies point to a possible association of H. pylori with some of the allergic diseases, no definite proof for causal relationship has been clearly demonstrated yet. A biological mechanism proposed to explain the preventive action of H. pylori to allergy is reduced exposure to a major stimulus for the generation of Treg cells in individuals without H. pylori infection. In addition, H. pylori could be an indicator for changes in gut microbiome, reflecting the complex interaction between microbes and immune system. PMID:26713280

  2. Relation between periodontitis and helicobacter pylori infection

    PubMed Central

    Zheng, Pei; Zhou, Weiying

    2015-01-01

    Objective: The correlation between periodontitis and Helicobacter pylori (H. pylori) infection in the mouth was analyzed. Method: 70 elderly patients with periodontitis treated at our hospital from January 2013 to December 2014 were recruited. Dental plaques and gargle were collected for H. pylori detection using PCR technique. Periodontal health status of the patients was recorded. 70 control cases with healthy periodontium were also included. The symptoms of H. pylori infection in the mouth were compared between the two groups, and the results were analyzed statistically. Results: The positive rate of urease C gene of H. pylori in the periodontitis group was 71.4%; the positive rate of cagA gene was 35.7%. The positive rate of urease C gene of H. pylori in the control group was 34.3% and that of cagA gene was 12.9%. The two groups did not show significant differences in these two indicators (P<0.05). The positive detection rate of urease C gene of H. pylori in subgingival plaques was higher than that in supragingival plaques, and the difference was of statistical significance (P<0.05). The positive detection rate of H. pylori in patients with moderate and severe periodontitis was obviously higher than that of patients with mild periodontitis (P<0.05). Conclusion: Periodontal health status of elderly people with periodontitis correlated with H. pylori infection in the stomach. PMID:26629215

  3. Chitosan as an adjuvant for a Helicobacter pylori therapeutic vaccine.

    PubMed

    Gong, Yanfeng; Tao, Liming; Wang, Fucai; Liu, Wei; Jing, Lei; Liu, Dongsheng; Hu, Sijun; Xie, Yong; Zhou, Nanjin

    2015-09-01

    The aim of the present study was to delineate the therapeutic effect of a Helicobacter pylori vaccine with chitosan as an adjuvant, as well as to identify the potential mechanism against H. pylori infection when compared with an H. pylori vaccine, with cholera toxin (CT) as an adjuvant. Mice were first infected with H. pylori and, following the establishment of an effective infection model, were vaccinated using an H. pylori protein vaccine with chitosan as an adjuvant. Levels of H. pylori colonization, H. pylori‑specific antibodies and cytokines were determined by enzyme‑linked immunosorbent assay. The TLR4 and Foxp3 mRNA and protein levels were determined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. It was identified that the H. pylori elimination rate of the therapeutic vaccine with chitosan as an adjuvant (58.33%) was greater than the therapeutic vaccine with CT as an adjuvant (45.45%). The therapeutic H. pylori vaccine with chitosan as an adjuvant induced significantly greater antibody and cytokine levels when compared with the control groups. Notably, the IL‑10 and IL‑4 levels in the groups with chitosan as an adjuvant to the H. pylori vaccine were significantly greater than those in the groups with CT as an adjuvant. The mRNA expression levels of TLR4 and Foxp3 were significantly elevated in the mice that were vaccinated with chitosan as an adjuvant to the H. pylori vaccine, particularly in mice where the H. pylori infection had been eradicated. The H. pylori vaccine with chitosan as an adjuvant effectively increased the H. pylori elimination rate, the humoral immune response and the Th1/Th2 cell immune reaction; in addition, the therapeutic H. pylori vaccine regulated the Th1 and Th2 response. The significantly increased TLR4 expression and decreased CD4+CD25+Foxp3+Treg cell number contributed to the immune clearance of the H. pylori infection. Thus, the present findings demonstrate that in mice the H

  4. Genome Sequencing Reveals a Phage in Helicobacter pylori

    PubMed Central

    Lehours, Philippe; Vale, Filipa F.; Bjursell, Magnus K.; Melefors, Ojar; Advani, Reza; Glavas, Steve; Guegueniat, Julia; Gontier, Etienne; Lacomme, Sabrina; Alves Matos, António; Menard, Armelle; Mégraud, Francis; Engstrand, Lars; Andersson, Anders F.

    2011-01-01

    ABSTRACT Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, likely to grow as more genomes are sampled. Here we describe the draft genome sequence (63 contigs; 26× mean coverage) of H. pylori strain B45, isolated from a patient with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The major finding was a 24.6-kb prophage integrated in the bacterial genome. The prophage shares most of its genes (22/27) with prophage region II of Helicobacter acinonychis strain Sheeba. After UV treatment of liquid cultures, circular DNA carrying the prophage integrase gene could be detected, and intracellular tailed phage-like particles were observed in H. pylori cells by transmission electron microscopy, indicating that phage production can be induced from the prophage. PCR amplification and sequencing of the integrase gene from 341 H. pylori strains from different geographic regions revealed a high prevalence of the prophage (21.4%). Phylogenetic reconstruction showed four distinct clusters in the integrase gene, three of which tended to be specific for geographic regions. Our study implies that phages may play important roles in the ecology and evolution of H. pylori. PMID:22086490

  5. Recent "omics" advances in Helicobacter pylori.

    PubMed

    Berthenet, Elvire; Sheppard, Sam; Vale, Filipa F

    2016-09-01

    The development of high-throughput whole genome sequencing (WGS) technologies is changing the face of microbiology, facilitating the comparison of large numbers of genomes from different lineages of a same organism. Our aim was to review the main advances on Helicobacter pylori "omics" and to understand how this is improving our knowledge of the biology, diversity and pathogenesis of H. pylori. Since the first H. pylori isolate was sequenced in 1997, 510 genomes have been deposited in the NCBI archive, providing a basis for improved understanding of the epidemiology and evolution of this important pathogen. This review focuses on works published between April 2015 and March 2016. Helicobacter "omics" is already making an impact and is a growing research field. Ultimately these advances will be translated into a routine clinical laboratory setting in order to improve public health. PMID:27531533

  6. Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of β-catenin signaling axis in gastric cancer-initiating cells.

    PubMed

    Kang, Dong Woo; Noh, Yu Na; Hwang, Won Chan; Choi, Kang-Yell; Min, Do Sik

    2016-08-01

    Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced β-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-β-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA-expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential. PMID:27265143

  7. Interaction between Helicobacter pylori and host genetic variants in gastric carcinogenesis.

    PubMed

    Jia, Zhi-Fang; Zhang, Song-Ling; Cao, Xue-Yuan; Zhou, Bao-Sen; Jiang, Jing

    2016-09-01

    Helicobacter pylori (H. pylori) is the definite carcinogen of gastric cancer. H. pylori infection induces chronic inflammation, causes DNA damage and aberrant methylation of genes and these pathways are involved in H. pylori-related gastric carcinogenesis. Polymorphisms of the genes involved in these pathways could alter susceptibility to gastric cancer. In this mini review, we focused on the role of polymorphisms in these genes on the susceptibility to gastric cancer, with a particular emphasis on their possible interactions with H. pylori infection. We found that many studies on this theme did not simultaneously report H. pylori infection and the interactions remained inconclusive. PMID:27324311

  8. Phytoceuticals: mighty but ignored weapons against Helicobacter pylori infection.

    PubMed

    Lee, Sun-Young; Shin, Yong Woon; Hahm, Ki-Baik

    2008-08-01

    Helicobacter pylori (H. pylori) infection causes peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas, for which the pathogenesis of chronic gastric inflammation prevails and provides the pathogenic basis. Since the role of H. pylori infection is promoting carcinogenesis rather than acting as a direct carcinogen, as several publications show, eradication alone cannot be the right answer for preventing H. pylori-associated gastric cancer. Therefore, a non-antimicrobial approach has been suggested to attain microbe-associated cancer prevention through controlling H. pylori-related chronic inflammatory processes and mediators responsible for carcinogenesis. Phytoceutical is a term for plant products that are active on biological systems. Phytoceuticals such as Korean red ginseng, green tea, red wine, flavonoids, broccoli sprouts, garlic, probiotics and flavonoids are known to inhibit H. pylori colonization, decrease gastric inflammation by inhibiting cytokine and chemokine release, and repress precancerous changes by inhibiting nuclear factor-kappa B DNA binding, inducing profuse levels of apoptosis and inhibiting mutagenesis. Even though further unsolved issues are awaited before phytoceuticals are accepted as a standard treatment for H. pylori infection, phytoceuticals can be a mighty weapon for either suppressing or modulating the disease-associated footprints of H. pylori infection. PMID:18956590

  9. Antimicrobial activity of natural products against Helicobacter pylori: a review.

    PubMed

    Bonifácio, Bruna Vidal; dos Santos Ramos, Matheus Aparecido; da Silva, Patricia Bento; Bauab, Taís Maria

    2014-01-01

    Throughout the genetic and physiological evolution of microorganisms, the microbiological sciences have been expanding the introduction of new therapeutic trials against microbial diseases. Special attention has been paid to the bacterium Helicobacter pylori, which induces gastric infections capable of causing damage, ranging from acute and chronic gastritis to the development of gastric cancer and death. The use of compounds with natural origins has gained popularity in scientific research focused on drug innovation against H. pylori because of their broad flexibility and low toxicity. The aim of this study was to describe the use of natural products against H. pylori in order to clarify important parameters for related fields. The study demonstrated the vast therapeutic possibilities for compounds originating from natural sources and revealed the need for innovations from future investigations to expand the therapeutic arsenal in the fight against H. pylori infection. PMID:25406585

  10. Helicobacter pylori Diversity and Gastric Cancer Risk

    PubMed Central

    2016-01-01

    ABSTRACT Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI). Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed. PMID:26814181

  11. Helicobacter pylori infection in laryngeal diseases.

    PubMed

    Siupsinskiene, Nora; Jurgutaviciute, Vilma; Katutiene, Inga; Janciauskas, Dainius; Vaitkus, Saulius; Adamonis, Kęstutis

    2013-08-01

    Clinical studies have shown that Helicobacter pylori can be found not only in the mucosa of the stomach, but in the pharyngeal and laryngeal regions as well. The aim of this prospective case-control study was to identify H. pylori infection in the biopsy material from the larynx of the patients suffering from benign laryngeal diseases (vocal fold polyps, laryngitis) and laryngeal cancer and to investigate the possible relationships between the laryngeal H. pylori and patients' socio-demographic data and laryngopharyngeal reflux. The results of the biopsy material from 67 adult patients treated for benign laryngeal diseases and laryngeal cancer and 11 individuals of the control group revealed that H. pylori infection could be identified in more than one-third of the patients. In the majority of cases H. pylori was found in the patients with chronic laryngitis (45.5%) and laryngeal cancer (46.2%). The findings of these sub-groups significantly differed from those of the control group (9.1%) (p < 0.05). No significant relationships between H. pylori infection found in the laryngeal region and patients' demographic data, their unhealthy habits and reflux-related symptoms or signs were obtained. It could be concluded that H. pylori can colonize in the larynx of patients with benign laryngeal diseases and laryngeal cancer. To clarify the role of H. pylori as a risk factor for laryngeal diseases further research is needed. PMID:23572292

  12. Correlation Between Tympanosclerosis and Helicobacter pylori

    PubMed Central

    Saki, Nader; Jahani, Mojtaba; Samarbaf, Alireza; Kaydani, Gholam Abbas; Nikakhlagh, Soheila; Kenani, Malek; Mogehi, Sasan

    2015-01-01

    Background: Tympanosclerosis is a condition caused by calcification of tissues in the middle ear mucosa that sometimes results hearing loss. Helicobacter pylori is one of the pathological and etiologic factors in the development of tympanosclerosis. Objectives: The purpose of this study was to show the role of H. pylori in the different aspects of chronic suppurative otitis media using the polymerase chain reaction (PCR) technique. Patients and Methods: This case-control and cross-sectional study was performed on all patients with chronic otitis media, candidates for surgical operations, in 2013. They were allocated into the case group with tympanosclerosis and the control group without tympanosclerosis. During the surgical operation, biopsy was done from middle ear and the samples were studied to see if they contained H. pylori using the PCR method. Results: From a total of 19 patients with tympanosclerosis , 16 cases (84.2%) were H. pylori positive, while in the control group 15 (45.4%) cases out of the 37 cases were H. pylori positive, which showed a significant difference (P = 0.002). Age and gender of the patients, ear dryness and perforation size were not correlated with the presence or absence of H. pylori. Conclusions: There is a significant correlation between tympanosclerosis and H. pylori (P = 0.002). This correlation can single out H. pylori as a pathological factor in the development of tympanosclerosis; however, further studies are needed to prove this correlation. PMID:26568799

  13. Are probiotics useful in Helicobacter pylori eradication?

    PubMed

    Homan, Matjaž; Orel, Rok

    2015-10-01

    Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects. PMID:26457024

  14. Are probiotics useful in Helicobacter pylori eradication?

    PubMed Central

    Homan, Matjaž; Orel, Rok

    2015-01-01

    Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects. PMID:26457024

  15. A Conserved Helicobacter pylori Gene, HP0102, Is Induced Upon Contact With Gastric Cells and Has Multiple Roles in Pathogenicity.

    PubMed

    Bhattacharya, Saurabh; Mukherjee, Oindrilla; Mukhopadhyay, Asish K; Chowdhury, Rukhsana

    2016-07-15

    Contact with host cells is recognized as a signal capable of triggering expression of bacterial genes important for host pathogen interaction. Adherence of Helicobacter pylori to the gastric epithelial cell line AGS strongly upregulated expression of a gene, HP0102, in the adhered bacteria in all strains examined, including several Indian clinical isolates. The gene is highly conserved and ubiquitously present in all 69 sequenced H. pylori genomes at the same genomic locus, as well as in 15 Indian clinical isolates. The gene is associated with 2 distinct phenotypes related to pathogenicity. In AGS cell-adhered H. pylori, it has a role in upregulation of cagA expression from a specific σ(28)-RNAP promoter and consequent induction of the hummingbird phenotype in the infected AGS cells. Furthermore, HP0102 has a role in chemotaxis and a ΔHP0102 mutant exhibited low acid-escape response that might account for the poor colonization efficiency of the mutant. PMID:27056952

  16. Helicobacter pylori therapy: a paradigm shift.

    PubMed

    Graham, David Y; Dore, Maria Pina

    2016-06-01

    Helicobacter pylori (H. Pylori) is a leading cause of gastroduodenal disease, including gastric cancer. H. pylori eradication therapies and their efficacy are summarized. A number of current treatment regimens will reliably yield >90% or 95% cure rates with susceptible strains. None has proven to be superior. We show how to predict the efficacy of a regimen in any population provided one knows the prevalence of antibiotic resistance. As with other infectious diseases, therapy should always be susceptibility-based. Susceptibility testing should be demanded. We provide recommendations for empiric therapies when that is the only option and describe how to distinguish studies providing misinformation from those providing reliable and interpretable data. When treated as an infectious disease, high H. pylori cure rates are relatively simple to reliably achieve. PMID:27077447

  17. Helicobacter pylori vaccination: Is there a path to protection?

    PubMed Central

    Anderl, Florian; Gerhard, Markus

    2014-01-01

    Helicobacter pylori (H. pylori) is a pathogenic, extracellular bacterium that colonizes the stomach in approximately 50% of the world population. It strongly interacts with the gastric epithelium and mostly causes asymptomatic gastritis. The colonization of H. pylori leads to ulcer development in around 20% of infected patients and may progress to gastric cancer or mucosa-associated lymphoid tissue lymphoma in 1%. Thus, H. pylori is the major cause of gastric cancer worldwide. It has been classified as a class I carcinogen by the World Health Organization. Since its discovery in the early eighties by Warren and Marshall, research has been focused on the investigation of H. pylori biology, host-pathogen interaction, prevention and treatment. Although H. pylori induces a strong humoral and local cellular immune response, the pathogen is not cleared and establishes a chronic infection after encounters in childhood. The ability to colonize the stomach is mediated by several virulence factors that change the host environment, promote adhesion to the epithelium, influence the gastric inflammation and induce immune evasion. H. pylori can be eradicated by antibiotic treatment in combination with a proton-pump inhibitor, but efficacy is decreasing. Current therapies are expensive, have side effects and contribute to increasing antibiotic resistance, underlining the need for novel therapeutics. PMID:25232229

  18. Role of Helicobacter pylori infection on nutrition and metabolism

    PubMed Central

    Franceschi, Francesco; Annalisa, Tortora; Teresa, Di Rienzo; Giovanna, D’Angelo; Ianiro, Gianluca; Franco, Scaldaferri; Viviana, Gerardi; Valentina, Tesori; Riccardo, Lopetuso Loris; Antonio, Gasbarrini

    2014-01-01

    Helicobacter pylori (H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world’s population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome. PMID:25278679

  19. Helicobacter pylori induces IL-1β and IL-18 production in human monocytic cell line through activation of NLRP3 inflammasome via ROS signaling pathway.

    PubMed

    Li, Xiang; Liu, Sheng; Luo, Jingjing; Liu, Anyuan; Tang, Shuangyang; Liu, Shuo; Yu, Minjun; Zhang, Yan

    2015-06-01

    This study investigated whether Helicobacter pylori could activate the nucleotide-binding oligomerization domain-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome in human macrophages and the involvement of reactive oxygen species (ROS) in inflammasome activation. Phorbol-12-myristate-13-acetate (PMA)-differentiated human acute monocytic leukemia cell line THP-1 was infected with H. pylori. The levels of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in supernatant were measured by ELISA. Intracellular ROS level was analyzed by flow cytometry. Quantitative real-time PCR and western blot analysis were employed to determine the mRNA and protein expression levels of NLRP3 and caspase-1 in THP-1 cells, respectively. Our results showed that H. pylori infection could induce IL-1β and IL-18 production in PMA-differentiated THP-1 cells in a dose- and time-dependent manner. Moreover, secretion of IL-1β and IL-18 in THP-1 cells following H. pylori infection was remarkably reduced by NLRP3-specific small interfering RNA treatment. In addition, the intracellular ROS level was elevated by H. pylori infection, which could be eliminated by the ROS scavenger N-acetylcysteine (NAC). Furthermore, NAC treatment could inhibit NLRP3 inflammasome formation and caspase-1 activation and suppress the release of IL-1β and IL-18 from H. pylori-infected THP-1 cells. These findings provide novel insights into the innate immune response against H. pylori infection, which could potentially be used for the prevention and treatment of H. pylori-related diseases. PMID:25834143

  20. [Alzheimer's disease and Helicobacter pylori infection: a possible link?].

    PubMed

    Roubaud Baudron, Claire; Varon, Christine; Mégraud, Francis; Salles, Nathalie

    2016-03-01

    Alzheimer's disease (AD) is associated with Aß peptide and Tau protein deposits, but the initial process inducing the disease and ultimately neurodegeneration has not yet been elucidated. An infectious hypothesis is suggested by the alteration of the blood-brain barrier and the activation of neuroinflammation in the brain, which could play a role, especially in the decrease of Aß peptide clearance. Several viral or bacterial agents have been incriminated, including Helicobacter pylori. Infection by H. pylori is acquired during childhood and often lifetime persisting, inducing a chronic gastric inflammation, which remains asymptomatic in approximately 80% of cases. However H. pylori infection can induce systemic inflammation and increase homocysteine levels, contributing to worsen AD lesions. Association between H. pylori and AD is suggested by 1) epidemiologic studies, which show higher AD prevalence and more pronounced cognitive impairment in infected than in non-infected subjects; 2) experimental studies in murine models: a) in a first study we evaluated the impact of H. pylori infection on the brain of non-AD predisposed C57BL/6J mice. After an 18-month infection, H. pylori induced a significant gastric inflammation but no brain Aβ deposit nor increased neuroinflammation was observed in their brain; b) we currently study the impact of Helicobacter species infection on behavior and cerebral lesions of AD transgenic (APPswe/PS1dE9) mice and their wild type littermate. The results of these studies do not allow to conclude a significant association between AD and H. pylory infection but may contribute to a better understanding of the role of brain neuroinflammation in AD. PMID:27005340

  1. Helicobacter pylori and gastroesophageal reflux disease

    PubMed Central

    Grande, Michele; Cadeddu, Federica; Villa, Massimo; Attinà, Grazia Maria; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio M

    2008-01-01

    Background The nature of the relationship between Helicobacter pylori and reflux oesophagitis is still not clear. To investigate the correlation between Helicobacter pylori infection and GERD taking into account endoscopic, pH-metric and histopathological data. Methods Between January 2001 and January 2003 a prospective study was performed in 146 patients with GERD in order to determine the prevalence of Helicobacter pylori infection at gastric mucosa; further the value of the De Meester score endoscopic, manometric and pH-metric parameters, i.e. reflux episodes, pathological reflux episodes and extent of oesophageal acid exposure, of the patients with and without Helicobacter pylori infection were studied and statistically compared. Finally, univariate analysis of the above mentioned data were performed in order to evaluate the statistical correlation with reflux esophagitis. Results There were no statistically significant differences between the two groups, HP infected and HP negative patients, regarding age, gender and type of symptoms. There was no statistical difference between the two groups regarding severity of symptoms and manometric parameters. The value of the De Meester score and the ph-metric parameters were similar in both groups. On univariate analysis, we observed that hiatal hernia (p = 0,01), LES size (p = 0,05), oesophageal wave length (p = 0,01) and pathological reflux number (p = 0,05) were significantly related to the presence of reflux oesophagitis. Conclusion Based on these findings, it seems that there is no significant evidence for an important role for H. pylori infection in the development of GERD and erosive esophagitis. Nevertheless, current data do not provide sufficient evidence to define the relationship between HP and GERD. Further assessments in prospective large studies are warranted. PMID:18601740

  2. Helicobacter pylori and gastric cancer: Indian enigma

    PubMed Central

    Misra, Vatsala; Pandey, Renu; Misra, Sri Prakash; Dwivedi, Manisha

    2014-01-01

    Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium. PMID:24587625

  3. Simple animal model of Helicobacter pylori infection

    PubMed Central

    Werawatganon, Duangporn

    2014-01-01

    Helicobacter pylori (H. pylori) has become accepted as a human pathogen for the development of gastritis and gastroduodenal ulcer. To develop a simple rat model of chronic H. pylori infection, male Sprague-Dawley rats were pretreated with streptomycin suspended in tap water (5 mg/mL) for 3 d. The rats were inoculated by gavage at 1 mL/rat with H. pylori suspension (5 × 108-5 × 1010 CFU/mL) twice daily at an interval of 4 h for three consecutive days. Two weeks after inoculation, rats were sacrificed and the stomachs were removed. Antral biopsies were performed for urease test and the stomachs were taken for histopathology. Successful H. pylori inoculation was defined as a positive urease test and histopathology. We reported a 69.8%-83.0% success rate for H. pylori infection using the urease test, and hematoxylin and eosin staining confirmed the results. Histopathological analysis detected bacteria along the mucous lining of the surface epithelium and crypt lumen and demonstrated mild to moderate gastric inflammation in successfully inoculated rats. We developed a simple rat model of chronic H. pylori infection for research into gastric microcirculatory changes and therapy with plant products. PMID:24914363

  4. Hematologic manifestations of Helicobacter pylori infection

    PubMed Central

    Campuzano-Maya, Germán

    2014-01-01

    Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases. PMID:25278680

  5. Metalloregulation of Helicobacter pylori physiology and pathogenesis

    PubMed Central

    Haley, Kathryn P.; Gaddy, Jennifer A.

    2015-01-01

    Helicobacter pylori is a Gram-negative spiral-shaped bacterium that colonizes over half of the world's population. Chronic H. pylori infection is associated with increased risk for numerous disease outcomes including gastritis, dysplasia, neoplasia, B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma), and invasive adenocarcinoma. The complex interactions that occur between pathogen and host are dynamic and exquisitely regulated, and the relationship between H. pylori and its human host are no exception. To successfully colonize, and subsequently persist, within the human stomach H. pylori must temporally regulate numerous genes to ensure localization to the gastric lumen and coordinated expression of virulence factors to subvert the host's innate and adaptive immune response. H. pylori achieves this precise gene regulation by sensing subtle environmental changes including host-mediated alterations in nutrient availability and responding with dramatic global changes in gene expression. Recent studies revealed that the presence or absence of numerous metal ions encountered in the lumen of the stomach, or within host tissues, including nickel, iron, copper and zinc, can influence regulatory networks to alter gene expression in H. pylori. These expression changes modulate the deployment of bacterial virulence factors that can ultimately influence disease outcome. In this review we will discuss the environmental stimuli that are detected by H. pylori as well as the trans regulatory elements, specifically the transcription regulators and transcription factors, that allow for these significant transcriptional shifts. PMID:26388855

  6. Role of Helicobacter pylori in gastric cancer: Updates

    PubMed Central

    Khatoon, Jahanarah; Rai, Ravi Prakash; Prasad, Kashi Nath

    2016-01-01

    Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC. PMID:26909129

  7. Agglutination of Helicobacter pylori coccoids by lectins

    PubMed Central

    Khin, Mar Mar; Hua, Jie Song; Ng, Han Cong; Wadström, Torkel; Ho, Bow

    2000-01-01

    AIM: To study the agglutination pattern of Helicobacter pylori coccoid and spiral forms. METHODS: Assays of agglutination and agglutination inhibition were applied using fifteen commercial lectins. RESULTS: Strong agglutination was observed with mannose-specific Concanavalin A (Con A), fucose-specific Tetragonolobus purpureas (Lotus A) and N-acetyl glucosamine-specific Triticum vulgaris (WGA) lectins. Mannose and fucose specific lectins were reactive with all strains of H. pylori coccoids as compared to the spirals. Specific carbohydrates, glycoproteins and mucin were shown to inhibit H. pylori lectin-agglutination reactions. Pre-treatment of the bacterial cells with formalin and sulphuric acid did not alter the agglutination patterns with lectins. However, sodium periodate treatment of bacterial cells were shown to inhibit agglutination reaction with Con A, Lotus A and WGA lectins. On the contrary, enzymatic treatment of coccoids and spirals did not show marked inhibition of H. pylori lectin agglutination. Interes tingly, heating of H. pylori cells at 60 °C for 1 h was shown to augment the agglutination with all of the lectins tested. CONCLUSION: The considerable differences in lectin agglutination patterns seen among the two differentiated forms of H. pylori might be attributable to the structural changes during the events of morphological transformation, resulting in exposing or masking some of the sugar residues on the cell surface. Possibility of various sugar residues on the cell wall of the coccoids may allow them to bind to different carbohydrate receptors on gastric mucus and epithelial cells. The coccoids with adherence characteristics like the spirals could aid in the pathogenic process of Helicobacter infection. This may probably lead to different clinical outcome of H. pylori associated gastroduodenal disease. PMID:11819557

  8. A fluid model for Helicobacter pylori

    NASA Astrophysics Data System (ADS)

    Reigh, Shang-Yik; Lauga, Eric

    2015-11-01

    Swimming microorganisms and self-propelled nanomotors are often found in confined environments. The bacterium Helicobacter pylori survives in the acidic environment of the human stomach and is able to penetrate gel-like mucus layers and cause infections by locally changing the rheological properties of the mucus from gel-like to solution-like. In this talk we propose an analytical model for the locomotion of Helicobacter pylori as a confined spherical squirmer which generates its own confinement. We solve analytically the flow field around the swimmer, and derive the swimming speed and energetics. The role of the boundary condition in the outer wall is discussed. An extension of our model is also proposed for other biological and chemical swimmers. Newton Trust.

  9. Helicobacter pylori Induced Gastric Immunopathology Is Associated with Distinct Microbiota Changes in the Large Intestines of Long-Term Infected Mongolian Gerbils

    PubMed Central

    Heimesaat, Markus M.; Fischer, André; Plickert, Rita; Wiedemann, Tobias; Loddenkemper, Christoph; Göbel, Ulf B.

    2014-01-01

    Background Gastrointestinal (GI) inflammation in mice and men are frequently accompanied by distinct changes of the GI microbiota composition at sites of inflammation. Helicobacter (H.) pylori infection results in gastric immunopathology accompanied by colonization of stomachs with bacterial species, which are usually restricted to the lower intestine. Potential microbiota shifts distal to the inflammatory process following long-term H. pylori infection, however, have not been studied so far. Methodology/Principal Findings For the first time, we investigated microbiota changes along the entire GI tract of Mongolian gerbils after 14 months of infection with H. pylori B8 wildtype (WT) or its isogenic ΔcagY mutant (MUT) strain which is defective in the type IV secretion system and thus unable to modulate specific host pathways. Comprehensive cultural analyses revealed that severe gastric diseases such as atrophic pangastritis and precancerous transformations were accompanied by elevated luminal loads of E. coli and enterococci in the caecum and together with Bacteroides/Prevotella spp. in the colon of H. pylori WT, but not MUT infected gerbils as compared to naïve animals. Strikingly, molecular analyses revealed that Akkermansia, an uncultivable species involved in mucus degradation, was exclusively abundant in large intestines of H. pylori WT, but not MUT infected nor naïve gerbils. Conclusion/Significance Taken together, long-term infection of Mongolian gerbils with a H. pylori WT strain displaying an intact type IV secretion system leads to distinct shifts of the microbiota composition in the distal uninflamed, but not proximal inflamed GI tract. Hence, H. pylori induced immunopathogenesis of the stomach, including hypochlorhydria and hypergastrinemia, might trigger large intestinal microbiota changes whereas the exact underlying mechanisms need to be further unraveled. PMID:24941045

  10. Vaccine against Helicobacter pylori: Inevitable approach

    PubMed Central

    Talebi Bezmin Abadi, Amin

    2016-01-01

    Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium. PMID:27003991

  11. Vaccine against Helicobacter pylori: Inevitable approach.

    PubMed

    Talebi Bezmin Abadi, Amin

    2016-03-21

    Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium. PMID:27003991

  12. Helicobacter pylori screening: options and challenges.

    PubMed

    Venerito, Marino; Goni, Elisabetta; Malfertheiner, Peter

    2016-01-01

    Helicobacter pylori gastritis is the most frequent infectious disease in the gastrointestinal tract. Clinical sequelae of the infection including peptic ulcer disease, sporadic gastric cancer (GC) and primary B-cell gastric lymphoma (MALT-lymphoma) may develop in up to 20% of the infected individuals. The H. pylori screen-and-treat strategy is addressed to members of communities with high GC incidence, and first-degree relatives of GC patients. For primary GC prevention, H. pylori screen-and-treat is most effective in patients without precancerous conditions. In populations at moderate risk, strategies for GC prevention need to be explored. A special clinical scenario for primary and secondary prevention of H. pylori related benign complications are patients on non-steroidal anti-inflammatory drugs and low-dose aspirin. Vaccination represents another option for eliminating H. pylori infection in the population and a new H. pylori vaccine has shown promising results. However, long-term effects with the use of vaccine are not available. PMID:26619972

  13. Clinical practice: Helicobacter pylori infection in childhood.

    PubMed

    Ertem, Deniz

    2013-11-01

    Helicobacter pylori infection is recognised as a cause of gastritis and peptic ulcer disease (PUD) and usually acquired during the first years of life. While there is a decline in the prevalence of H. pylori infection in northern and western European countries, the infection is still common in southern and eastern parts of Europe and Asia. Symptoms of H. pylori-related PUD are nonspecific in children and may include epigastric pain, nausea and/or vomiting, anorexia, iron deficiency anaemia and hematemesis. Besides, only a small proportion of children develop symptoms and clinically relevant gastrointestinal disease. H. pylori infection can be diagnosed either by invasive tests requiring endoscopy and biopsy or non-invasive tests including the (13)C-urea breath test, detection of H. pylori antigen in stool and detection of antibodies in serum, urine and saliva. The aim of treatment is at least 90 % eradication rate of the bacteria, and a combination of two antibiotics plus a proton pump inhibitor has been recommended as first-line treatment. However, frequent use of antibiotics during childhood is associated with a decline in eradication rates and the search for new treatment strategies as well. This is an overview of the latest knowledge and evidence-based guidelines regarding clinical presentation, diagnosis and treatment of H. pylori infection in childhood. PMID:23015042

  14. Helicobacter pylori: a poor man's gut pathogen?

    PubMed Central

    2010-01-01

    Helicobacter pylori is one of the human pathogens with highest prevalence around the world; yet, its principal mode of transmission remains largely unknown. The role of H. pylori in gastric disease and cancer has not been established until the end of the 20th century. Since then, its epidemiology has been extensively studied, and an accruing body of literature suggests that not all humans are equally at risk of infection by this gut pathogen. Here, we briefly review the different epidemiological aspects of H. pylori infection with emphasis on those factors related to human poverty. The epidemiology of H. pylori infection is characterized by marked differences between developing and developed countries, notably among children. In addition, congruent lines of evidence point out to socioeconomic factors and living standards as main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. These data are alarming in the light of the changing global climate and birth rate, which are expected to change the demography of our planet, putting more children at risk of H. pylori and its complications for years to come. PMID:20356368

  15. Helicobacter pylori: immunoproteomics related to different pathologies.

    PubMed

    Bernardini, Giulia; Braconi, Daniela; Lusini, Paola; Santucci, Annalisa

    2007-10-01

    Helicobacter pylori is a Gram-negative bacterium that causes ulcer, atrophic gastritis, adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Moreover, an ongoing controversial role of this bacterium infection has been suggested in the etiopathogenesis of some extradigestive diseases. The humoral response to H. pylori during a natural infection can be used for diagnostic purposes and as a basis for vaccine development. Host-pathogen interactions may be investigated by means of immunoproteomics, which provides global information about relevant specific and nonspecific antigens, and thus might be suitable to identify novel vaccine candidates or serological markers of H. pylori infection as well as of different related diseases. In this review, we describe how several research groups used H. pylori proteomics combined with western blotting analysis, using sera from patients affected with different H. pylori-related pathologies, to investigate potential associations between host immune response and clinical outcomes of H. pylori infection, resulting in the rapid identification of novel, highly immunoreactive antigens. PMID:17941822

  16. Helicobacter pylori: new developments and treatments

    PubMed Central

    Veldhuyzen van Zanten, S J; Sherman, P M; Hunt, R H

    1997-01-01

    The authors highlight new developments in research on Helicobacter pylori. There is now consensus that all patients with newly diagnosed or recurrent duodenal or gastric ulcers who have a positive test result for H. pylori should be treated for the infection. Patients presenting with complications of ulcers, such as bleeding, should also be treated. H. pylori has recently been classified as a definite human carcinogen by the International Agency for Research on Cancer. In treatment, new combination regimens, consisting of 3 or 4 different drugs, cure the infection in more than 80% of patients. Currently, the best combinations are: (1) omeprazole (or another proton-pump inhibitor), clarithromycin and metronidazole, (2) omeprazole (or another proton-pump inhibitor), clarithromycin and amoxicillin, (3) bismuth subsalicylate, tetracycline and metronidazole, and (4) omeprazole, bismuth subsalicylate, tetracycline and metronidazole. PMID:9176424

  17. Treatment of Helicobacter pylori infection 2016.

    PubMed

    O'Connor, Anthony; Fischbach, Wolfgang; Gisbert, Javier P; O'Morain, Colm

    2016-09-01

    Many interesting articles have been published from different parts of the world over the last year assessing various issues around Helicobacter pylori eradication therapy. This article will address the published literature over the last year pertaining to the topic of treatment of H. pylori infection. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized nonbismuth-containing and bismuth-containing quadruple therapies with some promising data also emerging on dual therapy. There was also considerable progress in investigating antibiotic resistance rates with much more data emerging from varied parts of the world compared to recent years. Advances in the use of adjunctive therapies, especially probiotic therapies have also been made. Undoubtedly, the eradication of H. pylori remains a worthwhile goal to alleviate the burden of diseases caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer. PMID:27531541

  18. Impact of Helicobacter Pylori on Mucus Rheology

    NASA Astrophysics Data System (ADS)

    Celli, Jonathan; Keates, Sarah; Kelly, Ciaran; Turner, Bradley; Bansil, Rama; Erramilli, Shyamsunder

    2006-03-01

    It is well known that the viscoelastic properties of gastric mucin are crucial to the protection of the lining of the stomach against its own acidic secretions and other agents. Helicobacter Pylori, a rod shaped, gram-negative bacteria that dwells in the mucus layer of approximately 50% of the world's population is a class I carcinogen and is associated with gastric ulcers and severe gastritis. The structural damage to the mucus layer caused by H. Pylori is an important aspect of infection with this bacteria. We are examining the impact of H. Pylori on mucin and mucus rheology quantitatively using a combination of dynamic light scattering and multiple particle tracking experiments. Video microscopy data will also be presented on the motility of this bacteria in mucin at different pH and in other viscoelastic gels.

  19. Helicobacter pylori induces miR-155 in T cells in a cAMP-Foxp3-dependent manner.

    PubMed

    Fassi Fehri, Lina; Koch, Manuel; Belogolova, Elena; Khalil, Hany; Bolz, Christian; Kalali, Behnam; Mollenkopf, Hans J; Beigier-Bompadre, Macarena; Karlas, Alexander; Schneider, Thomas; Churin, Yuri; Gerhard, Markus; Meyer, Thomas F

    2010-01-01

    Amongst the most severe clinical outcomes of life-long infections with Helicobacter pylori is the development of peptic ulcers and gastric adenocarcinoma--diseases often associated with an increase of regulatory T cells. Understanding H. pylori-driven regulation of T cells is therefore of crucial clinical importance. Several studies have defined mammalian microRNAs as key regulators of the immune system and of carcinogenic processes. Hence, we aimed here to identify H. pylori-regulated miRNAs, mainly in human T cells. MicroRNA profiling of non-infected and infected human T cells revealed H. pylori infection triggers miR-155 expression in vitro and in vivo. By using single and double H. pylori mutants and the corresponding purified enzymes, the bacterial vacuolating toxin A (VacA) and gamma-glutamyl transpeptidase (GGT) plus lipopolysaccharide (LPS) tested positive for their ability to regulate miR-155 and Foxp3 expression in human lymphocytes; the latter being considered as the master regulator and marker of regulatory T cells. RNAi-mediated knockdown (KD) of the Foxp3 transcription factor in T cells abolished miR-155 expression. Using adenylate cyclase inhibitors, the miR-155 induction cascade was shown to be dependent on the second messenger cyclic adenosine monophosphate (cAMP). Furthermore, we found that miR-155 directly targets the protein kinase A inhibitor alpha (PKIalpha) mRNA in its 3'UTR, indicative of a positive feedback mechanism on the cAMP pathway. Taken together, our study describes, in the context of an H. pylori infection, a direct link between Foxp3 and miR-155 in human T cells and highlights the significance of cAMP in this miR-155 induction cascade. PMID:20209161

  20. Helicobacter pylori Update: Gastric Cancer, Reliable Therapy, and Possible Benefits

    PubMed Central

    Graham, David Y.

    2015-01-01

    Helicobacter pylori infection contributes to development of diverse gastric and extra-gastric diseases. The infection is necessary but not sufficient for development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, so there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma, although there are no convincing data to support the benefits of H pylori infections. PMID:25655557

  1. Relationship between Helicobacter pylori and idiopathic chronic urticaria: effectiveness of Helicobacter pylori eradication

    PubMed Central

    Mogaddam, Majid Rostami; Yazdanbod, Abbas; Ardabili, Nastaran Safavi; Isazadeh, Sonia

    2015-01-01

    Introduction Chronic urticaria (CU) is defined as the presence of urticaria on most days of the week for a period of 6 weeks or longer. Some studies have reported an association between CU and Helicobacter pylori (H. pylori) infection. Aim To determine the prevalence of H. pylori infection using the stool antigen test in patients with idiopathic CU and to investigate the infected patients with CU following eradication of H. pylori. Material and methods One hundred patients with idiopathic CU and 100 healthy controls were referred to our clinic between May 2012 and June 2013 and were tested for H. pylori antigen. The patients infected with H. pylori received quadruple therapy for 2 weeks. To assess eradication efficacy, a repeated H. pylori stool antigen test was performed in each patient 6 weeks after the end of anti-H. pylori therapy. The effectiveness of eradication therapy on CU was assessed 3 months after treatment. Results Thirty-six percent patients with idiopathic CU were infected with H. pylori while 23% of the controls were infected. Response to eradication therapy was evident in 33 (91.67%) patients in whom H. pylori was eradicated while 3 (8.33%) patients showed no response despite eradication of H. pylori. Clinical follow-up of 33 successfully treated patients 3 months later revealed complete remission of urticaria in 54.5%, partial remission in 18.2%, and no improvement in 27.3%. Conclusions The results of our study suggest that H. pylori infection should be included in diagnostic workup of patients with no response to habitual treatment for CU or symptomatic gastrointestinal patients. For the diagnosis of H. pylori infection, one should consider the costs and accessibility of the population to the HpSA® stool antigen test and Urea breath test (UBT). PMID:25821422

  2. IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori.

    PubMed

    Dixon, Beverly R E A; Radin, Jana N; Piazuelo, M Blanca; Contreras, Diana C; Algood, Holly M Scott

    2016-01-01

    Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro-inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti-microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL-8, components of calprotectin (CP), lipocalin (LCN) and some β-defensins in both human and primary mouse gastric epithelial cells (GEC) and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response. PMID:26867135

  3. Helicobacter pylori-induced IL-1β secretion in innate immune cells is regulated by the NLRP3 inflammasome and requires the cag pathogenicity island.

    PubMed

    Semper, Raphaela P; Mejías-Luque, Raquel; Groß, Christina; Anderl, Florian; Müller, Anne; Vieth, Michael; Busch, Dirk H; Prazeres da Costa, Clarissa; Ruland, Jürgen; Groß, Olaf; Gerhard, Markus

    2014-10-01

    Infection with the gram-negative bacterium Helicobacter pylori is the most prevalent chronic bacterial infection, affecting ∼50% of the world's population, and is the main risk factor of gastric cancer. The proinflammatory cytokine IL-1β plays a crucial role in the development of gastric tumors and polymorphisms in the IL-1 gene cluster leading to increased IL-1β production have been associated with increased risk for gastric cancer. To be active, pro-IL-1β must be cleaved by the inflammasome, an intracellular multiprotein complex implicated in physiological and pathological inflammation. Recently, H. pylori was postulated to activate the inflammasome in murine bone marrow-derived dendritic cells; however, the molecular mechanisms as well as the bacterial virulence factor acting as signal 2 activating the inflammasome remain elusive. In this study, we analyzed the inflammasome complex regulating IL-1β upon H. pylori infection as well as the molecular mechanisms involved. Our results indicate that H. pylori-induced IL-1β secretion is mediated by activation of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 inflammasome. We also show that reactive oxygen species, potassium efflux, and lysosomal destabilization are the main cellular mechanisms responsible of nucleotide-binding oligomerization domain family, pyrin domain-containing 3 inflammasome activation upon H. pylori infection, and identify vacuolating cytotoxin A and cag pathogenicity island as the bacterial virulence determinants involved. Moreover, in vivo experiments indicate an important role for the inflammasome in the onset and establishment of H. pylori infection and in the subsequent inflammatory response of the host. PMID:25172489

  4. IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori

    PubMed Central

    Dixon, Beverly R. E. A.; Radin, Jana N.; Piazuelo, M. Blanca; Contreras, Diana C.; Algood, Holly M. Scott

    2016-01-01

    Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro-inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti-microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL-8, components of calprotectin (CP), lipocalin (LCN) and some β-defensins in both human and primary mouse gastric epithelial cells (GEC) and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response. PMID:26867135

  5. Can Helicobacter pylori infection influence human reproduction?

    PubMed Central

    Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio

    2014-01-01

    Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction. PMID:24914316

  6. Rare Helicobacter pylori Virulence Genotypes in Bhutan.

    PubMed

    Matsunari, Osamu; Miftahussurur, Muhammad; Shiota, Seiji; Suzuki, Rumiko; Vilaichone, Ratha-Korn; Uchida, Tomohisa; Ratanachu-Ek, Thawee; Tshering, Lotay; Mahachai, Varocha; Yamaoka, Yoshio

    2016-01-01

    Both the prevalence of Helicobacter pylori infection and the incidence of gastric cancer are high in Bhutan. The high incidence of atrophic gastritis and gastric cancer suggest the phylogeographic origin of an infection with a more virulent strain of H. pylori. More than 90% of Bhutanese strains possessed the highly virulent East Asian-type CagA and all strains had the most virulent type of vacA (s1 type). More than half also had multiple repeats in East Asian-type CagA, which are rare in other countries and are reported characteristictly found in assciation with atrophic gastritis and gastric cancer consistent with Bhutanese strains having multiple H. pylori virulence factors associated with an increase in gastric cancer risk. Phylogeographic analyses showed that most Bhutanese strains belonged to the East Asian population type with some strains (17.5%) sharing East Asian and Amerindian components. Only 9.5% belonged to the European type consistant with H. pylori in Bhutan representing an intermediate evolutionary stage between H. pylori from European and East Asian countries. PMID:26931643

  7. Rare Helicobacter pylori Virulence Genotypes in Bhutan

    PubMed Central

    Matsunari, Osamu; Miftahussurur, Muhammad; Shiota, Seiji; Suzuki, Rumiko; Vilaichone, Ratha-korn; Uchida, Tomohisa; Ratanachu-ek, Thawee; Tshering, Lotay; Mahachai, Varocha; Yamaoka, Yoshio

    2016-01-01

    Both the prevalence of Helicobacter pylori infection and the incidence of gastric cancer are high in Bhutan. The high incidence of atrophic gastritis and gastric cancer suggest the phylogeographic origin of an infection with a more virulent strain of H. pylori. More than 90% of Bhutanese strains possessed the highly virulent East Asian-type CagA and all strains had the most virulent type of vacA (s1 type). More than half also had multiple repeats in East Asian-type CagA, which are rare in other countries and are reported characteristictly found in assciation with atrophic gastritis and gastric cancer consistent with Bhutanese strains having multiple H. pylori virulence factors associated with an increase in gastric cancer risk. Phylogeographic analyses showed that most Bhutanese strains belonged to the East Asian population type with some strains (17.5%) sharing East Asian and Amerindian components. Only 9.5% belonged to the European type consistant with H. pylori in Bhutan representing an intermediate evolutionary stage between H. pylori from European and East Asian countries. PMID:26931643

  8. Helicobacter pylori Sequences Reflect Past Human Migrations.

    PubMed

    Moodley, Y; Linz, B

    2009-01-01

    The long association between the stomach bacterium Helicobacter pylori and humans, in combination with its predominantly within-family transmission route and its exceptionally high DNA sequence diversity, make this bacterium a reliable marker for discerning both recent and ancient human population movements. As much of the diversity in H. pylori sequences is generated by recombination and mutation on a local scale, the partitioning of H. pylori sequences from a large globally distributed data set into six geographic populations enabled the detection of recent ( < 500 years) human population movements including the European colonial expansion and the slave trade. The further separation of bacterial populations into distinct sub-populations traced prehistoric population movements like the settlement of the Americas by Asians across the Bering Strait and the Bantu migrations in Africa. The ability to deduce ancestral population structure from modern sequences was a key development that allowed the detection of zones of admixture, such as Europe, and the inference of multiple migration waves into these zones. The significantly similar global population structure of both H. pylori and humans confirmed not only an evolutionary time-scale association between host and parasite, but also that humans had carried H. pylori in their stomachs on their migrations out of Africa. PMID:19696494

  9. Helicobacter pylori modulation of gastric acid.

    PubMed Central

    Calam, J.

    1999-01-01

    Helicobacter pylori plays major causative roles in peptic ulcer disease and gastric cancer. Elevated acid secretion in patients with duodenal ulcers (DUs) contributes to duodenal injury, and diminished acid secretion in patients with gastric cancer allows carcinogen-producing bacteria to colonize the stomach. Eradication of H. pylori normalizes acid secretion both in hyper-secreting DU patients and hypo-secreting relatives of gastric cancer patients. Therefore, we and others have asked how H. pylori causes these disparate changes in acid secretion. H. pylori gastritis more or less restricted to the gastric antrum in DU patients is associated with increased acid secretion. This is probably because gastritis increases release of the antral acid-stimulating hormone gastrin and diminished mucosal expression of the inhibitory peptide somatostatin. Bacterial products and inflammatory cytokines including TNFalpha may cause these changes in endocrine function. Gastritis involving the gastric corpus tends to diminish acid secretion, probably because bacterial products and cytokines including IL-1 inhibit parietal cells. Pharmacological inhibition of acid secretion increases corpus gastritis in H. pylori-infected subjects, so it is envisaged that gastric hypo-secretion of any cause might become self-perpetuating. H. pylori-associated mucosal atrophy will also contribute to acid hypo-secretion and is more likely in when the diet is high in salt or lacking in antioxidant vitamins. Data on gastric acid secretion in patients with esophagitis are limited but suggest that acid secretion is normal or slightly diminished. Nevertheless, H. pylori infection may be relevant to the management of esophagitis because: (i) H. pylori infection increases the pH-elevating effect of acid inhibiting drugs; (ii) proton pump inhibitors may increase the tendency of H. pylori to cause atrophic gastritis; and (iii) successful eradication of H. pylori is reported to increase the likelihood of

  10. Optimizing the Growth of Stressed Helicobacter pylori

    PubMed Central

    Richards, Crystal L.; Buchholz, Brittany J.; Ford, Timothy E.; Broadaway, Susan C.; Pyle, Barry H.; Camper, Anne K.

    2010-01-01

    Helicobacter pylori is a Gram -negative bacterium that colonizes the human stomach and is responsible for causing gastric ulcers. H. pylori is known to become stressed and nonculturable after exposure to unfavorable conditions. In this study, we enhanced previously published resuscitation procedures, characterized conditions under which stressed H. pylori can be recovered, and formulated a selective and differential resuscitation medium. Results showed that a specialized broth supplemented with trace minerals and lysed human erythrocytes and serum is required for the recovery of nonculturable H. pylori. The type of stress was an important factor in the efficacy of resuscitation, with cells exposed to atmospheric oxygen more readily resuscitated than nutrient deprived cells. After resuscitation, culturable cells were recovered from previously nonculturable oxygen stressed cells (24 and 72 hours of exposure) and nonculturable nutrient deprived cells (24 hours of exposure). The length of time the cells were exposed to the stress was also an important factor in the recovery of stressed H. pylori. RNA levels were quantified and transcription of the cell division related gene, cdrA (HP0066), was assessed by qRT-PCR. The low levels of RNA detected in stressed cells, after resuscitation, support the idea that a small population of viable cells may be responsible for the colonies recovered on solid agar. The modification of the resuscitation broth into a selective and differential slant culture medium also allowed the recovery of stressed H. pylori. The methods presented here highlight the benefits and limitations of using human blood products for recovering nonculturable H. pylori. PMID:21129415

  11. Helicobacter Pylori Gastritis, a Presequeale to Coronary Plaque

    PubMed Central

    Raut, Shrikant C.; Patil, Vinayak W.; Dalvi, Shubhangi M.; Bakhshi, Girish D.

    2015-01-01

    Helicobacter pylori are considered the most common human pathogen colonizing gastric mucosa. Gastritis with or without H. pylori infection is associated with increase in levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) but a more pronounced increase is noted in gastritis with H. pylori infection. Increasing level of homocysteine, due to decreased absorption of vitamin B12 and folic acid, together with increased CRP levels in gastritis with H. pylori infection may be the earliest event in the process of atherosclerosis and plaque formation. Retrospective study conducted at tertiary care hospital in Mumbai by Department of Biochemistry in association with Department of Surgery. Eighty patients who underwent gastroscopy in view of gastritis were subjected to rapid urease test for diagnosis of H. pylori infection. Vitamin B12, folic acid, homocysteine and hs-CRP were analyzed using chemiluminescence immuno assay. Student’s t-test, Pearson’s correlation and linear regression used for statistical analysis. Patients with H. pylori gastritis had significantly lower levels of vitamin B12 (271.6±101.3 vs 390.6±176.7 pg/mL; P=0.0005), as well as higher levels of homocysteine (17.4±7.4 vs 13.8±7.8 µmol/L; P=0.037) and hs-CRP (2.5±2.9 vs 1.2±1.1 mg/L; P=0.017), than in patients without H. pylori gastritis. However, folic acid showed (8.9±3.2 vs 10.0±3.6 ng/mL; P=0.171) no significant difference. Elevated homocysteine and hs-CRP in H. pylori gastritis may independently induce endothelial dysfunction, leading to cardiovascular pathology. PMID:25918633

  12. Helicobacter pylori gastritis, a presequeale to coronary plaque.

    PubMed

    Raut, Shrikant C; Patil, Vinayak W; Dalvi, Shubhangi M; Bakhshi, Girish D

    2015-01-28

    Helicobacter pylori are considered the most common human pathogen colonizing gastric mucosa. Gastritis with or without H. pylori infection is associated with increase in levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) but a more pronounced increase is noted in gastritis with H. pylori infection. Increasing level of homocysteine, due to decreased absorption of vitamin B12 and folic acid, together with increased CRP levels in gastritis with H. pylori infection may be the earliest event in the process of atherosclerosis and plaque formation. Retrospective study conducted at tertiary care hospital in Mumbai by Department of Biochemistry in association with Department of Surgery. Eighty patients who underwent gastroscopy in view of gastritis were subjected to rapid urease test for diagnosis of H. pylori infection. Vitamin B12, folic acid, homocysteine and hs-CRP were analyzed using chemiluminescence immuno assay. Student's t-test, Pearson's correlation and linear regression used for statistical analysis. Patients with H. pylori gastritis had significantly lower levels of vitamin B12 (271.6±101.3 vs 390.6±176.7 pg/mL; P=0.0005), as well as higher levels of homocysteine (17.4±7.4 vs 13.8±7.8 µmol/L; P=0.037) and hs-CRP (2.5±2.9 vs 1.2±1.1 mg/L; P=0.017), than in patients without H. pylori gastritis. However, folic acid showed (8.9±3.2 vs 10.0±3.6 ng/mL; P=0.171) no significant difference. Elevated homocysteine and hs-CRP in H. pylori gastritis may independently induce endothelial dysfunction, leading to cardiovascular pathology. PMID:25918633

  13. Relationship between Helicobacter pylori Infections in Diabetic Patients and Inflammations, Metabolic Syndrome, and Complications

    PubMed Central

    Kayar, Yusuf; Pamukçu, Özgül; Eroğlu, Hatice; Kalkan Erol, Kübra; Ilhan, Aysegul; Kocaman, Orhan

    2015-01-01

    Helicobacter pylori infection and diabetes mellitus are two independent common diseases. It is showed that the worsening glycemic and metabolic control increases the rates of Helicobacter pylori infections and Helicobacter pylori is shown as one of the common problems in diabetic patients with complaints of gastrointestinal diseases. In this study, we aimed to investigate the prevalence and eradication rates of Helicobacter pylori in diabetic patients and the relationship of Helicobacter pylori with the risk factors and diabetic complications. In our study, in which we have included 133 patients, we have shown a significant relationship between Helicobacter pylori infections and metabolic syndrome, insulin resistance, inflammations, and diabetic complications. PMID:26464868

  14. Helicobacter pylori colonization of the oral cavity: A milestone discovery

    PubMed Central

    Yee, John KC

    2016-01-01

    Over the past several years, the severity of Helicobacter pylori (H. pylori) infections has not significantly diminished. After successful eradication, the annual H. pylori recurrence rate is approximately 13% due to oral H. pylori infection. Established clinical diagnostic techniques do not identify an oral etiologic basis of H. pylori prior to gastric infection. There has been disagreement as to whether oral infection of H. pylori exists or not, with no definite conclusion. In medical practice, negative results with the urea breath test suggest that the stomach infection of H. pylori is cured in these patients. In fact, patients can present negative urea breath test results and yet exhibit H. pylori infection due to oral infection. The present paper provides evidence that H. pylori oral infection is nonetheless present, and the oral cavity represents a secondary site for H. pylori colonization. PMID:26811613

  15. Gastric cancer and Helicobacter pylori infection.

    PubMed

    Konturek, P C; Konturek, S J; Brzozowski, T

    2006-09-01

    The Nobel prize in Physiology and Medicine in 2005 was presented to Barry Marshall and Robin Warren for their discovery of Helicobacter pylori (Hp), but only the involvement of this germ in gastritis and peptic ulcer has been mentioned in the award sentence, while numerous epidemiological, clinical and experimental studies and reports emphasized the crucial role of Hp in pathogenesis of gastric cancer (GC). This review is based on the old concept proposed by P. Correa much before the discovery of spiral bacteria in the stomach, postulating the cascade of mucosal changes from acute/chronic gastritis into the atrophic gastritis with intestinal metaplasia and finally to dysplasia and GC. It is now widely accepted view that Hp infection is the major initiator of the inflammatory and atrophic changes in gastric mucosa accompanied by an over-expression of certain growth factors such as gastrin as well as of cyclooxygenase-2 (COX-2) and anti-apoptotic proteins including survivin and B-cl(2), leading to proliferation of mutated atrophic cells, excessive angiogenesis, inhibition of apoptosis and formation of gastric tumour. All the morphological and biochemical changes associated with the transformation of mucosal cells into the cancer cells can be traced in excellent experimental model of gastric cancerogenesis induced by infection of Hp in Mongolian gerbils. Since the eradication therapy was proved in several prospective clinical trials to greatly reduce the incidence of GC and this was confirmed on the gerbil model of Hp-induced GC, it has been postulated; a) that Hp is the major causal factor in pathogenesis of GC and b) that the only rational approach in attempt to reduce the occurrence of GC is the global eradication of Hp. PMID:17033105

  16. Recombination and DNA Repair in Helicobacter pylori

    PubMed Central

    Dorer, Marion S.; Sessler, Tate H.; Salama, Nina R.

    2013-01-01

    All organisms have pathways that repair the genome, ensuring their survival and that of their progeny. But these pathways also serve to diversify the genome, causing changes on the level of nucleotide, whole gene, and genome structure. Sequencing of bacteria has revealed wide allelic diversity and differences in gene content within the same species, highlighting the importance of understanding pathways of recombination and DNA repair. The human stomach pathogen Helicobacter pylori is an excellent model system for studying these pathways. H. pylori harbors major recombination and repair pathways and is naturally competent, facilitating its ability to diversify its genome. Elucidation of DNA recombination, repair, and diversification programs in this pathogen will reveal connections between these pathways and their importance to infection. PMID:21682641

  17. Infection with Helicobacter pylori Is Associated with Protection against Tuberculosis

    PubMed Central

    Perry, Sharon; de Jong, Bouke C.; Solnick, Jay V.; la Luz Sanchez, Maria de; Yang, Shufang; Lin, Philana Ling; Hansen, Lori M.; Talat, Najeeha; Hill, Philip C.; Hussain, Rabia; Adegbola, Richard A.; Flynn, JoAnne; Canfield, Don; Parsonnet, Julie

    2010-01-01

    Background Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings We first examined M. tuberculosis-specific IFN-γ and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-γ responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36–0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63–2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12–0.80], p = 0.04). Conclusions/Significance H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for

  18. Characterization of Helicobacter pylori Bacteriophage KHP30

    PubMed Central

    Uchiyama, Jumpei; Takeuchi, Hiroaki; Kato, Shin-ichiro; Gamoh, Keiji; Takemura-Uchiyama, Iyo; Ujihara, Takako; Daibata, Masanori

    2013-01-01

    Helicobacter pylori inhabits the stomach mucosa and is a causative agent of stomach ulcer and cancer. In general, bacteriophages (phages) are strongly associated with bacterial evolution, including the development of pathogenicity. Several tailed phages have so far been reported in H. pylori. We have isolated an H. pylori phage, KHP30, and reported its genomic sequence. In this study, we examined the biological characteristics of phage KHP30. Phage KHP30 was found to be a spherical lipid-containing phage with a diameter of ca. 69 nm. Interestingly, it was stable from pH 2.5 to pH 10, suggesting that it is adapted to the highly acidic environment of the human stomach. Phage KHP30 multiplied on 63.6% of clinical H. pylori isolates. The latent period was ca. 140 min, shorter than the doubling time of H. pylori (ca. 180 min). The burst size was ca. 13, which was smaller than the burst sizes of other known tailed or spherical phages. Phage KHP30 seemed to be maintained as an episome in H. pylori strain NY43 cells, despite a predicted integrase gene in the KHP30 genomic sequence. Seven possible virion proteins of phage KHP30 were analyzed using N-terminal protein sequencing and mass spectrometry, and their genes were found to be located on its genomic DNA. The genomic organization of phage KHP30 differed from the genomic organizations in the known spherical phage families Corticoviridae and Tectiviridae. This evidence suggests that phage KHP30 is a new type of spherical phage that cannot be classified in any existing virus category. PMID:23475617

  19. Association between Parkinson's Disease and Helicobacter Pylori

    PubMed Central

    Oğuz, Sıdıka

    2016-01-01

    Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258

  20. Association between Parkinson's Disease and Helicobacter Pylori.

    PubMed

    Çamcı, Gülşah; Oğuz, Sıdıka

    2016-04-01

    Helicobacter pylori (HP) is a common infection of the gastrointestinal system that is usually related to peptic ulcers. However, recent studies have revealed relationships between HP and many other diseases. Although the exact mechanism is unknown, HP can prevent the absorption of certain drugs. A high prevalence of HP has been found in patients with Parkinson's disease, and this bacterium causes motor fluctuations by affecting the absorption of levodopa, which is the main drug used to treat Parkinson's disease. Eradicating HP from patients with Parkinson's disease by applying antibiotic treatment will increase the absorption of levodopa and decrease their motor fluctuations. PMID:26932258

  1. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits.

    PubMed

    Graham, David Y

    2015-04-01

    Helicobacter pylori infection contributes to the development of diverse gastric and extragastric diseases. The infection is necessary but not sufficient for the development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, therefore there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to the development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk-these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma. When tested, these hypotheses have not been confirmed and are therefore most likely false. PMID:25655557

  2. The Immune Battle against Helicobacter pylori Infection: NO Offense.

    PubMed

    Gobert, Alain P; Wilson, Keith T

    2016-05-01

    Helicobacter pylori is a successful pathogen of the human stomach. Despite a vigorous immune response by the gastric mucosa, the bacterium survives in its ecological niche, thus favoring diseases ranging from chronic gastritis to adenocarcinoma. The current literature demonstrates that high-output of nitric oxide (NO) production by the inducible enzyme NO synthase-2 (NOS2) plays major functions in host defense against bacterial infections. However, pathogens have elaborated several strategies to counteract the deleterious effects of NO; this includes inhibition of host NO synthesis and transcriptional regulation in response to reactive nitrogen species, allowing the bacteria to face the nitrosative stress. Moreover, NO is also a critical mediator of inflammation and carcinogenesis. In this context, we review the recent findings on the expression of NOS2 in H. pylori-infected gastric tissues and epithelial cells, the role of NO in H. pylori-related diseases and H. pylori gene expression, and the mechanisms whereby H. pylori regulates NO synthesis by host cells. PMID:26916789

  3. Helicobacter pylori: from the stomach to the heart.

    PubMed

    Pellicano, R; Broutet, N; Ponzetto, A; Mégraud, F

    1999-11-01

    A surprising number of extra-gastrointestinal diseases have been reported to be associated with Helicobacter pylori infection, including coronary heart disease and stroke. Since coronary heart disease is the principal cause of death in western countries, and since the known risk factors cannot fully explain the pathogenic mechanisms of the disease, the exploration of the role of possible causal agents has stimulated intense research. Infectious agents have been linked to coronary heart disease on epidemiological and pathogenic grounds. In 1994, H. pylori infection was reported to be one of them. Since then, a number of studies have been published with controversial results. Studies performed thus far show a high degree of heterogeneity in the selection of patients and also in the type of disease studied, i.e. coronary heart disease in general or acute myocardial infarction. Since the pathogenic development is most likely different for each of these two conditions (one chronic and the other acute) they should be studied separately. H. pylori infection can cause platelet aggregation and induces a procoagulant activity. H. pylori can also contribute to atherosclerosis, through increased concentration of homocysteine in the blood, caused by decreased levels of folic acid and cobalamin, or to an autoimmune process. Prospective cohort studies and interventional trials focusing separately on the chronic and acute phases of coronary heart disease and H. pylori infection should be performed in order to provide firm epidemiological data for a causal relationship. PMID:10563551

  4. Local Immune Response in Helicobacter pylori Infection.

    PubMed

    Kivrak Salim, Derya; Sahin, Mehmet; Köksoy, Sadi; Adanir, Haydar; Süleymanlar, Inci

    2016-05-01

    There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori-infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC).In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines-interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-β, IL-17A, IL-32-in H pylori-infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients.We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-β mRNA were increased in the GAC group with reference to H pylori-infected NGM group.This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID:27196487

  5. Helicobacter pylori infection - recent developments in diagnosis

    PubMed Central

    Lopes, Ana Isabel; Vale, Filipa F; Oleastro, Mónica

    2014-01-01

    Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance. PMID:25071324

  6. Helicobacter pylori infection in older people

    PubMed Central

    Pilotto, Alberto; Franceschi, Marilisa

    2014-01-01

    Since the discovery of Helicobacter pylori (H. pylori) infection as the major cause of gastroduodenal disorders three decades ago, H. pylori has been the focus of active research and debate in the scientific community. Its linkage to several diseases, such as peptic ulcer disease, gastritis and gastric malignancy is incontestable. In particular, it has been noticed that, as the aged population is increasing worldwide, older people are at increased risk of developing several gastroduodenal diseases and related complications. At the same time, gastric cancer is definitely more frequent in elderly than in adult and young people. In addition, it has been showed that peptic ulcer and related complications occur much more commonly in aged individuals than in young people, resulting in a significantly higher mortality. Although this infection plays a crucial role in gastrointestinal disorders affecting all age groups and in particular older people, only a few studies have been published regarding the latter. This article presents an overview of the epidemiology, diagnosis, clinical manifestations and therapy of H. pylori infection in elderly people. PMID:24914358

  7. Hybrid Therapy Regimen for Helicobacter Pylori Eradication

    PubMed Central

    Song, Zhi-Qiang; Liu, Jian; Zhou, Li-Ya

    2016-01-01

    Objective: Helicobacter pylori (H. pylori) eradication remains a challenge with increasing antibiotic resistance. Hybrid therapy has attracted widespread attention because of initial report with good efficacy and safety. However, many issues on hybrid therapy are still unclear such as the eradication efficacy, safety, compliance, influencing factors, correlation with antibiotic resistance, and comparison with other regimens. Therefore, a comprehensive review on the evidence of hybrid therapy for H. pylori infection was conducted. Data Sources: The data used in this review were mainly from PubMed articles published in English up to September 30, 2015, searching by the terms of “Helicobacter pylori” or “H. pylori”, and “hybrid”. Study Selection: Clinical research articles were selected mainly according to their level of relevance to this topic. Results: Totally, 1871 patients of 12 studies received hybrid therapy. The eradication rates were 77.6–97.4% in intention-to-treat and 82.6–99.1% in per-protocol analyses. Compliance was 93.3–100.0%, overall adverse effects rate was 14.5–67.5%, and discontinued medication rate due to adverse effects was 0–6.7%. H. pylori culture and sensitivity test were performed only in 13.3% patients. Pooled analysis showed that the eradication rates with dual clarithromycin and metronidazole susceptible, isolated metronidazole or clarithromycin resistance, and dual clarithromycin and metronidazole resistance were 98.5%, 97.6%, 92.9%, and 80.0%, respectively. Overall, the efficacy, compliance, and safety of hybrid therapy were similar with sequential or concomitant therapy. However, hybrid therapy might be superior to sequential therapy in Asians. Conclusions: Hybrid therapy showed wide differences in the efficacy but consistently good compliance and safety across different regions. Dual clarithromycin and metronidazole resistance were the key factor to efficacy. Hybrid therapy was similar to sequential or concomitant

  8. Modulation of Innate Cytokine Responses by Products of Helicobacter pylori

    PubMed Central

    Meyer, Frank; Wilson, Keith T.; James, Stephen P.

    2000-01-01

    The gastric inflammatory and immune response in Helicobacter pylori infection may be due to the effect of different H. pylori products on innate immune mechanisms. The aim of this study was to determine whether bacterial components could modulate cytokine production in vitro and thus contribute to Th1 polarization of the gastric immune response observed in vivo. The effect of H. pylori recombinant urease, bacterial lysate, intact bacteria, and bacterial DNA on proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) from H. pylori-negative donors was examined as a model for innate cytokine responses. Each of the different H. pylori preparations induced gamma interferon (IFN-γ) and interleukin-12p40 (IL-12p40), but not IL-2 or IL-5, production, and all but H. pylori DNA stimulated release of IL-10. Addition of anti-IL-12 antibody to cultures partially inhibited IFN-γ production. In addition, each bacterial product inhibited mitogen-stimulated IL-2 production by PBMCs and Jurkat T cells. The inhibitory effect of bacterial products on IL-2 production correlated with inhibition of mitogen-stimulated lymphocyte proliferation, although urease inhibited IL-2 production without inhibiting proliferation, suggesting that inhibition of IL-2 production alone is not sufficient to inhibit lymphocyte proliferation. The results of these studies demonstrate that Th1 polarization of the gastric immune response may be due in part to the direct effects of multiple different H. pylori components that enhance IFN-γ and IL-12 production while inhibiting both IL-2 production and cell proliferation that may be necessary for Th2 responses. PMID:11035734

  9. Transforming growth factor-B1 and matrix metalloproteinase-7 promoter variants induce risk for Helicobacter pylori-associated gastric precancerous lesions.

    PubMed

    Achyut, B R; Ghoshal, Uday C; Moorchung, Nikhil; Mittal, Balraj

    2009-06-01

    The expression of growth factors, proteolytic enzymes, fibrogenic factors, and cytokines is altered in the Helicobacter pylori-infected gastric mucosa. Therefore, we aimed to evaluate the association of functional promoter variants of transforming growth factor (TGF)-B1 and matrix metalloproteinase (MMP)-7 genes with gastritis and gastric precancerous lesions. After upper gastrointestinal endoscopy, a total of 130 rapid urease test-positive patients with nonulcer dyspepsia were examined for H. pylori infection using modified Giemsa stain and IgG anti-CagA ELISA. All patients and 200 asymptomatic controls were genotyped for TGF-B1 (-509 C>T) and MMP-7 (-181 A>G) substitutions using PCR-RFLP. The genotype and allele frequencies of TGF-B1 and MMP-7 polymorphisms did not differ between patients and controls (p > 0.05). However, the CagA-positive patients with TGF-B1 -509 T allele had higher risk for gastric atrophy (p = 0.026, odds ratio [OR] = 2.38) and lymphoid follicle development (p = 0.028, OR = 2.29). In addition, CagA-positive patients carrying MMP-7 -181 G allele had risk for lymphoid follicle formation (p = 0.027, OR = 2.30). Thus, the present study revealed significant association of functional MMP-7 and TGF-B1 gene variants toward susceptibility to H. pylori-induced precancerous gastric lesions. PMID:19317620

  10. [Reactive polyarthritis and painful dermatographism caused by Helicobacter pylori].

    PubMed

    Morfín Maciel, Blanca María; Castillo Ramos, Héctor Antonio

    2002-01-01

    This paper describes a 36 year-old white woman with six month history of epigastric abdominal pain, reactive arthritis and painful dermographism. Serum antibodies to Helicobacter pylori were identified. All symptoms subsided when she received eradication treatment. PMID:12190006

  11. Errors in Crystal structure of HINT from Helicobacter pylori

    PubMed Central

    Maize, Kimberly M.

    2016-01-01

    Inaccuracies in the article, Crystal structure of HINT from Helicobacter pylori by Tarique et al. [(2016) Acta Cryst. F72, 42–48] are presented, and a brief history of HINT nomenclature is discussed. PMID:27050269

  12. [Helicobacter pylori antibiotic sensitivity by microdilution].

    PubMed

    Rivas, F; Rivera, P; Hernández, F; Hevia, F; Guillén, F; Tamayo, G

    2000-01-01

    The gastric pathogen Helicobacter pylori has been recognized as the major aetiologic agent of chronic gastritis and peptic ulcers and also a risk factor for gastric cancer; eradication of H pylori prevents peptic ulcer recurrence and may also decrease the prevalence of gastric cancer in high risk populations around the world. Currently the only accepted indication for treatment is ulcer disease and maltosa, infected with Helicobacter pilory. However treatment is difficult and easily develops resistance. The elaboration of an antibiotic profile is recommended after a treatment failure. There is a lack of information in developing countries so the aim of this work was to determine the antibiotic profile of 51 strains isolated from patients gastric biopsies attended at Hospital San Juan de Dios in Costa Rica, using egg yolk broth and finding a resistance of 63.0% to metronidazole with a breakpoint of 8.0 microg/ml and 20.0% resistance to tetracycline (MIC1.0 microg/ml), 6.0% to clarithromicyn with a MIC of 0.125 microg/ml. There was no resistance to amoxicilin (MIC 0.015 microg/ml). The microdilution technique is very laborious, but highly reproducible with results accordingly to previous work, and we recommended it for the designing of therapeutical scheme. PMID:15881743

  13. [History of the discovery of Helicobacter pylori].

    PubMed

    Buzás, György Miklós

    2004-01-01

    The discovery of Helicobacter pylori is one of the greatest achievements in the modern history of gastroenterology, which led to fundamental changes in our approach to the pathogenesis and treatment of peptic ulcer disease. However, the road towards accepting the role of these spiral bacteria in the pathogenesis of certain diseases of the upper digestive tract was long and marked with repeated false interpretations and misunderstandings, even when--in retrospect--many times several researchers were very near to the discovery. The first observations concerning the presence of bacteria in animal/human stomachs dates from the dawn of medical microbiology, when the bacterial etiology of some other diseases (tuberculosis, cholera, dysentery, syphilis) was ascertained. In spite of many bacteriological, experimental, biochemical and therapeutic observations, the causative role of the microorganism in the pathogenesis of peptic ulcer was not recognised even in the case of most elegant demonstrations. Sometimes, head-strong thinking and excessive belief in opinion leaders statements set back the bacterial research. The identification of Helicobacter pylori by Barry J. Marshall and J. Robert Warren in 1983 can not be, in any case, considered as serendipitous: without the endeavour, youthful curiosity, talent and ambition of the former and solid classical knowledge in pathology of the latter, peptic ulcer might be considered even today as an acid-related or psychosomatic disease, as it was during the past century. PMID:15977368

  14. Inflammatory response of macrophages cultured with Helicobacter pylori strains was regulated by miR-155.

    PubMed

    Yao, Yongliang; Li, Guangxin; Wu, Jianhong; Zhang, Xian; Wang, Jianjun

    2015-01-01

    MicroRNA-155 plays an important role in the inflammatory response macrophages, while present studies identified that miR-155 was up-expressed in gastritis induced by Helicobacter pylori. We found that miR-155 was over expressed in macrophages infected with H. pylori in vivo or in vitro. Subsequently, inflammatory cytokines IL-23, IL-10, TNF-α and IL-8 were increased significantly, and the expression of CD80, CD86 or COX2, NOS2. Were enhanced in H. pylori infection macrophages by regulated with miR-155mimics. Furthermore, the apoptosis of macrophages induced by H. pylori was increased obviously due to the over-expression of miR-155. Therefore, these observations indicated that miR-155 may act as a inflammatory promoter in H. pylori infected macrophages. These findings contribute us to understand the functions of miR-155 in gastritis induced by H. pylori furtherly. PMID:26191144

  15. Exploring alternative treatments for Helicobacter pylori infection

    PubMed Central

    Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma

    2014-01-01

    Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy. PMID:24587621

  16. Antimicrobial Nanotherapeutics Against Helicobacter pylori Infection

    NASA Astrophysics Data System (ADS)

    Thamphiwatana, Soracha

    Helicobacter pylori (H. pylori) infection with its vast prevalence is responsible for various gastric diseases including gastritis, peptic ulcers, and gastric malignancy. While effective, current treatment regimens are challenged by a fast-declining eradication rate due to the increasing emergence of H. pylori strains resistant to existing antibiotics. Therefore, there is an urgent need to develop novel antibacterial strategies against H. pylori. The first area of this research, we developed a liposomal nanoformulation of linolenic acid (LipoLLA) and evaluated its bactericidal activity against resistant strains of H. pylori. We found that LipoLLA was effective in killing both spiral and dormant forms of the bacteria via disrupting bacterial membranes. LipoLLA eradicated all strains of the bacteria regardless of their antibiotic resistance status. Furthermore, the bacteria did not develop drug resistance toward LipoLLA. Our findings suggest that LipoLLA is a promising antibacterial nanotherapeutic to treat antibiotic-resistant H. pylori infection. The next step, we investigated the in vivo therapeutic potential of LipoLLA for the treatment of H. pylori infection. In vivo tests further confirmed that LipoLLA was able to kill H. pylori and reduce bacterial load in the mouse stomach. LipoLLA treatment was also shown to reduce the levels of proinflammatory cytokines including interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha, which were otherwise elevated due to the H. pylori infection. Finally, toxicity test demonstrated excellent biocompatibility of LipoLLA to normal mouse stomach. Collectively, results from this work indicate that LipoLLA is a promising, new, effective, and safe therapeutic agent for the treatment of H. pylori infection. The second area is stimuli-responsive liposomes development. By adsorbing small chitosan-modified gold nanoparticles (AuChi) onto the outer surface of liposomes, we show that at gastric pH the liposomes have

  17. [Peptic Ulcer Disease Associated with Helicobacter pylori Infection].

    PubMed

    Yeo, Se-Hwan; Yang, Chang-Hun

    2016-06-25

    Although the global prevalence of peptic ulcer disease (PUD) is decreasing, PUD is still one of the most common upper gastrointestinal diseases in the world due to Helicobacter pylori infection and increased use of non-steroidal anti-inflammatory drugs. In Korea, the prevalence of H. pylori infection is also declining, but it is still the major cause of PUD. The outcomes of H. pylori infection are caused by imbalances between bacterial virulence factors, host factors, and environmental influences. In this review, we describe the prevalence trends of H. pylori infection in Korea, the mechanism of H. pylori infection-related PUD, and treatment strategies. PMID:27312829

  18. Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice.

    PubMed

    De, Ronita; Kundu, Parag; Swarnakar, Snehasikta; Ramamurthy, T; Chowdhury, Abhijit; Nair, G Balakrish; Mukhopadhyay, Asish K

    2009-04-01

    Treatment failure is a major cause of concern for the Helicobacter pylori-related gastroduodenal diseases like gastritis, peptic ulcer, and gastric cancer. Curcumin, diferuloylmethane from turmeric, has recently been shown to arrest H. pylori growth. The antibacterial activity of curcumin against 65 clinical isolates of H. pylori in vitro and during protection against H. pylori infection in vivo was examined. The MIC of curcumin ranges from 5 microg/ml to 50 microg/ml, showing its effectiveness in inhibiting H. pylori growth in vitro irrespective of the genetic makeup of the strains. The nucleotide sequences of the aroE genes, encoding shikimate dehydrogenase, against which curcumin seems to act as a noncompetitive inhibitor, from H. pylori strains presenting differential curcumin MICs showed that curcumin-mediated growth inhibition of Indian H. pylori strains may not be always dependent on the shikimate pathway. The antimicrobial effect of curcumin in H. pylori-infected C57BL/6 mice and its efficacy in reducing the gastric damage due to infection were examined histologically. Curcumin showed immense therapeutic potential against H. pylori infection as it was highly effective in eradication of H. pylori from infected mice as well as in restoration of H. pylori-induced gastric damage. This study provides novel insights into the therapeutic effect of curcumin against H. pylori infection, suggesting its potential as an alternative therapy, and opens the way for further studies on identification of novel antimicrobial targets of curcumin. PMID:19204190

  19. OVERVIEW: DISINFECTION OF HELICOBACTER PYLORI AND AEROMONAS SPECIES

    EPA Science Inventory

    Helicobacter pylori and Aeromonas hydrophila are contaminants listed on the USEPA's 1998 Contaminant Candidate List (CCL).The sensitivity of H. pylori to chlorine and of Aeromonas spp. to inactivation by free chlorine, chloramine and ultraviolet (UV) was examined. Selective and...

  20. EVALUATION OF MONITORING METHODS FOR HELICOBACTER PYLORI IN POTABLE WATERS.

    EPA Science Inventory

    Helicobacter pylori is a newly recognized human pathogen, known to cause gastric ulcers and thought to be a contributing factor in gastric cancer. Recent studies in the scientific literature, using a variety of methodologies, report the presence of H. pylori bacteria in environm...

  1. SURVIVAL OF HELICOBACTER PYLORI IN A NATURAL FRESHWATER ENVIRONMENT

    EPA Science Inventory

    The mode by which Helicobacter pylori, the causative agent of most gastric ulcers, is transmitted remains undetermined. Epidemiological evidence suggests these organisms are waterborne; however, H. pylori has rarely been grown from potential water sources. This may be due to th...

  2. Development of gastric cancer associated with Helicobacter pylori infection.

    PubMed

    Sugiyama, Toshiro

    2004-09-01

    Helicobacter pylori infection is associated with histological gastritis, gastric atrophy, gastric cancer and mucosa-associated lymphoid tissue lymphoma in the stomach. However, gastric cancer only develops in a minority of infected individuals. Such clinical diversity is caused by variations in the interactions between H. pylori pathogenicity, host susceptibility, and environmental factors. Based on evidence from three prospective epidemiological studies, the International Agency for Research on Cancer and the World Health Organization (IARC/WHO) concluded in 1994 that H. pylori has a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. Two large-scale, prospective, epidemiological studies have recently been reported in Japan and have confirmed that H. pylori infection constitutes a high risk factor for the development of gastric cancer, at least in males. In order to obtain evidence that eradication of H. pylori leads to a reduction in the occurrence of gastric cancer, reversibility of precancerous lesions, gastric atrophy or intestinal metaplasia should be proven after eradication treatment. A biopsy specimen from the lesser curvature of the corpus is the most sensitive for evaluating the regression of gastric atrophy on histology, and the evaluation needs be conducted at least 13 months after treatment. In a Mongolian gerbil model with or without low-dose chemical carcinogens, it has been demonstrated that H. pylori can lead to the development of gastric cancer. Experimental studies have elucidated that virulence factors of H. pylori interact with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster; it encodes the type IV secretion machinery system forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird phenotype, a growth factor-like effect. The other gene products are

  3. Helicobacter pylori and Other Gastric Microbiota in Gastroduodenal Pathologies.

    PubMed

    Schulz, Christian; Schütte, Kerstin; Malfertheiner, Peter

    2016-01-01

    The discovery of Helicobacter pylori changed the traditional view of the stomach as a hostile organ to bacterial survival. H. pylori induces chronic gastritis, which has the potential to progress to severe complications such as peptic ulcer disease and gastric neoplasia. The development of modern nucleotide sequencing techniques and new biocomputational tools allow the possibility of studying the diversity and complexity of the microbiome in the whole gastrointestinal (GI) tract and overcome the limitations of culturing techniques. However, the differentiation of alive resident and transient microbes in the upper GI tract and their role in the pathogenesis of gastroduodenal diseases requires an analysis beyond the detection of bacterial genomic material alone. Metabolomic and transcriptomic analyses of the bacteria may add important insights into their interaction with the host. Currently, the interaction of H. pylori with other microbes in the stomach and duodenum and their role for health and disease is poorly understood. This review provides a concise overview on the current knowledge of H. pylori and other gastric microbiota in the relationship with gastroduodenal pathologies. PMID:27028228

  4. Metabolic consequences of Helicobacter pylori infection and eradication

    PubMed Central

    Buzás, György Miklós

    2014-01-01

    Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporotein cholesterol levels in some infected people creates an atherogenic lipid profile which could promote atherosclerosis with its complications, myocardial infarction, stroke and peripheral vascular disease. Well designed and adequately powered long-term studies are required to see whether eradication of the infection will prevent these conditions. In case of glucose metabolism, the most consistent association was found between H. pylori and insulin resistance: again, proof that eradication prevents this common metabolic disturbance is expected. The results of eradication with standard regimens in diabetics are significantly worse than in non-diabetic patients, thus, more active regimens must be found to obtain better results. Successful eradication itself led to an increase of body mass index and cholesterol levels in some populations, while in others no such changes were encountered. Uncertainities of the metabolic consequences of H. pylori infection must be clarified in the future. PMID:24833852

  5. Ischemic cardiovascular disease and Helicobacter pylori. Where is the link?

    PubMed

    Pellicano, R; Oliaro, E; Gandolfo, N; Aruta, E; Mangiardi, L; Orzan, F; Bergerone, S; Rizzetto, M; Ponzetto, A

    2000-12-01

    Coronary heart disease (CHD) is the leading cause of death in western countries. Although several major risk factors have been identified, they fail to account for all the epidemiological variants of the disease, thus warranting research into novel causal agents. Cardiovascular diseases have long been associated with chronic infections acting through the activation of inflammatory pathways, and antibiotic therapy has been shown to produce a dramatic decrease in the rate of disease recurrence in patients with a history of myocardial infarction or unstable angina. The link between Helicobacter pylori (H. pylori) infection and CHD, first described by Mendall et al. in 1994, has been the subject of a multitude of epidemiological and clinical studies; however, these have been so heterogeneous that not two of them are based on a comparable selection of patients and focused on the same kind of disease, e.g. stable coronary heart disease or acute myocardial infarction. Evidence from animal studies supports the thesis that H. pylori plays an extremely important role in the acute phase of myocardial infarction: the bacterium causes platelet aggregation and induces pro-coagulant activity in experimentally infected mice. H. pylori may also contribute to atherosclerosis through an auto-immune process against endothelial cells or an increased concentration of homocysteine in the blood due to decreased levels of folic acid and cobalamin. The exact role of H. pylori cannot yet be fully assessed: there is a clear and present need for further studies with appropriate epidemiological and clinical approaches to investigate through prospective and interventional trial the possible causal relationship between H. pylori and CHD. PMID:11232965

  6. Allergies, Helicobacter pylori and the continental enigmas

    PubMed Central

    Sitaraman, Ramakrishnan

    2015-01-01

    Helicobacter pylori, a gastric pathogen, is known to be associated with gastric and duodenal ulcers, and is also a strong risk factor for the development of gastric cancer and lymphoma of the mucosal-associated lymphoid tissue. Ordinarily, this should make a strong case for its eradication at par with any other infectious disease. However, the unique biology of H. pylori and the complexity of its interactions with humans, its only known natural host, do not permit the recommendation of unambiguous preventive and therapeutic measures. Moreover, this organism has co-evolved with humans as a practically universal member of the natural gastric microbiota over at least 100,000 years. H. pylori persists for a lifetime in mostly asymptomatic hosts, and causes clinical disease only in a minority of infections. Therefore, its potential contribution to the maintenance of human immune homeostasis, as is the case with the better-studied members of the intestinal microbiota, is certainly worthy of serious investigation. In this paper, we summarize some interesting and often anecdotal data drawn from recent studies, and examine their significance in the context of the hygiene hypothesis. We also examine whether the lower incidence of gastric cancer over large parts of the world in spite of a high prevalence of infection (the Asian and African enigmas) may be re-interpreted in terms of the hygiene hypothesis. Finally, it is suggested that an evolutionary-ecological approach to the study of H. pylori infection may help in the formulation of strategies for the management of this infection. This may well be an infectious disease wherein medical interventions may have to be personalized to ensure optimal outcomes. PMID:26106380

  7. Diagnosis of Helicobacter pylori: invasive methods.

    PubMed

    Pajares-García, J M

    1998-10-01

    The methods which require endoscopy for the examination of the gastric mucosa are called invasive (direct) methods. Several tests can be performed on the gastric mucosa obtained by endoscopy: Rapid urease test, histology, smear (cytology), culture and polymerase chain reaction. A combination of at least two tests with high sensitivity and specificity is recommended for clinical trials, and, when possible, for clinical management of patients. In clinical practice the invasive methods should be carried out only in those patients to be treated with eradication regimes. All invasive methods rely on gastric biopsy samples. Therefore, the specimens should be taken under optimal conditions. Several factors guide the site and the number of biopsy specimens for identification of Helicobacter pylori infection. In pre-treatment diagnosis, the biopsies should be taken from the distal antrum (2 cm from the pylorus). The number required depends on the diagnostic method used: in Helicobacter pylori eradicated patients the same number of biopsies for histology and culture should be taken from the antrum and corpus. The sensitivity and specificity of the Rapid urease test varies from 80-90% the results are known very quickly and the cost is very low. The maximal accuracy of histology is obtained with: an optimal specimen processing, an adequate staining and an experienced observer. This method of biopsy processing facilitates the identification of Helicobacter pylori which is commonly located on the superficial and foveolar epithelium. Sensitivity depends on the observer's experience and the extent of biopsy sampling. In general, the histological method has a sensitivity and specificity of 90-95%. In patients treated by proton pump inhibitors, antibiotics or bismuth salts two-four weeks prior to biopsy, the bacteria may be restricted to the corpus or fundus. Culture is strictly indicated in patients after failure of two or more eradication regimens to test for susceptibility and

  8. Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NFκB pathway in gastric cancer development.

    PubMed

    Zhang, Bao-Gui; Hu, Lei; Zang, Ming De; Wang, He-Xiao; Zhao, Wei; Li, Jian-Fang; Su, Li-Ping; Shao, Zhifeng; Zhao, Xiaodong; Zhu, Zheng-Gang; Yan, Min; Liu, Bingya

    2016-03-01

    Methylation of CpG islands in tumor suppressor gene prompter is one of the most characteristic abnormalities in Helicobacter pylori (HP)-associated gastric carcinoma (GC). Here, we investigated the pathogenic and molecular mechanisms underlying hypermethylation of tumor suppressor genes in HP induced GC development. We found that tumor suppressor genes hypermethylation, represented by MGMT, positively correlated with CagA in clinical specimens, gastric tissues from HP infected C57 mice and GC cell lines transfected by CagA or treated by HP infection. CagA enhanced PDK1 and AKT interaction and increased AKT phosphorylation. The P-AKT subsequent activated NFκB, which then bound to DNMT1 promoter and increased its expression. Finally, the upregulated DNMT1 promoted tumor suppressor genes hypermethylation with MGMT as a representative. In conclusion, CagA increased tumor suppressor genes hypermethylation via stimulating DNMT1 expression through the AKT-NFκB pathway. PMID:26848521

  9. Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NFκB pathway in gastric cancer development

    PubMed Central

    Wang, He-xiao; Zhao, Wei; Li, Jian-fang; Su, Li-ping; Shao, Zhifeng; Zhao, Xiaodong; Zhu, Zheng-gang; Yan, Min; Liu, Bingya

    2016-01-01

    Methylation of CpG islands in tumor suppressor gene prompter is one of the most characteristic abnormalities in Helicobacter pylori (HP)-associated gastric carcinoma (GC). Here, we investigated the pathogenic and molecular mechanisms underlying hypermethylation of tumor suppressor genes in HP induced GC development. We found that tumor suppressor genes hypermethylation, represented by MGMT, positively correlated with CagA in clinical specimens, gastric tissues from HP infected C57 mice and GC cell lines transfected by CagA or treated by HP infection. CagA enhanced PDK1 and AKT interaction and increased AKT phosphorylation. The P-AKT subsequent activated NFκB, which then bound to DNMT1 promoter and increased its expression. Finally, the upregulated DNMT1 promoted tumor suppressor genes hypermethylation with MGMT as a representative. In conclusion, CagA increased tumor suppressor genes hypermethylation via stimulating DNMT1 expression through the AKT-NFκB pathway. PMID:26848521

  10. Helicobacter pylori in human oral cavity and stomach.

    PubMed

    Bürgers, Ralf; Schneider-Brachert, Wulf; Reischl, Udo; Behr, Anke; Hiller, Karl-Anton; Lehn, Norbert; Schmalz, Gottfried; Ruhl, Stefan

    2008-08-01

    The oral cavity has been suspected as an extra-gastroduodenal reservoir for Helicobacter pylori infection and transmission, but conflicting evidence exists regarding the occurrence of H. pylori in the mouth, independently of stomach colonization. Ninety-four gastric biopsy patients were analysed for the concurrent presence of H. pylori in the mouth and stomach. Samples were collected from different areas within the mouth and H. pylori DNA was amplified by the polymerase chain reaction (PCR) and verified by sequencing. Helicobacter pylori-specific serology was performed, and stomach colonization was determined by culture. In addition, relevant dental and periodontal parameters, as well as general health parameters, were recorded. Helicobacter pylori was found in the stomach of 29 patients and in the oral cavity of 16 patients. In only six patients was the bacterium detected simultaneously in the stomach and mouth. Notably, the 10 patients in whom the bacterium was found solely in the mouth did not have serum antibodies to H. pylori. The occurrence of H. pylori in the mouth was found to be correlated neither to any general or oral health parameters, nor to any particular site of collection. This study shows that H. pylori can occur in the oral cavity independently of stomach colonization. PMID:18705796

  11. Helicobacter pylori HP0231 Influences Bacterial Virulence and Is Essential for Gastric Colonization

    PubMed Central

    Zhong, Yu; Anderl, Florian; Kruse, Tobias; Schindele, Franziska; Jagusztyn-Krynicka, Elżbieta Katarzyna; Fischer, Wolfgang; Gerhard, Markus

    2016-01-01

    The Dsb protein family is responsible for introducing disulfide bonds into nascent proteins in prokaryotes, stabilizing the structure of many proteins. Helicobacter pylori HP0231 is a Dsb-like protein, shown to catalyze disulfide bond formation and to participate in redox homeostasis. Notably, many H. pylori virulence factors are stabilized by the formation of disulfide bonds. By employing H. pylori HP0231 deficient strains we analyzed the effect of lack of this bacterial protein on the functionality of virulence factors containing putative disulfide bonds. The lack of H. pylori HP0231 impaired CagA translocation into gastric epithelial cells and reduced VacA-induced cellular vacuolation. Moreover, H. pylori HP0231 deficient bacteria were not able to colonize the gastric mucosa of mice, probably due to compromised motility. Together, our data demonstrate an essential function for H. pylori HP0231 in gastric colonization and proper function of bacterial virulence factors related to gastric pathology. PMID:27138472

  12. Echoes of a distant past: The cag pathogenicity island of Helicobacter pylori.

    PubMed

    Pacchiani, Nicola; Censini, Stefano; Buti, Ludovico; Covacci, Antonello

    2013-11-01

    This review discusses the multiple roles of the CagA protein encoded by the cag pathogenicity island of Helicobacter pylori and highlights the CagA degradation activities on p53. By subverting the p53 tumor suppressor pathway CagA induces a strong antiapoptotic effect. Helicobacter pylori infection has been always associated with an increased risk of gastric cancer. The pro-oncogenic functions of CagA also target the tumor suppressor ASPP2. In the absence of tumor suppressor genes, cells survive and proliferate at times and in places where their survival and proliferation are inappropriate. PMID:24097901

  13. Helicobacter pylori-induced chronic inflammation causes telomere shortening of gastric mucosa by promoting PARP-1-mediated non-homologous end joining of DNA.

    PubMed

    Lee, Wei-Ping; Hou, Ming-Chih; Lan, Keng-Hsin; Li, Chung-Pin; Chao, Yee; Lin, Han-Chieh; Lee, Shou-Dong

    2016-09-15

    Helicobacter pylori infection leads to chronic gastritis and increased risk of gastric cancer. The mechanism involves chronic inflammation. We aimed to determine the mechanism by which H. pylori infection causes telomere shortening in inflammatory gastric mucosa. Gastric biopsy specimens were obtained from 20 patients with chronic gastritis or peptic ulcer caused by H. pylori infection. The specimens showed increased NF-κB and superoxide dismutase activities and elevated expressions of PARP-1 and γ-H2AX, all of which returned to normal levels after anti-H. pylori treatment, suggesting that oxidative DNA damage and PARP-1 overexpression might cause telomere shortening. In this report, we adopted DNA end joining assay and showed that H. pylori-infected gastric mucosa had increased alternative NHEJ (non-homologous end joining), implicating that telomere shortening was caused by inflammation-mediated overproduction of reactive oxygen species and PARP-1, leading to telomere shortening. PMID:27450718

  14. Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient B6.129P2-Gulo tm1Umc/mmc...

  15. [Diseases linked to Helicobacter pylori infection].

    PubMed

    Gisbert, Javier P

    2014-09-01

    Below is a summary of the main conclusions that came from reports presented at this year's Digestive Disease Week (2014) relating to Helicobacter pylori infection. Despite the undeniable decline of the infection's frequency, in the near future, developed countries--or at least some sub-populations--will continue to have a significant prevalence of the infection. Clarithromycin, metronidazole and quinolone resistance rates are considerably high in most countries and these rates are on the rise. The eradication of H. pylori improves symptoms of functional dyspepsia, although only in a minority of patients; adding antidepressants to eradication therapy could improve long-term response. In patients who were admitted with gastrointestinal bleeding from peptic ulcers, it is necessary to thoroughly study the presence of H. pylori infection and administer eradication therapy as early as possible. Eradication of H. pylori in patients undergoing endoscopic resection of early-stage gastric cancer reduces incidence of metachronous tumors. We have some diagnostic innovations, such as carrying out various techniques--a rapid urease test, culture or PCR--based on gastric samples obtained by scraping the mucosa. The effectiveness of conventional triple therapy is clearly insufficient and continues to decline. The superiority of sequential therapy over conventional triple therapies has not been definitively established. Concomitant therapy is simpler and more effective than sequential therapy. Optimized concomitant therapy (with high doses of proton-pump inhibitors [PPI] and over 14 days) is highly effective, more so than standard concomitant therapy. For patients who are allergic to penicillin, 2 treatment options were essentially described: PPI-clarithromycin-metronidazole (clarithromycin-sensitive strains) and quadruple therapy with bismuth (when the bacterial sensitivity is unknown). If conventional triple therapy fails, second-line therapy with levofloxacin is effective and is

  16. Helicobacter pylori virulence and cancer pathogenesis

    PubMed Central

    Yamaoka, Yoshio; Graham, David Y

    2014-01-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro–in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies. PMID:25052757

  17. Crystal structure of HINT from Helicobacter pylori.

    PubMed

    Tarique, K F; Devi, S; Abdul Rehman, S A; Gourinath, S

    2016-01-01

    Proteins belonging to the histidine triad (HIT) superfamily bind nucleotides and use the histidine triad motif to carry out dinucleotidyl hydrolase, nucleotidyltransferase and phosphoramidite hydrolase activities. Five different branches of this superfamily are known to exist. Defects in these proteins in humans are linked to many diseases such as ataxia, diseases of RNA metabolism and cell-cycle regulation, and various types of cancer. The histidine triad nucleotide protein (HINT) is nearly identical to proteins that have been classified as protein kinase C-interacting proteins (PKCIs), which also have the ability to bind and inhibit protein kinase C. The structure of HINT, which exists as a homodimer, is highly conserved from humans to bacteria and shares homology with the product of fragile histidine triad protein (FHit), a tumour suppressor gene of this superfamily. Here, the structure of HINT from Helicobacter pylori (HpHINT) in complex with AMP is reported at a resolution of 3 Å. The final model has R and Rfree values of 26 and 28%, respectively, with good electron density. Structural comparison with previously reported homologues and phylogenetic analysis shows H. pylori HINT to be the smallest among them, and suggests that it branched out separately during the course of evolution. Overall, this structure has contributed to a better understanding of this protein across the animal kingdom. PMID:26750483

  18. Oral Cavity as an Extragastric Reservoir of Helicobacter pylori

    PubMed Central

    Anand, Pradeep S.; Kamath, Kavitha P.; Patil, Shankargouda; Preethanath, R. S.; Anil, Sukumaran

    2014-01-01

    Background. Several studies were reported on the prevalence, and relationship between the existence of Helicobacter pylori (H. pylori) in oral cavity and in stomach of patients. The purpose of this study was to systematically review the existing literature on the presence of H. pylori in the oral cavity and its link to gastric infection, the existence of coinfection, and the impact of anti-H. pylori therapy on the dental plaque and vice versa. Method. Two authors independently searched the Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus databases for relevant studies. The articles were analyzed critically and all qualified studies were included. The search was carried out by using a combined text and the MeSH search strategies: using the key words Helicobacter, Helicobacter pylori, and H. pylori in combination with dental plaque, periodontitis, and oral hygiene. Results. The data was presented in 8 tables and each topic separately discussed. Conclusion. Based on the systematic review of the available literature on H. pylori infection and its presence in the oral cavity, it can be concluded that dental plaque can act as a reservoir, and proper oral hygiene maintenance is essential to prevent reinfection. Due to the diversified methods and population groups involved in the available literature, no concrete evidence can be laid down. Further studies are necessary to establish the role of H. pylori in the oral cavity and its eradication on preventing the gastroduodenal infection. PMID:24701355

  19. Helicobacter pylori and gastric or duodenal ulcer.

    PubMed

    2016-01-01

    In patients with gastric or duodenal ulcer associated with Helicobacter pylori, treatment of the infection improves healing and prevents complications and recurrences. The drug regimen generally consists of a high-dose proton-pump inhibitor (PPI) such as omeprazole plus antibiotics. Using the standard Prescrire methodology, we conducted a review of the literature in order to determine the standard empirical antibiotic regimen for H. pylori infection in adults with gastric or duodenal ulcer in France. In 2015, due to an increase in H. pylori resistance to clarithromycin, a 7-day course of the PPI + clarithromycin + amoxicillin combination is effective in only about 70% of cases. A Cochrane systematic review and meta-analysis of trials involving thousands of patients suggests that prolonging treatment with a PPI + amoxicillin + clarithromycin or a PPI + amoxicillin + metronidazole to 10 or 14 days improves the rate of H. pylori eradication by 5% to 10%. A metanalysis of seven trials including a total of about 1000 patients showed that combination therapy with a PPI + amoxicillin + clarithromycin + metronidazole for 5 days eradicates H. pylori in about 90% of cases, compared to about 80% of cases with a PPI + amoxicillin + clarithromycin given for 7 days. Sequential treatment with amoxicillin for 5 days, followed by clarithromycin + metronidazole for 5 days, has also been tested in thousands of patients. Efficacy and adverse effects were similar to those observed when the same antibiotics were taken simultaneously for 5 days. In randomised trials, replacing clarithromycin or amoxicillin with a fluoroquinolone yielded conflicting results. In 2009, nearly 20% of H. pylori isolates were resistant to levofloxacin in France. Tetracycline has only been evaluated in combination with bismuth. The few available data on doxycycline suggest that its efficacy is similar to that of tetracycline. A fixed-dose combination of bismuth subcitrate potassium + metronidazole

  20. From the stomach to other organs: Helicobacter pylori and the liver

    PubMed Central

    Waluga, Marek; Kukla, Michał; Żorniak, Michał; Bacik, Agata; Kotulski, Rafał

    2015-01-01

    Many recent studies have examined the importance of Helicobacter pylori (H. pylori) infection in the pathogenesis of the diseases outside the stomach and explored the significance of this bacterium in the pathogenesis of some metabolic and cardiovascular diseases. Recent studies have provided evidence that H. pylori is also involved in the pathogenesis of some liver diseases. Many observations have proved that H. pylori infection is important in the development of insulin resistance, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, liver fibrosis and cirrhosis. The worsening of liver inflammation of different origins also occurs during H. pylori infection. Some studies have indicated that H. pylori infection induces autoimmunological diseases in the liver and biliary tract. The potential significance of this bacterium in carcinogenesis is unclear, but it is within the scope of interest of many studies. The proposed mechanisms through which H. pylori impacts the development of hepatobiliary diseases are complex and ambiguous. The importance of other Helicobacter species in the development of hepatobiliary diseases is also considered because they could lead to the development of inflammatory, fibrotic and necrotic injuries of the liver and, consequently, to hepatocellular carcinoma. However, many contrary viewpoints indicate that some evidence is not convincing, and further studies of the subject are needed. This review presents the current knowledge about the importance of H. pylori in the pathogenesis of liver and in biliary diseases. PMID:26328025

  1. Inflammation, immunity, and vaccines for Helicobacter pylori infection.

    PubMed

    Velin, Dominique; Straubinger, Kathrin; Gerhard, Markus

    2016-09-01

    The tight control of the innate and adaptive immune responses in the stomach mucosa during chronic Helicobacter pylori infection is of prime importance for the bacteria to persist and for the host to prevent inflammation-driven diseases. This review summarizes recent data on the roles of innate and adaptive immune responses during H. pylori/host interactions. In addition, the latest preclinical developments of H. pylori vaccines are discussed with a special focus on the clinical trial reported by Zeng et al., who provided evidence that oral vaccination significantly reduces the acquisition of natural H. pylori infection in children. PMID:27531535

  2. Relationship of Halitosis with Gastric Helicobacter Pylori Infection

    PubMed Central

    HajiFattahi, Farnaz; Hesari, Maryam; Zojaji, Homayoun; Sarlati, Fatemeh

    2015-01-01

    Objectives: Gastric infection with Helicobacter pylori may be one of the main causes of halitosis. This study was performed to evaluate the relationship of Helicobacter pylori infection with halitosis. Materials and Methods: This case control study was performed on 44 dyspeptic patients with a mean age of 34.29±13.71 years (range 17 to 76 years). The case group included 22 patients with halitosis and no signs of diabetes mellitus, renal or liver failure, upper respiratory tract infection, malignancies, deep carious teeth, severe periodontitis, coated tongue, dry mouth or poor oral hygiene. Control group included 22 patients without halitosis and the same age, sex, systemic and oral conditions as the case group. Halitosis was evaluated using organoleptic test (OLT) and Helicobacter pylori infection was evaluated by Rapid Urease Test (RUT) during endoscopy. The data were statistically analyzed using chi square, Mann Whitney and t-tests. Results: Helicobacter pylori infection was detected in 20 (91%) out of 22 halitosis patients, and 7 control subjects (32%) (P<0.001). Conclusion: Helicobacter pylori gastric infection can be a cause of bad breath. Dentists should pay more attention to this infection and refer these patients to internists to prevent further gastrointestinal (GI) complications and probable malignancies. PMID:26622273

  3. Helicobacter pylori neutrophil activating protein as target for new drugs against H. pylori inflammation

    PubMed Central

    Choli-Papadopoulou, Theodora; Kottakis, Filippos; Papadopoulos, Georgios; Pendas, Stefanos

    2011-01-01

    Helicobacter pylori (H. pylori) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer. Within this work we present the implication of C-terminal region of H. pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evidence that the C-terminal region of H. pylori activating protein is indispensable for neutrophil adhesion to endothelial cells, a step necessary to H. pylori inflammation. In addition we show that arabino galactan proteins derived from chios mastic gum, the natural resin of the plant Pistacia lentiscus var. Chia inhibit neutrophil activation in vitro. PMID:21677824

  4. Epidemiology of Helicobacter pylori infection in dyspeptic Ghanaian patients

    PubMed Central

    Archampong, Timothy Nii Akushe; Asmah, Richard Harry; Wiredu, Edwin Kwame; Gyasi, Richard Kwasi; Nkrumah, Kofi Nyaako; Rajakumar, Kumar

    2015-01-01

    Introduction Helicobacter pylori is a gram-negative urease-producing bacterium causally linked with gastritis, peptic ulcer disease and gastric adenocarcinoma. Infection is more frequent and acquired at an earlier age in developing countries compared to European populations. The incidence of Helicobacter pylori infection in dyspeptic Ghanaian patients was 75.4%. However, epidemiological factors associated with infection vary across populations. Methods This study used a cross-sectional design to consecutively sample dyspeptic patients at the Endoscopy Unit of the Korle-Bu Teaching Hospital, Accra between 2010 and 2012. The study questionnaire elicited their epidemiological clinical characteristics. Helicobacter pylori infection was confirmed by rapid-urease examination of antral biopsies at upper Gastro-intestinal endoscopy. Results The sample population of dyspeptic patients attending the Endoscopy Unit for upper GI endoscopy yielded 242 patients of which 47.5% were females. The age distribution of H. pylori-infection was even across most age – groups, ranging from 69.2% (61 – 70) years to 80% (21 – 30) years. Helicobacter pylori prevalence decreased across areas mapping to the three residential classes in accordance with increasing affluence with rural areas having the highest prevalence. The unemployed and patients in farming had relatively high Helicobacter pylori infection rates of 92.3% and 91.7% respectively. Conclusion Helicobacter pylori is endemic in Ghana but the persistently high prevalence across age groups despite significant community anti-microbial use suggests likely re-crudescence or re-infection from multiple sources in a developing country. Socio-cultural factors such as residential class and farming may be facilitating factors for its continued prevalence. PMID:26430475

  5. Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology

    PubMed Central

    Tsai, Hwei-Fang; Hsu, Ping-Ning

    2010-01-01

    Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, gastric carcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies have shown that apoptosis of gastric epithelial cells is increased during H. pylori infection. Apoptosis induced by microbial infections are factors implicated in the pathogenesis of H. pylori infection. The enhanced gastric epithelial cell apoptosis in H. pylori infection has been suggested to play an important role in the pathogenesis of chronic gastritis and gastric pathology. In addition to directly triggering apoptosis, H. pylori induces sensitivity to tumor-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells via modulation of TRAIL apoptosis signaling. Moreover, H. pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. pylori infection, there was significantly increased CCR6+CD3+ T-cell infiltration in the gastric mucosa, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These results implicate that the interaction between CCL20 and CCR6 may play a role in recruiting T cells to the sites of inflammation in the gastric mucosa during Helicobacter infection. Through these mechanisms, chemokine-mediated T lymphocyte trafficking into inflamed epithelium is initiated and the mucosal injury in Helicobacter infection is induced. This article will review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation, mucosal damage and development of MALT lymphomas. PMID:20190789

  6. Crude Preparations of Helicobacter pylori Outer Membrane Vesicles Induce Upregulation of Heme Oxygenase-1 via Activating Akt-Nrf2 and mTOR–IκB Kinase–NF-κB Pathways in Dendritic Cells

    PubMed Central

    Ko, Su Hyuk; Rho, Da Jeong; Jeon, Jong Ik; Kim, Young-Jeon; Woo, Hyun Ae; Kim, Nayoung

    2016-01-01

    Helicobacter pylori sheds outer membrane vesicles (OMVs) that contain many surface elements of bacteria. Dendritic cells (DCs) play a major role in directing the nature of adaptive immune responses against H. pylori, and heme oxygenase-1 (HO-1) has been implicated in regulating function of DCs. In addition, HO-1 is important for adaptive immunity and the stress response. Although H. pylori-derived OMVs may contribute to the pathogenesis of H. pylori infection, responses of DCs to OMVs have not been elucidated. In the present study, we investigated the role of H. pylori-derived crude OMVs in modulating the expression of HO-1 in DCs. Exposure of DCs to crude H. pylori OMVs upregulated HO-1 expression. Crude OMVs obtained from a cagA-negative isogenic mutant strain induced less HO-1 expression than OMVs obtained from a wild-type strain. Crude H. pylori OMVs activated signals of transcription factors such as NF-κB, AP-1, and Nrf2. Suppression of NF-κB or Nrf2 resulted in significant attenuation of crude OMV-induced HO-1 expression. Crude OMVs increased the phosphorylation of Akt and downstream target molecules of mammalian target of rapamycin (mTOR), such as S6 kinase 1 (S6K1). Suppression of Akt resulted in inhibition of crude OMV-induced Nrf2-dependent HO-1 expression. Furthermore, suppression of mTOR was associated with inhibition of IκB kinase (IKK), NF-κB, and HO-1 expression in crude OMV-exposed DCs. These results suggest that H. pylori-derived OMVs regulate HO-1 expression through two different pathways in DCs, Akt-Nrf2 and mTOR–IKK–NF-κB signaling. Following this induction, increased HO-1 expression in DCs may modulate inflammatory responses in H. pylori infection. PMID:27185786

  7. Crude Preparations of Helicobacter pylori Outer Membrane Vesicles Induce Upregulation of Heme Oxygenase-1 via Activating Akt-Nrf2 and mTOR-IκB Kinase-NF-κB Pathways in Dendritic Cells.

    PubMed

    Ko, Su Hyuk; Rho, Da Jeong; Jeon, Jong Ik; Kim, Young-Jeon; Woo, Hyun Ae; Kim, Nayoung; Kim, Jung Mogg

    2016-08-01

    Helicobacter pylori sheds outer membrane vesicles (OMVs) that contain many surface elements of bacteria. Dendritic cells (DCs) play a major role in directing the nature of adaptive immune responses against H. pylori, and heme oxygenase-1 (HO-1) has been implicated in regulating function of DCs. In addition, HO-1 is important for adaptive immunity and the stress response. Although H. pylori-derived OMVs may contribute to the pathogenesis of H. pylori infection, responses of DCs to OMVs have not been elucidated. In the present study, we investigated the role of H. pylori-derived crude OMVs in modulating the expression of HO-1 in DCs. Exposure of DCs to crude H. pylori OMVs upregulated HO-1 expression. Crude OMVs obtained from a cagA-negative isogenic mutant strain induced less HO-1 expression than OMVs obtained from a wild-type strain. Crude H. pylori OMVs activated signals of transcription factors such as NF-κB, AP-1, and Nrf2. Suppression of NF-κB or Nrf2 resulted in significant attenuation of crude OMV-induced HO-1 expression. Crude OMVs increased the phosphorylation of Akt and downstream target molecules of mammalian target of rapamycin (mTOR), such as S6 kinase 1 (S6K1). Suppression of Akt resulted in inhibition of crude OMV-induced Nrf2-dependent HO-1 expression. Furthermore, suppression of mTOR was associated with inhibition of IκB kinase (IKK), NF-κB, and HO-1 expression in crude OMV-exposed DCs. These results suggest that H. pylori-derived OMVs regulate HO-1 expression through two different pathways in DCs, Akt-Nrf2 and mTOR-IKK-NF-κB signaling. Following this induction, increased HO-1 expression in DCs may modulate inflammatory responses in H. pylori infection. PMID:27185786

  8. A multi-epitope vaccine CTB-UE relieves Helicobacter pylori-induced gastric inflammatory reaction via up-regulating microRNA-155 to inhibit Th17 response in C57/BL6 mice model.

    PubMed

    Lv, Xiaobo; Song, Hui; Yang, Jue; Li, Tong; Xi, Tao; Xing, Yingying

    2014-01-01

    Vaccination is an effective mean of preventing infectious diseases, including those caused by Helicobacter pylori. Th17 cell responses are critical for the pathogenesis of Helicobacter pylori infection. In view of Th17 responses to multi-epitope vaccine CTB-UE, the IL-17 production in antiserum was examined. CTB-UE immunization decreased IL-17 production, implying that Th17 responses may be inhibited. Furthermore, IL-17 aggravated GES-1 cell injury induced by H. pylori SS1; In contrast, CTB-UE antiserum could alleviate this cell injury, which suggesting that CTB-UE can protect GES-1 cell infected with H. pylori SS1 by inhibiting Th17 responses. Treatment of mice with CTB-UE significantly reduced the H. pylori burden and inflammation in the stomach. On the other hand, the production of IL-17 in the stomach in H. pylori-infected mice was increased; but the production of IL-17 in the stomach was decreased after treatment with CTB-UE. Furthermore, the expression of microRNA-155 in gastric tissue was significantly up-regulated. The results suggested that CTB-UE could relieve the H. pylori-induced gastric inflammatory reaction via up-regulating microRNA-155 to inhibit Th17 responses, implying that the microRNA-155/IL-17 pathway was involved. Further study is required to elucidate the relationship between miRNA-155 and IL-17. We found that the production of IL-17 was significantly increased after the expression of miRNA-155 being down-regulated; however, the production of IL-17 was significantly decreased after the expression of miRNA-155 being upregulated. PMID:25483699

  9. Helicobacter pylori and non-malignant upper gastrointestinal diseases.

    PubMed

    Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne

    2016-09-01

    Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD. PMID:27531536

  10. Detection of Helicobacter pylori in saliva and esophagus.

    PubMed

    Cellini, Luigina; Grande, Rossella; Artese, Luciano; Marzio, Leonardo

    2010-10-01

    The route of Helicobacter pylori transmission remains unclear and the currently suggested route is person-to-person transfer by faecal-oral and oral-oral mode. The aim of this study was to verify the presence of H. pylori in esophagus and saliva of humans. Saliva samples, mucosal biopsies from esophagus, gastric antrum and fundus were collected from 19 patients with positive Urea Breath Test (UBT). Gastric biopsies were used for H. pylori colture and antimicrobial susceptibility tests whereas saliva samples were collected to detect H. pylori with a Nested-PCR targeting 16S rRNA gene as well as esophagus biopsies which were also investigated with immunohistochemical staining. Helicobacter pylori was isolated in 18 patients both in gastric antrum and fundus. The molecular analysis, confirmed by comparative sequences evaluation, gave positive results in all saliva and esophageal samples whereas the immunohistochemistry revealed the presence of H. pylori in 15.8% (3/19) of the esophagus samples. Our data suggest that saliva and esophagus may be considered reservoirs for H. pylori in humans and emphasize the need to use more susceptible techniques for H. pylori detection, in particular in over-crowded sites. Identification of the transmission route of H. pylori is crucial in developing an effective plan of surveillance by finding new means of disease management. PMID:21213594

  11. Evolution of the Selenoproteome in Helicobacter pylori and Epsilonproteobacteria

    PubMed Central

    Cravedi, Pietro; Mori, Giulia; Fischer, Frédéric; Percudani, Riccardo

    2015-01-01

    By competing for the acquisition of essential nutrients, Helicobacter pylori has the unique ability to persist in the human stomach, also causing nutritional insufficiencies in the host. Although the H. pylori genome apparently encodes selenocysteine synthase (SelA, HP1513), a key pyridoxal phosphate (PLP)-dependent enzyme for the incorporation of selenium into bacterial proteins, nothing is known about the use of this essential element in protein synthesis by this pathogen. We analyzed the evolution of the complete machinery for incorporation of selenium into proteins and the selenoproteome of several H. pylori strains and related Epsilonproteobacteria. Our searches identified the presence of selenoproteins—including the previously unknown DUF466 family—in various Epsilonproteobacteria, but not in H. pylori. We found that a complete system for selenocysteine incorporation was present in the Helicobacteriaceae ancestor and has been recently lost before the split of Helicobacter acinonychis and H. pylori. Our results indicate that H. pylori, at variance with other gastric and enterohepatic Helicobacter, does not use selenocysteine in protein synthesis and does not use selenium for tRNA wobble base modification. However, selA has survived as a functional gene, having lost the domain for the binding of selenocysteine tRNA, but maintaining the ability to bind the PLP cofactor. The evolutionary modifications described for the SelA protein of H. pylori find parallels in other bacterial and archaeal species, suggesting that an alternative enzymatic function is hidden in many proteins annotated as selenocysteinyl-tRNA synthase. PMID:26342139

  12. Evolution of the Selenoproteome in Helicobacter pylori and Epsilonproteobacteria.

    PubMed

    Cravedi, Pietro; Mori, Giulia; Fischer, Frédéric; Percudani, Riccardo

    2015-09-01

    By competing for the acquisition of essential nutrients, Helicobacter pylori has the unique ability to persist in the human stomach, also causing nutritional insufficiencies in the host. Although the H. pylori genome apparently encodes selenocysteine synthase (SelA, HP1513), a key pyridoxal phosphate (PLP)-dependent enzyme for the incorporation of selenium into bacterial proteins, nothing is known about the use of this essential element in protein synthesis by this pathogen. We analyzed the evolution of the complete machinery for incorporation of selenium into proteins and the selenoproteome of several H. pylori strains and related Epsilonproteobacteria. Our searches identified the presence of selenoproteins-including the previously unknown DUF466 family-in various Epsilonproteobacteria, but not in H. pylori. We found that a complete system for selenocysteine incorporation was present in the Helicobacteriaceae ancestor and has been recently lost before the split of Helicobacter acinonychis and H. pylori. Our results indicate that H. pylori, at variance with other gastric and enterohepatic Helicobacter, does not use selenocysteine in protein synthesis and does not use selenium for tRNA wobble base modification. However, selA has survived as a functional gene, having lost the domain for the binding of selenocysteine tRNA, but maintaining the ability to bind the PLP cofactor. The evolutionary modifications described for the SelA protein of H. pylori find parallels in other bacterial and archaeal species, suggesting that an alternative enzymatic function is hidden in many proteins annotated as selenocysteinyl-tRNA synthase. PMID:26342139

  13. Helicobacter pylori infection: New pathogenetic and clinical aspects

    PubMed Central

    Hagymási, Krisztina; Tulassay, Zsolt

    2014-01-01

    Helicobacter pylori (H. pylori) infects more than half of the world’s human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial. PMID:24914360

  14. Biomarkers for Helicobacter pylori infection and gastroduodenal diseases

    PubMed Central

    Shiota, Seiji; Yamaoka, Yoshio

    2014-01-01

    Helicobacter pylori infection is a major cause of gastric cancer. Although identifying H. pylori infected subjects is the first approach for delineating the high-risk population for gastric cancer, the presence of H. pylori antibodies is not sufficient for gastric cancer screening. Among H. pylori infected subjects, only a minority of infected individuals develop gastric cancer. Serologic markers of H. pylori infection can serve as potential predictors for the development of gastric cancer. Serum or urinary H. pylori antibodies, cytotoxin-associated gene A antibodies, pepsinogen and microRNAs were reported to be associated with precancerous lesions or gastric cancer. In this review, we summarized the utilities and limitations of each strategy. PMID:25402582

  15. Extraintestinal manifestations of Helicobacter pylori: A concise review

    PubMed Central

    Wong, Frank; Rayner-Hartley, Erin; Byrne, Michael F

    2014-01-01

    Helicobacter pylori (H. pylori) infection has been clearly linked to peptic ulcer disease and some gastrointestinal malignancies. Increasing evidence demonstrates possible associations to disease states in other organ systems, known as the extraintestinal manifestations of H. pylori. Different conditions associated with H. pylori infection include those from hematologic, cardiopulmonary, metabolic, neurologic, and dermatologic systems. The aim of this article is to provide a concise review of the evidence that supports or refutes the associations of H. pylori and its proposed extraintestinal manifestations. Based on data from the literature, PUD, mucosal associated lymphoid tumors lymphoma, and gastric adenocarcinoma has well-established links. Current evidence most supports extraintestinal manifestations with H. pylori in immune thrombocytopenic purpura, iron deficiency anemia, urticaria, Parkinson’s, migraines and rosacea; however, there is still plausible link with other diseases that requires further research. PMID:25232230

  16. Helicobacter pylori infection, vitamin B12 and homocysteine. A review.

    PubMed

    Dierkes, Jutta; Ebert, Matthias; Malfertheiner, Peter; Luley, Claus

    2003-01-01

    It has been suggested that there is an association between Helicobacter pylori infection, reduced cobalamin absorption and cobalamin status and, consequently, elevated homocysteine levels. This would offer an explanation why H. pylori infection is associated with coronary heart disease. To date, more than 25 studies have been published that either deal with H. pylori infection and homocysteine, H. pylori infection and cobalamin status, or both. The design of these studies differs widely in terms of definition of H. pylori status, measuring cobalamin status, selection of study cohorts and geographical study areas. Therefore, results are fairly inconclusive at present and do not suggest a major role of H. pylori infection in the development of cobalamin deficiency and elevated homocysteine levels. PMID:14571097

  17. Basis of decreased risk of gastric cancer in severe atrophic gastritis with eradication of Helicobacter pylori.

    PubMed

    Tari, Akira; Kitadai, Yasuhiko; Sumii, Masaharu; Sasaki, Atsunori; Tani, Hiroshi; Tanaka, Sinji; Chayama, Kazuaki

    2007-01-01

    Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover. PMID:17151803

  18. Helicobacter pylori in Cholecystectomy Specimens-Morphological and Immunohistochemical Assessment

    PubMed Central

    Reddy, Venkatarami; Jena, Amitabh; Gavini, Siva; Thota, Asha; Nandyala, Rukamangadha; Chowhan, Amit Kumar

    2016-01-01

    Introduction Helicobacter pylori (H.pylori) is associated with gastritis, peptic ulcer, gastric carcinoma and gastric lymphoma. Current literature describes presence of H.pylori in various extra-gastric locations and its association with many diseases. Apart from the conventional location of gastric and duodenal mucosa, H.pylori have been isolated and cultured from gallbladder. Aim Analysis of cholecystectomy specimens to detect H.pylori by means of immunohistochemical staining. Materials and Methods There were a total of 118 cholecystectomy specimens received in the Department of Pathology in three months duration. We have performed immunostaining for H.pylori in 45 consecutive cases of cholecystectomy specimen. Clinical and other investigational information were retrieved from the medical records department. For each case, routine Haematoxylin and Eosin stain was studied. Immunohistochemistry (IHC) was done using purified polyclonal Helicobacter pylori antiserum. Results Majority of the patients had undergone laparoscopic cholecystectomy for the presenting complaint of right hypochondrial pain. Multiple pigmented stones were present in majority (27/45) of them. Immunostain for H.pylori was positive in ten cases. Six of these cases had pigmented gall stones, two had stones not specified and in two of the cases there were no stones. Conclusion Helicobacter pylori is present in gall bladder and is commonly seen in association with stones. A more detailed study of cholecystectomy cases (both neoplastic and non-neoplastic) with serological, culture and molecular data of H.pylori is desirable to study the pathogenesis of cholecystitis, its association with gall stones and other gall bladder disorders. PMID:27437221

  19. Probiotics for Standard Triple Helicobacter pylori Eradication

    PubMed Central

    Hauser, Goran; Salkic, Nermin; Vukelic, Karina; JajacKnez, Alenka; Stimac, Davor

    2015-01-01

    Abstract The primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori. The study was multicenter, prospective, randomized, placebo controlled, and double-blind. The subjects first filled out a specially designed questionnaire to assess the severity of the 10 symptoms, which can be related to eradication therapy to be monitored during the trial. Each subject then received 28 capsules of probiotic preparation or matching placebo capsules, which they were supposed to take over the following 14 days, twice a day, at least 2 hours prior to or after the antibiotic therapy administration. A total of 804 patients were enrolled in the trial, of which 650 (80.85%) were included in the analysis. The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm (87.38% vs 72.55%; P < 0.001). Additionally, presence and intensity of epigastric pain, bloating, flatulence, taste disturbance, loss of appetite, nausea, vomiting, heartburn, rash, and diarrhea were monitored over the study period. At 15 days postinclusion, probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms. Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group, 0.76 vs 0.55 (P < 0.001). Adding probiotics to the standard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease. PMID:25929897

  20. Role of Helicobacter pylori infection in Hispanic patients with anemia.

    PubMed

    Ortiz, Melissa; Rosado-Carrión, Bárbara; Bredy, Rafael

    2014-01-01

    Pernicious anemia represents the final phase of a process that begins with Helicobacter pylori-associated gastritis and evolves through progressive levels of atrophy until loss of parietal cell mass. Numerous studies have suggested an association between H. pylori infection, unexplained iron deficiency anemia and cobalamin deficiency. Our research question was to determine whether there is an association between with H. pylori infection and development of anemia in Hispanic patients. This cross sectional pilot study involved data analysis of individual from years 2010-2012 examining the association between H. pylori infection and hemoglobin levels in patients with Hispanic ethnicity. A total of 189 records were evaluated, of which 33 fulfilled the inclusion criteria. The study sample was divided in two groups. Group-A: 5 subjects with H. pylori infection and anemia; Group-B: 28 patients with H. pylori without anemia. Fisher exact test applied between categorical variables to determine the statistical significance of symptoms comparing anemic vs. non-anemic H. pylori infected patients yielded a p = 0.0027. In addition, restoration of anemia in two subjects following eradication therapy without previous iron or cobalamin replacement therapy suggested a potential role of this bacterium in the development of anemia in Hispanics. In conclusion, from the results of this study a potential association between Helicobacter pylori infection and anemia in Hispanic patients is suggested. Restoration of hemoglobin after eradication of bacteria further supports this concept. PMID:25065045

  1. Non-ulcer dyspepsia: does Helicobacter pylori matter?

    PubMed Central

    Sahay, P.; Axon, A. T.

    1995-01-01

    Non-ulcer dyspepsia is a heterogenous disorder characterised by chronic or recurrent abdominal or retrosternal discomfort lasting for more than four weeks for which no cause can be determined. Helicobacter pylori has been implicated as a potential cause in a subset of patients but the association has not been proven and H pylori eradication in patients with non-ulcer dyspepsia has had variable results. Large well-controlled studies are needed to clarify the relationship. PMID:7596927

  2. Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.

    PubMed

    Monteiro, L; Bonnemaison, D; Vekris, A; Petry, K G; Bonnet, J; Vidal, R; Cabrita, J; Mégraud, F

    1997-04-01

    A model was developed to study inhibitors present in feces which prevent the use of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with the same primers as H. pylori was used to spike samples before extraction by a modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column, were characterized. Inhibitors in feces are complex polysaccharides possibly originating from vegetable material in the diet. PMID:9157172

  3. In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription

    PubMed Central

    2010-01-01

    Background LuxS may function as a metabolic enzyme or as the synthase of a quorum sensing signalling molecule, auto-inducer-2 (AI-2); hence, the mechanism underlying phenotypic changes upon luxS inactivation is not always clear. In Helicobacter pylori, we have recently shown that, rather than functioning in recycling methionine as in most bacteria, LuxS (along with newly-characterised MccA and MccB), synthesises cysteine via reverse transsulphuration. In this study, we investigated whether and how LuxS controls motility of H. pylori, specifically if it has its effects via luxS-required cysteine metabolism or via AI-2 synthesis only. Results We report that disruption of luxS renders H. pylori non-motile in soft agar and by microscopy, whereas disruption of mccAHp or mccBHp (other genes in the cysteine provision pathway) does not, implying that the lost phenotype is not due to disrupted cysteine provision. The motility defect of the ΔluxSHp mutant was complemented genetically by luxSHp and also by addition of in vitro synthesised AI-2 or 4, 5-dihydroxy-2, 3-pentanedione (DPD, the precursor of AI-2). In contrast, exogenously added cysteine could not restore motility to the ΔluxSHp mutant, confirming that AI-2 synthesis, but not the metabolic effect of LuxS was important. Microscopy showed reduced number and length of flagella in the ΔluxSHp mutant. Immunoblotting identified decreased levels of FlaA and FlgE but not FlaB in the ΔluxSHp mutant, and RT-PCR showed that the expression of flaA, flgE, motA, motB, flhA and fliI but not flaB was reduced. Addition of DPD but not cysteine to the ΔluxSHp mutant restored flagellar gene transcription, and the number and length of flagella. Conclusions Our data show that as well as being a metabolic enzyme, H. pylori LuxS has an alternative role in regulation of motility by modulating flagellar transcripts and flagellar biosynthesis through production of the signalling molecule AI-2. PMID:20691071

  4. Integrin Engagement by the Helical RGD Motif of the Helicobacter pylori CagL Protein Is Regulated by pH-induced Displacement of a Neighboring Helix*

    PubMed Central

    Bonsor, Daniel A.; Pham, Kieu T.; Beadenkopf, Robert; Diederichs, Kay; Haas, Rainer; Beckett, Dorothy; Fischer, Wolfgang; Sundberg, Eric J.

    2015-01-01

    Arginine-aspartate-glycine (RGD) motifs are recognized by integrins to bridge cells to one another and the extracellular matrix. RGD motifs typically reside in exposed loop conformations. X-ray crystal structures of the Helicobacter pylori protein CagL revealed that RGD motifs can also exist in helical regions of proteins. Interactions between CagL and host gastric epithelial cell via integrins are required for the translocation of the bacterial oncoprotein CagA. Here, we have investigated the molecular basis of the CagL-host cell interactions using structural, biophysical, and functional analyses. We solved an x-ray crystal structure of CagL that revealed conformational changes induced by low pH not present in previous structures. Using analytical ultracentrifugation, we found that pH-induced conformational changes in CagL occur in solution and not just in the crystalline environment. By designing numerous CagL mutants based on all available crystal structures, we probed the functional roles of CagL conformational changes on cell surface integrin engagement. Together, our data indicate that the helical RGD motif in CagL is buried by a neighboring helix at low pH to inhibit CagL binding to integrin, whereas at neutral pH the neighboring helix is displaced to allow integrin access to the CagL RGD motif. This novel molecular mechanism of regulating integrin-RGD motif interactions by changes in the chemical environment provides new insight to H. pylori-mediated oncogenesis. PMID:25837254

  5. Diagnosis and treatment of Helicobacter pylori infection.

    PubMed

    Bytzer, Peter; Dahlerup, Jens Frederik; Eriksen, Jens Ravn; Jarbøl, Dorte Ejg; Rosenstock, Steffen; Wildt, Signe

    2011-04-01

    National Danish guidelines for the diagnosis and treatment of Helicobacter pylori (Hp) infection have been approved by the Danish Society for Gastroenterology. All patients with peptic ulcer disease, gastric cancer, and MALT lymphoma should be tested for Hp. We also recommend testing in first degree relatives to patients with gastric cancer, in NSAID-naive patients, who need long-term NSAID therapy, and in patients presenting with dyspepsia and no alarm symptoms. Non-endoscoped patients can be tested with a urea-breath test or a faecal antigen test. Endoscoped patients can be tested with a rapid urease test. Proton pump inhibitor therapy should be stopped at least 1 week prior to Hp testing. All infected patients should be offered Hp eradication therapy. First-line treatment is 7-day triple therapy with a proton pump inhibitor and clarithromycine in combination with metronidazole or amoxicilline. Quadruple therapy for 2 weeks with bismuthsubsalicylate, tetracycline, metronidazole and a proton pump inhibitor is recommended in case of treatment failure. Hp testing should be offered to all patients after eradication therapy but is mandatory in patients with ulcer disease, noninvasive gastric cancer or MALT lymphoma. Testing after eradication should not be done before 4 weeks after treatment has ended. PMID:21466771

  6. Local Immune Response in Helicobacter pylori Infection

    PubMed Central

    Kivrak Salim, Derya; Sahin, Mehmet; Köksoy, Sadi; Adanir, Haydar; Süleymanlar, Inci

    2016-01-01

    Abstract There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori–infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC). In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines—interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-β, IL-17A, IL-32—in H pylori–infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients. We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-β mRNA were increased in the GAC group with reference to H pylori–infected NGM group. This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID:27196487

  7. Extracellular galectin-3 counteracts adhesion and exhibits chemoattraction in Helicobacter pylori-infected gastric cancer cells.

    PubMed

    Subhash, Vinod Vijay; Ling, Samantha Shi Min; Ho, Bow

    2016-08-01

    Galectin-3 (Gal-3) is a β-galactoside lectin that is upregulated and rapidly secreted by gastric epithelial cells in response to Helicobacter pylori infection. An earlier study reported the involvement of H. pylori cytotoxin-associated gene A (cagA) in the expression of intracellular Gal-3. However, the role of extracellular Gal-3 and its functional significance in H. pylori-infected cells remains uncharacterized. Data presented here demonstrate secretion of Gal-3 is an initial host response event in gastric epithelial cells during H. pylori infection and is independent of CagA. Previously, Gal-3 was shown to bind to H. pylori LPS. The present study elaborates the significance of this binding, as extracellular recombinant Gal-3 (rGal-3) was shown to inhibit the adhesion of H. pylori to the gastric epithelial cells. Interestingly, a decrease in H. pylori adhesion to host cells also resulted in a decrease in apoptosis. Furthermore, the study also demonstrated a chemoattractant role of extracellular rGal-3 in the recruitment of THP-1 monocytes. This study outlines the previously unidentified roles of extracellular Gal-3 where it acts as a negative regulator of H. pylori adhesion and apoptosis in gastric epithelial cells, and as a chemoattractant to THP-1 monocytes. Our findings could contribute to the better understanding of how Gal-3 acts as a modulator under H. pylori-induced pathological conditions. PMID:27283429

  8. "Helicobacter Pylori" Infection in Five Inpatient Units for People with Intellectual Disability and Psychiatric Disorder

    ERIC Educational Resources Information Center

    Clarke, David; Vemuri, Murali; Gunatilake, Deepthi; Tewari, Sidhartha

    2008-01-01

    Background: A high prevalence of "Helicobacter pylori" infection has been reported among people with intellectual disability, especially those residing in hospital and similar settings. Surveys of inpatients have found unusually high rates of gastrointestinal malignancy, to which "H. pylori" infection predisposes. Methods: "Helicobacter pylori"…

  9. Biomarkers and diagnostic tools for detection of Helicobacter pylori.

    PubMed

    Khalilpour, Akbar; Kazemzadeh-Narbat, Mehdi; Tamayol, Ali; Oklu, Rahmi; Khademhosseini, Ali

    2016-06-01

    Helicobacter pylori is responsible for worldwide chronic bacterial infection in humans affecting approximately half of the world's population. H. pylori is associated with significant morbidity and mortality including gastric cancer. The infection has both direct and indirect impacts on economic and overall well-being of patients; hence, there is a great need for diagnostic markers that could be used in the development of diagnostic kits. Here, we briefly review general aspects of H. pylori infection and the diagnostic biomarkers used in laboratory tests today with a focus on the potential role of microfluidic systems in future immunodiagnosis platforms. PMID:27084783

  10. Helicobacter pylori - a seasoned pathogen by any other name

    PubMed Central

    2009-01-01

    Helicobacter pylori is a well known inhabitant of human stomach which is linked to peptic ulcer disease and gastric adenocarcinoma. It was recently shown in several studies that H. pylori can be harnessed as a surrogate marker of human migration and that its population structure and stratification patterns exactly juxtapose to those of Homo sapiens. This is enough a testimony to convey that H. pylori may have coevolved with their host. Several protective effects of H. pylori colonization have been considered as evidence of a presumed symbiotic relationship. Contrary to this assumption is the presence of a strong virulence apparatus within H. pylori; why a co-evolved parasite would try inflicting its host with serious infection and even causing cancer? The answer is perhaps embedded in the evolutionary history of both the bacterium and the host. We discuss a hypothetical scenario wherein H. pylori may have acquired virulence genes from donors within its environment that varied with change in human history and ecology. The H. pylori genomes sequenced to date portray fairly high abundance of such laterally acquired genes which have no assigned functions but could be linked to inflammatory responses or other pathogenic attributes. Therefore, the powerful virulence properties and survival strategies of Helicobacter make it a seasoned pathogen; thus the efforts to portray it as a commensal or a (harmless) 'bacterial parasite' need rethinking. PMID:20030808