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  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. 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

  4. Helicobacter pylori

    MedlinePlus

    ... illnesses. H. pylori , which used to be called Campylobacter pylori , also can cause peptic ulcers (commonly known ... H. Pylori Antigen Food Safety for Your Family Campylobacter Infections Pyloric Stenosis Peptic Ulcers Digestive System Vomiting ...

  5. 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-thirds of ... or stool to see if it contains H. pylori. The best treatment is a combination of antibiotics ...

  6. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    PubMed Central

    Williams, Jonathan M.

    2017-01-01

    ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

  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.

  8. Streptococcus mitis Induces Conversion of Helicobacter pylori to Coccoid Cells during Co-Culture In Vitro

    PubMed Central

    Khosravi, Yalda; Dieye, Yakhya; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna

    2014-01-01

    Helicobacter pylori (H. pylori) is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptocccus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes. PMID:25386948

  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.

  10. [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

  11. Early apoptosis of monocytes induced by Helicobacter pylori infection through multiple pathways.

    PubMed

    Zhang, Ying; Sun, Hui; Zhao, Huilin; Chen, Xingxing; Li, Jiaojiao; Li, Boqing

    2017-03-14

    Only a small percentage of people infected with Helicobacter pylori (H. pylori) will develop overt chronic gastric diseases. To understand the pathological mechanism, the action of H. pylori on monocyte apoptosis was detected. H. pylori co-culturing with peripheral blood monocytes, THP-1 or U937 cells result in early apoptosis at 6, 12, and 24 h after infection. The phosphorylated Bad and JNK were increased, and Bcl-2 was declined at 6, 12, and 24 h in peripheral blood monocytes after H. pylori infection. The phosphorylated Akt was augmented at 6 and 12 h post-infection. A slow apoptotic response was induced by H. pylori via Bad and Bcl-2 regulators, activated caspase-8 and caspase-9, and JNK at 24 h in THP-1 cells. Meanwhile, only Bad and JNK were involved in regulating U937 cells apoptosis at 24 h after infection. These results supported a novel mechanism of H. pylori escaping from monocytes by upregulation of early apoptosis and inhibition of late apoptosis. The differences among the three cells may reveal why H. pylori-derived disease occurs in relatively few people and provide a pathological mechanism whereby a treatment for H. pylori-derived disease may be developed.

  12. Helicobacter pylori TlyA agglutinates liposomes and induces fusion and permeabilization of the liposome membranes.

    PubMed

    Lata, Kusum; Chattopadhyay, Kausik

    2014-06-10

    Helicobacter pylori TlyA is a pore-forming hemolysin with potent cytotoxic activity. To explore the potential membrane-damaging activity of H. pylori TlyA, we have studied its interaction with the synthetic liposome vesicles. In our study, H. pylori TlyA shows a prominent ability to associate with the liposome vesicles without displaying an obligatory requirement for any protein receptor on the liposome membranes. Interaction of TlyA triggers agglutination of the liposome vesicles. Such agglutinating activity of TlyA could also be observed with erythrocytes before the induction of its pore-forming hemolytic activity. In addition to its agglutinating activity against liposomes, TlyA also induces fusion and disruption of the liposome membranes. Altogether, our study highlights novel membrane-damaging properties of H. pylori TlyA that have not been documented previously with any other TlyA family protein.

  13. Helicobacter pylori and Nonmalignant Diseases.

    PubMed

    Potamitis, Georgios S; Axon, Anthony T R

    2015-09-01

    Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy.

  14. Association of Helicobacter pylori infection with chemotherapy-induced thrombocytopenia in patients with stage III colon cancer: a pilot study.

    PubMed

    Tanriverdi, Ozgur

    2014-01-01

    In this study, the effects of the pre-treatment presence of Helicobacter pylori (H. pylori) infection on chemotherapy-induced thrombocytopenia (CIT) were investigated in patients with stage III colon cancer (CC). A cohort of 74 patients with early stage CC was analysed through a review of clinical records and personal interviews. Helicobacter pylori infections were diagnosed in these patients prior to chemotherapy. The subjects were divided into two groups according to H. pylori infection status: Group 1, H. pylori-positive and Group 2, H. pylori-negative. In all patients, bone marrow toxicity and other study variables were compared. Helicobacter pylori infections were detected in 31 of the 74 CC patients. Helicobacter pylori-infected patients (Group 1) showed significantly higher incidences of CIT than did non-infected patients (Group 2; p = 0.029). Helicobacter pylori infection status correlated significantly with tumour location (r = 0.547; p = 0.043) and the most common location of CC in H. pylori-infected patients was the ascending colon (n = 13, 42%) in comparison to non-infected patients (n = 6, 14%; p= 0.042). The relationship between CIT and H. pylori infection status in CC was determined to be independent from the other study variables (p = 0.037; OR = 3.32, CI 95% = 1.16-9.70). In this study, the small number of patients resulted in an inadequate demonstration of the relationship between H. pylori infection and CIT. Therefore, clinical and molecular studies that include more patients are warranted.

  15. 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

    2015-01-06

    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.

  16. 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

  17. Anti-inflammatory effect of cinnamaldehyde in Helicobacter pylori induced gastric inflammation.

    PubMed

    Muhammad, Jibran Sualeh; Zaidi, Syed Faisal; Shaharyar, Saeeda; Refaat, Alaa; Usmanghani, Khan; Saiki, Ikuo; Sugiyama, Toshiro

    2015-01-01

    Cinnamomum cassia is widely employed for gastrointestinal complaints such as dyspepsia, flatulence, diarrhea, and vomiting. Studies report cinnamaldehyde (CM) as a major active constituent of cinnamon. The aim of this study was to evaluate the anti-inflammatory mechanism of CM on Helicobacter (H.) pylori-infected gastric epithelial cells in order to validate cinnamon traditional use in gastrointestinal (GI)-related disorders. AGS/MKN-45 cells and H. pylori (193C) were employed for co-culture experiments. Anti-H. pylori cytotoxic and anti-adhesion activity of CM were determined. Enzyme linked immunosorbent assay, real time polymerase chain reaction analysis and immunoblotting were used to measure the effect on interleukin-8 (IL-8) secretion/expression. The effect on activation of nuclear factor kappa B (NF-κB) was determined by immunoblot analysis. The non-cytotoxic CM (≤125 µM) was also non-bactericidal at the given time, suggesting the effect in H. pylori/cell co-culture system was not due to alteration in H. pylori viability or the toxicity to the cells. Also, CM did not show any anti-adhesion effect against H. pylori/cell co-culture. However, pre-incubation of the cells with CM significantly inhibited the IL-8 secretion/expression from H. pylori-infected cells (p<0.01). In addition, CM suppressed H. pylori-induced NF-κB activation and prevented degradation of inhibitor (I)-κB This study provides evidence that the anti-inflammatory effect of C. cassia on H. pylori-infected gastric cells is due to blockage of the NF-κB pathway by cinnamaldehyde. This agent can be considered as a potential candidate for in vivo and clinical studies against various H. pylori related gastric pathogenic processes.

  18. Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration.

    PubMed

    Beckett, Amber C; Piazuelo, M Blanca; Noto, Jennifer M; Peek, Richard M; Washington, M Kay; Algood, Holly M Scott; Cover, Timothy L

    2016-12-01

    Epidemiologic studies have provided conflicting data regarding an association between Helicobacter pylori infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of H. pylori infection, as well as a possible role of diet, in H. pylori-associated IDA. Mongolian gerbils (either H. pylori infected or uninfected) received a normal diet or one of three diets associated with increased H. pylori virulence: high-salt, low-iron, or a combination of a high-salt and low-iron diet. In an analysis of all infected animals compared to uninfected animals (independent of diet), H. pylori-infected gerbils had significantly lower hemoglobin values than their uninfected counterparts at 16 weeks postinfection (P < 0.0001). The mean corpuscular volume (MCV) and serum ferritin values were significantly lower in H. pylori-infected gerbils than in uninfected gerbils, consistent with IDA. Leukocytosis and thrombocytosis were also detected in infected gerbils, indicating the presence of a systemic inflammatory response. In comparison to uninfected gerbils, H. pylori-infected gerbils had a higher gastric pH, a higher incidence of gastric ulcers, and a higher incidence of fecal occult blood loss. Anemia was associated with the presence of gastric ulceration but not gastric cancer. Infected gerbils consuming diets with a high salt content developed gastric ulcers significantly more frequently than gerbils consuming a normal-salt diet, and the lowest hemoglobin levels were in infected gerbils consuming a high-salt/low-iron diet. These data indicate that H. pylori infection can cause IDA and that the composition of the diet influences the incidence and severity of H. pylori-induced IDA.

  19. Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases.

    PubMed

    Lewinska, Anna; Wnuk, Maciej

    2017-04-01

    Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.

  20. Inhibitory effect of Raphanobrassica on Helicobacter pylori-induced gastritis in Mongolian gerbils.

    PubMed

    Yamada, Takanori; Wei, Min; Toyoda, Takeshi; Yamano, Shoutaro; Wanibuchi, Hideki

    2014-08-01

    Helicobacter pylori (H. pylori) infection is well known to be associated with chronic gastritis and also development of gastric cancer. Raphanobrassica (RB) is an intergeneric hybrid of the genera Raphanus (radish) and Brassica (cabbages) containing appreciable amounts of glucoraphanin (GR) and glucoraphenin (GRe), which are actively hydrolyzed by the enzyme myrosinase to sulforaphane and sulforaphene, respectively. Both of these metabolites exert antimicrobial and anti-inflammatory activity. The purpose of the present study was to investigate the effect of two freeze-dried products of RB (RB1 and RB2) on H. pylori-induced gastritis in Mongolian gerbils. Six-week-old male Mongolian gerbils were inoculated orally with H. pylori (ATCC 43504), and 2weeks later were fed diets containing no additives or diets supplemented with 2% RB1 (containing both GR and GRe) or 2% RB2 (containing GR only) for 10weeks. In the RB1, but not the RB2 group, mononuclear cell infiltration, mRNA expression of IL-6, and cell proliferation in the gastric mucosa were significantly suppressed. These results indicate that RB1 containing both GR and GRe exerted significant inhibitory effects on H. pylori-induced gastritis in Mongolian gerbils apparently mediated via suppression of IL-6 expression and chronic inflammation.

  1. Helicobacter pylori eradication therapy.

    PubMed

    Suzuki, Hidekazu; Nishizawa, Toshihiro; Hibi, Toshifumi

    2010-04-01

    Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.

  2. Gastric and enterohepatic non-Helicobacter pylori Helicobacters.

    PubMed

    Flahou, Bram; Haesebrouck, Freddy; Smet, Annemieke; Yonezawa, Hideo; Osaki, Takako; Kamiya, Shigeru

    2013-09-01

    A substantial number of reports published in the last year have contributed to a better understanding of both human and animal infection with non-Helicobacter pylori Helicobacter species (NHPH). Gastric infection of humans with Helicobacter suis and Helicobacter felis as well as unidentified NHPH has been described to cause a chronic gastritis and a variety of clinical symptoms, whereas enterohepatic NHPH, including Helicobacter cinaedi, Helicobacter bilis, and Helicobacter canis, have been reported to be associated with human diseases such as bacteremia, cellulitis, cutaneous diseases, and fever of unknown origin in immunocompromised hosts. In various animal species, including dogs and laboratory mice, high rates of infection with NHPH were described. For gastric NHPH, mainly H. suis and H. felis infection was studied, revealing that differences in the immune response evoked in the host do exist when compared to Helicobacter pylori. Pathogenic mechanisms of infection with Helicobacter pullorum, H. bilis, and Helicobacter hepaticus were investigated, as well as immune responses involved in H. bilis-, Helicobacter typhlonius-, and H. hepaticus-induced intestinal inflammation. Complete genome sequences of Helicobacter heilmannii strain ASB1 and a H. cinaedi strain isolated in a case of human bacteremia were published, as well as comparative genomics of a human-derived Helicobacter bizzozeronii strain and proteome or secretome analyses for H. hepaticus and Helicobacter trogontum, respectively. Molecular analysis has revealed a function for type VI secretion systems of H. hepaticus and H. pullorum, the Helicobacter mustelae iron urease, and several other functional components of NHPH. In each section of this chapter, new findings on gastric NHPH will first be discussed, followed by those on enterohepatic Helicobacter species.

  3. [Helicobacter pylori -- 2014].

    PubMed

    Buzás, György Miklós

    2015-02-08

    The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.

  4. Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro.

    PubMed

    Whitmore, Laura C; Weems, Megan N; Allen, Lee-Ann H

    2017-03-01

    Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62L(dim), CD16(bright), CD11b(bright), CD66b(bright), CD63(bright) surface phenotype, proinflammatory cytokine secretion, and cytotoxicity. Hypersegmentation requires direct neutrophil-H. pylori contact as well as transcription and both host and bacterial protein synthesis, but not urease, NapA, VacA, CagA, or CagT. The concept of neutrophil plasticity is new and, to our knowledge, these data are the first evidence that neutrophils can undergo subtype differentiation in vitro in response to bacterial pathogen infection. We hypothesize that these changes favor H. pylori persistence and disease.

  5. Helicobacter pylori CagA induced interleukin-8 secretion in gastric epithelial cells

    PubMed Central

    Fazeli, Zeinab; Alebouyeh, Masoud; Rezaei Tavirani, Mostafa; Azimirad, Masoumeh; Yadegar, Abbas

    2016-01-01

    Aim: Since, contradictory data have been reported about the effect of diverse variants of H. pylori virulence factors on IL-8 induction, we aimed to analyze the effect of this diversity on levels of IL-8 secretion in AGS cell line. Background: Helicobacter pylori colonizes the human stomach and induces the activation of inflammatory cytokines, including interleukin (IL)-8, in the gastric mucosa. This induction promotes neutrophil and monocyte recruitment that causes gastric tissue damage. Methods: To determine whether different strains of H. pylori and their CagA variants have possible roles on IL-8 induction, polarized AGS cell line was infected with CagA+ H. pylori strains carrying different EPIYA motifs (ABCCC and ABC) and CagA- strain for 24 hours. Difference in stimulation of IL-8 was measured by ELISA. Results: IL-8 secretion was elevated in the treated cells with CagA encoding strains compared with the negative one. Furthermore, a noticeably increased level of IL-8 induction was measured by the CagA-EPIYA type ABCCC encoding strain in compare to that carried EPIYA type ABC Conclusion: Results of this study provide new evidence about different effects of H. pylori strains and possible roles of their CagA variants on IL-8 induction. It seems that not only carriage of cagA and its expression, but also diversity in EPIYA motif be involved in IL-8 induction in the gastric epithelial cells. PMID:28224027

  6. Cutting Edge: Helicobacter pylori Induces Nuclear Hypersegmentation and Subtype Differentiation of Human Neutrophils In Vitro

    PubMed Central

    Whitmore, Laura C.; Weems, Megan N.

    2017-01-01

    Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62Ldim, CD16bright, CD11bbright, CD66bbright, CD63bright surface phenotype, proinflammatory cytokine secretion, and cytotoxicity. Hypersegmentation requires direct neutrophil–H. pylori contact as well as transcription and both host and bacterial protein synthesis, but not urease, NapA, VacA, CagA, or CagT. The concept of neutrophil plasticity is new and, to our knowledge, these data are the first evidence that neutrophils can undergo subtype differentiation in vitro in response to bacterial pathogen infection. We hypothesize that these changes favor H. pylori persistence and disease. PMID:28148734

  7. JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression.

    PubMed

    Han, Fengjuan; Ren, Juchao; Zhang, Jinjin; Sun, Yundong; Ma, Fang; Liu, Zhifang; Yu, Han; Jia, Jihui; Li, Wenjuan

    2016-06-21

    Helicobacter pylori (H. pylori) infection is the strongest risk factor for the initiation and progression of gastric cancer. However, the mechanism of H. pylori-induced pathogenesis remains unclear. In this study, we investigate the role of H. pylori infection in JMJD2B upregulation and the mechanism underlying gastric carcinogenesis. We find that JMJD2B can be induced by H. pylori infection via β-catenin pathway. β-catenin directly binds to JMJD2B promoter and stimulates JMJD2B expression following H. pylori infection. Increased JMJD2B, together with NF-κB, binds to COX-2 promoter to enhance its transcription by demethylating H3K9me3 locally. JMJD2B and COX-2 expression is upregulated in H. pylori infected mice in vivo. Furthermore, JMJD2B and COX-2 expression is gradually increased in human gastric tissues from gastritis to gastric cancer. The level of JMJD2B and COX-2 in H. pylori-positive gastritis tissues is significantly higher than that in H. pylori-negative tissues. Moreover, a positive correlation between JMJD2B and COX-2 expression is found in both gastritis and gastric cancer tissues. Therefore, JMJD2B is a crucial factor in triggering H. pylori-induced chronic inflammation and progression of gastric carcinogenesis and it may serve as a novel target for the intervention of gastric cancer.

  8. JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression

    PubMed Central

    Zhang, Jinjin; Sun, Yundong; Ma, Fang; Liu, Zhifang; Yu, Han; Jia, Jihui; Li, Wenjuan

    2016-01-01

    Helicobacter pylori (H. pylori) infection is the strongest risk factor for the initiation and progression of gastric cancer. However, the mechanism of H. pylori-induced pathogenesis remains unclear. In this study, we investigate the role of H. pylori infection in JMJD2B upregulation and the mechanism underlying gastric carcinogenesis. We find that JMJD2B can be induced by H. pylori infection via β-catenin pathway. β-catenin directly binds to JMJD2B promoter and stimulates JMJD2B expression following H. pylori infection. Increased JMJD2B, together with NF-κB, binds to COX-2 promoter to enhance its transcription by demethylating H3K9me3 locally. JMJD2B and COX-2 expression is upregulated in H. pylori infected mice in vivo. Furthermore, JMJD2B and COX-2 expression is gradually increased in human gastric tissues from gastritis to gastric cancer. The level of JMJD2B and COX-2 in H. pylori-positive gastritis tissues is significantly higher than that in H. pylori-negative tissues. Moreover, a positive correlation between JMJD2B and COX-2 expression is found in both gastritis and gastric cancer tissues. Therefore, JMJD2B is a crucial factor in triggering H. pylori-induced chronic inflammation and progression of gastric carcinogenesis and it may serve as a novel target for the intervention of gastric cancer. PMID:27232941

  9. In-vivo evaluation of apocynin for prevention of Helicobacter pylori-induced gastric carcinogenesis.

    PubMed

    Horemans, Tessa; Boulet, Gaëlle; van Kerckhoven, Marian; Bogers, Johannes; Thys, Sofie; Vervaet, Chris; Vervaeck, Anouck; Delputte, Peter; Maes, Louis; Cos, Paul

    2017-01-01

    The emergence of antibiotic-resistant Helicobacter pylori strains impacts the efficacy of eradication therapy and promotes the development of alternative treatment strategies. Apocynin inhibits neutrophil NADPH oxidase and hence may decrease reactive oxygen species-mediated tissue damage in H. pylori-infected stomach tissue. Apocynin was tested in vitro for its cytotoxic and direct antibacterial effects. The therapeutic efficacy of orally administered apocynin (100 mg/kg/day through drinking water or 200 mg/kg/day through combined administration of drinking water and slow-release formulation) was assessed at 9 weeks after infection in the Mongolian gerbil model. Bacterial burdens were quantified by viable plate count and quantitative PCR. Histopathological evaluation of antrum and pylorus provided insight into mucosal inflammation and injury. Apocynin showed no cytotoxic or direct antibacterial effects in vitro or in vivo. Nine weeks of apocynin treatment at 200 mg/kg/day reduced active H. pylori gastritis as neutrophil infiltration in the mucous neck region and pit abscess formation decreased significantly. In our gerbil model, prolonged high-dose apocynin treatment significantly improved H. pylori-induced pit abscess formation without indications of drug toxicity and thus further investigation of the dosage regimen and formulation and the long-term impact on neoplastic development should be carried out.

  10. 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.

  11. 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.

  12. Antibacterial and anti-atrophic effects of a highly soluble, acid stable UDCA formula in Helicobacter pylori-induced gastritis.

    PubMed

    Thao, Tran Dang Hien; Ryu, Ho-Cheol; Yoo, Seo-Hong; Rhee, Dong-Kwon

    2008-06-01

    Helicobacter pylori is one of the main causes of atrophic gastritis and gastric carcinogenesis. Gastritis can also occur in the absence of H. pylori as a result of bile reflux suggesting the eradication of H. pylori by bile acids. However, the bile salts are unable to eradicate H. pylori due to their low solubility and instability at acidic pH. This study examined the effect of a highly soluble and acid stable ursodeoxycholic acid (UDCA) formula on H. pylori-induced atrophic gastritis. The H. pylori infection decreased the body weight, mitochondrial membrane potential and ATP level in vivo. Surprisingly, H. pylori-induced expression of malate dehydrogenase (MDH), a key enzyme in the tricarboxylic acid cycle, at both the protein and mRNA levels. However, the UDCA formula repressed MDH expression and increased the membrane potential thereby increasing the ATP level and body weight in vivo. Moreover, UDCA scavenged the reactive oxygen species (ROS), increased the membrane potential, and inhibited apoptosis in AGS cells exposed to H(2)O(2) in vitro through the mitochondria-mediated pathway. Taken together, UDCA decreases the MDH and ROS levels, which can prevent apoptosis in H. pylori-induced gastritis.

  13. Helicobacter pylori infection and skin disorders.

    PubMed

    Kutlubay, Zekayi; Zara, Tuba; Engin, Burhan; Serdaroğlu, Server; Tüzün, Yalçin; Yilmaz, Erkan; Eren, Bülent

    2014-08-01

    Helicobacter pylori is a Gram-negative bacterium that has been linked to peptic ulcer disease, gastric lymphoma, and gastric carcinoma. Apart from its well-demonstrated role in gastroduodenal diseases, some authors have suggested a potential role of Helicobacter pylori infection in several extra-intestinal pathologies including haematological, cardiovascular, neurological, metabolic, autoimmune, and dermatological diseases. Some studies suggest an association between Helicobacter pylori infection and skin diseases such as chronic idiopathic urticaria and rosacea. There have also been few case reports documenting association between Helicobacter pylori and psoriasis vulgaris, Behçet's disease, alopecia areata, Henoch-Schönlein purpura, and Sweet's syndrome. However, more systematic studies are required to clarify the proposed association between Helicobacter pylori and skin diseases; most of the studies do not show relevant relationships of these diseases with Helicobacter pylori infections. This review discusses skin diseases that are believed to be associated with Helicobacter pylori.

  14. Brefeldin A enhances Helicobacter pylori vacuolating cytotoxin-induced vacuolation of epithelial cells.

    PubMed

    Argent, Richard H; McGarr, Christine; Atherton, John C

    2004-08-01

    Intracellular VacA localises to the vacuolar (late endosome/lysosome) membrane, but little is known about the trafficking of the toxin beyond this region. We show that the Golgi-disturbing agent brefeldin A (BFA) enhances VacA-induced vacuolation of epithelial cells by Helicobacter pylori co-culture and, importantly, BFA treatment induces vacuolation by less toxic forms of VacA. The effect is BFA dose-dependent and occurs within 2.5 h. These data suggest that VacA may be routed deeper within the cell than the vacuole, and that vacuolation is minimised when this occurs efficiently. This may explain why some forms of VacA do not cause vacuolation and why vacuolation is minimal at the low bacteria:cell ratios observed in vivo.

  15. High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis.

    PubMed

    Gaddy, Jennifer A; Radin, Jana N; Loh, John T; Zhang, Feng; Washington, M Kay; Peek, Richard M; Algood, Holly M Scott; Cover, Timothy L

    2013-06-01

    Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA(+) H. pylori strain or an isogenic cagA mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the cagA mutant strain (P < 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the in vitro results, we detected increased cagA transcription in vivo in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the cagA mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of cagA(+) H. pylori strains.

  16. Free recombination within Helicobacter pylori

    PubMed Central

    Suerbaum, Sebastian; Smith, John Maynard; Bapumia, Khairun; Morelli, Giovanna; Smith, Noel H.; Kunstmann, Erdmute; Dyrek, Isabelle; Achtman, Mark

    1998-01-01

    Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori strains isolated from patients in Germany, Canada, and South Africa were analyzed for diversity and for linkage equilibrium by using the Homoplasy Test and compatibility matrices. Horizontal genetic exchange in H. pylori is so frequent that different loci and polymorphisms within each locus are all at linkage equilibrium. These results indicate that H. pylori is panmictic. Comparisons with sequences from Escherichia coli, Neisseria meningitidis, and Drosophila melanogaster showed that recombination in H. pylori was much more frequent than in other species. In contrast, when multiple family members infected with H. pylori were investigated, some strains were indistinguishable at all three loci. Thus, H. pylori is clonal over short time periods after natural transmission. PMID:9770535

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

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    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.

  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. Irregular arrangement of collecting venules (IRAC) provides a critical endoscopic insight in Helicobacter pylori-induced gastritis: A secondary publication.

    PubMed

    Katake, Yoshiki; Ichikawa, Kazuhito; Fujio, Chikau; Tomita, Shigeki; Imura, Johji; Fujimori, Takahiro

    2013-01-01

    The aim of this study was to evaluate the significance of an endoscopic atrophic border and irregular arrangement of collecting venules (IRAC) in the diagnosis of Helicobacter pylori (H. pylori)-induced gastritis. Upper gastrointestinal tract endoscopy was performed on 723 patients, who were screened them for H. pylori infection. Any patients who had undergone H. pylori eradication therapy were excluded from the study. The endoscopic atrophic border and IRAC in each patient were assessed. The H. pylori status was determined in the patients by combination of a serological test and/or histopathological examination. The H. pylori infection rates were 95.4% (455/477) in the group with an endoscopic atrophic border and 22.3% (55/246) in the group without an endoscopic atrophic border. In the diagnostic validity check, presence of an endoscopic atrophic border had a sensitivity of 89.2% and a specificity of 89.7%. Furthermore, the H. pylori infection rates were 95.5% (506/530) in the IRAC group and 2.1% (4/193) in the regular arrangement of collecting venules (RAC) group. In the diagnostic validity check, IRAC had a sensitivity of 99.2% and a specificity of 88.7%. In conclusion, the presence of an endoscopic atrophic border and IRAC are highly indicative of an H. pylori-infected gastric mucosa.

  20. Endoscopic transmission of Helicobacter pylori.

    PubMed

    Tytgat, G N

    1995-01-01

    The contamination of endoscopes and biopsy forceps with Helicobacter pylori occurs readily after endoscopic examination of H. pylori-positive patients. Unequivocal proof of iatrogenic transmission of the organism has been provided. Estimates for transmission frequency approximate to 4 per 1000 endoscopies when the infection rate in the endoscoped population is about 60%. Iatrogenic transmission has also been shown to be the cause of the so-called 'acute mucosal lesion' syndrome in Japan. Traditional cleaning and alcohol rinsing is insufficient to eliminate endoscope/forceps contamination. Only meticulous adherence to disinfection recommendations guarantees H. pylori elimination.

  1. Helicobacter pylori and non-malignant diseases.

    PubMed

    Furuta, Takahisa; Delchier, Jean-Charles

    2009-09-01

    It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.

  2. 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

  3. 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

  4. Synthesis and bioevaluation of novel 3,4,5-trimethoxybenzylbenzimidazole derivatives that inhibit Helicobacter pylori-induced pathogenesis in human gastric epithelial cells.

    PubMed

    Chang, Chih-Shiang; Liu, Ju-Fang; Lin, Hwai-Jeng; Lin, Chia-Der; Tang, Chih-Hsin; Lu, Dah-Yuu; Sing, Yu-Ting; Chen, Li-Yu; Kao, Min-Chuan; Kuo, Sheng-Chu; Lai, Chih-Ho

    2012-02-01

    Helicobacter pylori infection is associated with gastritis, peptic ulcer, and even gastric malignancy. H. pylori's antibiotic resistance is the major obstacle preventing its eradication. A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized and evaluated for their anti-H. pylori activity. The compound, 2-fluorophenyl-5-methyl-1-(3,4,5-trimethoxybenzyl)benzimidazole (FMTMB), was determined as the most potent in the inhibition of H. pylori growth and pathogenesis of host cells. An in vitro H. pylori infection model revealed that FMTMB inhibited H. pylori adhesion and invasion of gastric epithelial cells. Results from this study provide evidence that FMTMB is a potent therapeutic agent that exhibits both anti-H. pylori growth properties and anti-H. pylori-induced pathogenesis of cells.

  5. Halitosis and helicobacter pylori infection

    PubMed Central

    Dou, Wenhuan; Li, Juan; Xu, Liming; Zhu, Jianhong; Hu, Kewei; Sui, Zhenyu; Wang, Jianzong; Xu, Lingling; Wang, Shaofeng; Yin, Guojian

    2016-01-01

    Abstract Background: Halitosis is used to describe any disagreeable odor of expired air regardless of its origin. Numerous trials published have investigated the relation between Helicobacter pylori (H pylori) infection and halitosis, and even some regimes of H pylori eradication have been prescribed to those patients with halitosis in the clinic. We conducted a meta-analysis to define the correlation between H pylori infection and halitosis. Objectives: To evaluate whether there is a real correlation between H pylori infection and halitosis, and whether H pylori eradication therapy will help relieve halitosis. Methods: We searched several electronic databases (The Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, and Wanfangdata) up to December 2015. Studies published in English and Chinese were considered in this review. After a final set of studies was identified, the list of references reported in the included reports was reviewed to identify additional studies. Screening of titles and abstracts, data extraction and quality assessment was undertaken independently and in duplicate. All analyses were done using Review Manager 5.2 software. Results: A total of 115 articles were identified, 21 of which met the inclusion criteria and presented data that could be used in the analysis. The results showed that the OR of H pylori infection in the stomach between halitosis-positive patients and halitosis-negative patients was 4.03 (95% CI: 1.41–11.50; P = 0.009). The OR of halitosis between H pylori-positive patients and H pylori-negative patients was 2.85 (95% CI: 1.40–5.83; P = 0.004); The RR of halitosis after successful H pylori eradication in those H pylori-infected halitosis-positive patients was 0.17 (95% CI: 0.08–0.39; P <0.0001), compared with those patients without successful H pylori eradication. And the RR of halitosis before successful H pylori eradication therapy was 4.78 (95% CI: 1.45–15.80; P = 0.01), compared with after successful H

  6. 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...

  7. Involvement of the CD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis.

    PubMed Central

    Rudi, J; Kuck, D; Strand, S; von Herbay, A; Mariani, S M; Krammer, P H; Galle, P R; Stremmel, W

    1998-01-01

    Helicobacter pylori infection is associated with chronic gastritis, peptic ulceration, and gastric carcinoma. The potential role of CD95-mediated apoptosis was investigated in a panel of gastric biopsies obtained from patients with H. pylori-associated chronic gastritis (n = 29) and with noninfected normal mucosa (n = 10). Immunohistochemistry revealed increased CD95 receptor expression in epithelial and lamina propria cells in chronic gastritis. By in situ hybridization, CD95 ligand mRNA was absent or low in normal mucosa but expressed at high levels in lamina propria lymphocytes and, unexpectedly, in epithelial cells in chronic gastritis. Apoptotic cells were rare in normal mucosa but were observed regularly in chronic gastritis in close proximity to CD95 ligand mRNA expression throughout the epithelial and lamina propria cells. In a functional analysis gastric epithelial cell lines were incubated with supernatants of H. pylori. Treatment with the cytotoxic isolate H. pylori 60190 but not with the noncytotoxic isolate Tx30a upregulated CD95 in up to 50% of gastric epithelial cells and induced apoptosis in these cells. H. pylori-induced apoptosis was partially prevented by blocking CD95, demonstrating the functional role of the CD95 system. These findings suggest that H. pylori-associated chronic gastritis involves apoptosis of gastric epithelial cells by activation of the CD95 receptor and ligand system. PMID:9788963

  8. Epidemiology of Helicobacter pylori infection.

    PubMed

    Eusebi, Leonardo H; Zagari, Rocco M; Bazzoli, Franco

    2014-09-01

    Medline and PubMed databases were searched on epidemiology of Helicobacter pylori for the period of April 2013-March 2014. Several studies have shown that the prevalence of H. pylori is still high in most countries. In north European and North American populations, about one-third of adults are still infected, whereas in south and east Europe, South America, and Asia, the prevalence of H. pylori is often higher than 50%. H. pylori remains highly prevalent in immigrants coming from countries with high prevalence of H. pylori. However, the lower prevalence of infection in the younger generations suggests a further decline of H. pylori prevalence in the coming decades. Low socioeconomic conditions in childhood are confirmed to be the most important risk factors for H. pylori infection. Although the way the infection is transmitted is still unclear, interpersonal transmission appears to be the main route. Finally, H. pylori recurrence after successful eradication can still occur, but seems to be an infrequent event.

  9. Autophagy impairment by Helicobacter pylori-induced methylation silencing of MAP1LC3Av1 promotes gastric carcinogenesis.

    PubMed

    Muhammad, Jibran Sualeh; Nanjo, Sohachi; Ando, Takayuki; Yamashita, Satoshi; Maekita, Takao; Ushijima, Toshikazu; Tabuchi, Yoshiaki; Sugiyama, Toshiro

    2017-05-15

    Helicobacter pylori (H. pylori) infection induces methylation silencing of tumor suppressor genes causing gastric carcinogenesis. Impairment of autophagy induces DNA damage leading to genetic instability and carcinogenesis. We aimed to identify whether H. pylori infection induced methylation silencing of host autophagy-related (Atg) genes, impairing autophagy and enhancing gastric carcinogenesis. Gastric mucosae were obtained from 41 gastric cancer patients and 11 healthy volunteers (8 H. pylori-uninfected and 3 H. pylori-infected). Methylation status of Atg genes was analyzed by a methylation microarray and quantitative methylation-specific PCR (qMSP); mRNA expression was assessed by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, migration and invasion were assessed in normal rat gastric epithelial cells. Gene knock-down was performed by siRNA. Autophagy was assessed by western blotting. Of 34 Atg genes, MAP1LC3A variant 1 (MAP1LC3Av1) and ULK2 were identified by methylation microarray analysis as exhibiting specific methylation in H. pylori-infected mucosae and gastric cancer tissues. Methylation silencing of MAP1LC3Av1 was confirmed by qMSP, qRT-PCR and de-methylation treatment in two gastric cancer cell lines. Knock-down of map1lc3a, the rat homolog of the human MAP1LC3Av1, inhibited autophagy response and increased cell proliferation, migration and invasion in normal rat gastric epithelial cells, despite the presence of map1lc3b, the rat homolog of the human MAP1LC3B gene important for autophagy. Furthermore, MAP1LC3Av1 was methylation-silenced in 23.3% of gastric cancerous mucosae and 40% of non-cancerous mucosae with H. pylori infection. MAP1LC3Av1 is essential for autophagy and H. pylori-induced methylation silencing of MAP1LC3Av1 may impair autophagy, facilitating gastric carcinogenesis.

  10. Helicobacter pylori and nonmalignant diseases.

    PubMed

    Ierardi, Enzo; Goni, Elisabetta; Losurdo, Giuseppe; Di Mario, Francesco

    2014-09-01

    Peptic ulcer bleeding and recurrence rate are strongly linked to Helicobacter pylori infection even if nonsteroidal anti-inflammatory drugs (NSAIDs) play a relevant role in this setting. Further studies confirm that H. pylori eradication lowers the risk of recurrent peptic ulcer bleeding. Therefore, a test-and-treat strategy appears to be mandatory for patients with a history of ulcer bleeding and NSAIDs and/or aspirin use. Concerning gastroesophageal reflux disease (GERD), evidence clearly shows that H. pylori status has no effect on symptoms and treatment. Therefore, H. pylori treatment is not contraindicated in patients with GERD. The exact role of H. pylori in functional dyspepsia (FD) remains controversial. Novel possible mechanisms by which H. pylori may elicit dyspeptic symptoms include alterations of gastric motility, as well as endocrine and acid-secretory abnormalities. Hunger sensations, acid secretion, and gastrointestinal motility are regulated by ghrelin, particularly produced by the gastric enteroendocrine cell compartment. The improvement of symptoms correlates with enhanced plasma ghrelin levels. Apart from the need for more trials on this topic, these findings may give insight into the underlying pathophysiology of FD symptoms. Recent reports suggest that the presence of bacterial DNA in the oral cavity may be relevant to its transmission. A potential protective role of H. pylori on inflammatory bowel diseases needs to be better elucidated.

  11. Helicobacter pylori as an oncogenic pathogen, revisited.

    PubMed

    Miftahussurur, Muhammad; Yamaoka, Yoshio; Graham, David Y

    2017-03-21

    Gastric cancer is an inflammation-associated malignancy aetiologically related to infection with the bacterium, Helicobacter pylori, which is considered a necessary but insufficient cause. Unless treated, H. pylori causes life-long acute and chronic gastric inflammation resulting in progressive gastric mucosal damage that may result in gastric cancer. The rate of progression from superficial gastritis, to an atrophic metaplastic mucosa, and ultimately to cancer relates to the virulence of the infecting H. pylori as well as host and environmental factors. H. pylori virulence is a reflection of its propensity to cause severe gastric inflammation. Both mucosal inflammation and H. pylori can cause host genomic instability, including dysregulation of DNA mismatch repair, stimulation of expression of activation-induced cytidine deaminase, abnormal DNA methylation and dysregulation of  micro RNAs, which may result in an accumulation of mutations and loss of normal regulation of cell growth. The difference in cancer risk between the most and least virulent H. pylori strain is only approximately 2-fold. Overall, none of the putative virulence factors identified to date have proved to be disease-specific. The presence, severity, extent and duration of inflammation appear to be the most important factors and current evidence suggests that any host, environmental or bacterial factor that reliably enhances the inflammatory response to the H. pylori infection increases the risk of gastric cancer.

  12. Helicobacter pylori in lacrimal secretions.

    PubMed

    Batioglu-Karaaltin, Aysegul; Saatci, Ozlem; Akpinar, Meltem; Celik, Melih Ozgür; Develioglu, Omer; Yigit, Ozgur; Külekçi, Mehmet; Akarsubaşı, Alper Tunga

    2016-03-01

    The aim of this study was to investigate the presence of Helicobacter pylori in human lacrimal and nasal secretions. Eighty patients with complaints of dyspepsia who had undergone endoscopies and gastric antrum biopsies were included in the study. A total of five specimens, including 2 lacrimal secretion samples, 2 nasal mucosal swab samples, and 1 gastric antrum biopsy, were collected from each patient and investigated with polymerase chain reaction (PCR) methods consisting of the urease enzyme coding gene GlmM (UreC) and the H pylori-specific 16S rRNA coding gene. The Reflux Symptom Index and ophthalmologic complaints of the patients were recorded. The detected positivity rates of the H pylori 16S rRNA coding gene in gastric biopsies and nasal mucous and lacrimal secretions were 55, 11.2, and 20%, respectively. The patients were grouped as gastric-antrum-biopsy-negative (Group I [n = 36]) and -positive (Group II [n = 44). In Group II, H pylori positivity in the lacrimal and nasal mucous secretions was 36.3 and 18%, respectively. A comparison between the groups in terms of H pylori presence in nasal mucous and lacrimal secretions yielded statistically significant differences (p = 0.0001, p = 0.003). The simultaneous presence of H pylori in nasal mucous and lacrimal secretions was 13.6% in Group II. H pylori positivity in nasal mucous and lacrimal secretions had a positive moderate correlation (r = 0.40; p = 0.0003). The present study is the first report on the presence of H pylori in lacrimal secretions through nested PCR, which suggested the presence of a number of mechanisms for H pylori transmission to lacrimal secretions.

  13. Diet and Helicobacter pylori infection

    PubMed Central

    Imiela, Jacek

    2016-01-01

    Helicobacter pylori infection has accompanied man for thousands of years. In some infected patients, a complex and dynamic pathogen-host reaction triggers pathogenic pathways resulting in development, inter alia, of atrophic gastritis, peptic ulcer disease (both gastric and duodenal), gastric adenocarcinoma, and MALT lymphoma. Large-scale eradication therapy is associated with a rapid increase in antibiotic resistance, gut flora composition disturbances, and increased risk of development, inter alia, of paediatric infectious diarrhoeas, atopic diseases, and oesophageal adenocarcinoma. Our diet contains many substances with potent antibacterial activity against H. pylori. Dietary interventions enable a decrease in H. pylori colonisation and result in a decrease in gastritis prevalence, thus potentially lowering the risk of gastric adenocarcinoma development. PMID:27713775

  14. Matrix metalloproteinase 7 restrains Helicobacter pylori-induced gastric inflammation and premalignant lesions in the stomach by altering macrophage polarization.

    PubMed

    Krakowiak, M S; Noto, J M; Piazuelo, M B; Hardbower, D M; Romero-Gallo, J; Delgado, A; Chaturvedi, R; Correa, P; Wilson, K T; Peek, R M

    2015-04-02

    Helicobacter pylori is the strongest risk factor for the development of gastric cancer. Although the specific mechanisms by which this pathogen induces carcinogenesis have not been fully elucidated, high-expression interleukin (IL)-1β alleles are associated with increased gastric cancer risk among H. pylori-infected persons. In addition, loss of matrix metalloproteinase 7 (MMP7) increases mucosal inflammation in mouse models of epithelial injury, and we have shown that gastric inflammation is increased in H. pylori-infected MMP7(-/-) C57BL/6 mice. In this report, we define mechanisms that underpin such responses and extend these results into a genetic model of MMP7 deficiency and gastric cancer. Wild-type (WT) or MMP7(-/-) C57BL/6 mice were challenged with broth alone as an uninfected control or the H. pylori strain PMSS1. All H. pylori-challenged mice were successfully colonized. As expected, H. pylori-infected MMP7(-/-) C57BL/6 mice exhibited a significant increase in gastric inflammation compared with uninfected or infected WT C57BL/6 animals. Loss of MMP7 resulted in M1 macrophage polarization within H. pylori-infected stomachs, as assessed by Luminex technology and immunohistochemistry, and macrophages isolated from infected MMP7-deficient mice expressed significantly higher levels of the M1 macrophage marker IL-1β compared with macrophages isolated from WT mice. To extend these findings into a model of gastric cancer, hypergastrinemic WT INS-GAS or MMP7(-/-) INS-GAS mice were challenged with H. pylori strain PMSS1. Consistent with findings in the C57BL/6 model, H. pylori-infected MMP7-deficient INS-GAS mice exhibited a significant increase in gastric inflammation compared with either uninfected or infected WT INS-GAS mice. In addition, the incidence of gastric hyperplasia and dysplasia was significantly increased in H. pylori-infected MMP7(-/-) INS-GAS mice compared with infected WT INS-GAS mice, and loss of MMP7 promoted M1 macrophage polarization. These

  15. 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

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

    PubMed

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

    2015-12-07

    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.

  17. 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

  18. Bacteriology of Helicobacter pylori.

    PubMed

    Owen, R J

    1995-09-01

    The discovery and first isolation of H. pylori in pure culture from gastric biopsies in 1982 provided the basis for a completely new area of microbiology. Since then, H. pylori has been an intensively pursued topic world-wide, and extensive data have been acquired on all aspects of its basic microbiology, both at the conventional phenotypic level and at the molecular level. H. pylori is a remarkable microorganism because of its ability to readily colonize a major proportion of human population worldwide and to persist successfully for long periods (probably decades) in a hostile environment. At the same time it interacts with the host immune system in such a way as to permit long-term survival. Blaser (1993) proposed a model in which both host and parasite adapt to down regulate inflammatory phenomena to promote survival. Urease production by H. pylori (an important factor in that process) is one of its most distinct features with a key role in its success as an infective agent. Another less obvious yet highly significant feature of H. pylori is the ability to achieve a high degree of interstrain diversity in genomic DNA nucleotide sequences, while maintaining overall genetic homology and phenotypic homogeneity amongst strains. The selective advantage this diversity provides the bacterium is not understood. A key objective of future microbiological studies should be to understand the population genetic structure of H. pylori. Most species of bacteria are clonal in natural population structure, yet all genomic data suggest the contrary is true for H. pylori. Furthermore, it is not clear if all strains of H. pylori are equally pathogenic, and that some subsets may possess additional pathogenicity factors that are responsible for the development of different disease pathologies. A phylogenetic framework of the genetic relationships of the clones within H. pylori would enable an examination of the total genetic diversity, with respect to ethnic or geographical

  19. 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.

  20. 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.

  1. Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription.

    PubMed

    Ritter, Birgit; Kilian, Petra; Reboll, Marc Rene; Resch, Klaus; DiStefano, Johanna Kay; Frank, Ronald; Beil, Winfried; Nourbakhsh, Mahtab

    2011-02-01

    Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

  2. 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.

  3. 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

  4. 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

  5. Modulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by Helicobacter pylori in immune pathogenesis of gastric mucosal damage.

    PubMed

    Tsai, Hwei-Fang; Hsu, Ping-Ning

    2017-02-01

    Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphomas. Apoptosis induced by microbial infections is implicated in the pathogenesis of H. pylori infection. Enhanced gastric epithelial cell apoptosis during H. pylori infection was 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-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells. Human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death-receptor signaling. The induction of TRAIL sensitivity by H. pylori is dependent upon the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex through downregulation of cellular FLICE-inhibitory protein. Moreover, H. pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. pylori infection, significant increases in CCR6(+) CD3(+) T cell infiltration in the gastric mucosa was observed, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These mechanisms initiate chemokine-mediated T lymphocyte trafficking into inflamed epithelium and induce mucosal injury during Helicobacter infection. This article will review recent findings on the interactions of H. pylori with host-epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation and mucosal damage.

  6. Helicobacter pylori Adhesion to Carbohydrates

    PubMed Central

    Aspholm, Marina; Kalia, Awdhesh; Ruhl, Stefan; Schedin, Staffan; Arnqvist, Anna; Lindén, Sara; Sjöström, Rolf; Gerhard, Markus; Semino-Mora, Cristina; Dubois, Andre; Unemo, Magnus; Danielsson, Dan; Teneberg, Susann; Lee, Woo-Kon; Berg, Douglas E.; Borén, Thomas

    2008-01-01

    Adherence of bacterial pathogens to host tissues contributes to colonization and virulence and typically involves specific interactions between bacterial proteins called adhesins and cognate oligosaccharide (glycan) or protein motifs in the host that are used as receptors. A given pathogen may have multiple adhesins, each specific for a different set of receptors and, potentially, with different roles in infection and disease. This chapter provides strategies for identifying and analyzing host glycan receptors and the bacterial adhesins that exploit them as receptors, with particular reference to adherence of the gastric pathogen Helicobacter pylori. PMID:17132512

  7. Helicobacter pylori: Friend or foe?

    PubMed Central

    Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob

    2014-01-01

    Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world’s population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is “anyone with a fear of gastric cancer” which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection. PMID:25083071

  8. Helicobacter pylori: friend or foe?

    PubMed

    Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob

    2014-07-21

    Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.

  9. Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.

    PubMed

    Zhang, Songhua; Lee, Dong Soo; Morrissey, Rhiannon; Aponte-Pieras, Jose R; Rogers, Arlin B; Moss, Steven F

    2014-12-01

    H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.

  10. Gastric and enterohepatic helicobacters other than Helicobacter pylori.

    PubMed

    Ménard, Armelle; Péré-Védrenne, Christelle; Haesebrouck, Freddy; Flahou, Bram

    2014-09-01

    During the past year, research on non-Helicobacter pylori species has intensified. H. valdiviensis was isolated from wild birds, and putative novel species have been isolated from Bengal tigers and Australian marsupials. Various genomes have been sequenced: H. bilis, H. canis, H. macacae, H. fennelliae, H. cetorum, and H. suis. Several studies highlighted the virulence of non-H. pylori species including H. cinaedi in humans and hyperlipidemic mice or H. macacae in geriatric rhesus monkeys with intestinal adenocarcinoma. Not surprisingly, increased attention has been paid to the position of Helicobacter species in the microbiota of children and animal species (mice, chickens, penguins, and migrating birds). A large number of experimental studies have been performed in animal models of Helicobacter induced typhlocolitis, showing that the gastrointestinal microbial community is involved in modulation of host pathways leading to chronic inflammation. Animal models of H. suis, H. heilmannii, and H. felis infection have been used to study the development of severe inflammation-related pathologies, including gastric MALT lymphoma and adenocarcinoma.

  11. Inflammation, DNA Damage, Helicobacter pylori and Gastric Tumorigenesis

    PubMed Central

    Kalisperati, Polyxeni; Spanou, Evangelia; Pateras, Ioannis S.; Korkolopoulou, Penelope; Varvarigou, Anastasia; Karavokyros, Ioannis; Gorgoulis, Vassilis G.; Vlachoyiannopoulos, Panayiotis G.; Sougioultzis, Stavros

    2017-01-01

    Helicobacter pylori (H. pylori) is a Gram negative bacterium that colonizes the stomach of almost half human population. It has evolved to escape immune surveillance, establishes lifelong inflammation, predisposing to genomic instability and DNA damage, notably double strand breaks. The epithelial host cell responds by activation of DNA damage repair (DDR) machinery that seems to be compromised by the infection. It is therefore now accepted that genetic damage is a major mechanism operating in cases of H. pylori induced carcinogenesis. Here, we review the data on the molecular pathways involved in DNA damage and DDR activation during H. pylori infection. PMID:28289428

  12. 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

  13. Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death

    PubMed Central

    Jain, Prashant; Luo, Zhao-Qing; Blanke, Steven R.

    2011-01-01

    A number of pathogenic bacteria target mitochondria to modulate the host's apoptotic machinery. Studies here revealed that infection with the human gastric pathogen Helicobacter pylori disrupts the morphological dynamics of mitochondria as a mechanism to induce host cell death. The vacuolating cytotoxin A (VacA) is both essential and sufficient for inducing mitochondrial network fragmentation through the mitochondrial recruitment and activation of dynamin-related protein 1 (Drp1), which is a critical regulator of mitochondrial fission within cells. Inhibition of Drp1-induced mitochondrial fission within VacA-intoxicated cells inhibited the activation of the proapoptotic Bcl-2–associated X (Bax) protein, permeabilization of the mitochondrial outer membrane, and cell death. Our data reveal a heretofore unrecognized strategy by which a pathogenic microbe engages the host's apoptotic machinery. PMID:21903925

  14. Deletion of IQGAP1 promotes Helicobacter pylori-induced gastric dysplasia in mice and acquisition of cancer stem cell properties in vitro

    PubMed Central

    Bessède, Emilie; Molina, Silvia; Amador, Luis Acuña; Dubus, Pierre; Staedel, Cathy; Chambonnier, Lucie; Buissonnière, Alice; Sifré, Elodie; Giese, Alban; Bénéjat, Lucie; Rousseau, Benoît; Costet, Pierre; Sacks, David B.; Mégraud, Francis; Varon, Christine

    2016-01-01

    Helicobacter pylori infection is responsible for gastric carcinogenesis but host factors are also implicated. IQGAP1, a scaffolding protein of the adherens junctions interacting with E-cadherin, regulates cellular plasticity and proliferation. In mice, IQGAP1 deficiency leads to gastric hyperplasia. The aim of this study was to elucidate the consequences of IQGAP1 deletion on H. pylori-induced gastric carcinogenesis. Transgenic mice deleted for iqgap1 and WT littermates were infected with Helicobacter sp., and histopathological analyses of the gastric mucosa were performed. IQGAP1 and E-cadherin expression was evaluated in gastric tissues and in gastric epithelial cell lines in response to H. pylori infection. The consequences of IQGAP1 deletion on gastric epithelial cell behaviour and on the acquisition of cancer stem cell (CSC)-like properties were evaluated. After one year of infection, iqgap1+/- mice developed more preneoplastic lesions and up to 8 times more gastro-intestinal neoplasia (GIN) than WT littermates. H. pylori infection induced IQGAP1 and E-cadherin delocalization from cell-cell junctions. In vitro, knock-down of IQGAP1 favoured the acquisition of a mesenchymal phenotype and CSC-like properties induced by H. pylori infection. Our results indicate that alterations in IQGAP1 signalling promote the emergence of CSCs and gastric adenocarcinoma development in the context of an H. pylori infection. PMID:27729612

  15. Iron deficiency and Helicobacter pylori-induced gastric cancer: too little, too bad.

    PubMed

    El-Omar, Emad M

    2013-01-01

    Clinical vignette: A 38-year-old man consults you in the GI clinic because of frequent episodes of epigastric pain, nausea, and tiredness. His blood count shows signs of mild iron deficiency anemia. Upper GI endoscopy was normal, but antral and corpus biopsy specimens show evidence of gastric atrophy and Helicobacter pylori infection. Colonoscopy and capsule endoscopy showed no evidence of lesions in the large or small bowel. He receives a standard one-week course eradication therapy consisting of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin. His symptoms improve, but his infection persists and he remains mildly anemic. He asks you whether the infection must be eradicated, as he read on the Internet that it can cause stomach cancer. He is also concerned about the anemia.

  16. 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

  17. Acid-induced gene expression in Helicobacter pylori: study in genomic scale by microarray.

    PubMed

    Ang, S; Lee, C Z; Peck, K; Sindici, M; Matrubutham, U; Gleeson, M A; Wang, J T

    2001-03-01

    To understand the RNA expression in response to acid stress of Helicobacter pylori in genomic scale, a microarray membrane containing 1,534 open reading frames (ORFs) from strain 26695 was used. Total RNAs of H. pylori under growth conditions of pH 7.2 and 5.5 were extracted, reverse transcribed into cDNA, and labeled with biotin. Each microarray membrane was hybridized with cDNA probe from the same strain under two different pH conditions and developed by a catalyzed reporter deposition method. Gene expression of all ORFs was measured by densitometry. Among the 1,534 ORFs, 53 ORFs were highly expressed (> or = 30% of rRNA control in densitometry ratios). There were 445 ORFs which were stably expressed (<30% of rRNA in densitometry) under both pH conditions without significant variation. A total of 80 ORFs had significantly increased expression levels at low pH, while expressions of 4 ORFs were suppressed under acidic condition. The remaining 952 ORFs were not detectable under either pH condition. These data were highly reproducible and comparable to those obtained by the RNA slot blot method. Our results suggest that microarray can be used in monitoring prokaryotic gene expression in genomic scale.

  18. Helicobacter pylori VacA suppresses Lactobacillus acidophilus-induced interferon beta signaling in macrophages via alterations in the endocytic pathway.

    PubMed

    Weiss, Gudrun; Forster, Sam; Irving, Aaron; Tate, Michelle; Ferrero, Richard L; Hertzog, Paul; Frøkiær, Hanne; Kaparakis-Liaskos, Maria

    2013-06-11

    Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus. IMPORTANCE Approximately half of the world's population is infected with Helicobacter pylori. The factors that allow this pathogen to persist in the stomach and cause chronic infections have not yet been fully elucidated. In particular, how H. pylori avoids killing by macrophages, one of the main types of immune cell underlying the

  19. Genetic Manipulation of a Naturally Competent Bacterium, Helicobacter pylori

    PubMed Central

    Noto, Jennifer M.; Peek, Richard M.

    2013-01-01

    Genetic manipulation of Helicobacter pylori facilitates characterization and functional analysis of individual H. pylori genes. This chapter discusses the methods involved in H. pylori chromosomal DNA isolation, mutagenesis of individual genes, and natural transformation. PMID:23015491

  20. Immunobiological activities of Helicobacter pylori porins.

    PubMed Central

    Tufano, M A; Rossano, F; Catalanotti, P; Liguori, G; Capasso, C; Ceccarelli, M T; Marinelli, P

    1994-01-01

    Studies were carried out on some biological activities of Helicobacter pylori porins in vitro. We extracted and purified a porin with an apparent molecular mass of 30 kDa. Human polymorphonuclear leukocytes preincubated with H. pylori porins showed a decrease of chemotaxis, of adherence to nylon wool, and of chemiluminescence. Used as chemotaxins in place of zymosan-activated serum or as chemotaxinogens in place of zymosan, the porins induced polymorphonuclear leukocyte migration. Human monocytes and lymphocytes cultivated in the presence of H. pylori porins released cytokines. Release of the various cytokines studied was obtained with differentiated kinetics and at various porin concentrations. Starting only 3 h after culture, tumor necrosis factor alpha is released quickly, reaching a peak at 18 h, at a porin concentration of 1 microgram/ml/10(6) cells. Interleukin-6 (IL-6) appears later, with a peak at 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells. Lymphocytes stimulated by H. pylori porins release gamma interferon after 18 h of culture at higher concentrations of porins (20 micrograms/ml/10(6) cells). Granulocyte macrophage colony-stimulating factor is released from 6 to 48 h at a concentration of 1 microgram/ml/10(6) cells, while both IL-3 and IL-4 are released after 18 h of culture at different porin concentrations (0.1 and 1 microgram/ml/10(6) cells, respectively). Our results lead us to think that during H. pylori infection, surface components, porins in particular, are able to induce a series of chain reactions ranging from the inflammatory to the immunological responses. Images PMID:8132346

  1. The histopathology of non-steroidal anti-inflammatory drug induced gastroduodenal damage: correlation with Helicobacter pylori, ulcers, and haemorrhagic events

    PubMed Central

    Frezza, M; Gorji, N; Melato, M

    2001-01-01

    Aims—The spectrum of microscopic lesions resulting from the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), known as chemical gastritis, remains unclear, and the variable prevalence reported in different studies makes this issue a matter of lively debate. The aim of this study was to evaluate the prevalence and importance of chemical gastritis in patients regularly taking NSAIDs. Owing to the high prevalence of Helicobacter pylori infection, particularly in subjects over 60 years of age, and in view of a possible association with damage, the presence of H pylori infection in the same tissue sample was also determined in all patients. Methods—One hundred and ninety seven subjects were enrolled, 118 of whom were receiving chronic treatment with NSAIDs and 79 of whom were controls, pair matched for age, sex, and clinical symptoms (ulcer-like dyspepsia or upper digestive tract haemorrhage). Antral biopsies taken during upper gastroduodenal endoscopy were assessed for chemical gastritis according to a modified version of Dixon's score, and for helicobacter correlated chronic active gastritis, according to the updated Sydney system. Results—Chemical gastritis was identified in 11 patients taking NSAIDs (9%) and in four controls (5%) (p < 0.05). Helicobacter pylori was detected in 53 patients taking NSAIDs (45%) and in 34 controls (43%). Patients taking NSAIDs had a significantly higher number of erosions and ulcers and worse endoscores than controls. The presence of H pylori did not appear to increase histological damage, ulcer prevalence, or haemorrhagic events. Conclusions—Chemical gastritis is present in a limited number of patients regularly taking NSAIDs, and is not strongly correlated with NSAID induced damage. In many cases of peptic ulcer or upper gastrointestinal bleeding in patients taking NSAIDs, the presence of chemical gastritis or H pylori infection cannot solely account for the development of mucosal damage. Key Words: chemical

  2. Epigenetic silencing of miR-124 prevents spermine oxidase regulation: implications for Helicobacter pylori-induced gastric cancer.

    PubMed

    Murray-Stewart, T; Sierra, J C; Piazuelo, M B; Mera, R M; Chaturvedi, R; Bravo, L E; Correa, P; Schneider, B G; Wilson, K T; Casero, R A

    2016-10-20

    Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2 production by >50% within 24 h. Reporter assays indicated that direct interaction of miR-124 with the 3'-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 before infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer.

  3. Epigenetic silencing of miR-124 prevents spermine oxidase regulation: Implications for Helicobacter pylori-induced gastric cancer

    PubMed Central

    Murray-Stewart, Tracy; Sierra, Johanna C.; Piazuelo, M. Blanca; Mera, Robertino M.; Chaturvedi, Rupesh; Bravo, Luis E.; Correa, Pelayo; Schneider, Barbara G.; Wilson, Keith T.; Casero, Robert A.

    2016-01-01

    Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2 production by >50% within 24 hours. Reporter assays indicated that direct interaction of miR-124 with the 3′-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 prior to infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer. PMID:27041578

  4. 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

  5. Bactericidal activity of Pistacia lentiscus mastic gum against Helicobacter pylori.

    PubMed

    Marone, P; Bono, L; Leone, E; Bona, S; Carretto, E; Perversi, L

    2001-12-01

    In this study we evaluated the antibacterial activity of mastic gum, a resin obtained from the Pistacia lentiscus tree, against clinical isolates of Helicobacter pylori. The minimal bactericidal concentrations (MBCs) were obtained by a microdilution assay. Mastic gum killed 50% of the strains tested at a concentration of 125 microg/ml and 90% at a concentration of 500 microg/ml. The influence of sub-MBCs of mastic gum on the morphologies of H. pylori was evaluated by transmission electron microscopy. The lentiscus resin induced blebbing, morphological abnormalities and cellular fragmentation in H. pylori cells.

  6. A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori-Induced Il-8 Expression.

    PubMed

    Wiedemann, Tobias; Hofbaur, Stefan; Loell, Eva; Rieder, Gabriele

    2016-09-29

    Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H. pylori infection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression in H. pylori-infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate the H. pylori-induced IL-8 expression on the transcriptional level, we transiently transfected gastric epithelial cells (AGS) with a human IL-8 luciferase reporter construct. The results of this study demonstrate that specifically the C-terminal coiled-coil region of the H. pylori CagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for several in vitro observations: 1) H. pylori-induced IL-8 secretion via the transforming growth factor (TGF)-α activated epidermal growth factor-receptor (EGF-R) signaling pathway; 2) H. pylori-induced elongation of the cells, a typical CagA-induced phenotype; and 3) the bridging of the T4SS to its human target cells. This novel bacterial-host recognition sequence allows a new insight into how H. pylori induces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions.

  7. A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori-Induced Il-8 Expression

    PubMed Central

    Wiedemann, Tobias; Hofbaur, Stefan; Loell, Eva; Rieder, Gabriele

    2016-01-01

    Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H. pylori infection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression in H. pylori-infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate the H. pylori-induced IL-8 expression on the transcriptional level, we transiently transfected gastric epithelial cells (AGS) with a human IL-8 luciferase reporter construct. The results of this study demonstrate that specifically the C-terminal coiled-coil region of the H. pylori CagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for several in vitro observations: 1) H. pylori-induced IL-8 secretion via the transforming growth factor (TGF)-α activated epidermal growth factor-receptor (EGF-R) signaling pathway; 2) H. pylori-induced elongation of the cells, a typical CagA-induced phenotype; and 3) the bridging of the T4SS to its human target cells. This novel bacterial-host recognition sequence allows a new insight into how H. pylori induces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions. PMID:27766167

  8. 3rd Brazilian Consensus on Helicobacter pylori.

    PubMed

    Coelho, Luiz Gonzaga; Maguinilk, Ismael; Zaterka, Schlioma; Parente, José Miguel; do Carmo Friche Passos, Maria; Moraes-Filho, Joaquim Prado P

    2013-04-01

    Signicant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  9. Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease

    PubMed Central

    Kim, J S; Chung, S J; Choi, Y S; Cheon, J H; Kim, C W; Kim, S G; Jung, H C; Song, I S

    2007-01-01

    A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2–3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11–125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10–22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication. PMID:17406363

  10. 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

  11. Helicobacter Pylori Bacteremia: An Unusual Finding

    PubMed Central

    De Luca, Concetta; Mancin, Annalisa; Calabrò, Maria; Daleno, Cristina; Ferrario, Antonella; Renzulli, Raffaella; Scuderi, Cristina; Casari, Erminia

    2016-01-01

    We report a case of Helicobacter pylori transient bacteremia in a woman with ulcerated antral gastric cancer. The patient was hospitalized for laparoscopy and subtotal gastrectomy. After surgery she developed fever (39°C) and was empirically treated with levofloxacin. Blood cultures, collected and sent immediately to Laboratory, were positive for a spiral Gram-negative bacterium. This isolate was identified as H. pylori and the specific susceptibility test was performed. One day after the fever was decreased but antibiotic treatment with levofloxacin was continued and it was maintained until discharge. In summary, H. pylori transient bacteremia may occur as a rare complication after stomach surgery. Further studies are necessary to elucidate the potential role of Helicobacter pylori presence in blood.

  12. Catechins and Sialic Acid Attenuate Helicobacter pylori-Triggered Epithelial Caspase-1 Activity and Eradicate Helicobacter pylori Infection

    PubMed Central

    Yang, Jyh-Chin; Yang, Hung-Chih; Shun, Chia-Tung; Wang, Teh-Hong; Chien, Chiang-Ting; Kao, John Y.

    2013-01-01

    The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium during Helicobacter pylori infection is yet to be elucidated. Here, we investigated the effect of catechins (CAs), sialic acid (SA), or combination of CA and SA (CASA) on H. pylori-induced caspase-1-mediated epithelial damage, as well as H. pylori colonization in vitro (AGS cells) and in vivo (BALB/c mice). Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1β were upregulated in H. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa of H. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pylori activity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicated H. pylori infection in up to 95% of H. pylori-infected mice. Taken together, we suggest that the pathogenesis of H. pylori involves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicate H. pylori infection. PMID:23653660

  13. [Celiac disease associated with Helicobacter pylori infection].

    PubMed

    Cârdei, E; Moraru, D; Trandafir, Laura; Bozomitu, Laura; Mihăilă, Doina

    2003-01-01

    Celiac disease, also known as gluten-sensitive enteropathy, is an autoimmune enteropathy caused by the ingestion of gluten-containing grains in susceptible subjects. The authors present a 3 years and 5 months old girl diagnosed with celiac disease at 1 year and 5 months old. Initially, the evolution after gluten-free diet was favorable. After 2 years the child presented abdominal pain and anorexia. The IgA antigliadin antibodies had normal values. The gastric biopsy found Helicobacter pylori gastritis. After treatment for Helicobacter pylori eradication the symptoms disappeared.

  14. 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.

  15. Effectiveness of Citrus Fruits on Helicobacter pylori

    PubMed Central

    2017-01-01

    It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current knowledge on the effect of Citrus fruits and their derivatives against H. pylori, highlighting the remaining outstanding questions on the development of novel therapeutic strategies.

  16. Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative stress.

    PubMed

    Wang, Ge; Hong, Yang; Olczak, Adriana; Maier, Susan E; Maier, Robert J

    2006-12-01

    Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

  17. Helicobacter pylori VacA Suppresses Lactobacillus acidophilus-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway

    PubMed Central

    Weiss, Gudrun; Forster, Sam; Irving, Aaron; Tate, Michelle; Ferrero, Richard L.; Hertzog, Paul; Frøkiær, Hanne; Kaparakis-Liaskos, Maria

    2013-01-01

    ABSTRACT Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus. PMID:23760466

  18. The effect of trimethylamine N-oxide on Helicobacter pylori-induced changes of immunoinflammatory genes expression in gastric epithelial cells.

    PubMed

    Wu, Daoyan; Cao, Mei; Peng, Jingshan; Li, Ningzhe; Yi, Sijun; Song, Liju; Wang, Xuege; Zhang, Mao; Zhao, Jian

    2017-02-01

    Colonization of Helicobacter pylori (H. pylori) induces immune and inflammatory response in gastric mucosa. Trimethylamine N-oxide (TMAO), from diet and metabolite through the action of gut microbiota, has been linked to inflammatory diseases. To investigate the effects of TMAO and H. pylori infection on gene expression in gastric epithelial cells, Human gene chip Affymetrix HTA 2.0 was used in this study. 1312 genes were identified as differentially expressed genes in GES-1 cells with H. pylori and TMAO co-treatment compared to the control. GO and KEGG analyses indicated that the functions of these differentially expressed genes were related closely with immune inflammation. GO-network showed that Toll-like receptor signaling pathway was the most important biological processes and 49 up-regulated genes related to immune inflammation were obtained. The synergistic effects of H. pylori and TMAO enhanced the genes expression of IL-6, CXCL1, CXCL2, FOS and C3 related to immune inflammation in comparison with those of non-infected control cells, H. pylori-infected cells, and TMAO-stimulated cells. RT-PCR verified the expression levels of IL-6, CXCL1. Additionally, expression levels of 2053 genes were altered and 52 immunoinflammatory genes were upregulated in comparison with H. pylori-infected cells. This study suggested that TMAO altered the expression levels of immunoinflammatory genes induced by H. pylori infection, and the synergistic effects of H. pylori and TMAO provided novel insights into the development of chronic gastritis, gastric ulcer and gastric cancer.

  19. Helicobacter pylori induces Snail expression through ROS-mediated activation of Erk and inactivation of GSK-3β in human gastric cancer cells.

    PubMed

    Ngo, Hoang-Kieu-Chi; Lee, Hee Geum; Piao, Juan-Yu; Zhong, Xiancai; Lee, Ha-Na; Han, Hyeong-Jun; Kim, Wonki; Kim, Do-Hee; Cha, Young-Nam; Na, Hye-Kyung; Surh, Young-Joon

    2016-12-01

    Helicobacter pylori (H. pylori) infection has been known to be implicated in human gastric carcinogenesis. Snail, the zinc-finger transcription factor known as a key inducer of changes in the cell shape and morphogenetic movement, is aberrantly overexpressed and correlates with lymph node metastasis in gastric cancer. In the present study, we investigated whether H. pylori could induce Snail activation to provoke these changes. Using a cell scatter assay, we noticed that human gastric cancer AGS cells infected with H. pylori underwent morphological changes as well as disruption of cell-cell interaction, which was then reversed by silencing of Snail by use of small interfering RNA (siRNA). In addition, infection with H. pylori resulted in an increased intracellular level of Snail in gastric cancer cells, which was abrogated in the presence of U0126 and LY294002, inhibitors of MEK/Erk and PI3K/Akt pathways, respectively. Cycloheximide pulse-chase experiments coupled with immunocytochemical analysis revealed that the induction of Snail by H. pylori was regulated at multiple levels, including increased transcription of Snail mRNA, inhibition of protein degradation, and enhancement of nuclear translocation of Snail. Pre-treatment of AGS cells with N-acetylcysteine, a well-known reactive oxygen species (ROS) scavenger, attenuated the H. pylori-induced activation of Erk, its binding to Snail promoter, inactivation of GSK-3β, and accumulation of Snail. Collectively, these findings suggest that the upregulation of Snail expression induced by H. pylori and transformation to a spindle-like shape as a consequence in gastric cancer cells are attributable to ROS-mediated activation of Erk and the inhibition of GSK-3β signaling. © 2016 Wiley Periodicals, Inc.

  20. Bacteriology and taxonomy of Helicobacter pylori.

    PubMed

    Windsor, H M; O'Rourke, J

    2000-09-01

    As the scientific community approaches the twentieth anniversary of the first isolation of H. pylori, it appears that despite the wealth of articles published in journals throughout the world every month, there are still many unanswered questions about the microbiology of this bacterium and others in the genus Helicobacter.

  1. 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

  2. Host pathogen interactions in Helicobacter pylori related gastric cancer.

    PubMed

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-03-07

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

  3. Host pathogen interactions in Helicobacter pylori related gastric cancer

    PubMed Central

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  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.

  6. Helicobacter pylori vaccine: from past to future.

    PubMed

    Agarwal, Kanishtha; Agarwal, Shvetank

    2008-02-01

    Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.

  7. Helicobacter pylori Outer Membrane Protein-Related Pathogenesis.

    PubMed

    Matsuo, Yuichi; Kido, Yasutoshi; Yamaoka, Yoshio

    2017-03-11

    Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system.

  8. Helicobacter pylori Outer Membrane Protein-Related Pathogenesis

    PubMed Central

    Matsuo, Yuichi; Kido, Yasutoshi; Yamaoka, Yoshio

    2017-01-01

    Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system. PMID:28287480

  9. Clinicopathological characteristics of invasive gastric Helicobacter pylori.

    PubMed

    Dudley, Jonathan; Wieczorek, Tad; Selig, Martin; Cheung, Hoiwan; Shen, Jeanne; Odze, Robert; Deshpande, Vikram; Zukerberg, Lawrence

    2017-03-01

    Helicobacter pylori organisms have been observed deep within the stomach mucosa with an "intracellular" appearance, although the clinicopathological characteristics of such cases remain poorly understood. We analyzed 18 cases of deep mucosal H pylori and associated clinical (sex, age, history of H pylori infection, or proton pump inhibitor [PPI] use, medications, smoking, alcohol use, comorbidities, treatment response) and pathological (presence of lymphoid aggregates, intestinal metaplasia, PPI effect, active and/or chronic inflammation, quantity of invasive versus surface H pylori) characteristics. Electron microscopy was performed on 6 cases with the highest burden of invasive H pylori. Within our sample, 3 of 16 had a history of H pylori infection, 10 of 15 were receiving PPIs at the time of biopsy, and 12 of 13 had a negative posttreatment follow-up. Histology revealed that invasive H pylori were more commonly associated with chronic inflammation, in both the antrum (15/15 chronic, 8/15 acute) and fundus (17/18 chronic, 8/18 acute). Electron microscopy showed organisms within intercellular and luminal spaces, but no intracellular organisms. Deep mucosal H pylori often have an intracellular appearance but are contained within intercellular and luminal spaces and are responsive to standard therapy.

  10. 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

  11. Effects of curcumin on Helicobacter pylori infection

    PubMed Central

    Vetvickova, Jana; Fernandez-Botran, Rafael

    2016-01-01

    Background Curcumin is a well-established natural molecule with significant biological and pharmaceutical effects. Its effects on Helicobacter pylori (H. pylori) infection have been repeatedly confirmed both in animal and human models. This study directly compared five different samples to evaluate if the effects are general or if they differ among samples. Methods Using a mouse model, we studied the effects of curcumin on lipid peroxide (LPO) level, myeloperoxidase (MPO) and urease activity, number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. In addition, we evaluated the effects on biofilm production and antibacterial antibody response. Results In all tests, one sample (Sabinsa) was consistently the most active. Conclusions All curcumin samples showed some anti-H. pylori effects, but only some of the tested samples had significant activity. PMID:28149841

  12. Thailand Consensus on Helicobacter pylori Treatment 2015.

    PubMed

    Mahachai, Varocha; Vilaichone, Ratha-Korn; Pittayanon, Rapat; Rojborwonwitaya, Jarin; Leelakusolvong, Somchai; Kositchaiwat, Chomsri; Mairiang, Pisaln; Praisontarangkul, Ong-Ard; Ovartlarnporn, Buncha; Sottisuporn, Jaksin; Pisespongsa, Pises; Maneerattanaporn, Monthira; Sony, Ravin; Sirinthornpunya, Siam; Chaiyamahapurk, Orawan; Wiwattanachang, Olarn; Sansak, Inchaya; Harnsomboon, Piyathida; Chitapanarux, Taned; Chuenrattanakul, Surapon

    2016-01-01

    Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes.

  13. Epidemiology and Diagnosis of Helicobacter pylori infection.

    PubMed

    Mentis, Andreas; Lehours, Philippe; Mégraud, Francis

    2015-09-01

    During the period reviewed, prevalence studies were essentially performed in less economically advanced countries and a high prevalence was found. The traditional risk factors for Helicobacter pylori positivity were mostly found. Transmission studied by molecular typing showed a familial transmission. The eventual role of water transmission was explored in several studies with controversial results. Concerning diagnosis, most of the invasive and noninvasive methods used for the diagnosis of H. pylori infection are long standing with efficient performance. The most interesting recent improvements in H. pylori diagnosis include advances in endoscopy, developments in molecular methods, and the introduction of omics-based techniques. Interpretation of old or newer method should take into account the pretest probability and the prevalence of H. pylori in the population under investigation.

  14. 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

  15. MicroRNAs up-regulated by CagA of Helicobacter pylori induce intestinal metaplasia of gastric epithelial cells.

    PubMed

    Zhu, Yongliang; Jiang, Qiaoli; Lou, Xiaojun; Ji, Xiaowei; Wen, Zhenzhen; Wu, Jia; Tao, Haiying; Jiang, Tingting; He, Wei; Wang, Caihua; Du, Qin; Zheng, Shu; Mao, Jianshan; Huang, Jian

    2012-01-01

    CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA.

  16. 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

  17. 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

  18. Acetaldehyde and ethanol production by Helicobacter pylori.

    PubMed

    Salmela, K S; Roine, R P; Höök-Nikanne, J; Kosunen, T U; Salaspuro, M

    1994-04-01

    By virtue of possessing alcohol dehydrogenase activity, cytosol prepared from Helicobacter pylori produces toxic acetaldehyde from ethanol in vitro. To approach the in vivo situation in the stomach, we have now investigation whether intact H. pylori--without addition of exogenous nicotinamide adenine dinucleotide--also forms acetaldehyde. Furthermore, to assess the energy metabolism of H. pylori, we determined whether the alcohol dehydrogenase-catalyzed reaction can run in the opposite direction with ethanol as the end-product and thereby yield energy for the organism. Intact H. pylori formed acetaldehyde already at low ethanol concentrations (at 0.5% ethanol, acetaldehyde, 64 +/- 21 and 75 +/- 9 mumol/l (mean +/- SEM) for strains NCTC 11637 and NCTC 11638, respectively). H. pylori produced ethanol in concentrations that can be significant for the energy metabolism of the organism. Acetaldehyde production by H. pylori may be an important factor in the pathogenesis of gastroduodenal diseases associated with the organism. The primary function of H. pylori alcohol dehydrogenase may, however, be alcoholic fermentation and consequent energy production under microaerobic conditions.

  19. Helicobacter pylori and gastric cancer: Indian enigma.

    PubMed

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

    2014-02-14

    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.

  20. [Relation between Helicobacter pylori and atopic diseases].

    PubMed

    López Pérez, Gerardo; Alcántara Rodríguez, Fernando

    2002-01-01

    The rise in the incidence of atopic diseases in the last years is associated to a greater prevalence of viral and bacterial infections. The infections facilitate a chronic inflammatory process that is directly related to the sensibilization of mast cells which favors manifestations of allergic diseases. Within the proposed bacteriological agents as causes of is Helicobacter pylori. This work is a bibliographical revision and concludes that there is not evidence of the direct causal relation between infection by Helicobacter and allergic diseases; however, it can play an indirect role. Controlled and randomized studies are necessary to know accurately this relation because the eradication treatment could be a real alternative in these patients handling.

  1. The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation.

    PubMed

    Winter, Susann; Loddenkemper, Christoph; Aebischer, Anton; Räbel, Katrin; Hoffmann, Kirstin; Meyer, Thomas F; Lipp, Martin; Höpken, Uta E

    2010-11-01

    Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Statin Decreases Helicobacter pylori Burden in Macrophages by Promoting Autophagy

    PubMed Central

    Liao, Wei-Chih; Huang, Mei-Zi; Wang, Michelle Lily; Lin, Chun-Jung; Lu, Tzu-Li; Lo, Horng-Ren; Pan, Yi-Jiun; Sun, Yu-Chen; Kao, Min-Chuan; Lim, Hui-Jing; Lai, Chih-Ho

    2017-01-01

    Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been found to provide protective effects against several bacterial infectious diseases. Although the use of statins has been shown to enhance antimicrobial treated Helicobacter pylori eradication and reduce H. pylori-mediated inflammation, the mechanisms underlying these effects remain unclear. In this study, in vitro and ex vivo macrophage models were established to investigate the molecular pathways involved in statin-mediated inhibition of H. pylori-induced inflammation. Our study showed that statin treatment resulted in a dose-dependent decrease in intracellular H. pylori burden in both RAW264.7 macrophage cells and murine peritoneal exudate macrophages (PEMs). Furthermore, statin yielded enhanced early endosome maturation and subsequent activation of the autophagy pathway, which promotes lysosomal fusion resulting in degradation of sequestered bacteria, and in turn attenuates interleukin (IL)-1β production. These results indicate that statin not only reduces cellular cholesterol but also decreases the H. pylori burden in macrophages by promoting autophagy, consequently alleviating H. pylori-induced inflammation. PMID:28144585

  9. Changing epidemiology of Helicobacter pylori in Japan.

    PubMed

    Inoue, Manami

    2017-03-01

    Helicobacter pylori (H. Pylori) is known as the most important cause of gastric cancer. The prevalence of H. pylori infection varies widely by geographic area, age, and socioeconomic status. In Japan, H. pylori infection has been highly correlated with the incidence rate of gastric cancer, and a reduction in H. pylori infection is therefore crucial for decreasing the incidence of gastric cancer, especially at the population level. Infection occurs during childhood, commonly before 5 years of age. In Japan, where gastric cancer has ranked as the most common cancer by incidence and mortality for the last several decades, the prevalence of H. pylori infection has dramatically declined by birth cohort effect, mainly due to improvements in the general hygiene environment in childhood. Older generations born before around 1950 show a high prevalence of around 80-90 %, decreasing with age to reach around 10 % or less in those born around the 1990s, and less than 2 % for children born after the year 2000. This change will have generational effects on gastric cancer prevention strategies, both primary and secondary. The risk-stratified approach to gastric cancer prevention should be considered in Japan and other countries which have similarly experienced rapid economic development.

  10. Helicobacter pylori and early gastric cancer.

    PubMed Central

    Craanen, M E; Blok, P; Dekker, W; Tytgat, G N

    1994-01-01

    The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer (p < 0.05 and p < 0.001, respectively). H pylori was found in 61.3% of intestinal type early gastric cancer and in 54.5% of diffuse type early gastric cancer (NS). The age adjusted prevalence of intestinal metaplasia in the patients with antral gastritis was higher in H pylori positive patients in all age groups studied. Comparing gastritis patients with patients with intestinal type early gastric cancer showed the age adjusted prevalence of intestinal metaplasia to be significantly higher in the patients with early gastric cancer in all age groups studied. In conclusion, H pylori is associated with both types of early gastric carcinoma. Intestinal metaplasia formation seems to be a multifactorial process in which H pylori may play a part. These findings suggest that gastric cancer may be included in the spectrum of H pylori associated diseases, although many questions about causality remain to be answered. PMID:7959189

  11. Heat shock protein produced by Helicobacter pylori.

    PubMed

    Yokota, K; Hirai, Y; Haque, M; Hayashi, S; Isogai, H; Sugiyama, T; Nagamachi, E; Tsukada, Y; Fujii, N; Oguma, K

    1994-01-01

    The cells of Helicobacter pylori were suspended in the medium containing 35S-methionine. After a heat shock of the cells at 42 C for 5, 10, and 30 min, the production of proteins was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Out of many proteins produced by the cells, only 66 kDa protein production was dramatically increased by heat treatment. The N-terminal amino acid sequence of 66 kDa protein was quite similar to that of 62 kDa and 54 kDa proteins previously suggested as heat shock protein (HSP) of H. pylori based on the reaction with polyclonal and monoclonal antibodies against HSP 60 family proteins produced by other bacteria. Therefore, it was concluded that H. pylori produces the 66 kDa protein as its major heat shock protein which belongs to HSP 60 family.

  12. Helicobacter pylori Detection and Antimicrobial Susceptibility Testing

    PubMed Central

    Mégraud, Francis; Lehours, Philippe

    2007-01-01

    The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed. PMID:17428887

  13. 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.

  14. Rate and extent of Helicobacter pylori phagocytosis.

    PubMed

    Allen, Lee-Ann H

    2008-01-01

    Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric epithelium and plays a causative role in the development of peptic ulcers and gastric cancer. Phagocytosis is an element of innate defense used by macrophages and neutrophils to engulf microorganisms. We and others have shown that strains of H. pylori that contain the cag pathogenicity island actively retard their entry into phagocytes. Consequently, there is a lag of several minutes between bacterial binding and the onset of engulfment, and relative to other particles and microbes, the rate of internalization is slow. Herein, we describe in detail the use of synchronized phagocytosis and indirect immunofluorescence microscopy to quantify the rate and extent of H. pylori phagocytosis. This method is appropriate for primary phagocytes as well as transformed cell lines. More importantly, the effects of opsonins, virulence factors, and other agents on infection can be measured independent of bacterial viability or intracellular locale.

  15. Construction of a Helicobacter pylori-Escherichia coli shuttle vector for gene transfer in Helicobacter pylori.

    PubMed Central

    Lee, W K; An, Y S; Kim, K H; Kim, S H; Song, J Y; Ryu, B D; Choi, Y J; Yoon, Y H; Baik, S C; Rhee, K H; Cho, M J

    1997-01-01

    In this study, a Helicobacter pylori-Escherichia coli shuttle vector was constructed for transferring DNA into H. pylori. The smallest cryptic plasmid (1.2 kb), pHP489, among those harbored by 77 H. pylori isolates was selected as a base replicon for constructing vectors. HindIII-digested pHP489 was ligated with a kanamycin resistance gene [aph(3')-III], which originated from Campylobacter jejuni, to produce the recombinant plasmid pHP489K. pHP489K was efficiently transformed into and stably maintained in H. pylori strains. The shuttle vector pBHP489K (3.6 kb) was constructed by the recombination of pHP489, ColE1, and aph(3')-III sequences. pBHP489K was reciprocally transformed into and maintained in both H. pylori and E. coli. Introduction of the shuttle vector clone DNA (pBHP489K/AB; 6.7 kb), containing the ureA and ureB genes of H. pylori, into urease-negative mutants of H. pylori led to the restoration of their urease activity. The transformants were confirmed to contain the incoming plasmid DNA. pBHP489K satisfied the requirements for an H. pylori-E. coli shuttle vector, implying that it might be a useful vector for investigating pathogenicity and restriction-modification systems of H. pylori. PMID:9406406

  16. From inflammation to gastric cancer: Role of Helicobacter pylori

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying; Aboul-Soud, Mourad A.M.

    2017-01-01

    Gastric cancer is a multifactorial disease and a leading cause of mortality and the risk factors for this include environmental factors and factors that influence host-pathogen interaction and complex interplay between these factors. Gastric adenocarcinomas are of two types, namely intestinal and diffuse type, and Helicobacter pylori (H. pylori) infection has been suspected of being causally linked to the initiation of chronic active gastritis, which leads to adenocarcinoma of the intestinal type. Even though most individuals with H. pylori infection do not show any clinical symptoms, long-term infection leads to inflammation of gastric epithelium and approximately 10% of infected patients develop peptic ulcers and 1–3% of patients develop gastric adenocarcinoma. Among the several mechanisms involved in tumorigenesis, CagA and peptidoglycan of H. pylori, which enter the infected gastric epithelial cells play an important role by triggering oncogenic pathways. Inflammation induced by H. pylori in gastric epithelium, which involves the cyclooxygenase-2/prostaglandin E2 pathway and IL-1β, is also an important factor that triggers chronic active gastritis and adenocarcinoma. H. pylori infection induced oxidative stress and dysregulated E-cadherin/β-catenin/p120 interactions and function also play a critical role in tumorigenesis. Environmental and dietary factors, in particular salt intake, are known to modify the pathogenesis induced by H. pylori. Gastric cancer induced by H. pylori appears to involve several mechanisms, making this mode of tumorigenesis a highly complicated process. Nevertheless, there are many events in this tumorigenesis that remain to be clarified and investigated. PMID:28356927

  17. Helicobacter pylori Induces miR-155 in T Cells in a cAMP-Foxp3-Dependent Manner

    PubMed Central

    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 γ-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 α (PKIα) 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

  18. Characterization of Helicobacter pylori urease mutants.

    PubMed Central

    Segal, E D; Shon, J; Tompkins, L S

    1992-01-01

    The association between Helicobacter pylori, gastritis, and peptic ulcer is well established, and the association of infection with gastric cancer has been noted in several developing countries. However, the pathogenic mechanism(s) leading to disease states has not been elucidated. The H. pylori urease is thought to be a determinant of pathogenicity, since the enzyme is produced by all H. pylori clinical isolates. Evidence indicates that some H. pylori strains are more cytotoxic than others, with a correlation between the activity of the urease and the presence of a vacuolating cytotoxin having been made. However, the number of cytotoxins remains unknown at this time. The relationship between the urease and cytotoxicity has previously been examined with chemical inhibitors. To examine the role of the urease and its relationship to cytotoxicity, urease-deficient mutants were produced following ethyl methanesulfonate mutagenesis of H. pylori 87A300. Two mutants (the ure1 and ure5 mutants) which were entirely deficient in urease activity (Ure-) were selected. Characterization of the isolates at the protein level showed that the urease subunits lacked the ability to complex and form the active urease enzyme. The ure1 mutant was shown to be sensitive to the effects of low pH in vitro and exhibited no cytotoxicity to eucaryotic cells, whereas the parental strain (Ure+) produced a cytotoxic effect in the presence of urea. Interaction between the H. pylori Ure+ and Ure- strains and Caco-2 cells appeared to be similar in that both bacterial types elicited pedestal formation and actin condensation. These results indicate that the H. pylori urease may have many functions, among them (i) protecting H. pylori against the acidic environment of the stomach, (ii) acting as a cytotoxin, with human gastric cells especially susceptible to its activity, and (iii) disrupting cell tight junctions in such a manner that the cells remain viable but an ionic flow between the cells occurs

  19. 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

  20. Differential regulation of urease activity in Helicobacter hepaticus and Helicobacter pylori.

    PubMed

    Belzer, Clara; Stoof, Jeroen; Beckwith, Catherine S; Kuipers, Ernst J; Kusters, Johannes G; van Vliet, Arnoud H M

    2005-12-01

    Helicobacter hepaticus is a pathogen of rodents, which causes diverse enteric and hepatic inflammatory diseases and malignancies. The urease enzyme is an important colonization factor of gastric Helicobacter species like Helicobacter pylori, but little is known about the role and regulation of urease in enterohepatic Helicobacter species. Here it is reported that urease activity of H. hepaticus does not contribute to acid resistance, and that it is nickel-responsive at the post-translational level. H. hepaticus strain ATCC 51449 did not grow or survive at pH 3.0, and supplementation with urea or NiCl2 did not abrogate this acid sensitivity. Furthermore, urease enzyme activity of H. hepaticus was acid-independent, which contrasts with the acid-induced urease system of H. pylori. Nickel supplementation of Brucella medium resulted in a tenfold increase in urease activity in both H. hepaticus and H. pylori, but the maximum level of urease activity in H. hepaticus was still three- to fivefold lower when compared to H. pylori in the same conditions. The increase in urease activity of H. hepaticus was not associated with elevation of urease mRNA or protein levels. Inhibition of protein synthesis by chloramphenicol did not affect nickel-responsive induction of urease activity in H. hepaticus, and confirmed that nickel induction occurs at the post-translational level, probably by activation of preformed apo-enzyme. In conclusion, both the role of the urease enzyme and the regulation of urease activity differ between the enterohepatic pathogen H. hepaticus and the gastric pathogen H. pylori.

  1. Furazolidone therapy for Helicobacter pylori: Is it effective and safe?

    PubMed Central

    Francesco, Vincenzo De; Ierardi, Enzo; Hassan, Cesare; Zullo, Angelo

    2009-01-01

    Some aspects related with the use of furazolidone as a rescue therapy for Helicobacter pylori (H pylori) infection should be remarked, especially regarding its potential oncologic risk. The inclusion of furazolidone in a treatment regimen for H pylori infection is, at least, controversial, and it does not appear to be safe. PMID:19370795

  2. Effects of radix curcumae-derived diterpenoid C on Helicobacter pylori-induced inflammation and nuclear factor kappa B signal pathways

    PubMed Central

    Huang, Xuan; Lv, Bin; Zhang, Shuo; Dai, Qun; Chen, Bing-Bing; Meng, Li-Na

    2013-01-01

    AIM: To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori (H. pylori)-infected inflammation, intestinal metaplasia, and nuclear factor kappa B (NF-κB) signaling pathway in vitro. METHODS: We used I-type H. pylori to infect human gastric epithelial gastric epithelium cell line (GES-1) cell lines, and then H. pylori-infected GES-1 cells were treated with radix curcumae (RC)-derived diterpenoid C of different concentrations (5, 10, 20 μg/mL) and amoxicillin. The expression of p65, IκB kinase (IKK) α and IKKγ proteins was detected with Western blotting, and the expression of interleukin (IL)-8, IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method. Data were analyzed using SPSS software ver18.0. For comparisons between groups of more than two unpaired values, one-way analysis of variance (ANOVA) was used. If an ANOVA F value was significant, post hoc comparisons were performed between groups. If results were not normally distributed, the Mann-Whitney U test was used to compare two groups of unpaired values, whereas for comparisons between groups of more than two unpaired values, the Kruskal-Wallis H test was used. Statistical significance was established at P < 0.05. RESULTS: The MTT assay results revealed the inhibited rate of GES-1, and indicated that the IC5 of RC-derived diterpenoid C and amoxicillin all were 5 μg/mL for gastric GES-1 cells. The expression of IL-8 was significantly increased, especially at 12 h time point; and the expression of IL-4 was decreased in H. pylori-infected GES-1 cells. After H. pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin, the expression of IL-8 was decreased at 12, 24, 48, 72 h points (P < 0.01), especially in high-concentration diterpenoid C (20 μg/mL) group; and the expression of IL-4 was increased, especially in moderate and high-concentration diterpenoid C (10 and 20 μg/mL) groups. RC

  3. Multiple in vivo passages enhance the ability of a clinical Helicobacter pylori isolate to colonize the stomach of Mongolian gerbils and to induce gastritis.

    PubMed

    Bleich, A; Köhn, I; Glage, S; Beil, W; Wagner, S; Mähler, M

    2005-04-01

    The Mongolian gerbil is an excellent animal model for Helicobacter pylori-induced gastritis in humans. In this study, initially low colonization rates of the H. pylori strains ATCC 43504, SS1, or HP87 inoculated into gerbils caused difficulties in establishing this model. In order to increase the colonization ability and pathogenicity, the clinical HP87 isolate was selected for adaptation to the gerbil stomach by multiple in vivo passages through gerbils. Development of gastritis was examined histologically at 4-52 weeks after infection. The proportion of gerbils which tested positive for H. pylori by culture at four weeks after inoculation gradually increased from 11.1% of gerbils inoculated with HP87 without prior in vivo passage (P0) to 100% of gerbils inoculated with HP87 with seven in vivo passages (P7). In addition, adaptation of HP87 resulted in more severe histopathological changes. Gerbils infected with adapted HP87 (P7) exhibited severe infiltration by monomorphonuclear and polymorphonuclear leukocytes in the mucosa, submucosa, and subserosa of the gastric antrum, as well as epithelial changes consisting of hyperplasia, erosion, and ulceration. Histopathological changes increased in severity from four to 52 weeks after infection. Adaptation of HP87 during its passages through gerbils could be due to genetic changes in bacterial colonization factors. Identification of these changes might be useful to understand the underlying mechanism of gastric adaptation and pathogenesis of H. pylori.

  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. TNF-α-inducing protein of Helicobacter pylori induces epithelial-mesenchymal transition (EMT) in gastric cancer cells through activation of IL-6/STAT3 signaling pathway.

    PubMed

    Chen, Guodong; Tang, Na; Wang, Chao; Xiao, Linqiao; Yu, Minjun; Zhao, Lanhua; Cai, Hengling; Han, Liang; Xie, Chengyuan; Zhang, Yan

    2017-03-04

    Tumor necrosis factor (TNF)-α-inducing protein (Tipα) is a newly identified carcinogenic factor secreted by Helicobacter pylori (H. pylori). Although it has been proved that Tipα is a strong inducer of epithelial-mesenchymal transition (EMT), a crucial process of migration, the exact molecular mechanism is unknown. Current evidence indicates that the oncogenic transcription factor signal transducers and activators of transcription 3 (STAT3) is inappropriately activated in multiple malignancies, including gastric cancer. In this study, we showed that Tipα significantly down-regulated the expression of EMT-related markers E-cadherin as well as up-regulated N-cadherin and vimentin in SGC7901 cells, with typical morphological changes of EMT. Tipα also promoted proliferation and migration of SGC7901 cells. Furthermore, Tipα activated interleukin-6 (IL-6)/STAT3 signaling pathway in SGC7901 cells. The effects of Tipα treatment observed was abolished when we block IL-6/STAT3 signaling pathway. Altogether, our data demonstrated that Tipα may accelerate tumor aggressiveness in gastric cancer by promoting EMT through activation of IL-6/STAT3 pathway.

  6. Can Helicobacter pylori infection influence human reproduction?

    PubMed

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

    2014-05-21

    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.

  7. Breath ammonia measurement in Helicobacter pylori infection.

    PubMed

    Kearney, David J; Hubbard, Todd; Putnam, David

    2002-11-01

    Our aim was to define the utility of breath ammonia measurement in assessing Helicobacter pylori infection. Volunteers breathed into a device containing three fiberoptic NH3 sensors at baseline and after ingesting 300 mg of urea. Breath ammonia levels were compared to the [14C]urea breath test. Thirteen subjects were tested. Before urea ingestion, H. pylori-positive subjects had significantly lower breath ammonia levels than negative subjects (mean +/- SD, 0.04 ppm +/- 0.09 vs 0.49 ppm +/- 0.24, P = 0.002) and had a significantly greater increases in breath ammonia after urea ingestion (range 198-1,494% vs 6-98%). One H. pylori-positive subject underwent treatment and breath ammonia levels shifted from the pattern seen in positive subjects to that seen in negative subjects. In conclusion, breath ammonia measurement for H. Pylori-positive and negative subjects showed distinct patterns. Breath ammonia measurement may be feasible as a diagnostic test for H. pylori.

  8. Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori.

    PubMed

    Li, Hong; Liao, Tingting; Debowski, Aleksandra W; Tang, Hong; Nilsson, Hans-Olof; Stubbs, Keith A; Marshall, Barry J; Benghezal, Mohammed

    2016-12-01

    This review covers the current knowledge and gaps in Helicobacter pylori lipopolysaccharide (LPS) structure and biosynthesis. H. pylori is a Gram-negative bacterium which colonizes the luminal surface of the human gastric epithelium. Both a constitutive alteration of the lipid A preventing TLR4 elicitation and host mimicry of the Lewis antigen decorated O-antigen of H. pylori LPS promote immune escape and chronic infection. To date, the complete structure of H. pylori LPS is not available, and the proposed model is a linear arrangement composed of the inner core defined as the hexa-saccharide (Kdo-LD-Hep-LD-Hep-DD-Hep-Gal-Glc), the outer core composed of a conserved trisaccharide (-GlcNAc-Fuc-DD-Hep-) linked to the third heptose of the inner core, the glucan, the heptan and a variable O-antigen, generally consisting of a poly-LacNAc decorated with Lewis antigens. Although the glycosyltransferases (GTs) responsible for the biosynthesis of the H. pylori O-antigen chains have been identified and characterized, there are many gaps in regard to the biosynthesis of the core LPS. These limitations warrant additional mutagenesis and structural studies to obtain the complete LPS structure and corresponding biosynthetic pathway of this important gastric bacterium.

  9. Immune evasion strategies used by Helicobacter pylori.

    PubMed

    Lina, Taslima T; Alzahrani, Shatha; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E

    2014-09-28

    Helicobacter pylori (H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival.

  10. 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

  11. Analysis of Helicobacter pylori Prevalence in Chittagong, Bangladesh, Based on PCR and CLO Test

    PubMed Central

    Habib, Abdul Musaweer; Alam, Md. Jibran; Rudra, Bashudev; Quader, Md. Abdul; Al-Forkan, Mohammad

    2016-01-01

    The pathogenic bacterium Helicobacter pylori is a causative agent of gastric diseases in Bangladesh as well as throughout the world. This study aimed at analyzing the prevalence of H. pylori infection among dyspeptic patients in Chittagong, the second most populous city of Bangladesh, using 16S rRNA-based H. pylori-specific Polymerase Chain Reaction and Campylobacter-like organism test. We found that 67% of the population under study was positive for H. pylori infection. Gastric ulcer and duodenal ulcer disease showed statistically significant association with H. pylori infection; however, no association of H. pylori infection was observed in terms of age and gender. This study would play a crucial role in managing H. pylori-induced gastric diseases by understanding the current trend of H. pylori infection in the Chittagong region of Bangladesh. PMID:27891051

  12. 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

  13. 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

  14. Immune Homeostasis of Human Gastric Mucosa in Helicobacter pylori Infection.

    PubMed

    Reva, I V; Yamamoto, T; Vershinina, S S; Reva, G V

    2015-05-01

    We present the results of electron microscopic, microbiological, immunohistochemical, and molecular genetic studies of gastric biopsy specimens taken for diagnostic purposes according by clinical indications during examination of patients with gastrointestinal pathology. Immune homeostasis of the gastric mucosa against the background of infection with various pathogen strains of Helicobacter pylori was studied in patients of different age groups with peptic ulcer, gastritis, metaplasia, and cancer. Some peculiarities of Helicobacter pylori contamination in the gastric mucosa were demonstrated. Immune homeostasis of the gastric mucosa in different pathologies was analyzed depending on the Helicobacter pylori genotype.

  15. 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

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

    PubMed

    Yee, John K C

    2016-01-14

    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.

  17. Helicobacter pylori virulence and cancer pathogenesis.

    PubMed

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    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.

  18. Detection of Helicobacter pylori in Oral Lesions

    PubMed Central

    Irani, Soussan; Monsef Esfahani, Alireza; Bidari Zerehpoush, Farahnaz

    2013-01-01

    Background and aims. Helicobacter pylori is a microaerophilic gram-negative spiral organism. It is recognized as the etiologic factor for peptic ulcers, gastric adenocarcinoma and gastric lymphoma. Recently, it has been isolated from dental plaque and the dorsum of the tongue. This study was designed to assess the association between H. pylori and oral lesions such as ulcerative/inflammatory lesions, squamous cell carcinoma (SCC) and primary lymphoma. Materials and methods. A total of 228 biopsies diagnosed as oral ulcerative/inflammatory lesions, oral squamous cell carcinoma (OSCC) and oral primary lymphoma were selected from the archives of the Pathology Department. Thirty-two samples that were diagnosed as being without any pathological changes were selected as the control group. All the paraffin blocks were cut for hematoxylin and eosin staining to confirm the diagnoses and then the samples were prepared for immunohistochemistry staining. Data were collected and analyzed. Results. Chi-squared test showed significant differences between the frequency of H. pylori positivity in normal tissue and the lesions were examined (P=0.000). In addition, there was a statistically significant difference between the lesions examined (P=0.042). Chi-squared test showed significant differences between H. pylori positivity and different tissue types except inside the muscle layer as follows: in epithelium and in lamina propria (P=0.000), inside the blood vessels (P=0.003), inside the salivary gland duct (P=0.036), and muscle layer (P=0.122). Conclusion. There might be a relation between the presence of H. pylori and oral lesions. Therefore, early detection and eradication of H. pylori in high-risk patients are suggested. PMID:24578822

  19. 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

  20. 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

  1. 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

  2. Helicobacter pylori infection - recent developments in diagnosis.

    PubMed

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

    2014-07-28

    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.

  3. [Role of Helicobacter pylori coccoid forms in infection and recrudescence].

    PubMed

    Sarem, Muhannad; Corti, Rodolfo

    2016-01-01

    Helicobacter pylori is a spiral Gram-negative bacillus, which colonizes the human stomach and plays a key role in the pathogenesis of a number of gastroduodenal diseases. However, when expose to environmental stressed conditions, such as increased oxygen tension, extended incubation and exposure to antibiotics, Helicobacter pylori is able to entering the viable but nonculturable state, in which the bacterium modifies its morphology from a spiral to coccoid form, as a manifestation of cell adaptation to these adverse conditions. In gastric tissues, viable coccoid forms may remain latent for long time and retain virulence factors, so these forms possibly contribute to the treatment failures and recurrence of Helicobacter pylori infection and gastroduodenal diseases as well. In this review, we will discuss several aspects of cellular adaptation and survival of Helicobacter pylori, antibiotic susceptibility and virulence of coccoid forms and its involvement with recrudescence.

  4. Helicobacter Pylory infection in patients with esophageal squamous cell carcinoma

    PubMed Central

    Poyrazoglu, Omer Bilgehan; Dulger, Ahmet Cumhur; Gultepe, Bilge Sumbul

    2017-01-01

    OBJECTIVE: Esophageal squamous cell carcinoma is one of the most common esophageal diseases in the developing world, but the relationship between esophageal squamous cell carcinoma and Helicobacter pylori infection remains a neglected topic. The primary objective of this study was to determine the association between Helicobacter pylori infection and esophageal squamous cell carcinoma. A second purpose was to determine the incidence and factors associated with Helicobacter pylori infection following esophagectomy. METHOD: The microorganism was identified by testing the gastric biopsy materials from 95 esophageal squamous cell carcinoma patients (66 females; 39 were esophagectomized) for urease activity in a medium containing urea and a power of hydrogen detection reagent and comparing the results with those from a healthy population. Differences in patient characteristics were assessed with chi-square tests and t-tests for categorical and continuous factors, respectively. RESULTS: The patients with esophageal squamous cell carcinoma had a significantly lower prevalence of Helicobacter pylori compared with the healthy population (p<0.001). The naive and esophagectomized patients, in contrast, showed no significant differences in Helicobacter pylori infection (p>0.005). Patients with esophageal squamous cell carcinoma showed a significant association between leukocytosis and hypoglobulinemia and the presence of Helicobacter pylori infection (p=0.023 and p=0.045, respectively). CONCLUSION: These results suggest that Helicobacter pylori is not an etiological factor in patients with esophageal squamous cell carcinoma. We found a statistically significant negative correlation between esophageal squamous cell cancer and Helicobacter pylori infection. These findings may guide new strategies for esophageal squamous cell carcinoma therapy. PMID:28355360

  5. Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR Activation Increases Hypoxia Inducible Factor-1α to Promote Loss of Cyclin D1 and G0/G1 Cell Cycle Arrest in Human Gastric Cells

    PubMed Central

    Canales, Jimena; Valenzuela, Manuel; Bravo, Jimena; Cerda-Opazo, Paulina; Jorquera, Carla; Toledo, Héctor; Bravo, Denisse; Quest, Andrew F. G.

    2017-01-01

    Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection.

  6. Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR Activation Increases Hypoxia Inducible Factor-1α to Promote Loss of Cyclin D1 and G0/G1 Cell Cycle Arrest in Human Gastric Cells.

    PubMed

    Canales, Jimena; Valenzuela, Manuel; Bravo, Jimena; Cerda-Opazo, Paulina; Jorquera, Carla; Toledo, Héctor; Bravo, Denisse; Quest, Andrew F G

    2017-01-01

    Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection.

  7. The design of vaccines against Helicobacter pylori and their development.

    PubMed

    Del Giudice, G; Covacci, A; Telford, J L; Montecucco, C; Rappuoli, R

    2001-01-01

    Helicobacter pylori is a gram negative, spiral, microaerophylic bacterium that infects the stomach of more than 50% of the human population worldwide. It is mostly acquired during childhood and, if not treated, persists chronically, causing chronic gastritis, peptic ulcer disease, and in some individuals, gastric adenocarcinoma and gastric B cell lymphoma. The current therapy, based on the use of a proton-pump inhibitor and antibiotics, is efficacious but faces problems such as patient compliance, antibiotic resistance, and possible recurrence of infection. The development of an efficacious vaccine against H. pylori would thus offer several advantages. Various approaches have been followed in the development of vaccines against H. pylori, most of which have been based on the use of selected antigens known to be involved in the pathogenesis of the infection, such as urease, the vacuolating cytotoxin (VacA), the cytotoxin-associated antigen (CagA), the neutrophil-activating protein (NAP), and others, and intended to confer protection prophylactically and/or therapeutically in animal models of infection. However, very little is known of the natural history of H. pylori infection and of the kinetics of the induced immune responses. Several lines of evidence suggest that H. pylori infection is accompanied by a pronounced Th1-type CD4(+) T cell response. It appears, however, that after immunization, the antigen-specific response is predominantly polarized toward a Th2-type response, with production of cytokines that can inhibit the activation of Th1 cells and of macrophages, and the production of proinflammatory cytokines. The exact effector mechanisms of protection induced after immunization are still poorly understood. The next couple of years will be crucial for the development of vaccines against H. pylori. Several trials are foreseen in humans, and expectations are that most of the questions being asked now on the host-microbe interactions will be answered.

  8. [The diagnostic of chronic infection Helicobacter pylori in children].

    PubMed

    Tereschenko, S Yu; Olkhovskiy, I A

    2014-02-01

    The epidemiological studies testify an extremely high prevalence of chronic infection of children with Helicobacter pylori in Russia. The affection consists from 50% to 80% depending on region and age of examined children. The currently in force recommendations "Maastricht IV" concerning diagnostic and treatment of Helicobacter pylori infection adult patients are applied not in its fullness to children adolescent population. At the same time recently published joint conciliatory document of the European and North American associations of pediatric gastroenterologists is oriented to populations with low prevalence of Helicobacter pylori infection and particular profile of drug resistance. Hence, an urgent need exists to develop modern local algorithm concerning diagnostic, treatment and control of eradication of Helicobacter pylori infection among children and adolescents in Russia. The review presents analysis of admissibility of application in Russia's conditions of the international conciliatory documents concerning diagnostic of Helicobacter pylori infection in children. The data from conciliatory document of the European (ESPGHAN) and North American (NASPGHAN) associations of pediatric gastroenterologists, particular orginal research studies and one's own clinical experience were used. The advantages and shortcomings of actual methods of laboratory diagnostic of Helicobacter pylori infection are discussed. The approaches to application of particular diagnostic methods are considered. The enhanced indications to detection of infection and implementation of eradication therapy are proposed.

  9. The eradication treatments of Helicobacter pylori.

    PubMed

    Wermeille, J; Zelger, G; Cunningham, M

    1998-02-01

    The eradication of Helicobacter pylori is at present widely recognized as the adequate therapeutic approach for gastric and duodenal ulcers in infected patients. In those with dyspepsia but no ulcer as well as in those with type B chronic gastritis, eradication remains controversial. It is difficult to have a clear opinion on the advantages and disadvantages of the numerous existing therapies. Therefore, a systematic review of published treatments has been made by the authors. Ideally, the eradication treatment of H. pylori should have the following advantages: 1. eradication superior to 90%, 2. simplicity, 3. short duration, 4. safety, 5. low cost, 6. reproducibility of results. Dual therapies (2 antibiotics or a proton pump inhibitor in combination with an antibiotic) rarely allow an eradication greater than 90% and the results have poor reproducibility. Consequently, they do not represent an ideal anti-H. pylori treatment. Triple therapies come closer to the requirements for an ideal treatment, with eradication rates generally close to 90%, varying little between studies and the countries in which they were performed. The triple therapy bismuth-imidazole-tetracycline (or amoxicillin) still represents for many authors the standard reference therapy. It has the advantage of low cost, high efficacy and widespread use. It is the therapy that has been the most studied. However, the increasing emergence of strains resistant to imidazoles, the complexity of the treatment (10 to 12 tablets per day), the numerous adverse effects and the lack of availability of bismuth salts in certain countries has led to the elaboration of therapeutic schemes combining an antisecretory drug with 2 antibiotics. Among these, the combination PPI-clarithromycine-imidazole during 7 days represents the most studied triple therapy of short duration for some authors, it already represents a new standard. However, the efficacy of this therapy seems dependent on the sensitivity of the bacteria to

  10. Exploring alternative treatments for Helicobacter pylori infection.

    PubMed

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

    2014-02-14

    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.

  11. 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

  12. Molecular Dynamics Study of Helicobacter pylori Urease.

    PubMed

    Minkara, Mona S; Ucisik, Melek N; Weaver, Michael N; Merz, Kenneth M

    2014-05-13

    Helicobacter pylori have been implicated in an array of gastrointestinal disorders including, but not limited to, gastric and duodenal ulcers and adenocarcinoma. This bacterium utilizes an enzyme, urease, to produce copious amounts of ammonia through urea hydrolysis in order to survive the harsh acidic conditions of the stomach. Molecular dynamics (MD) studies on the H. pylori urease enzyme have been employed in order to study structural features of this enzyme that may shed light on the hydrolysis mechanism. A total of 400 ns of MD simulation time were collected and analyzed in this study. A wide-open flap state previously observed in MD simulations on Klebsiella aerogenes [Roberts et al. J. Am. Chem. Soc.2012, 134, 9934] urease has been identified in the H. pylori enzyme that has yet to be experimentally observed. Critical distances between residues on the flap, contact points in the closed state, and the separation between the active site Ni(2+) ions and the critical histidine α322 residue were used to characterize flap motion. An additional flap in the active site was elaborated upon that we postulate may serve as an exit conduit for hydrolysis products. Finally we discuss the internal hollow cavity and present analysis of the distribution of sodium ions over the course of the simulation.

  13. 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

  14. Helicobacter pylori Genetic Diversity and Gastro-duodenal Diseases in Malaysia

    PubMed Central

    Gunaletchumy, Selva Perumal; Seevasant, Indran; Tan, Mun Hua; Croft, Laurence J.; Mitchell, Hazel M.; Goh, Khean Lee; Loke, Mun Fai; Vadivelu, Jamuna

    2014-01-01

    Helicobacter pylori infection results in diverse clinical conditions ranging from chronic gastritis and ulceration to gastric adenocarcinoma. Among the multiethnic population of Malaysia, Indians consistently have a higher H. pylori prevalence as compared with Chinese and Malays. Despite the high prevalence of H. pylori, Indians have a relatively low incidence of peptic ulcer disease and gastric cancer. In contrast, gastric cancer and peptic ulcer disease incidence is high in Chinese. H. pylori strains from Chinese strains predominantly belong to the hspEAsia subpopulation while Indian/Malay strains mainly belong to the hspIndia subpopulation. By comparing the genome of 27 Asian strains from different subpopulations, we identified six genes associated with risk of H. pylori-induced peptic ulcer disease and gastric cancer. This study serves as an important foundation for future studies aiming to understand the role of bacterial factors in H. pylori-induced gastro-duodenal diseases. PMID:25503415

  15. 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...

  16. 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...

  17. Caveolin-1 Protects B6129 Mice against Helicobacter pylori Gastritis

    PubMed Central

    Hitkova, Ivana; Yuan, Gang; Anderl, Florian; Gerhard, Markus; Kirchner, Thomas; Reu, Simone; Röcken, Christoph; Schäfer, Claus; Schmid, Roland M.; Vogelmann, Roger; Ebert, Matthias P. A.; Burgermeister, Elke

    2013-01-01

    Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies (“humming bird”) compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells. PMID:23592983

  18. Functional study of gene hp0169 in Helicobacter pylori pathogenesis.

    PubMed

    Zhao, Huilin; Ji, Xiaofei; Chen, Xingxing; Li, Jiaojiao; Zhang, Ying; Du, Zhenzhen; Zhang, Yumei; Li, Boqing

    2017-03-01

    Many virulence genes have been reported to play important roles in Helicobacter pylori pathogenesis. However the detailed mechanisms of many of them have not been completely clear. In this study, we found gene hp0169, encoding a putative collagenase (HpPrtC), was involved in pathogenesis of H. pylori. Recombinant HpPrtC shows activities to both native and heat-denatured collagens. This result indicated that HpPrtC may act as a virulence factor to help the bacterium colonize in their host stomach by degrading surrounding collagens. hp0169 was deleted by homologous recombination to study its function in bacterium-host cell interaction. For the pathogenic functions on the host cells, the hp0169 mutant exhibits no significant changes on inducing apoptosis of GES-1 cells. However, the viability and proliferation rate of GES-1 cells infected with mutant strain were higher than the cells infected with wild-type strain. These results indicated that except for its collagenolytic activity, HpPrtC might participate in H. pylori pathogenesis through an additional pathway. Functional studies on hp0169 involved in pathogenesis would shed light on deep understanding of the pathogenic mechanism of H. pylori.

  19. Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection.

    PubMed

    Walduck, Anna; Andersen, Leif P; Raghavan, Sukanya

    2015-09-01

    During the last year, a variety of studies have been published that increases our understanding of the basic mechanisms of immunity and inflammation in Helicobacter pylori infection and progression to gastric cancer. Innate immune regulation and epithelial cell response were covered by several studies that contribute with new insights in the host response to H. pylori infection. Also, the adaptive immune response to H. pylori and particularly the role of IL-22 have been addressed in some studies. These advances may improve vaccine development where new strategies have been published. Two major studies analyzed H. pylori genomes of 39 worldwide strains and looked at the protein profiles. In addition, multi-epitope vaccines for therapeutic use have been investigated. Studies on different adjuvants and delivery systems have also given us new insights. This review presents articles from the last year that reveal detailed insight into immunity and regulation of inflammation, the contribution of immune cells to the development of gastric cancer, and understanding mechanisms of vaccine-induced protection.

  20. 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

  1. Impact of reactive oxygen species generation on Helicobacter pylori-related extragastric diseases: a hypothesis.

    PubMed

    Kountouras, Jannis; Boziki, Marina; Polyzos, Stergios A; Katsinelos, Panagiotis; Gavalas, Emmanouel; Zeglinas, Christos; Tzivras, Dimitri; Romiopoulos, Iordanis; Giorgakis, Nikolaos; Anastasiadou, Kyriaki; Vardaka, Elizabeth; Kountouras, Constantinos; Kazakos, Evangelos; Xiromerisiou, Georgia; Dardiotis, Efthimios; Deretzi, Georgia

    2017-01-01

    Helicobacter pylori (H. pylori) induces reactive oxygen species (ROS) production that contribute to pathogenesis of a variety of H. pylori-related gastric diseases, as shown in animal and human studies. Helicobacter pylori infection is also associated with variety of systemic extragastric diseases in which H. pylori-related ROS production might also be involved in the pathogenesis of these systemic conditions. We proposed that Hp-related ROS may play a crucial role in the pathophysiology of Hp-related systemic diseases including Alzheimer's disease, multiple sclerosis, glaucoma and other relative neurodegenerative diseases, thereby suggesting introduction of relative ROS scavengers as therapeutic strategies against these diseases which are among the leading causes of disability and are associated with a large public health global burden. Moreover, we postulated that H. pylori-related ROS might also be involved in the pathogenesis of extragastric common malignancies, thereby suggesting that H. pylori eradication might inhibit the development or delay the progression of aforementioned diseases. However, large-scale future studies are warranted to elucidate the proposed pathophysiological mechanisms, including H. pylori-related ROS, involved in H. pylori-associated systemic and malignant conditions.

  2. Echoes of a Distant Past: The cag Pathogenicity Island of Helicobacter pylori

    PubMed Central

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

    2013-01-01

    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

  3. 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...

  4. Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes.

    PubMed

    Ito, Takashi; Kobayashi, Daisuke; Uchida, Keisuke; Takemura, Tamiko; Nagaoka, Sakae; Kobayashi, Intetsu; Yokoyama, Tetsuji; Ishige, Ikuo; Ishige, Yuki; Ishida, Noriko; Furukawa, Asuka; Muraoka, Hiroe; Ikeda, Satoshi; Sekine, Masaki; Ando, Noboru; Suzuki, Yoshimi; Yamada, Tetsuo; Suzuki, Takashige; Eishi, Yoshinobu

    2008-06-01

    Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.

  5. Evidence for ethnic tropism of Helicobacter pylori.

    PubMed Central

    Campbell, S; Fraser, A; Holliss, B; Schmid, J; O'Toole, P W

    1997-01-01

    Helicobacter pylori infection in humans is linked to gastritis, gastric and duodenal ulcers, and gastric cancer. Peptic ulcer disease, as distinct from chronic asymptomatic infection, is strongly associated with expression of bacterial virulence markers, including a major antigen, CagA, and the vacuolating cytotoxin VacA. We have previously described significant differences in colonization rates, independent of socioeconomic status, among ethnic groups in New Zealand. To evaluate relative risks for peptic ulcer disease, we examined the frequency of two virulence markers in H. pylori strains infecting these ethnic groups. Although these markers occurred significantly more frequently in strains isolated from Polynesians than in strains from Europeans, this frequency was not reflected in the incidence of peptic ulcer disease in the two groups. DNA fingerprinting of the urease gene showed that Polynesians are more frequently infected by a group of strains which are genetically distinct from those affecting European New Zealanders. Our data suggest that separate bacterial lineages may have evolved in parallel with race-specific specialization. PMID:9284141

  6. 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

  7. A Case of Small Bowel Ulcer Associated with Helicobacter pylori

    PubMed Central

    Kim, Eun Young; Kim, Ji Hyun; Woo, Saet Byul; Lee, Jeong Won; Lee, Kon Hee; Shin, Su Rin

    2012-01-01

    The etiology of peptic ulcer disease in children may be primary, associated with Helicobacter pylori infection, or secondary, relied on underlying disease. Ulcerative lesions by H. pylori are mainly distributed in the duodenal bulb and they are rare below the ampulla of Vater because H. pylori growth is inhibited by bile juice. In this reason, there are only some restrictive reports presented small bowel ulcer associated H. pylori. We found multiple small bowel ulcerative lesions associated with H. pylori in an 11-year-old girl without any systemic disease while performing esophagogastroenteroscopy to the level of the proximal jejunum for differentiating bezoar. The abdominal pain improved after the patient was administered H. pylori eradication therapy. Because a small bowel ulcer associated with H. pylori has rarely been reported, we report it here with literature review. PMID:24010097

  8. Prevalence of Helicobacter pylori in United States Navy submarine crews.

    PubMed

    Jackman, R P; Schlichting, C; Carr, W; Dubois, A

    2006-06-01

    Helicobacter pylori prevalence is elevated in German submarine crews and in United States Navy (USN) surface fleet personnel, but H. pylori prevalence in USN submariners was unknown. The goal of the study was to determine the prevalence of H. pylori in the crews of USN nuclear submarines compared to other military personnel and to the general US population. The presence of H. pylori IgG antibodies was determined in serum samples using a commercial ELISA. Only 47 out of 451 submariners (9.4%) were H. pylori positive, which is similar to that of the US general population with a similar level of education. In contrast, H. pylori prevalence is significantly higher in US Army recruits (26%), USN surface fleet personnel (25%), and German diesel submariners (38%). These data demonstrate that submarine service (and by inference activity requiring isolation and close contact, per se) is not a risk factor for H. pylori infection.

  9. Helicobacter pylori infection in Canada's arctic: searching for the solutions.

    PubMed

    Cheung, Justin; Goodman, Karen; Munday, Rachel; Heavner, Karen; Huntington, Janis; Morse, John; Veldhuyzen van Zanten, Sander; Fedorak, Richard N; Corriveau, Andre; Bailey, Robert J

    2008-11-01

    The Canadian North Helicobacter pylori (CANHelp) working group is a team composed of investigators, health officials and community leaders from Alberta and the Northwest Territories. The group's initial goals are to investigate the impact of H pylori infection on Canada's Arctic communities; subsequent goals include identifying treatment strategies that are effective in this region and developing recommendations for health policy aimed at management of H pylori infection. The team's investigations have begun with the Aklavik H pylori Project in the Aboriginal community of Aklavik, Northwest Territories.

  10. Helicobacter pylori infection, gastrin and cyclooxygenase-2 in gastric carcinogenesis.

    PubMed

    Shao, Yun; Sun, Kun; Xu, Wei; Li, Xiao-Lin; Shen, Hong; Sun, Wei-Hao

    2014-09-28

    Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.

  11. 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.

  12. A novel chimeric flagellum fused with the multi-epitope vaccine CTB-UE prevents Helicobacter pylori-induced gastric cancer in a BALB/c mouse model.

    PubMed

    Song, Hui; Lv, Xiaobo; Yang, Jue; Liu, Wei; Yang, Huan; Xi, Tao; Xing, Yingying

    2015-11-01

    Helicobacter pylori (H. pylori) infection causes peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. The eradication of H. pylori might be an effective means of preventing gastric cancer. A dual-antigen epitope and dual-adjuvant vaccine called CTB-UE-CF (CCF) was constructed by combining a multi-epitope vaccine CTB-UE with a novel chimeric flagellum (CF) to simultaneously activate Toll-like receptor (TLR) 5-agonist activity and preserve the immunogenicity of H. pylori flagellum FlaA. The evaluation of efficacy to reduce H. pylori colonization was performed using BALB/c mice by oral immunization with a triple dose of this vaccine strain. Two weeks after the last immunization, mice were sacrificed to determine specific antibody levels and proinflammatory cytokine production. To determine the presence of H. pylori, we detected the number of H. pylori by real-time quantitative PCR (qPCR) and measured the urease activity in the gastric tissue. The results showed that the immunogenicity and mucosal immune responses of CCF performed significantly better than those of CTB-UE. This dual-antigen epitope and dual-adjuvant system might greatly contribute to the development of a safe and efficient therapeutic vaccine for humans against H. pylori infection.

  13. 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.

  14. 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

  15. 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.

  16. Helicobacter pylori infection in Canadian and related Arctic Aboriginal populations.

    PubMed

    Goodman, K J; Jacobson, K; Veldhuyzen van Zanten, S

    2008-03-01

    In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities.

  17. Antibiotics resistance of Helicobacter pylori and treatment modalities in children with H. pylori infection.

    PubMed

    Seo, Ji-Hyun; Woo, Hyang-Ok; Youn, Hee-Shang; Rhee, Kwang-Ho

    2014-02-01

    Pediatric infection with Helicobacter pylori may occur early in childhood and persist lifelong. Global pediatric clinical studies have reported a decreasing tendency in the overall rate of H. pylori eradication. In pediatric patients with H. pylori infection, pediatric patients with peptic ulcer, and the first-degree relatives of patients with a history of gastric cancer, it is commonly recommended that H. pylori strains be eradicated. Antibiotic drug resistance to H. pylori, which has been reported to vary widely between geographic regions, is mainly associated with treatment failure in these patients. It is therefore imperative that the antibiotic resistance rates of H. pylori in children and adolescents be meticulously monitored across countries and throughout geographic regions. This paper particularly focuses on the antibiotic drug resistance of H. pylori and the thearpy of pediatric H. pylori infection cases.

  18. 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

  19. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

    PubMed

    Zhu, Xinyan; Liu, Fei

    2017-03-10

    Over 80% population with Helicobacter pylori (H. pylori) infection is asymptomatic. H. pylori was considered as a primary reason for various natural gastric physiopathology. Increased antibiotic resistance and less medication compliance lead to the failure of antibiotic eradication therapy. Probiotics have been applied as a supplementary treatment in H. pylori eradication therapy in recent years. They have direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials. Because of the improvement in eradication rates and therapy-related side effects, probiotics have been considered as the useful supplementation to current eradication therapy although the treatment outcomes were controversial due to the heterogeneity of probiotics in species, strains, doses and therapeutic duration. Despite the positive role of probiotics, several factors need to be further considered during the application of probiotics. At last, the adverse effects of probiotics are notable. Further investigation into the safety of adjuvant probiotics to present H. pylori eradication therapy is still needed.

  20. 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

  1. 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

  2. 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.

  3. [IMMUNOLOGIC MONITORING OF HELICOBACTER PYLORI PERSISTENCE IN THE ORGANISM].

    PubMed

    Belaya, Yu A; Belaya, O F; Petrukhin, V G; Vakhrameeva, M S; Bystrova, S M; Pronin, A V

    2015-01-01

    Generalized results of 15-year prospective studies of frequency of occurrence and dynamics of circulation of pathogenetically significant LPS/O-antigens, high molecular weight proteins, including CagA, and VacA of Helicobacter pylori in biological media of organism in patients with gastrointestinal diseases and asymptomatic volunteers due to effects of external and internal factors are presented. Features of antigen circulation and reciprocal immune reaction of the organism are established, that reflect their interaction in the parasite-host tandem, risk and prognosis of possible complications in the process of long-term persistence of Helicobacter pylori in the organism.

  4. CONVENTIONAL VIDEOENDOSCOPY CAN IDENTIFY HELICOBACTER PYLORI GASTRITIS?

    PubMed Central

    GOMES, Alexandre; SKARE, Thelma Larocca; PRESTES, Manoel Alberto; COSTA, Maiza da Silva; Petisco, Roberta Dombroski; RAMOS, Gabriela Piovezani

    2016-01-01

    ABSTRACT Background: Studies with latest technologies such as endoscopy with magnification and chromoendoscopy showed that various endoscopic aspects are clearly related to infection by Helicobacter pylori (HP). The description of different patterns of erythema in gastric body under magnification of images revived interest in identifying these patterns by standard endoscopy. Aim: To validate the morphologic features of gastric mucosa related to H. pylori infection gastritis allowing predictability of their diagnosis as well as proper targeting biopsies. Methods: Prospective study of 339 consecutive patients with the standard videoendoscope image analysis were obtained, recorded and stored in a program database. These images were studied with respect to the presence or absence of H. pylori, diagnosed by rapid urease test and/or by histological analysis. Were studied: a) normal mucosa appearance; b) mucosal nodularity; c) diffuse nonspecific erythema or redness (with or without edema of folds and exudate) of antrum and body; d) mosaic pattern with focal area of hyperemia; e) erythema in streaks or bands (red streak); f) elevated (raised) erosion; g) flat erosions; h) fundic gland polyps. The main exclusion criteria were the use of drugs, HP pre-treatment and other entities that could affect results. Results: Applying the exclusion criteria, were included 170 of the 339 patients, of which 52 (30.58%) were positive for HP and 118 negative. On the positive findings, the most associated with infection were: nodularity in the antrum (26.92%); presence of raised erosion (15.38%) and mosaic mucosa in the body (21.15%). On the negative group the normal appearance of the mucosa was 66.94%; erythema in streaks or bands in 9.32%; flat erosions 11.86%; and fundic gland polyps 11.86%. Conclusion: Endoscopic findings are useful in the predictability of the result and in directing biopsies. The most representative form of HP related gastritis was the nodularity of the antral mucosa

  5. BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced gastritis and is localized to the mitochondria of inflammatory cells in the gastric mucosa.

    PubMed

    Akazawa, Yuko; Matsuda, Katsuya; Isomoto, Hajime; Matsushima, Kayoko; Kido, Yoko; Urabe, Shigetoshi; Yamaghchi, Naoyuki; Ohnita, Ken; Takeshima, Fuminao; Kondo, Hisayoshi; Tsugawa, Hitoshi; Suzuki, Hidekazu; Moss, Joel; Nakao, Kazuhiko; Nakashima, Masahiro

    2015-09-01

    BH3-only protein, Bim, is a pro-apoptotic protein that mediates mitochondria-dependent cell death. However, the role of Bim in Helicobacter pylori-associated gastritis remains unclear. This study aimed to assess the cellular localization of Bim and its possible role in H. pylori-induced gastritis. The study was conducted on biopsy specimens obtained from 80 patients who underwent upper gastrointestinal endoscopy (H. pylori-negative: n=30, positive: n=50). Association between Bim mRNA expression and severity of gastritis was evaluated and the localization of Bim was examined by immunofluorescence. Bim mRNA expression was positively correlated with the degree of gastritis, as defined by the Sydney system. Immunohistochemical analysis confirmed increased Bim expression in H. pylori-infected gastric mucosa compared with uninfected mucosa in both humans and mice. Bim localized in myeloperoxidase- and CD138-positive cells of H. pylori-infected lamina propria and submucosa of the gastric tract, indicating that this protein is predominantly expressed in neutrophils and plasma cells. In contrast, Bim did not localize in CD20-, CD3-, or CD68-positive cells. Bim was expressed in the mitochondria, where it was partially co-localized with activated Bax and cleaved-PARP. In conclusion, Bim is expressed in neutrophils and plasma cells in H. pylori-associated gastritis, where it may participate in the termination of inflammatory response by causing mitochondria-mediated apoptosis in specific leucocytes.

  6. 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

  7. Integrin engagement by the helical RGD motif of the Helicobacter pylori CagL protein is regulated by pH-induced displacement of a neighboring helix.

    PubMed

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

    2015-05-15

    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.

  8. Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

    PubMed

    Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

    2011-07-01

    The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P < .05). Medians of pH 3 holding time and mean 24-hour pH values with the lansoprazole regimen were significantly higher than those with famotidine (P < .05). No significant differences in MLS were observed among the different CYP2C19 genotype groups in any of the treatment regimens. In this 7-day study, lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

  9. 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.

  10. 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

  11. Role of dupA in virulence of Helicobacter pylori.

    PubMed

    Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo

    2016-12-14

    Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.

  12. Role of dupA in virulence of Helicobacter pylori

    PubMed Central

    Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo

    2016-01-01

    Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery. PMID:28028359

  13. Genotyping of Peroxisome Proliferator-Activated Receptor gamma in Iranian Patients with Helicobacter pylori Infection.

    PubMed

    Goudarzi, Hossein; Seyedjavadi, Sima Sadat; Fazeli, Maryam; Azad, Mehdi; Goudarzi, Mehdi

    2015-01-01

    Helicobacter pylori (H. pylori) infection as a serious problem in both adults and children can induce chronic gastritis, peptic ulcer disease (PUD), and possibly gastric cancer. The aim of the current study was to survey antibiotic resistance and also to determine influence of PPARγ polymorphism in patients with H. pylori infection. During an 11-month-period, 98 H. pylori isolates were collected from 104 biopsy specimens. In vitro susceptibility of H. pylori isolates to 4 antimicrobial agents metronidazole, clarithromycin, amoxicillin and tetracycline were assessed by quantitative method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PPARγ polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of H. pylori infection in our study was 94.2%. In vitro susceptibility data showed that highest level of resistance was related to metronidazole (66.3%), and the majority of H. pylori isolates were highly susceptible to amoxicillin and tetracycline (94.9% and 96.9%, respectively). Genotypic frequencies were 25.5% for CC (Pro12Pro), 40.8% for GC (Pro12Ala) and 33.7% for GG (Ala12Ala). In our study, CG genotype had highest distributions among infected patients with H. pylori. The study suggests that the PPAR-γ Pro12Ala polymorphism could be evaluated as a potential genetic marker for susceptibility to gastric cancer in the presence of H. pylori infection.

  14. Helicobacter pylori's cholesterol uptake impacts resistance to docosahexaenoic acid.

    PubMed

    Correia, Marta; Casal, Susana; Vinagre, João; Seruca, Raquel; Figueiredo, Ceu; Touati, Eliette; Machado, José C

    2014-05-01

    Helicobacter pylori colonizes half of the world population and is associated with gastric cancer. We have previously demonstrated that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid known for its anti-inflammatory and antitumor effects, directly inhibits H. pylori growth in vitro and in mice. Nevertheless, the concentration of DHA shown to reduce H. pylori mice gastric colonization was ineffective in vitro. Related to the auxotrophy of H. pylori for cholesterol, we hypothesize that other mechanisms, in addition to DHA direct antibacterial effect, must be responsible for the reduction of the infection burden. In the present study we investigated if DHA affects also H. pylori growth, by reducing the availability of membrane cholesterol in the epithelial cell for H. pylori uptake. Levels of cholesterol in gastric epithelial cells and of cholesteryl glucosides in H. pylori were determined by thin layer chromatography and gas chromatography. The consequences of epithelial cells' cholesterol depletion on H. pylori growth were assessed in liquid cultures. We show that H. pylori uptakes cholesterol from epithelial cells. In addition, DHA lowers cholesterol levels in epithelial cells, decreases its de novo synthesis, leading to a lower synthesis of cholesteryl glucosides by H. pylori. A previous exposition of H. pylori to cholesterol influences the bacterium response to the direct inhibitory effect of DHA. Overall, our results suggest that a direct effect of DHA on H. pylori survival is modulated by its access to epithelial cell cholesterol, supporting the notion that cholesterol enhances the resistance of H. pylori. The cholesterol-dependent resistance of H. pylori to antimicrobial compounds raises new important aspects for the development of new anti-bacterial strategies.

  15. "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"…

  16. Helicobacter pylori-associated idiopathic thrombocytopenic purpura: a narrative review.

    PubMed

    Franchini, Massimo; Vescovi, Pier Paolo; Garofano, Massimo; Veneri, Dino

    2012-07-01

    The Gram-negative bacterium Helicobacter pylori has a well-demonstrated role in several gastroduodenal diseases, including peptic ulcer disease, chronic active gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In addition, more recently, several studies have focused on the possible causal role of H. pylori in various extragastric disorders, such as cardiovascular, respiratory, neurological, skin, and autoimmune conditions. The current status of the research on the pathogenesis, clinical and therapeutic aspects of H. pylori-associated idiopathic thrombocytopenic purpura in adults and children will be addressed in this narrative review.

  17. Acid-Induced Activation of the Urease Promoters Is Mediated Directly by the ArsRS Two-Component System of Helicobacter pylori

    PubMed Central

    Pflock, Michael; Kennard, Simone; Delany, Isabel; Scarlato, Vincenzo; Beier, Dagmar

    2005-01-01

    The nickel-containing enzyme urease is an essential colonization factor of the human gastric pathogen Helicobacter pylori which enables the bacteria to survive the low-pH conditions of the stomach. Transcription of the urease genes is positively controlled in response to increasing concentrations of nickel ions and acidic pH. Here we demonstrate that acid-induced transcription of the urease genes is mediated directly by the ArsRS two-component system. Footprint analyses identify binding sites of the phosphorylated ArsR response regulator within the ureA and ureI promoters. Furthermore, deletion of a distal upstream ArsR binding site of the ureA promoter demonstrates its role in acid-dependent activation of the promoter. In addition, acid-induced transcription of the ureA gene is unaltered in a nikR mutant, providing evidence that pH-responsive regulation and nickel-responsive regulation of the ureA promoter are mediated by independent mechanisms involving the ArsR response regulator and the NikR protein. PMID:16177315

  18. Identification of Helicobacter pylori in skin biopsy of prurigo pigmentosa.

    PubMed

    Missall, Tricia A; Pruden, Samuel; Nelson, Christine; Fohn, Laurel; Vidal, Claudia I; Hurley, M Yadira

    2012-06-01

    A 23-year-old Chinese man presented with a 3-year history of a pruritic eruption. On examination, pink urticarial papules associated with hyperpigmented reticulated patches were noted on his neck, back, and upper chest. Histopathology revealed vacuolar interface dermatitis and numerous gram-negative rods within a dilated hair follicle. The organisms were reactive with anti-Helicobacter pylori immunohistochemisty. The histologic findings and clinical presentation support the diagnosis of prurigo pigmentosa. Additional testing demonstrated a positive urease breath test and serum H. pylori IgG antibodies. The patient was referred to gastroenterology and treated with appropriate antibiotics. After treatment, esophagogastroduodenoscopy revealed chronic gastritis without evidence of H. pylori infection and his skin showed reticulated hyperpigmented patches without evidence of active inflammatory papules. Although previous reports have associated prurigo pigmentosa to H. Pylori gastritis, this is the first report of H. pylori organisms identified in a skin biopsy of prurigo pigmentosa.

  19. [Helicobacter pylori eradication therapy with omeprazole and amoxicillin: current status].

    PubMed

    Bayerdörffer, E; Miehlke, S; Mannes, G A

    1994-11-01

    Combined therapy with the proton pump inhibitor omeprazole and amoxicillin has become an important alternative in the treatment of ulcer disease associated with Helicobacter pylori infection. Due to the high efficacy in eradicating H.pylori, missing resistance of H.pylori against amoxicillin and high tolerability and digestibility this regimen may be recommended for widespread routine use. In a randomized, double-blind multicenter trial an H.pylori eradication rate of over 90% has been achieved for the first time by dual therapy using a daily omeprazole dose of 120 mg (3x40 mg) in combination with 3 x 750 mg amoxicillin for 14 days, which is comparable with classical triple therapy containing bismuth and two antibiotics. On the basis of an "intention-to-treat-analysis" dual therapy of omeprazole 3x40 mg + 3x750 mg amoxicillin is considered at present to be the most effective regimen for the treatment of H.pylori-associated diseases.

  20. Immunology and vaccines and nanovaccines for Helicobacter pylori infection.

    PubMed

    Milani, Morteza; Sharifi, Yaeghob; Rahmati-Yamchi, Mohammad; Somi, Mohammad H; Akbarzadeh, Abolfazl

    2015-06-01

    Helicobacter pylori infection is very common worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. Since the eradication requires treatment with multidrug regimens, prevention of primary infection by a suitable vaccine is attractive. Developing vaccines on the spot when and where an infection is breaking out might be possible, thanks to engineered nanoparticles. In this review, the nature of the host immune response to H. pylori infection is considered. We explain recent candidate vaccines and prophylactic or therapeutic immunization strategies for use against H. pylori. We also describe identification of different types of immune responses that may be related to protection against H. pylori infection. Thus, it seems that there is still a strong need to clarify the main protective immune response against H. pylori.

  1. Helicobacter pylori does not release cysteamine into gastric juice.

    PubMed Central

    Leonard, M B; Neithercut, W D; Gillen, D; McColl, K E

    1997-01-01

    AIM: To determine whether Helicobacter pylori releases cysteamine into gastric juice as cysteamine is known to be ulcerogenic. METHODS: Samples of fasting gastric juice were collected from 22 individuals (four women); 10 subjects were H pylori negative. The presence of infection was confirmed by examination and culture of gastric biopsies. Cysteamine in gastric juice was measured by reversed phase gradient high performance liquid chromatography with a detection limit of 10 mumol/l. RESULTS: Cysteamine was not detected in any of the gastric juice samples or in extracts of cultured H pylori. CONCLUSIONS: If H pylori produces cysteamine then the amounts produced are insignificant and are unlikely to explain the association between H pylori infection and the development of duodenal ulcer disease. PMID:9389979

  2. Regulation of Helicobacter pylori Virulence Within the Context of Iron Deficiency.

    PubMed

    Noto, Jennifer M; Lee, Josephine Y; Gaddy, Jennifer A; Cover, Timothy L; Amieva, Manuel R; Peek, Richard M

    2015-06-01

    Helicobacter pylori strains that harbor the oncoprotein CagA increase gastric cancer risk, and this risk is augmented under iron-deficient conditions. We demonstrate here that iron depletion induces coccoid morphology in strains lacking cagA. To evaluate the stability of augmented H. pylori virulence phenotypes stimulated by low-iron conditions, H. pylori isolated from iron-depleted conditions in vivo were serially passaged in vitro. Long-term passage decreased the ability of hypervirulent strains to translocate CagA or induce interleukin 8, indicating that hypervirulent phenotypes stimulated by low-level iron conditions are reversible. Therefore, rectifying iron deficiency may attenuate disease among H. pylori-infected persons with no response to antibiotics.

  3. Role of Toll-like receptors in Helicobacter pylori infection and immunity

    PubMed Central

    Smith, Sinéad M

    2014-01-01

    The gram-negative bacterium Helicobacter pylori (H. pylori) infects the stomachs of approximately half of the world’s population. Although infection induces an immune response that contributes to chronic gastric inflammation, the response is not sufficient to eliminate the bacterium. H. pylori infection causes peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease outcome is linked to the severity of the host inflammatory response. Gastric epithelial cells represent the first line of innate immune defence against H. pylori, and respond to infection by initiating numerous cell signalling cascades, resulting in cytokine induction and the subsequent recruitment of inflammatory cells to the gastric mucosa. Pathogen recognition receptors of the Toll-like receptor (TLR) family mediate many of these cell signalling events. This review discusses recent findings on the role of various TLRs in the recognition of H. pylori in distinct cell types, describes the TLRs responsible for the recognition of individual H. pylori components and outlines the influence of innate immune activation on the subsequent development of the adaptive immune response. The mechanistic identification of host mediators of H. pylori-induced pathogenesis has the potential to reveal drug targets and opportunities for therapeutic intervention or prevention of H. pylori-associated disease by means of vaccines or immunomodulatory therapy. PMID:25133016

  4. Influence of efflux pump inhibitors on the multidrug resistance of Helicobacter pylori

    PubMed Central

    Zhang, Zhan; Liu, Zhi-Qiang; Zheng, Peng-Yuan; Tang, Fu-Ai; Yang, Ping-Chang

    2010-01-01

    AIM: To evaluate the effect of efflux pump inhibitors (EPIs) on multidrug resistance of Helicobacter pylori (H. pylori). METHODS: H. pylori strains were isolated and cultured on Brucella agar plates with 10% sheep’s blood. The multidrug resistant (MDR) H. pylori were obtained with the inducer chloramphenicol by repeated doubling of the concentration until no colony was seen, then the susceptibilities of the MDR strains and their parents to 9 antibiotics were assessed with agar dilution tests. The present study included periods before and after the advent of the EPIs, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), reserpine and pantoprazole), and the minimum inhibitory concentrations (MICs) were determined accordingly. In the same way, the effects of 5 proton pump inhibitors (PPIs), used in treatment of H. pylori infection, on MICs of antibiotics were evaluated. RESULTS: Four strains of MDR H. pylori were induced successfully, and the antibiotic susceptibilities of MDR strains were partly restored by CCCP and pantoprazole, but there was little effect of reserpine. Rabeprazole was the most effective of the 5 PPIs which could decrease the MICs of antibiotics for MDR H. pylori significantly. CONCLUSION: In vitro, some EPIs can strengthen the activities of different antibiotics which are the putative substrates of the efflux pump system in H. pylori. PMID:20222174

  5. NikR mediates nickel-responsive transcriptional induction of urease expression in Helicobacter pylori.

    PubMed

    van Vliet, Arnoud H M; Poppelaars, Sophie W; Davies, Beverly J; Stoof, Jeroen; Bereswill, Stefan; Kist, Manfred; Penn, Charles W; Kuipers, Ernst J; Kusters, Johannes G

    2002-06-01

    The important human pathogen Helicobacter pylori requires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity of H. pylori urease were previously demonstrated to be induced by nickel supplementation of growth media. Here it is demonstrated that the HP1338 protein, an ortholog of the Escherichia coli nickel regulatory protein NikR, mediates nickel-responsive induction of urease expression in H. pylori. Mutation of the HP1338 gene (nikR) of H. pylori strain 26695 resulted in significant growth inhibition of the nikR mutant in the presence of supplementation with NiCl(2) at > or =100 microM, whereas the wild-type strain tolerated more than 10-fold-higher levels of NiCl(2). Mutation of nikR did not affect urease subunit expression or urease enzyme activity in unsupplemented growth media. However, the nickel-induced increase in urease subunit expression and urease enzyme activity observed in wild-type H. pylori was absent in the H. pylori nikR mutant. A similar lack of nickel responsiveness was observed upon removal of a 19-bp palindromic sequence in the ureA promoter, as demonstrated by using a genomic ureA::lacZ reporter gene fusion. In conclusion, the H. pylori NikR protein and a 19-bp operator sequence in the ureA promoter are both essential for nickel-responsive induction of urease expression in H. pylori.

  6. [Helicobacter pylori, nonsteroidal anti-inflammatory agents and gastroduodenal changes].

    PubMed

    Teixeira, A V

    1995-09-01

    The author discusses the possible interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (Hp) which may play an important role in the unleashing of gastroduodenal lesions. To our knowledge, AINEs have no influence on the prevalence of infection by Hp and the latter does not seem to influence the development and intensity of the lesions caused by NSAIDs.

  7. A METHOD TO DETECT VIABLE HELICOBACTER PYLORI BACTERIA IN GROUNDWATER

    EPA Science Inventory

    The inability to detect the presence of viable Helicobacter pylori bacteria in environmental waters has hindered the public health community in assessing the role water may playin the transmission of this pathogen. This work describes a cultural enrichment method coupled with an...

  8. Helicobacter pylori protein oxidation influences the colonization process.

    PubMed

    Godlewska, Renata; Dzwonek, Artur; Mikuła, Michał; Ostrowski, Jerzy; Pawłowski, Marcin; Bujnicki, Janusz M; Jagusztyn-Krynicka, Elzbieta K

    2006-08-01

    Dsb proteins control the formation and rearrangement of disulfide bonds during the folding of membrane and exported proteins. Here we examined the role of DsbI protein in Helicobacter pylori pathogenesis and demonstrated that a dsbI mutant impaired in disulfide bond formation revealed a greatly reduced ability to colonize mice gastric mucosa.

  9. [Therapeutics of infection by Helicobacter pylori in 2008].

    PubMed

    Corti, Rodolfo; Doweck, Judith; Schenone, Liliana; Améndola, Rafael; Giordano Romano, Adriana

    2008-01-01

    Eradication therapy for Helicobacter pylori is recommended in a number of clinical conditions as developed in Maastricht Consensus (I, II, III). In this state of art we discuss the results of current eradication therapies, the new approaches to the management of infection (new antibiotics and eradication schemes) and antimicrobial resistance.

  10. Effects of Helicobacter Pylori Eradication Among Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Wallace, R. A.; Schluter, P. J.; Webb, P. M.

    2004-01-01

    Compared to the general population, Helicobacter pylori infection is more common among adults with intellectual disability (ID) and is associated with greater levels of disability, maladaptive behaviour, and institutionalization. Little information exists about the effects of eradication therapy in this group, so we aimed to evaluate: (1) success…

  11. The Effect of Helicobacter Pylori on Gastroesophageal Reflux Disease

    PubMed Central

    Polat, Sabriye

    2012-01-01

    Background and Objectives: Helicobacter pylori infection represents one of the most common and medically prominent infections worldwide. Gastroesophageal reflux disease (GERD) has a multifactorial etiology. The nature of the relationship between Helicobacter pylori infection (HP) and reflux esophagitis is still not clear. This study is designed to find the influence of HP on GERD. Patients and Methods: The study was conducted retrospectively at Sakarya Newcity Hospital between January 2006 and January 2009. Data were collected on patient's age, sex, weight, the grade of GERD and the severity of HP. Results: There were 1,307 women and 1,135 men in this review with a mean age of 39,54 (range, 17 to 70) years. Helicobacter pylori positive (1 to 3 severity) was frequently seen in patients with GERD. A statistically significant relationship was found between HP positivity and the grade of GERD. The Helicobacter pylori infection (1 to 3 severity) was found in 1,437 (82.5%) of patients with GERD in our series. Conclusions: Controversy still exists about the association between GERD and HP infection. Based on our findings, significant evidence suggests the potential role of HP infection in the development of GERD. Also, the current data provide sufficient evidence to define the relationship between GERD and HP infection. PMID:23477175

  12. Helicobacter pylori infection following partial gastrectomy for gastric cancer

    PubMed Central

    Park, Sanghoon; Chun, Hoon Jai

    2014-01-01

    Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer. The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer. Helicobacter pylori (H. pylori) infection is also a well-known characteristic of gastric carcinogenesis. H. pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis; however, the H. pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis. For instance, H. pylori infection of the gastric stump produced controversial results in several recent studies. The prevalence of H. pylori infection in the gastric stump has varied among recent reports. Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ. Bile refluxate also has a significant influence on the colonization of the stomach stump, with several studies reporting mixed results as well. In contrast, the elimination of H. pylori from the gastric stump has shown a dramatic impact on eradication rate. H. pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers. To overcome the current discrepancies in the literature regarding the role of H. pylori in the gastric stump, further research is required. PMID:24659869

  13. Growth in children with Helicobacter pylori infection and dyspepsia

    PubMed Central

    Sood, M; Joshi, S; Akobeng, A; Mitchell, J; Thomas, A

    2005-01-01

    Aims: To compare the height, weight, and body mass index (BMI) of children presenting with dyspeptic symptoms and Helicobacter pylori infection, to those with dyspepsia but without the infection. Methods: A retrospective chart review of 257 children was performed. 13C urea breath test was performed to detect H pylori infection; weight and height were recorded and BMI was calculated. Weight, height, and BMI SD scores were determined using the 1990 UK normative data. The Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation at small area level, were calculated from the patients' postcodes. Results: Ninety seven of the 257 children were H pylori positive. The mean age at diagnosis and presenting symptoms of H pylori positive and negative patients were similar. The mean IMD 2004 scores for children with H pylori infection were significantly higher compared to H pylori negative patients, suggesting that children with the infection came from relatively more deprived areas. The mean weight and height SD score were significantly lower for children with H pylori infection compared to those without. However, this difference was no longer significant after adjusting for socioeconomic deprivation and ethnic differences between the groups. Conclusion: Children with dyspepsia and H pylori infection were shorter and lighter than patients with similar symptoms but no infection. The differences in anthropometry may be due to socioeconomic and ethnic factors rather than H pylori infection. PMID:15956048

  14. Management of Helicobacter pylori infection after gastric surgery.

    PubMed

    Lin, Yang-Sheng; Chen, Ming-Jen; Shih, Shou-Chuan; Bair, Ming-Joug; Fang, Ching-Ju; Wang, Horng-Yuan

    2014-05-14

    The Maastricht IV/Florence Consensus Report and the Second Asia-Pacific Consensus Guidelines strongly recommend eradication of Helicobacter pylori (H. pylori) in patients with previous gastric neoplasia who have undergone gastric surgery. However, the guidelines do not mention optimal timing, eradication regimens, diagnostic tools, and follow-up strategies for patients undergoing gastrectomy and do not indicate if eradication of H. pylori reduces the risk of marginal ulcer or stump cancer in the residual stomach after gastrectomy. The purpose of this review is to provide an update which may help physicians to properly manage H. pylori infection in patients who have undergone gastric surgery. This review focuses on (1) the microenvironment change in the stomach after gastrectomy; (2) the phenomenon of spontaneous clearance of H. pylori after gastrectomy; (3) the effects of H. pylori on gastric atrophy and intestinal metaplasia after gastrectomy; (4) incidence and clinical features of ulcers developing after gastrectomy; (5) does eradication of H. pylori reduce the risk of gastric stump cancer in the residual stomach? (6) does eradication of H. pylori reduce the risk of secondary metachronous gastric cancer in the residual stomach? and (7) optimal timing and regimens for H. pylori eradication, diagnostic tools and follow-up strategies for patients undergoing gastrectomy.

  15. Helicobacter pylori infection and expression of DNA mismatch repair proteins

    PubMed Central

    Mirzaee, Vahid; Molaei, Mahsa; Shalmani, Hamid Mohaghegh; Zali, Mohammad Reza

    2008-01-01

    AIM: To determine the expression of DNA (MMR) proteins, including hMLH1 and hMSH2, in gastric epithelial cells in the patients with or without Helicobacter pylori (H pylori)-infected gastritis. METHODS: Fifty H pylori-positive patients and 50 H pylori-negative patients were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, two antral and two corpus biopsies were taken for histological examination (Giemsa stain) and for immunohistochemical staining of hMLH1 and hMSH2. RESULTS: The percentage of epithelial cell nuclei that demonstrated positivity for hMLH1 staining was 84.14 ± 7.32% in H pylori-negative patients, while it was 73.34 ± 10.10% in H pylori-positive patients (P < 0.0001). No significant difference was seen between the two groups regarding the percentage of epithelial cell nuclei that demonstrated positivity for hMSH2 staining (81.16 ± 8.32% in H pylori-negative versus 78.24 ± 8.71% in H pylori-positive patients; P = 0.09). CONCLUSION: This study indicates that H pylori might promote development of gastric carcinoma at least in part through its ability to affect the DNA MMR system. PMID:19034977

  16. Prevalence of Helicobacter pylori in Gastric Hyperplastic Polyps.

    PubMed

    Horvath, Bela; Pai, Rish K

    2016-12-01

    Hyperplastic polyps of the stomach are routinely encountered during upper endoscopy and often arise in the setting of abnormal surrounding mucosa, particularly Helicobacter pylori, autoimmune gastritis, and reactive gastropathy. Not infrequently gastroenterologists fail to biopsy the surrounding mucosa, thus determining the underlying etiology of the gastric hyperplastic polyp can be difficult. Recently, the Rodger C. Haggitt Gastrointestinal Pathology Society published guidelines on the use of special stains. The society guidelines indicate that H pylori are not usually present in hyperplastic polyps and special stains in this setting may have limited utility. We analyzed the histologic features of 32 gastric hyperplastic polyps in which the nonpolypoid mucosa demonstrated H pylori gastritis. A consecutive series of 50 hyperplastic polyps in which no surrounding mucosa was sampled was also analyzed. When H pylori are identified in biopsies of the nonpolypoid mucosa, it is also commonly present within the polyp tissue (22/32, 69%). The majority of H pylori organisms were identified on routine hematoxylin and eosin stain (16/22, 72%). In contrast, H pylori were only seen in 2/50 consecutive hyperplastic polyps in which the surrounding mucosa was not sampled. Compared with the hyperplastic polyps that lack the organisms, H pylori associated hyperplastic polyps more commonly had dense lymphoplasmacytic inflammation (P = .0001) and neutrophils within gastric epithelium (P = .036). Polyp location, number, size, and presence of intestinal metaplasia was not associated with H pylori These results provide empirical data to guide evaluation of hyperplastic polyps for H pylori.

  17. Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

    NASA Astrophysics Data System (ADS)

    Odenbreit, Stefan; Püls, Jürgen; Sedlmaier, Bettina; Gerland, Elke; Fischer, Wolfgang; Haas, Rainer

    2000-02-01

    The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA+) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

  18. Effect of Helicobacter pylori infection on chronic periodontitis by the change of microecology and inflammation

    PubMed Central

    Hu, Zhekai; Zhang, Yu; Li, Zhiyu; Yu, Yuedi; Kang, Wenyan; Han, Yingnan; Geng, Xiwen; Ge, Shaohua; Sun, Yundong

    2016-01-01

    Helicobacter pylori (H. pylori), a pathogen inducing peptic disease, is recently found to be binding to the progress of periodontitis. Most previous studies are case-controlled, and they investigate the risk of H. pylori infection in disease the development of while few studies evaluate the correlation between H. pylori and periodontal pathogens. Therefore, we investigated the correlation between H. pylori infection with periodontal parameters, periodontal pathogens and inflammation. The results indicated that patients with H. pylori showed significantly higher probing depth and attachment loss than those without (p < 0.05). Among 28 subgingival plaque samples from 14 patients, the frequencies of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Treponema denticola were significantly higher with H. pylori infection than those without H. pylori infection (p < 0.05). However, the frequency of Aggregatibacter actinomycetemcomitans was lower (p < 0.05). Furthermore, after human acute monocytic leukemia cell line (THP-1) was stimulated with cagA-positive standard strains (cagA+ H. pylori 26695), the expression of periodontitis-related molecules Wnt5a, interleukin 8 (IL-8), interleukin 6 (IL-6) and interferon gamma (IFN-γ) significantly increased (p < 0.05). Conversely, the expression of tumor necrosis factor alpha (TNF-α) was almost stable. Meanwhile, cagA+ H. pylori promoted significantly higher expression of IL-8 and Wnt5a than isogenic cagA mutants strains (cagA− H. pylori 26695) did. Taken together, our data suggested that H. pylori might promote the growth of some periodontal pathogens and aggravate the progress of chronic periodontitis. PMID:27602578

  19. Heme Oxygenase-1 Dysregulates Macrophage Polarization and the Immune Response to Helicobacter pylori

    PubMed Central

    Gobert, Alain P.; Verriere, Thomas; Asim, Mohammad; Barry, Daniel P.; Piazuelo, M. Blanca; de Sablet, Thibaut; Delgado, Alberto G.; Bravo, Luis E.; Correa, Pelayo; Peek, Richard M.; Chaturvedi, Rupesh; Wilson, Keith T.

    2014-01-01

    Helicobacter pylori incites a futile inflammatory response, which is the key feature of its immunopathogenesis. This leads to the ability of this bacterial pathogen to survive in the stomach and cause peptic ulcers and gastric cancer. Myeloid cells recruited to the gastric mucosa during Helicobacter pylori infection have been directly implicated in the modulation of host defense against the bacterium and gastric inflammation. Heme oxygenase-1 (HO-1) is an inducible enzyme that exhibits anti-inflammatory functions. Our aim was to analyze the induction and role of HO-1 in macrophages during H. pylori infection. We now show that phosphorylation of the H. pylori virulence factor cytotoxin associated gene A (CagA) in macrophages results in expression of hmox-1, the gene encoding HO-1, through p38/nuclear factor (erythroid-derived 2)-like 2 signaling. Blocking phagocytosis prevented CagA phosphorylation and HO-1 induction. The expression of HO-1 was also increased in gastric mononuclear cells of human patients and macrophages of mice infected with cagA+ H. pylori strains. Genetic ablation of hmox-1 in H. pylori-infected mice increased histologic gastritis, which was associated with enhanced M1/Th1/Th17 responses, decreased Mreg response, and reduced H. pylori colonization. Gastric macrophages of H. pylori-infected mice and macrophages infected in vitro with this bacterium showed an M1/Mreg mixed polarization type; deletion of hmox-1 or inhibition of HO-1 in macrophages caused an increased M1 and a decreased of Mreg phenotype. These data highlight a mechanism by which H. pylori impairs the immune response and favors its own survival via activation of macrophage HO-1. PMID:25108023

  20. Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion

    PubMed Central

    Koike, T; Ohara, S; Sekine, H; Iijima, K; Abe, Y; Kato, K; Toyota, T; Shimosegawa, T

    2001-01-01

    BACKGROUND—Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly.
AIMS—We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects.
SUBJECTS—A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis.
METHODS—The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test.
RESULTS—H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis.
CONCLUSION—In Japan, erosive reflux oesophagitis occurs most often in the absence of H pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.


Keywords: Helicobacter pylori; gastro-oesophageal reflux disease; reflux oesophagitis; acid secretion PMID:11511552

  1. Association between thyroid autoimmunity and Helicobacter pylori infection

    PubMed Central

    Choi, Yun Mi; Kim, Tae Yong; Kim, Eui Young; Jang, Eun Kyung; Jeon, Min Ji; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2017-01-01

    Background/Aims There have been controversial reports linking Helicobacter pylori infection to autoimmune thyroid disease (AITD). However, data regarding the relationship are limited for Asian populations, which have an extremely high prevalence of H. pylori infection. We performed this study to investigate the association between H. pylori infection and AITD in Koreans. Methods This study involved adults aged 30 to 70 years who had visited a health promotion center. A total of 5,502 subjects were analysed. Thyroid status was assessed by free thyroxine, thyroid stimulating hormone, and anti-thyroid peroxidase antibody (TPO-Ab). Immunoglobulin G (IgG) antibodies to H. pylori were measured as an indication of H. pylori infection. We compared the prevalence of TPO-Ab in subjects with and without H. pylori infection. Results H. pylori IgG antibodies were found in 2,875 subjects (52.3%), and TPO-Ab were found in 430 (7.8%). Individuals positive for H. pylori Ab were older than those negative for H. pylori Ab (p < 0.01). The proportion of females was significantly higher in the TPO-Ab positive group (41.0% vs. 64.2%, p < 0.01). Prevalence of TPO-Ab positivity was higher in subjects with H. pylori infection (8.6% vs. 7.00%, p = 0.03), and this association was significant after adjusting for age, sex, and body mass index (odds ratio, 1.02; 95% confidence interval, 1.00 to 1.03; p = 0.04). Conclusions In our study, prevalence of TPO-Ab positivity is more frequent in subjects with H. pylori infection. Our findings suggest H. pylori infection may play a role in the development of autoimmune thyroiditis. PMID:28092700

  2. [On the rating of Helicobacter pylori in drinking water].

    PubMed

    Fedichkina, T P; Solenova, L G; Zykova, I E

    2014-01-01

    There are considered the issues related to the possibility to rate of Helicobacter pylori (H. pylori) content in drinking water. There is described the mechanism of of biofilm formation. The description refers to the biofilm formation mechanism in water supply systems and the existence of H. pylori in those systems. The objective premises of the definition of H. pylori as a potential limiting factor for assessing the quality of drinking water have been validated as follows: H. pylori is an etiologic factor associated to the development of chronic antral gastritis, gastric ulcer and duodenal ulcer, and gastric cancer either, in the Russian population the rate of infection with H. pylori falls within range of 56 - 90%, water supply pathway now can be considered as a source of infection of the population with H. pylori, the existence of WHO regulatory documents considering H. pylori as a candidate for standardization of the quality of the drinking water quite common occurrence of biocorrosion, the reduction of sanitary water network reliability, that creates the possibility of concentrating H. pylori in some areas of the water system and its delivery to the consumer of drinking water, and causes the necessity of the prevention of H. pylori-associated gastric pathology of the population. A comprehensive and harmonized approach to H. pylori is required to consider it as a candidate to its rating in drinking water. Bearing in mind the large economic losses due to, on the one hand, the prevalence of disease caused by H. pylori, and, on the other hand, the biocorrosion of water supply system, the problem is both relevant in terms of communal hygiene and economy.

  3. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    PubMed

    Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran

    2009-06-08

    Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.

  4. Geranylgeranylacetone selectively binds to the HSP70 of Helicobacter pylori and alters its coccoid morphology

    PubMed Central

    Grave, Ewa; Yokota, Shin-ichi; Yamamoto, Soh; Tamura, Arisa; Ohtaki-Mizoguchi, Takako; Yokota, Kenji; Oguma, Keiji; Fujiwara, Kazuhiko; Ogawa, Nobuaki; Okamoto, Tomoya; Otaka, Michiro; Itoh, Hideaki

    2015-01-01

    Geranylgeranylacetone (GGA) is used to treat patients suffering from peptic ulcers and gastritis. We examined the effect of GGA on Helicobacter pylori, which is a causative factor of gastrointestinal diseases. Previously, we have reported that GGA binds specifically to the molecular chaperone HSP70. In this paper, we report that GGA bounds to H. pylori HSP70 (product of the DnaK gene) with 26-times higher affinity than to human HSP70, and induced large conformational changes as observed from surface plasmon resonance and circular dichroism. Binding of GGA suppressed the activity of the H. pylori chaperone. GGA also altered several characteristics of H. pylori cells. GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells. GGA also caused morphological alterations in H. pylori as reflected in fewer coccoid-like cells, suggesting that GGA converts H. pylori to an actively dividing, spiral state (vegetative form) from a non-growing, coccoid state. This morphological conversion by GGA resulted in accelerated growth of H. pylori. These results suggest a model in which GGA sensitizes H. pylori to antibiotic treatment by converting the cells to an actively growing state. PMID:26345206

  5. Urease-positive bacteria in the stomach induce a false-positive reaction in a urea breath test for diagnosis of Helicobacter pylori infection.

    PubMed

    Osaki, Takako; Mabe, Katsuhiro; Hanawa, Tomoko; Kamiya, Shigeru

    2008-07-01

    This study investigated the influence of urease-positive non-Helicobacter pylori bacteria on the results of a urea breath test (UBT) to evaluate the diagnostic utility of a UBT using film-coated [(13)C]urea tablets. The UBT was performed in 102 patients treated with a proton pump inhibitor and antibiotics for the eradication of H. pylori. Urease-producing bacteria other than H. pylori were isolated and identified from the oral cavity and stomach. In 4/102 patients, the UBT gave false-positive results. These false-positive results were found to be caused by the presence of urease-positive bacteria in the oral cavity and stomach. Five bacterial species with urease activity (Proteus mirabilis, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae and Staphylococcus aureus) were subsequently isolated from the oral cavity and/or stomach. As there was no correlation between the in vitro urease activity of urease-positive non-H. pylori bacteria and the UBT value, and all of the patients with a false-positive UBT result were suffering from atrophic gastritis, it is possible that the false-positive results in the UBT were a result of colonization of urease-positive bacteria and gastric hypochlorhydric conditions. Thus, for the diagnosis of H. pylori infection using a UBT, the influence of stomach bacteria must be considered when interpreting the results.

  6. Helicobacter pylori activates the TLR2/NLRP3/caspase-1/IL-18 axis to induce regulatory T-cells, establish persistent infection and promote tolerance to allergens.

    PubMed

    Koch, Katrin N; Müller, Anne

    2015-01-01

    The Gram-negative bacterium Helicobacter pylori is both a normal constituent of the human gastric microbiota as well as a pathogen tightly associated with severe gastric disorders. The ability of H. pylori to activate the inflammasome and caspase-1 in antigen-presenting and other cells, and the resulting processing and release of caspase-1-dependent cytokines, impacts both the immunomodulatory and pathogenic activities of H. pylori. This article summarizes recent insights by us and others on the bacterial and host prerequisites of inflammasome activation. H. pylori predominantly activates the NLRP3 inflammasome through a process that requires TLR2-dependent licensing. We identified the urease enzyme, a colonization determinant known to be required for acid adaptation, as critically required for activation of the TLR2/NLRP3/caspase-1 axis. The phenotypes of urease mutants, as well as mouse strains defective for TLR2 or NLRP3, are discussed with respect to their ability to support persistent colonization, immune tolerance and immunity to H. pylori.

  7. Helicobacter pylori activates the TLR2/NLRP3/caspase-1/IL-18 axis to induce regulatory T-cells, establish persistent infection and promote tolerance to allergens

    PubMed Central

    Koch, Katrin N; Müller, Anne

    2015-01-01

    The Gram-negative bacterium Helicobacter pylori is both a normal constituent of the human gastric microbiota as well as a pathogen tightly associated with severe gastric disorders. The ability of H. pylori to activate the inflammasome and caspase-1 in antigen-presenting and other cells, and the resulting processing and release of caspase-1-dependent cytokines, impacts both the immunomodulatory and pathogenic activities of H. pylori. This article summarizes recent insights by us and others on the bacterial and host prerequisites of inflammasome activation. H. pylori predominantly activates the NLRP3 inflammasome through a process that requires TLR2-dependent licensing. We identified the urease enzyme, a colonization determinant known to be required for acid adaptation, as critically required for activation of the TLR2/NLRP3/caspase-1 axis. The phenotypes of urease mutants, as well as mouse strains defective for TLR2 or NLRP3, are discussed with respect to their ability to support persistent colonization, immune tolerance and immunity to H. pylori. PMID:26727421

  8. Methods to evaluate alterations in polyamine metabolism caused by Helicobacter pylori infection

    PubMed Central

    Gobert, Alain P.; Chaturvedi, Rupesh; Wilson, Keith T.

    2011-01-01

    Helicobacter pylori is a Gram-negative bacteria that infects the human stomach of half of the world’s population. Colonization is followed by infiltration of the gastric mucosa by lymphocytes and myeloid cells. These cells are activated by various bacterial factors, causing them to release immune/inflammatory mediators, including reactive nitrogen species and polyamines that contribute to cellular damage and the pathogenesis of H. pylori-associated gastric cancer. In vitro experiments have revealed that H. pylori induces macrophage polyamine production by upregulation of the arginase 2/ornithine decarboxylase (ODC) metabolic pathway and enhances hydrogen peroxide synthesis through the activity of spermidine oxidase (SMO). In this chapter, we present a survey of the methods used to analyze the induction and the role of the enzymes related to polyamine metabolism, i.e. arginase, ODC, and SMO in H. pylori-infected macrophages. PMID:21318889

  9. Identification and characterization of a vitamin D₃ decomposition product bactericidal against Helicobacter pylori.

    PubMed

    Hosoda, Kouichi; Shimomura, Hirofumi; Wanibuchi, Kiyofumi; Masui, Hisashi; Amgalanbaatar, Avarzed; Hayashi, Shunji; Takahashi, Takashi; Hirai, Yoshikazu

    2015-03-09

    This study demonstrated that the vitamin D₃ decomposition product VDP1 exerts an antibacterial action against Helicobacter pylori but not against other bacteria. Treatment with VDP1 induced a collapse of cell membrane structures of H. pylori and ultimately lysed the bacterial cells. A unique dimyristoyl phosphatidylethanolamine in the membrane lipid compositions contributed to the interaction of VDP1 with H. pylori cells. In separate experiments, VDP1 had no influence on the viability of the human cancer cell lines MKN45 and T47D and lacked any vitamin D₃-like hormonal action against the latter. In both (1)H and (13)C NMR analyses, the spectra patterns of VDP1 corresponded with those of Grundmann's ketone. These results suggest that VDP1 (or Grundmann's ketone-type indene compound) may become a fundamental structure for the development of new antibacterial substances with selective bactericidal action against H. pylori.

  10. Oxidative DNA Damage Response in Helicobacter pylori-Infected Mongolian Gerbils.

    PubMed

    Bae, Minkyung; Lim, Joo Weon; Kim, Hyeyoung

    2013-09-01

    Helicobacter pylori (H. pylori) induced DNA damage which may be related to gastric cancer development. The DNA damage response coordinates DNA repair, cell-cycle transition, and apoptosis through activation of DNA damage response molecules. The damaged DNA is repaired through non-homologous end joining (NHEJ) or homologous recombination (HR). In the present study, we investigated the changes of HR DNA repair proteins (ataxia-telangiectasia-mutated; ATM, ATM and Rad3-related; ATR), NHEJ repair proteins (Ku70/80), cell cycle regulators (Chk1, Chk2), and apoptosis marker (p53/p-p53) were determined in H. pylori-infected Mongolian gerbils. In addition, the effect of an antioxidant N-acetylcysteine (NAC) on H. pylori-induced DNA damage response was determined to assess the involvement of oxidative stress on DNA damage of the animals infected with H. pylori. One week after intragastric inoculation with H. pylori, Mongolian gerbils were fed with basal diet with or without 3% NAC for 6 weeks. After 6 week, the expression levels of DNA repair proteins (Ku70/80, ATM, ATR), cell cycle regulators (Chk1, Chk2) and apoptosis marker (p-p53/p53) were increased in gastric mucosa of Mongolian gerbils, which was suppressed by NAC treatment. In conclusion, oxidative stress mediates H. pylori-induced DNA damage response including NHEJ and HR repairing processes, cell cycle arrest and apoptosis in gastric mucosa of Mongolian gerbils.

  11. Helicobacter pylori and oral pathology: relationship with the gastric infection.

    PubMed

    Adler, Isabel; Muiño, Andrea; Aguas, Silvia; Harada, Laura; Diaz, Mariana; Lence, Adriana; Labbrozzi, Mario; Muiño, Juan Manuel; Elsner, Boris; Avagnina, Alejandra; Denninghoff, Valeria

    2014-08-07

    Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.

  12. Biofilm formation enhances Helicobacter pylori survivability in vegetables.

    PubMed

    Ng, Chow Goon; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna; Ho, Bow

    2017-04-01

    To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment.

  13. Probiotics for the treatment of Helicobacter pylori infection in children

    PubMed Central

    Pacifico, Lucia; Osborn, John Frederick; Bonci, Enea; Romaggioli, Sara; Baldini, Rossella; Chiesa, Claudio

    2014-01-01

    The combination of a proton pump inhibitor and two antibiotics (clarithromycin plus amoxicillin or metronidazole) has been the recommended first-line therapy since the first guidelines for Helicobacter pylori (H. pylori) infection in children were published. In recent years, the success of eradication therapies has declined, in part due to the development of H. pylori resistant strains. Alternative anti-H. pylori treatments are currently becoming more popular than the traditional eradication methods. Components that may be used either as a monotherapy or, in combination with antimicrobials, resulting in a more effective anti-H. pylori therapy have been investigated in depth by several researchers. One of the potential therapies is probiotic cultures; promising results have been observed in initial studies with numerous probiotic strains. Nevertheless, many questions remain unanswered. In this article, we comprehensively review the possible mechanisms of action of probiotics on H. pylori infection, and present the results of published studies using probiotics as possible agents to control H. pylori infection in children. The effect of the addition of probiotics to the standard H. pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed. PMID:24574741

  14. [Second Brazilian Consensus Conference on Helicobacter pylori infection].

    PubMed

    Coelho, Luiz Gonzaga Vaz; Zaterka, Schlioma

    2005-01-01

    Significant progress has been obtained since the First Brazilian Consensus Conference on H. pylori Infection held in 1995, in Belo Horizonte, MG, and justify a second meeting to establish updated guidelines on the current management of H. pylori infection. The Second Brazilian Consensus Conference on H. pylori Infection was organized by the Brazilian Federation of Gastroenterology and Brazilian Nucleus for the Study of Helicobacter and took place on June, 19-20, 2004 in São Paulo, SP. Thirty six delegates coming from 15 different Brazilian states including gastroenterologists, pathologists, microbiologists and pediatricians undertook the meeting. The participants were allocated in one the five main topics of the meeting: H. pylori and dyspepsia, H. pylori and NSAIDs, H. pylori and gastroesophageal reflux disease, H. pylori treatment, and H. pylori retreatment. Seventy per cent and more votes were considered as acceptance for the final statement. The results were presented during a special session on the VI Brazilian Week of Digestive System, in Recife, PE (October 2004), and this publication represents the summary of the main recommendations and conclusions emerged from the meeting.

  15. Probiotics for the treatment of Helicobacter pylori infection in children.

    PubMed

    Pacifico, Lucia; Osborn, John Frederick; Bonci, Enea; Romaggioli, Sara; Baldini, Rossella; Chiesa, Claudio

    2014-01-21

    The combination of a proton pump inhibitor and two antibiotics (clarithromycin plus amoxicillin or metronidazole) has been the recommended first-line therapy since the first guidelines for Helicobacter pylori (H. pylori) infection in children were published. In recent years, the success of eradication therapies has declined, in part due to the development of H. pylori resistant strains. Alternative anti-H. pylori treatments are currently becoming more popular than the traditional eradication methods. Components that may be used either as a monotherapy or, in combination with antimicrobials, resulting in a more effective anti-H. pylori therapy have been investigated in depth by several researchers. One of the potential therapies is probiotic cultures; promising results have been observed in initial studies with numerous probiotic strains. Nevertheless, many questions remain unanswered. In this article, we comprehensively review the possible mechanisms of action of probiotics on H. pylori infection, and present the results of published studies using probiotics as possible agents to control H. pylori infection in children. The effect of the addition of probiotics to the standard H. pylori eradication therapy for the prevention of antibiotic associated side-effects is also discussed.

  16. Strategy for the treatment of Helicobacter pylori infection.

    PubMed

    Shiota, Seiji; Yamaoka, Yoshio

    2014-01-01

    The eradication of Helicobacter pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer and other H. pylori-associated disorders. H. pylori eradication heals gastritis and may prevent the spread of infection, reducing the future costs required for the treatment of subsequent H. pylori-associated diseases. There are various guidelines for the management of H. pylori infection worldwide, such as the guidelines of the American College of Gastroenterology, Maastricht IV, the Second Asia-Pacific Consensus Conference, and Japan. The Japanese health insurance system approved H. pylori eradication therapy for H. pylori-related chronic gastritis in 2013. Triple therapy regimens comprising 1 proton pump inhibitor and 2 antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, levofloxacin, or tetracycline have been widely used to eradicate this bacterium. The rate of successful eradication has declined owing to the increased rate of drug resistance stemming from the wide usage of antibiotics. This issue is of particular relevance with regard to clarithromycin. In worldwide, clarithromycin-based triple therapy should be abandoned, as it is no longer effective. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. First-line treatment should be recommended on the basis of an understanding of the local prevalence of H. pylori antimicrobial resistance.

  17. Helicobacter pylori infection and chronic gastritis in gastric cancer.

    PubMed Central

    Sipponen, P.; Kosunen, T. U.; Valle, J.; Riihelä, M.; Seppälä, K.

    1992-01-01

    AIMS: To investigate the prevalence of Helicobacter pylori associated chronic gastritis in patients with gastric cancer. METHODS: Serum IgG antibodies for H pylori were determined in 54 consecutive patients with gastric carcinoma. The prevalence of H pylori in gastric mucosa was also examined histologically (modified Giemsa) in 32 patients from whom adequate biopsy specimens of the antrum and corpus were available. Thirty five patients with gastrointestinal tumours outside the stomach and 48 with non-gastrointestinal malignancies served as controls. RESULTS: Of the 54 patients, 38 (70%) had H pylori antibodies (IgG) in their serum (three additional patients had H pylori antibodies IgA, class specific but not IgG specific). This prevalence was significantly higher (p less than 0.05) than that (49%) in the 35 controls. No differences in prevalence of H pylori antibodies were found between gastric cancer cases of intestinal (IGCA) or diffuse (DGCA) type, both these types showing H pylori antibodies (IgG) in 71% of the patients. In the subgroup of 32 subjects, five patients had normal gastric mucosa and four showed corpus limited atrophy ("pernicious anaemia type" atrophy of type A). All of these nine patients had no evidence of current or previous H pylori infection in serum (no IgG antibodies) or in tissue sections (negative Giemsa staining). The remaining 23 patients had antral or pangastritis, and all had evidence of current or previous H pylori infection. CONCLUSIONS: H pylori associated chronic gastritis was the associated disease in 75% of the patients with gastric cancer occurring equally often in both IGCA and DGCA groups. About 25% of cases seem to have a normal stomach or severe corpus limited atrophy, neither of which showed evidence of concomitant H pylori infection. PMID:1577969

  18. Helicobacter pylori-Negative Gastritis: Prevalence and Risk Factors

    PubMed Central

    Nordenstedt, Helena; Graham, David Y.; Kramer, Jennifer R.; Rugge, Massimo; Verstovsek, Gordana; Fitzgerald, Stephanie; Alsarraj, Abeer; Shaib, Yasser; Velez, Maria E.; Abraham, Neena; Anand, Bhupinderjit; Cole, Rhonda; El-Serag, Hashem B.

    2014-01-01

    OBJECTIVES Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis. METHODS Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire. RESULTS Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P = 0.06). CONCLUSIONS We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known. PMID:23147524

  19. Helicobacter pylori: A Possible Risk Factor for Bone Health

    PubMed Central

    Chung, Yun Hee; Gwak, Jong Seop; Hong, Sung Woo; Hyeon, Jung Hyeon; Lee, Cheol Min; Oh, Seung Won

    2015-01-01

    Background Helicobacter pylori (H. pylori) infection may cause systemic inflammation and increase the production of tumor necrosis factor-α, interleukin-1, and interleukin-6. Unfortunately, bone mineral density also may be affected by these cytokines. This study aimed to evaluate the association between bone mineral density and H. pylori infection. Methods A cross-sectional study evaluated 1,126 men undergoing a comprehensive health screening in a private Korean screening center. Subjects' sera were tested for H. pylori antibodies (immunoglobulin G) using an enzyme-linked immunosorbent assay, and bone mineral densities (g/cm2) of the lumbar spine, femoral neck, and total femur were obtained using dual-energy X-ray absorptiometry. To evaluate the difference in bone mineral density according to H. pylori infection status, the adjusted mean bone mineral densities at each site were compared after adjusting for potential confounders, including age, sex, body mass index, smoking, alcohol consumption, and exercise. Results H. pylori infection was associated with a significant decrease in mean lumbar bone mineral density (H. pylori-positive, 1.190 g/cm2; H. pylori-negative, 1.219 g/cm2; P=0.006), which was greatest among men who were ≥50 years old (H. pylori-positive, 1.193 g/cm2; H. pylori-negative, 1.233 g/cm2; P=0.006). However, no significant association was observed in the bone mineral densities of the total femur and femoral neck. Conclusion In men, H. pylori infection was negatively associated with lumbar bone mineral density. This association may be useful in the early detection, prevention, and management of male osteoporosis. PMID:26435815

  20. Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

    PubMed

    Aihara, Eitaro; Closson, Chet; Matthis, Andrea L; Schumacher, Michael A; Engevik, Amy C; Zavros, Yana; Ottemann, Karen M; Montrose, Marshall H

    2014-07-01

    Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (10(6)) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6)) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby

  1. Oral Helicobacter pylori, its relationship to successful eradication of gastric H. pylori and saliva culture confirmation.

    PubMed

    Wang, X M; Yee, K C; Hazeki-Taylor, N; Li, J; Fu, H Y; Huang, M L; Zhang, G Y

    2014-08-01

    The present study was designed to explore the existence of oral Helicobacter pylori (H. pylori), its relationship in the oral cavity to the success rate of eradication of the gastric H. pylori infection, and to determine if the mouthwash solution contained lysine (0.4%) and glycerol monolaurate (0.2%) (LGM) could eliminate oral H. pylori, as well as using the saliva H. pylori culture to confirm the existence of oral H. pylori. A total of 159 symptomatic individuals with stomach pain and 118 asymptomatic individuals with no stomach complaints, were recruited and tested using the saliva H. pylori antigen test (HPS), the H. pylori flagellin test (HPF), the urea breath test (UBT C(13)) and the polymerase chain reaction (PCR) test, which tests were also confirmed by saliva culture. The test subjects also received various treatments. It was found that the H. pylori antigen exists in the oral cavity in UBT C(13) negative individuals. Traditional treatment for gastric eradication had only a 10.67 percent (10.67%) effectiveness rate on the oral H. pylori infection. In groups of patients with the oral H. pylori infection, but with negative UBT C(13), a mouthwash solution provided a 72.58% effectiveness rate in the 95% of the confidence interval (CI) ranges on the oral H. pylori infection. Traditional drug gastric eradication and teeth cleaning (TC) had less than a 10% effectiveness rate. Treatment of the oral infection increased the success rate of eradication of the stomach infection from 61.33% to 82.26% in the 95% CI ranges. We concluded that the successful rate of eradication of gastric H. pylori bears a significant relationship to the oral infection from H. pylori.

  2. Diagnostic methods for Helicobacter pylori detection and eradication

    PubMed Central

    Goddard, A F; Logan, R P H

    2003-01-01

    Helicobacter pylori is the principal cause of peptic ulcer disease and an important risk factor for the development of gastric cancer. The efficacy of 1 week triple therapies, which often have eradication rates of > 90%, is undermined by poor patient compliance and bacterial antimicrobial resistance. The development of new anti-H. pylori therapies presents enormous challenges to clinical pharmacologists, not only in the identification of novel targets, but also in ensuring adequate drug delivery to the unique gastric mucus niche of H. pylori. Animal models of H. pylori infection have been developed but their clinical validity has yet to be established. Vaccination, to prevent or treat infection, has been demonstrated in animal models, but human studies have not been so encouraging. PMID:12919175

  3. The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

    PubMed Central

    Sheh, Alexander; Fox, James G

    2013-01-01

    The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values < 4 were capable of sterilizing the stomach. H. pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota. PMID:23962822

  4. Antibacterial activity of Chamomilla recutita oil extract against Helicobacter pylori.

    PubMed

    Shikov, Alexander N; Pozharitskaya, Olga N; Makarov, Valery G; Kvetnaya, Asya S

    2008-02-01

    The antibacterial activity of an oil extract of Chamomilla recutita flowers against Helicobacter pylori (H. pylori) was evaluated by the agar dilution method using Colombia agar with 10% sheep blood, an inoculum of McFarland 0.5 and incubation in an anaerobic atmosphere at 37 degrees C for 3 days. The oil extract was prepared by olive oil extraction of Chamomilla recutita flowers using rotary pulsation. The MIC(90) (minimal inhibitory concentration) and MIC(50) were 125 mg/mL and 62.5 mg/mL, respectively. It was shown that the Chamomilla recutita oil extract inhibited the production of urease by H. pylori. In addition, it was found that the morphological and fermentative properties of H. pylori were affected by application of the Chamomilla recutita oil extract.

  5. Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice.

    PubMed

    Burns, Monika; Amaya, Aldo; Bodi, Caroline; Ge, Zhongming; Bakthavatchalu, Vasudevan; Ennis, Kathleen; Wang, Timothy C; Georgieff, Michael; Fox, James G

    2017-01-01

    Helicobacter pylori (H.pylori), a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA), enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40) were used; half were placed on a moderately iron deficient (ID) diet immediately post-weaning, and the other half were maintained on an iron replete (IR) diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet) as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet). All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001). Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05), independent of infection status. At 12 months postinfection, hematocrit (Hct) and hemoglobin (Hgb) concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA.

  6. Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

    PubMed Central

    Burns, Monika; Amaya, Aldo; Bodi, Caroline; Ge, Zhongming; Bakthavatchalu, Vasudevan; Ennis, Kathleen; Wang, Timothy C.; Georgieff, Michael

    2017-01-01

    Helicobacter pylori (H.pylori), a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA), enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40) were used; half were placed on a moderately iron deficient (ID) diet immediately post-weaning, and the other half were maintained on an iron replete (IR) diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet) as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet). All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001). Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05), independent of infection status. At 12 months postinfection, hematocrit (Hct) and hemoglobin (Hgb) concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA. PMID:28355210

  7. HelicoVax: epitope-based therapeutic Helicobacter pylori vaccination in a mouse model.

    PubMed

    Moss, Steven F; Moise, Leonard; Lee, Dong Soo; Kim, Woojin; Zhang, Songhua; Lee, Jinhee; Rogers, Arlin B; Martin, William; De Groot, Anne S

    2011-03-03

    Helicobacter pylori is the leading cause of gastritis, peptic ulcer disease and gastric adenocarcinoma and lymphoma in humans. Due to the decreasing efficacy of anti-H. pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-H. pylori vaccines. In this study an in silico-based approach was utilized to develop a multi-epitope DNA-prime/peptide-boost immunization strategy using informatics tools. The efficacy of this construct was then assessed as a therapeutic vaccine in a mouse model of gastric cancer induced by chronic H. pylori infection. The multi-epitope vaccine administered intranasally induced a broad immune response as determined by interferon-gamma production in ELISpot assays. This was associated with a significant reduction in H. pylori colonization compared with mice immunized with the same vaccine intramuscularly, given an empty plasmid, or given a whole H. pylori lysate intranasally as the immunogen. Total scores of gastric histological changes were not significantly different among the 4 experimental groups. These results suggest that further development of an epitope-based mucosal vaccine may be beneficial in eradicating H. pylori and reducing the burden of the associated gastric diseases in humans.

  8. New transport medium for cultural recovery of Helicobacter pylori.

    PubMed

    Cellini, Luigina; Di Campli, Emanuela; Di Bartolomeo, Soraya; Bessa, Lucinda Janete; Baffoni, Marina; Di Giulio, Mara

    2014-12-01

    We developed a new transport medium (GESA--Helicobacter pylori transport medium [publication no. WO/2014/019696, patent pending no. PCT/EP2013/002292; Liofilchem s.r.l., Roseto degli Abruzzi, Teramo, Italy]) for recovery of Helicobacter pylori from gastric biopsy samples. GESA transport medium, in a semisolid state, provides the optimal conditions for maintaining the viability of the microorganism over time. The efficacy of the transport medium was assessed through in vitro and ex vivo experiments. We were able to recover different suspensions of H. pylori ATCC 43629 and H. pylori 13 A in GESA transport medium stored at 4 °C for up to 10 days. In particular, with a starting inoculum of ∼ 10(5) CFU, after 7 days of storage, 150 ± 25 CFU and 40 ± 7 CFU of the reference and clinical strains were detected, respectively. H. pylori colonies were isolated from gastric specimens taken from both the antrum and the fundus in 68 (90.66%) of 75 urea breath test (UBT)-positive patients. Moreover, GESA transport medium allowed the recovery and isolation of H. pylori colonies from additional biopsy samples from 13 of the 75 detected subjects at up to 10 days of biopsy sample storage at 4 °C. Finally, GESA transport medium preserved its characteristics when stored at 4°C for 1 year from its preparation, thus allowing good recovery of H. pylori. GESA transport medium can be considered a standardized transport medium with high performance that optimizes the recovery rate of H. pylori grown by culture.

  9. Myeloid HIF-1 is protective in Helicobacter pylori-mediated gastritis.

    PubMed

    Matak, Pavle; Heinis, Mylène; Mathieu, Jacques R R; Corriden, Ross; Cuvellier, Sylvain; Delga, Stéphanie; Mounier, Rémi; Rouquette, Alexandre; Raymond, Josette; Lamarque, Dominique; Emile, Jean-François; Nizet, Victor; Touati, Eliette; Peyssonnaux, Carole

    2015-04-01

    Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer. The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but, surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H. pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes in driving this pathology.

  10. Complete Genome Sequence of Helicobacter pylori Strain 7C Isolated from a Mexican Patient with Chronic Gastritis

    PubMed Central

    Mucito-Varela, Eduardo; Castillo-Rojas, Gonzalo; Cevallos, Miguel A.; Lozano, Luis; Merino, Enrique; López-Leal, Gamaliel

    2016-01-01

    Helicobacter pylori-induced gastritis is a risk factor for developing gastric pathologies. Here, we report the complete genome sequence of a multidrug-resistant H. pylori strain isolated from a chronic gastritis patient in Mexico City, Mexico. Nonvirulent VacA and cag-pathogenicity island (PAI) genotypes were found, but the presence of a potential mobilizable plasmid carrying an IS605 element is of outstanding interest. PMID:26744372

  11. Advances in diagnosis and treatment of Helicobacter pylori infection.

    PubMed

    Ranjbar, Reza; Behzadi, Payam; Farshad, Shohreh

    2017-03-06

    Helicobacter pylori is a Gram-negative motile bacterium causative agent of acute and chronic digestive and extra-digestive human infections. According to different reports worldwide, H. pylori symptomatic and asymptomatic infections are a global problem. The statistical investigations show a percentage of 50 for people who are involved in H. pylori acute/chronic digestive and/or extra-digestive infections around the world. This review focuses on digestive and extra-digestive diseases caused by H. pylori, the related virulence factors, diagnostic techniques including non-invasive and invasive diagnostics and treatment. There is an abundance of diagnostics for detection and identification of H. pylori. The availability, cost, and the condition of test performance may differ from place to place. To increase the level of reliability in association with diagnostic tools for detecting H. pylori, several techniques must be applied at once as multi-diagnostic technique. Furthermore, there are several pharmacotherapies which can be used for complete eradication of H. pylori infection.

  12. Treatment of Helicobacter pylori infection: Current and future insights

    PubMed Central

    Safavi, Maliheh; Sabourian, Reyhaneh; Foroumadi, Alireza

    2016-01-01

    Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects. PMID:26798626

  13. Lipid Profile in Cardiac Syndrome X: Association with Helicobacter pylori

    PubMed Central

    Zeynalzadeh, Javad; Shirpoor, Alireza; Seyedmohammadzad, Mirhossein; Hajhosseini, Reza

    2016-01-01

    Introduction Chronic inflammation caused by Helicobacter pylori (H.pylori) infection has a pathogenic role in Cardiac Syndrome X (CSX). In addition, it has shown that bacterial infection may affect blood lipids. Aim To assess if H.pylori affects the level of lipid profile in CSX. Materials and Methods Eighty-eight CSX patients and 97 healthy controls were enrolled. The Total Cholesterol (TC), Triglyceride (TG), Lipoprotein A (LP{A}), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Apoprotein A1 (APOA1), and Apoprotein B (APOB) was estimated colorimetrically. In addition, the presence of IgG antibody to H.pylori was tested in plasma samples by using enzyme linked immunosorbent assay method. Results TC, LP{A}, LDL, APOA1 and APOB levels in CSX group were significantly higher than those of the control group (p<0.05). But, these parameters in H.pylori positive and H.pylori negative, among CSX and control groups were not significant. Conclusion Increased plasma level of lipid profile and H.pylori infection were associated with CSX; it seems that plasma lipid disorders have a significant role in the development of CSX. PMID:27630835

  14. Serologic Evidence for Fecal–Oral Transmission of Helicobacter pylori

    PubMed Central

    Bui, David; Brown, Heidi E.; Harris, Robin B.; Oren, Eyal

    2016-01-01

    Helicobacter pylori infection is among the most prevalent infections in the world and a key cause of gastric diseases; however, its route of transmission remains unclear. This study aimed to assess the potential for fecal–oral transmission of H. pylori by leveraging its association with a disease with known etiology. Utilizing serology data from the National Health and Nutrition Examination Survey (NHANES 1999; N = 6,347), the association between H. pylori and hepatitis A virus (HAV), a sensitive indicator for fecal–oral exposure, was assessed. Survey-weighted kappa and multiple logistic regression were used to quantify the association between H. pylori and HAV after controlling for age, sex, race, poverty, birthplace, crowding, smoking, and alcohol use. Concordant serological results were found among 69.8% of participants (survey-weighted κ = 0.30, 95% confidence interval [CI] = 0.26, 0.35). The adjusted odds of H. pylori seropositivity were over two times higher after adjusting for confounders (odds ratio = 2.27, 95% CI = 1.79, 2.87). Results from this study suggest H. pylori and HAV infections are strongly associated. Since HAV is primarily transmitted through the fecal–oral route, fecal–oral transmission may be an important pathway for H. pylori spread. PMID:26598563

  15. Helicobacter pylori seropositivity in subjects with acute myocardial infarction.

    PubMed Central

    Rathbone, B.; Martin, D.; Stephens, J.; Thompson, J. R.; Samani, N. J.

    1996-01-01

    OBJECTIVE: To determine whether Helicobacter pylori infection increases the risk of myocardial infarction. DESIGN: Case-control study. SETTING: University teaching hospital. METHODS: Serological evidence of H pylori infection was determined in 342 consecutive patients with acute myocardial infarction admitted into the coronary care unit and in 236 population-based controls recruited from visitors to patients on medical and surgical wards. RESULTS: 206/342 (60.2%) of cases were H pylori positive compared with 132/236 (55.9%) of controls (P = 0.30). Age and sex stratified odds ratio for myocardial infarction associated with H pylori seropositivity was 1.05 (95% CI 0.7 to 1.53, P = 0.87) and this remained non-significant (P = 0.46) when other risk factors for ischaemic heart disease were taken into account using logistic regression analysis. H pylori seropositivity was not associated with several coronary risk factors in either cases or controls. CONCLUSION: No increase was found in H pylori seropositivity in subjects with acute myocardial infarction. This suggests that previous H pylori infection is not a major risk factor for acute myocardial infarction. Images PMID:8983674

  16. Helicobacter pylori and Antibiotic Resistance, A Continuing and Intractable Problem.

    PubMed

    Hu, Yue; Zhang, Meng; Lu, Bin; Dai, Jinfeng

    2016-10-01

    Helicobacter pylori, a human pathogen with a high global prevalence, is the causative pathogen for multiple gastrointestinal diseases, especially chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric malignancies. Antibiotic therapies remain the mainstay for H. pylori eradication; however, this strategy is hampered by the emergence and spread of H. pylori antibiotic resistance. Exploring the mechanistic basis of this resistance is becoming one of the major research questions in contemporary biomedical research, as such knowledge could be exploited to devise novel rational avenues for counteracting the existing resistance and devising strategies to avoid the development of a novel anti-H. pylori medication. Encouragingly, important progress in this field has been made recently. Here, we attempt to review the current state and progress with respect to the molecular mechanism of antibiotic resistance for H. pylori. A picture is emerging in which mutations of various genes in H. pylori, resulting in decreased membrane permeability, altered oxidation-reduction potential, and a more efficient efflux pump system. The increased knowledge on these mechanisms produces hope that antibiotic resistance in H. pylori can ultimately be countered.

  17. Anti-Helicobacter pylori Potential of Artemisinin and Its Derivatives

    PubMed Central

    Goswami, Suchandra; Chinniah, Annalakshmi; Pal, Anirban; Kar, Sudip K.

    2012-01-01

    The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative β-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC90, and minimum bactericidal concentration range values of 0.25 to 1.0 μg/ml, 1.0 μg/ml, and 1 to 16 μg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, β-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted. PMID:22687518

  18. Structure, function and localization of Helicobacter pylori urease.

    PubMed Central

    Dunn, B. E.; Phadnis, S. H.

    1998-01-01

    Helicobacter pylori is the causative agent of most cases of gastritis. Once acquired, H. pylori establishes chronic persistent infection; it is this long-term infection that, is a subset of patients, leads to gastric or duodenal ulcer, gastric cancer or gastric MALT lymphoma. All fresh isolates of H. pylori express significant urease activity, which is essential to survival and pathogenesis of the bacterium. A significant fraction of urease is associated with the surface of H. pylori both in vivo and in vitro. Surface-associated urease is essential for H. pylori to resist exposure to acid in the presence of urea. The mechanism whereby urease becomes associated with the surface of H. pylori is unique. This process, which we term "altruistic autolysis," involves release of urease (and other cytoplasmic proteins) by genetically programmed autolysis with subsequent adsorption of the released urease onto the surface of neighboring intact bacteria. To our knowledge, this is the first evidence of essential communal behavior in pathogenic bacteria; such behavior is crucial to understanding the pathogenesis of H. pylori. PMID:10378351

  19. In vitro antagonistic activity of Lactobacillus casei against Helicobacter pylori

    PubMed Central

    Enany, Shymaa; Abdalla, Salah

    2015-01-01

    Helicobacter pylori is one of the most common causes of chronic infections in humans. Curing H. pylori infection is difficult because of the habitat of the organism below the mucus adherent layer of gastric mucosa. Lactobacilli are known as acid-resistant bacteria and can remain in stomach for a long time than any other organism, we aimed in this study to examine the efficacy of Lactobacillus casei as a probiotic against H. pylori in humans. Particularly, L. casei was opted as it is considered to be one of the widely used probiotics in dairy products. One hundred and seven strains of H. pylori were isolated from dyspeptic patients and were tested for their antibiotic susceptibility to metronidazole (MTZ), clarithromycin (CLR), tetracycline (TET), and amoxicillin (AMX) by the disc diffusion method. The strains were examined for their susceptibility toward L. casei - present in fermented milk products - by well diffusion method. It was found that 74.7% strains were resistant to MTZ; 1.8% to MTZ, TET, and CLR; 3.7% to MTZ and CLR; 4.6% to MTZ and TET; and 0.9% were resistant to MTZ, TET, and AMX. The antibacterial activity of L. casei against H. pylori was determined on all the tested H. pylori isolates including antibiotic resistant strains with different patterns. Our study proposed the use of probiotics for the treatment of H. pylori infection as an effective approach. PMID:26691482

  20. Does Helicobacter pylori eradication play a role in immune thrombocytopenia?

    PubMed

    Llovet, Valentina; Rada, Gabriel

    2016-09-05

    Helicobacter pylori infection has been implicated as trigger or disease modifier in immune thrombocytopenia (ITP). So, eradication treatment for this agent could have clinical benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews comprising 40 studies addressing the question of this article overall, including one randomized controlled trial. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded Helicobacter eradication might decrease risk of bleeding in patients with immune thrombocytopenia but the certainty of the evidence is low.

  1. Helicobacter pylori HP(2-20) induces eosinophil activation and accumulation in superficial gastric mucosa and stimulates VEGF-alpha and TGF-beta release by interacting with formyl-peptide receptors.

    PubMed

    Prevete, N; Rossi, F W; Rivellese, F; Lamacchia, D; Pelosi, C; Lobasso, A; Necchi, V; Solcia, E; Fiocca, R; Ceppa, P; Staibano, S; Mascolo, M; D'Argenio, G; Romano, M; Ricci, V; Marone, G; De Paulis, A

    2013-01-01

    Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2-20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells. The aim of the present study was to investigate whether eosinophils play a role in the repair of gastric mucosa tissue during H. pylori infection. Immuno-histochemistry and transmission electron microscopy were used to detect eosinophils in gastric mucosal biopsies. Eosinophil re-distribution occurred in the gastric mucosa of H. pylori-infected patients: their density did not change in the deep mucosal layer, whereas it increased in the superficial lamina propria just below the foveolar epithelium; eosinophils entered the epithelium itself as well as the lumen of foveolae located close to the area harboring bacteria, which in turn were also engulfed by eosinophils. The H. pylori-derived peptide Hp(2-20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-beta, two key mediators of tissue remodelling. We also demonstrate that Hp(2-20) in vivo induced eosinophil infiltration in rat gastric mucosa after injury brought about by indomethacin. This study suggests that eosinophil infiltrate could modulate the capacity of gastric mucosa to maintain or recover its integrity thereby shedding light on the role of eosinophils in H. pylori infection.

  2. Epidemiological study on food intake and Helicobacter pylori infection.

    PubMed

    Toyonaga, A; Okamatsu, H; Sasaki, K; Kimura, H; Saito, T; Shimizu, S; Fukuizumi, K; Tsuruta, O; Tanikawa, K; Sata, M

    2000-01-01

    We conducted an epidemiological study to investigate the relation of food intake to Helicobacter pylori (H. pylori) infection in an area endemic for H. pylori. In this study, 365 subjects, 104 men and 261 women, were randomly selected from 7,389 adult (over age 20) inhabitants of town A, Japan. The prevalence of immunoglobulin G (IgG) class antibody to H. pylori (anti-H. pylori) was 83.7% and the prevalence of anti-H. pylori increased with age significantly (P < 0.05). Subjects with anamnesis of gastritis, gastroduodenal ulcer and gastric cancer tended to have a higher anti-H. pylori positive ratio (93.5%) than those without (81.0%). But there was no relationship between anti-H. pylori prevalence and sex, blood type, smoking or drinking habits. Daily intake of foods by food groups, nutrients and the concentrations of serum ingredients were compared between 37 anti-H. pylori-positive and 40 negative subjects selected from 365 inhabitants by matching up according to sex and age. The daily intake of cereals, potatoes and starches, and milks tended to be higher in positive than negative subjects, while the daily intake of algae and tea appeared to be a little higher in negative than in positive subjects. The daily zinc intake of antibody-positive subjects was significantly higher (P < 0.05) than in antibody negative subjects. On the other hand, the daily iron intake in negative subjects was significantly higher (P < 0.05) than in positive subjects. The serum concentrations of copper, zinc, and vitamin E tended to be higher in positive than negative subjects. But there were no significant differences in serum ingredients concentrations between antibody negative and positive subjects. Our findings suggest that iron and zinc intakes may effect on H. pylori infection.

  3. Persistence of Helicobacter pylori in heterotrophic drinking-water biofilms.

    PubMed

    Gião, M S; Azevedo, N F; Wilks, S A; Vieira, M J; Keevil, C W

    2008-10-01

    Although the route of transmission of Helicobacter pylori remains unknown, drinking water has been considered a possible transmission vector. It has been shown previously that, in water, biofilms are a protective niche for several pathogens, protecting them from stressful conditions, such as low carbon concentration, shear stress, and less-than-optimal temperatures. In this work, the influence of these three parameters on the persistence and cultivability of H. pylori in drinking-water biofilms was studied. Autochthonous biofilm consortia were formed in a two-stage chemostat system and then inoculated with the pathogen. Total numbers of H. pylori cells were determined by microscopy using a specific H. pylori 16S rRNA peptide nucleic acid probe, whereas cultivable cells were assessed by standard plating onto selective H. pylori medium. Cultivable H. pylori could not be detected at any time point, but the ability of H. pylori cells to incorporate, undergo morphological transformations, persist, and even agglomerate in biofilms for at least 31 days without a noticeable decrease in the total cell number (on average, the concentration was between 1.54 x 10(6) and 2.25 x 10(6) cells cm(-2)) or in the intracellular rRNA content may indicate that the loss of cultivability was due to entry into a viable but noncultivable state. Unlike previous results obtained for pure-culture H. pylori biofilms, shear stress did not negatively influence the numbers of H. pylori cells attached, suggesting that the autochthonous aquatic bacteria have an important role in retaining this pathogen in the sessile state, possibly by providing suitable microaerophilic environments or linking biomolecules to which the pathogen adheres. Therefore, biofilms appear to provide not only a safe haven for H. pylori but also a concentration mechanism so that subsequent sloughing releases a concentrated bolus of cells that might be infectious and that could escape routine grab sample microbiological

  4. Helicobacter pylori and Helicobacter heilmannii in untreated Bulgarian children over a period of 10 years.

    PubMed

    Boyanova, Lyudmila; Lazarova, Elena; Jelev, Christo; Gergova, Galina; Mitov, Ivan

    2007-08-01

    The aims of the study were to evaluate the incidence of Helicobacter pylori and Helicobacter heilmannii in untreated Bulgarian children from 1996 to 2006, to analyse the performance of diagnostic tests, and to look at H. pylori density in specimens by culture. Antral specimens from children with chronic gastritis (n=513), peptic ulcers (n=54) and other diseases (n=91) were evaluated by direct Gram staining (DGS), in-house rapid urease test (RUT) and culture. The living environment and semi-quantitative H. pylori density were assessed in 188 and 328 children, respectively. H. pylori infection was found in children with ulcers (77.8 %), chronic gastritis (64.5 %) and other diseases (36.3 %). Half (51.4 %) of patients aged 1-5 years and 77.4 % of those aged 16-17 years were H. pylori-positive. Of all children, 328 (49.8 %) showed positive DGS, 184 (28 %) had a positive RUT, and 386 (58.7 %) were culture-positive. Unlike gastric mucus specimens, frozen biopsy specimens provided reliable diagnosis. H. heilmannii was observed in two (0.3 %) children. High H. pylori density (growth into all quadrants of plates) was found in 18 % of 328 children evaluated, involving 31 % of ulcer and 16.7 % of non-ulcer patients. H. pylori infection was more common in rural children with chronic gastritis (91.3 %) than in the remainder (66.7 %). In conclusion, H. pylori infection was common in symptomatic Bulgarian children. The infection prevalence was >77 % in patients aged 16-17 years, in children with a duodenal ulcer, and in rural patients. H. heilmannii infection was uncommon. The performance of the bacterial culture was good. The impact of H. pylori density on the clinical expression and eradication of the infection requires further evaluation. The results highlight the need for routine H. pylori diagnosis in rural children with chronic gastritis.

  5. [Eradication therapy of antibiotic-resistant strains of Helicobacter pylori].

    PubMed

    Shcherbakov, P L; Belousova, N L; Shcherbakova, M Iu; Kashnikov, V S

    2010-01-01

    Treatment of inflammatory diseases of the upper digestive tract, associated with Helicobacter pylori has recently greatly complicated by the presence of significant number of resistant strains of this microorganism to traditionally used drugs for eradication therapy. Average resistance to metronidazole and clarithromycin in Russia is about 30 and 25% respectively. The article presents the experience of treating patients with metronidazole resistant strains of H. pylori with using triple therapy, which included a drug used nitrofurans--nifuroxazide in suspension, proton pump inhibitors and clarithromycin.

  6. Biomarkers of Helicobacter pylori-associated gastric cancer

    PubMed Central

    Cooke, Cara L; Torres, Javier; Solnick, Jay V

    2013-01-01

    Helicobacter pylori-associated gastric cancer is a major cause of morbidity and mortality worldwide, and is predicted to become even more common in developing countries as the population ages. Since gastric cancer develops slowly over years to decades, and typically progresses though a series of well-defined histologic stages, cancer biomarkers have potential to identify asymptomatic individuals in whom surgery might be curative, or even those for whom antibiotics to eradicate H. pylori could prevent neoplastic transformation. Here we describe some of the challenges of biomarker discovery, summarize current approaches to biomarkers of gastric cancer, and explore some recent novel strategies. PMID:23851317

  7. The Multiple Carbohydrate Binding Specificities of Helicobacter pylori

    NASA Astrophysics Data System (ADS)

    Teneberg, Susann

    Persistent colonization of the human stomach by Helicobacter pylori is a risk factor for the development of peptic ulcer disease and gastric cancer. Adhesion of microbes to the target tissue is an important determinant for successful initiation, establishment and maintenance of infection, and a variety of different candidate carbohydrate receptors for H. pylori have been identified. Here the different the binding specifities, and their potential role in adhesion to human gastric epithelium are described. Finally, recent findings on the roles of sialic acid binding SabA adhesin in interactions with human neutrophils and erythrocytes are discussed.

  8. Is There a Role for Probiotics in Helicobacter pylori Therapy?

    PubMed

    Dore, Maria P; Goni, Elisabetta; Di Mario, Francesco

    2015-09-01

    The role of probiotics in Helicobacter pylori therapy remains unclear. Lactobacilli can be shown to inhibit H pylori in vitro. Some strains of Lactobacilli may exert specific antimicrobial effects. There is no strong evidence of a benefit on eradication rate when probiotics are added to a regimen. Despite promising results obtained using compounds of L reuteri and S boulardii, high-quality trials are needed to define the role of probiotics as adjuvant therapy. Variables that remain to be studied with L reuteri, currently the most promising strain, include dosage, frequency of administration, administration in relation to meals, and duration of therapy.

  9. Helicobacter pylori infection does not promote hepatocellular cancer in a transgenic mouse model of hepatitis C virus pathogenesis

    PubMed Central

    García, Alexis; Feng, Yan; Parry, Nicola MA; McCabe, Amanda; Mobley, Melissa W; Lertpiriyapong, Kvin; Whary, Mark T; Fox, James G

    2013-01-01

    Helicobacter pylori (H. pylori) and hepatitis C virus (HCV) infect millions of people and can induce cancer. We investigated if H. pylori infection promoted HCV-associated liver cancer. Helicobacter-free C3B6F1 wild-type (WT) and C3B6F1-Tg(Alb1-HCVN)35Sml (HT) male and female mice were orally inoculated with H. pylori SS1 or sterile media. Mice were euthanized at ~12 mo postinoculation and samples were collected for analyses. There were no significant differences in hepatocellular tumor promotion between WT and HT mice; however, HT female mice developed significantly larger livers with more hepatic steatosis than WT female mice. H. pylori did not colonize the liver nor promote hepatocellular tumors in WT or HT mice. In the stomach, H. pylori induced more corpus lesions in WT and HT female mice than in WT and HT male mice, respectively. The increased corpus pathology in WT and HT female mice was associated with decreased gastric H. pylori colonization, increased gastric and hepatic interferon gamma expression, and increased serum Th1 immune responses against H. pylori. HT male mice appeared to be protected from H. pylori-induced corpus lesions. Furthermore, during gastric H. pylori infection, HT male mice were protected from gastric antral lesions and hepatic steatosis relative to WT male mice and these effects were associated with increased serum TNF-α. Our findings indicate that H. pylori is a gastric pathogen that does not promote hepatocellular cancer and suggest that the HCV transgene is associated with amelioration of specific liver and gastric lesions observed during concurrent H. pylori infection in mice. PMID:23929035

  10. Natural products and food components with anti-Helicobacter pylori activities

    PubMed Central

    Takeuchi, Hiroaki; Trang, Vu Thu; Morimoto, Norihito; Nishida, Yoshie; Matsumura, Yoshihisa; Sugiura, Tetsuro

    2014-01-01

    The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world’s population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-duodenal diseases and a wide variety of non-gastrointestinal tract conditions such as immune thrombocytopenia. Triple therapy which consists of a proton pump inhibitor and combinations of two antibiotics (amoxicillin, clarithromycin or amoxicillin, metronidazol) is commonly used for H. pylori eradication. Recently, the occurrence of drug-resistant H. pylori and the adverse effect of antibiotics have severely weakened eradication therapy. Generally antibiotics induce the disturbance of human gastrointestinal microflora. Furthermore, there are inappropriate cases of triple therapy such as allergy to antibiotics, severe complications (liver and/or kidney dysfunction), the aged and people who reject the triple therapy. These prompt us to seek alterative agents instead of antibiotics and to develop more effective and safe therapy with these agents. The combination of these agents actually may result in lower a dose of antibiotics. There are many reports world-wide that non-antibiotic substances from natural products potentially have an anti-H. pylori agent. We briefly review the constituents derived from nature that fight against H. pylori in the literature with our studies. PMID:25083070

  11. Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori

    PubMed Central

    2014-01-01

    Background Epidemiological investigations have indicated that Helicobacter pylori induces inflammation in the gastric mucosa regulated by several interleukins. The genes IL1B and IL8 are suggested as key factors in determining the risk of gastritis. The aim of this paper was to evaluate the association of gene polymorphism of interleukin-1 and interleukin-8 with chronic gastrits in H. pylori infected patients. A total of 60 patients underwent endoscopic procedure. Biopsy samples were collected for urease test, histopathological and molecular exams. The DNA of theses samples was extracted for detection of H. pylori and analysis of the genes mentioned above. Patients with gastritis had a higher frequency of H. pylori-positive samples. Results H. pylori was detected in 30/60 patients (50%) by PCR. As for polymorphism of interleukin 8 (-251) gene we observed a statistical difference when analyzed TA (p = 0.039) and TT (p = 0.047) genotypes. In the IL1B31 there was a statistical difference in TT (p = 0.01) genotype and in the IL1B-511 there wasn’t any statistical difference. Conclusion Our results suggest a strong correlation between the presence of chronic gastritis and infection by H. pylori and that IL1B-31TT and IL8-251TT genotypes appear to act as protective factors against H. pylori infection while IL8-251TA genotype may comprise a risk factor for infection with this bacterium. PMID:24803922

  12. Genipin-cross-linked fucose-chitosan/heparin nanoparticles for the eradication of Helicobacter pylori.

    PubMed

    Lin, Yu-Hsin; Tsai, Shih-Chang; Lai, Chih-Ho; Lee, Che-Hsin; He, Zih Sian; Tseng, Guan-Chin

    2013-06-01

    Helicobacter pylori is a significant human pathogen that recognizes specific carbohydrate receptors, such as the fucose receptor, and produces the vacuolating cytotoxin, which induces inflammatory responses and modulates the cell-cell junction integrity of the gastric epithelium. The clinical applicability of topical antimicrobial agents was needed to complete the eradication of H. pylori in the infected fundal area. In the present study, we combined fucose-conjugated chitosan and genipin-cross-linking technologies in preparing multifunctional genipin-cross-linked fucose-chitosan/heparin nanoparticles to encapsulate amoxicillin of targeting and directly make contact with the region of microorganism on the gastric epithelium. The results show that the nanoparticles effectively reduced drug release at gastric acids and then released amoxicillin in an H. pylori survival situation to inhibit H. pylori growth and reduce disruption of the cell-cell junction protein in areas of H. pylori infection. Furthermore, with amoxicillin-loaded nanoparticles, a more complete H. pylori clearance effect was observed, and H. pylori-associated gastric inflammation in an infected animal model was effectively reduced.

  13. Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group.

    PubMed Central

    1997-01-01

    There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine. The European Helicobacter Pylori Study Group therefore organised a meeting in Maastricht of H pylori experts, primary care physicians and representatives of National Societies of Gastroenterology from Europe to establish consensus guidelines on the management of H pylori at the primary care and specialist levels, and to consider general health care issues associated with the infection. As in previous guidelines, eradication therapy was recommended in all H pylori positive patients with peptic ulcer disease. Additionally, at the primary care level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis is recommended by non-invasive means (13C urea breath test, serology) and if H pylori positive the patient should be treated. Moreover, at the specialist level the indications for eradication of H pylori were also broadened to include H pylori positive patients with functional dyspepsia in whom no other possible causes of symptoms are identified by the specialist (after a full investigation including endoscopy, ultrasound and other necessary investigations), patients with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed in specialised centres) and those with gastritis with severe macro- or microscopic abnormalities. There was consensus that treatment regimens should be simple, well tolerated and achieve an eradication rate of over 80% on an intention to treat basis. It was strongly recommended, therefore, that eradication treatment should be with proton pump inhibitor based triple therapy for seven days, using a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin. PMID:9274464

  14. Brain-gut axis in the pathogenesis of Helicobacter pylori infection

    PubMed Central

    Budzyński, Jacek; Kłopocka, Maria

    2014-01-01

    Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis, similar to other microorganisms present in the alimentary tract. The brain-gut axis integrates the central, peripheral, enteric and autonomic nervous systems, as well as the endocrine and immunological systems, with gastrointestinal functions and environmental stimuli, including gastric and intestinal microbiota. The bidirectional relationship between H. pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it, resulting in alterations in cognitive functions, food intake and appetite, immunological response, and modification of symptom sensitivity thresholds. Furthermore, disturbances in the upper and lower digestive tract permeability, motility and secretion can occur, mainly as a form of irritable bowel syndrome. Many of these abnormalities disappear following H. pylori eradication. H. pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes, or by microelement deficiency secondary to functional and morphological changes in the digestive tract. In digestive tissue, H. pylori can alter signaling in the brain-gut axis by mast cells, the main brain-gut axis effector, as H. pylori infection is associated with decreased mast cell infiltration in the digestive tract. Nevertheless, unequivocal data concerning the direct and immediate effect of H. pylori infection on the brain-gut axis are still lacking. Therefore, further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H. pylori infection pathophysiology and suggest new therapeutic approaches. PMID:24833851

  15. The Anti-inflammatory Effects of Acidic Polysaccharide from Artemisia capillaris on Helicobacter pylori Infection

    PubMed Central

    Park, Jong-Min; Hahm, Ki-Baik; Kwon, Sang-Oh; Kim, Eun-Hee

    2013-01-01

    Background: Helicobacter pylori infection is associated with diverse upper gastrointestinal diseases, such as peptic and duodenal ulcers as well as gastric cancer. Longstanding period of infection impose great risk of H. pylori-related gastric disease, based on the evidence that early childhood infection is responsible for ensuing atrophic gastritis and gastric cancer related to H. pylori infection. Artemisiahas been known to be beneficial for heath for a long time. In spite of well-acknowledged cytoprotective and anti-inflammatory actions of Artemisia, the effects of the acidic polysaccharide fractions on the gastroprotection remain to be investigated. Methods: In the current study, we compared anti-inflammatory actions of the acidic polysaccharide fraction between Artemisia and Panax ginseng against H. pylori infection in vitro. The polysaccharide fractions were pretreated 1 h before H. pylori infection on normal gastric mucosal RGM-1 cells and gastric cancer MKN-28 cells. RT-PCR and Western blot was performed to check anti-inflammatory actions. Results: The expressions of inflammatory markers including COX-2, iNOS and IL-8 increased after H. pylori infection, of which levels were significantly decreased when treating with the polysaccharide fractions from Artemisia and ginseng in RGM1 and gastric cancer MKN-28 cells. In addition, the polysaccharide fractions significantly ameliorated H. pylori-induced angiogenic and invasive markers such as HIF-1α and ICAM1. Moreover, H. pylori-induced apoptosis were prevented by pretreatment with the polysaccharide fractions. The polysaccharide fraction from Artemisia showed the most protective effects among the several polysaccharide fractions used in this study. Conclusions: The polysaccharide fraction of Artemisia capillariscan is a candidate substance which can attenuate either H. pylori-induced gastritis or tumorigenesis based on potent anti-inflammatory action. PMID:25337542

  16. Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility.

    PubMed

    Poppe, M; Feller, S M; Römer, G; Wessler, S

    2007-05-24

    Helicobacter pylori induces a strong motogenic response in infected gastric epithelial host cells, which is enhanced by translocation of the pathogenic factor cytotoxin-associated gene A (CagA) into host cells via a specialized type IV secretion system. Once injected into the cytosol CagA is rapidly tyrosine phosphorylated by Src family kinases followed by Src inactivation. Hence, it remained unknown why CagA is constantly phosphorylated in sustained H. pylori infections to induce cell migration, whereas other substrates of Src kinases are dephosphorylated. Here, we identify the non-receptor tyrosine kinase c-Abl as a crucial mediator of H. pylori-induced migration and novel CagA kinase in epithelial cells. Upon H. pylori infection c-Abl directly interacts with CagA and localizes in focal adhesion complexes and membrane ruffles, which are highly dynamic cytoskeletal structures necessary for cell motility. Selective inhibition of c-Abl kinase activity by STI571 or shRNA abrogates sustained CagA phosphorylation and epithelial cell migration, indicating a pivotal role of c-Abl in H. pylori infection and pathogenicity. These results implicate c-Abl as a novel molecular target for therapeutic intervention in H. pylori-related gastric diseases.

  17. [Diagnosis and treatment guidelines for Helicobacter pylori infection in Korea].

    PubMed

    Kim, Nayoung; Kim, Jae J; Choe, Yon Ho; Kim, Hyun Soo; Kim, Jin Il; Chung, In-Sik

    2009-11-01

    Eleven years has passed since the guideline of the Korean College of Helicobacter and Upper Gastrointestinal Research group for H. pylori infection was produced in 1998. During this period the research for H. pylori has much progressed that H. pylori is now regarded as the major cause of gastric cancer. The seroprevalence of H. pylori in Korea was found to be decreased especially below the age of 40s and in the area of Seoul-Gyeonggi province, and annual reinfection rate of H. pylori has decreased up to 2.94%. In the aspect of diagnostic tests of H. pylori the biopsy is recommended in the body instead of antrum in the subjects with atrophic gastritis and/or intestinal metaplasia for the modified Giemsa staining or Warthin Starry silver staining. The urea breath test is the test of choice to confirm eradication when follow-up endoscopy is not necessary. Definite indication for H. pylori eradication is early gastric cancer in addition to the previous indications of peptic ulcer including scar and Marginal zone B cell lymphoma (MALT type). Treatment is also recommended for the relatives of gastric cancer patient, unexplained iron deficiency anemia, and chronic idiopathic thrombocytopenic purpura. One or two week treatment of proton pump inhibitor (PPI) based triple therapy consisting of one PPI and two antibiotics, clarithromycin and amoxicillin, is recommended as the first line treatment regimen. In the case of treatment failure, one or two weeks of quadruple therapy (PPI+metronidazole+tetracycline+bismuth) is recommended. Herein, Korean College of Helicobacter and Upper Gastrointestinal Research proposes a diagnostic and treatment guideline based on currently available evidence.

  18. N-acetylcysteine, a novel treatment for Helicobacter pylori infection.

    PubMed

    Huynh, Hien Quoc; Couper, Richard T L; Tran, Cuong D; Moore, Lynette; Kelso, Richard; Butler, Ross N

    2004-01-01

    N-Acetylcysteine (NAC), being both a mucolytic agent and a thiol-containing antioxidant, may affect the establishment and maintenance of H. pylori infection within the gastric mucus layer and mucosa. Agar and broth dilution susceptibility tests determined the MIC of H. pylori strain SSI to NAC. H. pylori load in SSI strain-infected C57BL mice was determined as colony forming units per gram of gastric tissue. Gastritis assessment was scored and gastric surface hydrophobicity was determined by contact angle measurement. MICs of NAC were 5 to 10 and 10 to 15 mg/ml using the agar dilution and broth dilution methods, respectively. NAC (120 mg per day for 14 days) reduced the H. pylori load in mice by almost 1 log compared with sham treatment. Pretreatment with NAC (40 mg/day) also significantly reduced the H. pylori load but did not prevent H. pylori colonization. Both H. pylori infection and NAC reduced the surface hydrophobicity of murine gastric mucosa. No significant differences were observed in the gastritis scores of H. felis- or H. pylori-infected mice receiving either NAC or sham treatments. This study demonstrates that NAC inhibits the growth of H. pylori in both agar and broth susceptibility tests and in H. pylori-infected mice. NAC did not alter the severity of H. pylori- or H. felis-induced gastritis.

  19. Activation of Helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract.

    PubMed

    Astl, J; Šterzl, I

    2015-01-01

    Helicobacter pylori has been implicated in stimulation of immune system, development of autoimmune endocrinopathies as autoimmune thyroiditis (AT) and on other hand induction of immunosupresion activates gastric and extra-gastric diseases such as gastric ulcer or cancer. It causes persistent lifelong infection despite local and systemic immune response. Our results indicate that Helicobacter pylori might cause inhibition of the specific cellular immune response in Helicobacter pylori-infected patients with or without autoimmune diseases such as AT. We cannot also declare the carcinogenic effect in oropharynx. However the association of any infection agents and cancerogenesis exists. The adherence of Helicobacter pylori expression and enlargement of benign lymphatic tissue and the high incidence of the DNA of Helicobacter pylori in laryngopharyngeal and oropharyngeal cancer is reality. LTT appears to be a good tool for detection of immune memory cellular response in patients with Helicobacter pylori infection and AT. All these complications of Helicobacter pylori infection can be abrogated by successful eradication of Helicobacter pylori.

  20. Helicobacter pylori associated Asian enigma: Does diet deserve distinction?

    PubMed Central

    Zaidi, Syed Faisal

    2016-01-01

    Helicobacter pylori (H. pylori) is one of the most widespread infections in humans worldwide that chronically infects up to 50% of the world’s population. The infection is involved in the pathogenesis of chronic active gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer, therefore, it has been classified as class I definite carcinogen by the World Health Organization. Despite the established etiological role of H. pylori, its actual distribution and association with related diseases is controversial and there is a large intercountry variation especially among Asian countries. H. pylori infection is more frequent in developing countries like India, Pakistan, and Bangladesh as compared to developed Asian countries like Japan, China and South Korea. However, the frequency of gastric cancer is comparatively lower in India, Pakistan, and Bangladesh with that of Japan, China and South Korea. Such phenomenon of clinical diversity, defined as enigma, is judged by genetic variability of the infecting H. pylori strains, differences in the host genetic background in various ethnic groups, and environmental factors such as dietary habits. Most of the studies have so far focused on the bacterial factor while environmental issues, including dietary components, were not given due attention as one of the factors related with H. pylori associated gastric carcinogenesis. The dietary factor has been suggested to play an important role in H. pylori related carcinogenesis, and in this respect several studies have corroborated the intake of various dietary components as modulatory factors for gastric cancer risk. In this review, such studies, from in vitro experiments to clinical trials, are being focused in detail with respect to enigma associated with H. pylori. It may be conceivably concluded from the available evidence that dietary factor can be a game changer in the scenario of Asian enigma, particularly in high risk population infected with

  1. Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori

    PubMed Central

    Suzuki, Rumiko; Shiota, Seiji; Yamaoka, Yoshio

    2012-01-01

    Helicobacter pylori infection is linked to various gastroduodenal diseases; however, only approximately 20% of infected individuals develop severe diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. Furthermore, the incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors, especially cagA, vacA, and the right end of the cag pathogenicity island. The genotype of the virulence genes is also useful as a tool to track human migration utilizing the high genetic diversity and frequent recombination between different H. pylori strains. Multilocus sequence typing (MLST) analysis using 7 housekeeping genes can also help predict the history of human migrations. Population structure analysis based on MLST has revealed 7 modern population types of H. pylori, which derived from 6 ancestral populations. Interestingly, the incidence of gastric cancer is closely related to the distribution of H. pylori populations. The different incidence of gastric cancer can be partly attributed to the different genotypes of H. pylori circulating in different geographic areas. Although approaches by MLST and virulence factors are effective, these methods focus on a small number of genes and may miss information conveyed by the rest of the genome. Genome-wide analyses using DNA microarray or whole-genome sequencing technology give a broad view on the genome of H. pylori. In particular, next-generation sequencers, which can read DNA sequences in less time and at lower costs than Sanger sequencing, enabled us to efficiently investigate not only the evolution of H. pylori, but also novel virulence factors and genomic changes related to drug resistance. PMID:22197766

  2. Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia?

    PubMed Central

    Mearin, F; de Ribot, X; Balboa, A; Salas, A; Varas, M J; Cucala, M; Bartolomé, R; Armengol, J R; Malagelada, J R

    1995-01-01

    The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension. PMID:7672680

  3. Helicobacter pylori associated Asian enigma: Does diet deserve distinction?

    PubMed

    Zaidi, Syed Faisal

    2016-04-15

    Helicobacter pylori (H. pylori) is one of the most widespread infections in humans worldwide that chronically infects up to 50% of the world's population. The infection is involved in the pathogenesis of chronic active gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer, therefore, it has been classified as class I definite carcinogen by the World Health Organization. Despite the established etiological role of H. pylori, its actual distribution and association with related diseases is controversial and there is a large intercountry variation especially among Asian countries. H. pylori infection is more frequent in developing countries like India, Pakistan, and Bangladesh as compared to developed Asian countries like Japan, China and South Korea. However, the frequency of gastric cancer is comparatively lower in India, Pakistan, and Bangladesh with that of Japan, China and South Korea. Such phenomenon of clinical diversity, defined as enigma, is judged by genetic variability of the infecting H. pylori strains, differences in the host genetic background in various ethnic groups, and environmental factors such as dietary habits. Most of the studies have so far focused on the bacterial factor while environmental issues, including dietary components, were not given due attention as one of the factors related with H. pylori associated gastric carcinogenesis. The dietary factor has been suggested to play an important role in H. pylori related carcinogenesis, and in this respect several studies have corroborated the intake of various dietary components as modulatory factors for gastric cancer risk. In this review, such studies, from in vitro experiments to clinical trials, are being focused in detail with respect to enigma associated with H. pylori. It may be conceivably concluded from the available evidence that dietary factor can be a game changer in the scenario of Asian enigma, particularly in high risk population infected with

  4. Optimizing enrichment culture conditions for detecting Helicobacter pylori in foods.

    PubMed

    Jiang, Xiuping; Doyle, Michael P

    2002-12-01

    The survival and growth of Helicobacter pylori under enrichment conditions in fresh, autoclaved and irradiated ground beef were determined. H. pylori grew in autoclaved ground beef at 37 degrees C under microaerobic conditions in brain heart infusion broth with 7% horse serum at pH 7.3 after 3 to 7 days of lag time but did not grow within 7 days in irradiated (10 kGy) ground beef under the same enrichment conditions. Adjustment of the enrichment broth to pH 5.5 enabled the growth (ca. 2 log10 CFU/ml) of H. pylori within 7 days in the presence of irradiated ground beef and the prolific growth (ca. 3 to 4 log10 CFU/ml) of H. pylori within 3 days in the presence of autoclaved beef. H. pylori in fresh ground beef could not be isolated from enrichment media with antibiotics; however. H. pylori ureA could be detected by polymerase chain reaction (PCR) in such enrichment media after 1 to 3 days of incubation at 37 degrees C. The addition of supplements, i.e., 0.3% mucin, 0.05% ferrous sulfate, and 0.05% sodium pyruvate or 0.008 M urea, or the adjustment of the enrichment broth pH to 5.5 or 4.5 enabled the detection of H. pylori ureA in enrichment media incubated for 1, 2, 3, and/or 7 days at 37 degrees C. H. pylori in sterile milk refrigerated at 4 degrees C at an initial level of 10(6) CFU/ml was inactivated to an undetectable level within 6 days; however, H. pylori was not detected either by a PCR assay or by the plating of enrichment cultures of 120 raw bovine milk samples.

  5. Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

    PubMed

    Bimczok, Diane; Smythies, Lesley E; Waites, Ken B; Grams, Jayleen M; Stahl, Richard D; Mannon, Peter J; Peter, Shajan; Wilcox, C Mel; Harris, Paul R; Das, Soumita; Ernst, Peter B; Smith, Phillip D

    2013-06-15

    Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.

  6. Helicobacter pylori and Its Virulence Factors' Effect on Serum Oxidative DNA Damages in Adults With Dyspepsia.

    PubMed

    Shahi, Heshmat; Bahreiny, Rasoul; Reiisi, Somayeh

    2016-11-01

    Helicobacter Pylori infection is a common gastrointestinal infection that can cause pathological effects, increase oxidative stress and induce an inflammatory response in gastric mucosa. Inflammatory aspects may prompt the production of radical oxygen substance (ROS) which may damage cells and release 8-hydroxydyoxyguanosine (8-OHdG) to serum. In this study, we evaluate the prevalence of H. pylori virulence factors and the association between serum level of 8-OHdG, H. pylori infection, and its various virulence factors. The presence of H. pylori and prevalence of cagA, babA and oipA genes in samples were determined by rapid urease test (RUT), histopathological exam (HE) and polymerase chain reaction (PCR) and oxidative DNA damage situation were assessed by using serum level of 8-OHdG. There was not any direct relation between H. pylori negative and H. pylori oipA+specimens by 8-OHdG serum level (P>0.05). In all clinical observations, the presence of cagA and oipA genes was common. There was a statistical relationship between the presence of cagA, babA factors, and high serum level of 8-OHdG (P<0.05). The presence of cagA and babA virulence factors may be associated with increased serum 8-OHdG in dyspeptic patients and may induce the damage to gastric cells.

  7. A 20-minute breath test for helicobacter pylori

    SciTech Connect

    Marshall, B.J.; Plankey, M.W.; Hoffman, S.R.; Boyd, C.L.; Dye, K.R.; Frierson, H.F. Jr.; Guerrant, R.L.; McCallum, R.W. )

    1991-04-01

    In this study, we evaluated a simplified rapid {sup 14}C-urea breath test for the diagnosis of Helicobacter pylori. Fasting patients undergoing initial assessment for H. pylori drank 5 microCi of {sup 14}C-urea in 20 ml of water. Breath was collected at intervals for 30 min. Samples were counted in a beta-counter, and the results were expressed as counts per minute (cpm). In the same week, patients underwent endoscopy, and a blinded investigator examined biopsy samples of gastric mucosa by culture and histology for H. pylori. There were 49 H. pylori-negative (HP-) and 104 H. pylori-positive (HP+) patients in the study. HP+ patients expired a mean of 4398 cpm (SD 2468) per mmol CO{sub 2} in a sample taken 20 min after ingestion of the isotope. In contrast, HP--patients expired only 340 cpm (SD 196). If the mean +3 SD of HP- patients was used as a cutoff value, the 20-minute sample gave a sensitivity of 97% and a specificity of 100% for detecting H. pylori. The radiation exposure from this test is less than 1% of that received from an upper gastrointestinal series, and the short collection time makes it both convenient and cost effective.

  8. Lymphocytic gastritis and Helicobacter pylori infection in gastric lymphoma.

    PubMed Central

    Miettinen, A; Karttunen, T J; Alavaikko, M

    1995-01-01

    Lymphocytic gastritis and primary gastric lymphoma are rare conditions with unknown aetiology. It has recently been suggested that Helicobacter pylori has a role in the pathogenesis of both of them. The occurrence of lymphocytic gastritis and H pylori was studied in a series of patients with primary gastric lymphoma. The cases of primary gastric lymphomas (n = 35) diagnosed in years 1970-1993 were identified. The specimens of 22 cases contained gastric mucosa sufficiently so that the number of intra-epithelial lymphocytes, severity of gastritis, and occurrence of H pylori could be studied. Lymphocytic gastritis was detected in seven of 22 patients (32%), and in most cases both in antral and body mucosa. Atrophy of the body glands was significantly more severe in lymphocytic gastritis patients. H pylori was detected in 13 of all 22 patients (59%); two of seven lymphocytic gastritis patients (29%), and 11 of 15 (73%) of patients without lymphocytic gastritis were H pylori positive. Patients with gastric lymphoma have significantly increased prevalence of lymphocytic gastritis. Rarity of H pylori in these patients might be connected with atrophic changes in body mucosa. Further studies are needed to show the significance of lymphocytic gastritis as a precursor of gastric lymphoma. Images Figure 2 Figure 3 Figure 4 PMID:7489930

  9. Diagnosis of Helicobacter pylori infection by invasive and noninvasive tests.

    PubMed

    Pourakbari, Babak; Ghazi, Mona; Mahmoudi, Shima; Mamishi, Setareh; Azhdarkosh, Hossein; Najafi, Mehri; Kazemi, Bahram; Salavati, Ali; Mirsalehian, Akbar

    2013-01-01

    Although several invasive and noninvasive tests have been developed for the diagnosis of Helicobacter pylori infection, all of the tests have their limitations. We conducted a study to investigate and compare the suitability of rapid urease test (RUT), serology, histopathology and stool antigen tests with polymerase chain reaction (PCR) for detection of H. pylori, and correlate the diagnostic methods with PCR. Eighty nine patients (61 adults, 28 children) referred to the Firoozgar Hospital and Children Medical Center Hospital for diagnostic upper gastrointestinal endoscopy entered to the study and noninvasive tests such as immunoassay for serological antibodies against H. pylori and detection of its antigen in feces were measured. The biopsies were utilized for histological examination, RUT and PCR. The H. pylori statuses were evaluated by the positivity of ureC PCR in biopsy specimens and 53 subjects had H. pylori positive result. Histopathology showed high overall performance in adults and children with sensitivity and specificity 100% and 90%, respectively. Sensitivity, specificity, and accuracy for stool antigen test were 87.8%, 75% and 82%, respectively. Correlation of RUT, serology (IgG), histopathology and stool antigen tests with PCR were 0.82, 0.32, 0.91 and 0.63, respectively. In conclusion, the RUT and histopathology are as accurate as the PCR of biopsy and stool antigen test can consider as appropriate noninvasive test for detection of H. pylori infection.

  10. [Helicobacter pylori gastritis: assessment of OLGA and OLGIM staging systems].

    PubMed

    Ben Slama, Sana; Ben Ghachem, Dorra; Dhaoui, Amen; Jomni, Mohamed Taieb; Dougui, Mohamed Hédi; Bellil, Khadija

    2016-01-01

    Helicobacter pylori (H pylori) gastritis presents a risk of cancer related to atrophy and intestinal metaplasia. Two recent classifications OLGA (Operative Link on Gastritis Assessment) and OLGIM (Operative Link on Gastritic Intestinal Metaplasia assessment) have been proposed to identify high-risk forms (stages III and IV). The aim of this study is to evaluate the OLGA and OLGIM staging systems in H pylori gastritis. A descriptive study of 100 cases of chronic H pylori gastritis was performed. The revaluation of Sydney System parameters of atrophy and intestinal metaplasia, of gastric antrum and corpus, allowed identifying respectively the stages of OLGA and OLGIM systems. The progressive risk of our H pylori gastritis was 6% according to OLGA staging and 7% according to OLGIM staging. Significant correlation was revealed between age and OLGA staging. High-risk gastritis according to OLGIM staging was significantly associated with moderate to severe atrophy. High-risk forms according to OLGA staging were associated in 80% of the cases to intestinal metaplasia. OLGA and OLGIM systems showed a highly significant positive correlation between them with a mismatch at 5% for H pylori gastritis. The OLGA and OLGIM staging systems in addition to Sydney System, allow selection of high risk forms of chronic gastritis requiring accurate observation.

  11. Methods for Detecting the Environmental Coccoid Form of Helicobacter pylori

    PubMed Central

    Mazaheri Assadi, Mahnaz; Chamanrokh, Parastoo; Whitehouse, Chris A.; Huq, Anwar

    2015-01-01

    Helicobacter pylori is recognized as the most common pathogen to cause gastritis, peptic and duodenal ulcers, and gastric cancer. The organisms are found in two forms: (1) spiral-shaped bacillus and (2) coccoid. H. pylori coccoid form, generally found in the environment, is the transformed form of the normal spiral-shaped bacillus after exposed to water or adverse environmental conditions such as exposure to sub-inhibitory concentrations of antimicrobial agents. The putative infectious capability and the viability of H. pylori under environmental conditions are controversial. This disagreement is partially due to the fact of lack in detecting the coccoid form of H. pylori in the environment. Accurate and effective detection methods of H. pylori will lead to rapid treatment and disinfection, and less human health damages and reduction in health care costs. In this review, we provide a brief introduction to H. pylori environmental coccoid forms, their transmission, and detection methods. We further discuss the use of these detection methods including their accuracy and efficiency. PMID:26075197

  12. Growth phase-dependent composition of the Helicobacter pylori exoproteome.

    PubMed

    Snider, Christina A; Voss, Bradley J; McDonald, W Hayes; Cover, Timothy L

    2016-01-01

    Helicobacter pylori colonizes the human stomach and is associated with an increased risk of gastric cancer and peptic ulcer disease. Analysis of H. pylori protein secretion is complicated by the occurrence of bacterial autolysis. In this study, we analyzed the exoproteome of H. pylori at multiple phases of bacterial growth and identified 74 proteins that are selectively released into the extracellular space. These include proteins known to cause alterations in host cells, antigenic proteins, and additional proteins that have not yet been studied in any detail. The composition of the H. pylori exoproteome is dependent on the phase of bacterial growth. For example, the proportional abundance of the vacuolating toxin VacA in culture supernatant is higher during late growth phases than early growth phases, whereas the proportional abundance of many other proteins is higher during early growth phases. We detected marked variation in the subcellular localization of putative secreted proteins within soluble and membrane fractions derived from intact bacteria. By providing a comprehensive view of the H. pylori exoproteome, these results provide new insights into the array of secreted H. pylori proteins that may cause alterations in the gastric environment.

  13. Antibiotic treatment for Helicobacter pylori: Is the end coming?

    PubMed Central

    Kim, Su Young; Choi, Duck Joo; Chung, Jun-Won

    2015-01-01

    Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication. PMID:26558152

  14. Helicobacter pylori infection in India from a western perspective.

    PubMed

    Thirumurthi, Selvi; Graham, David Y

    2012-10-01

    Helicobacter pylori is a common bacterial infectious disease whose manifestations predominately affect the gastrointestinal tract. India is the prototypical developing country as far as H. pylori infection is concerned and more than 20 million Indians are estimated to suffer from peptic ulcer disease. Considering the high level of medical research and of the pharmaceutical industry, one would expect that India would be the source of much needed information regarding new therapies and approaches that remain effective in the presence of antimicrobial resistance, new methods to reliably prevent reinfection, and the development of therapeutic and preventive vaccines. Here we discuss H. pylori as a problem in India with an emphasis on H. pylori infection as a serious transmissible infectious disease. We discuss the pros and cons of eradication of H. pylori from the entire population and come down on the side of eradication. The available data from India regarding antimicrobial use and resistance as well as the effectiveness of various treatments are discussed. Rigorous ongoing studies to provide current regional antibiotic resistance patterns coupled with data concerning the success rate with different treatment regimens are needed to guide therapy. A systematic approach to identify reliably effective (e.g., 90% or greater treatment success) cost-effective regimens is suggested as well as details of regimens likely to be effective in India. H. pylori is just one of the health care problems faced in India, but one where all the resources are on hand to understand and solve it.

  15. Helicobacter pylori infection in India from a western perspective.

    PubMed

    Thirumurthi, Selvi; Graham, David Y

    2010-09-01

    Helicobacter pylori is a common bacterial infectious disease whose manifestations predominately affect the gastrointestinal tract. India is the prototypical developing country as far as H. pylori infection is concerned and more than 20 million Indians are estimated to suffer from peptic ulcer disease. Considering the high level of Medicine and of the pharmaceutical industry, one would expect that India would be the source of much needed information regarding new therapies and approaches that remain effective in the presence of antimicrobial resistance, new methods to reliably prevent reinfection, and the development of therapeutic and preventive vaccines. Here, we discuss H. pylori as an Indian problem with an emphasis on H. pylori infection as a serious transmissible infectious disease. We discuss the pros and cons of eradication of H. pylori from the entire population and come down on the side of eradication. The available data from India regarding antimicrobial use and resistance as well as the effectiveness of various treatments is discussed. Rigorous ongoing studies to provide current regional antibiotic resistance patterns coupled with data concerning the success rate with different treatment regimens are needed to guide therapy. A systematic approach to identify reliably effective (e.g., 90% or greater treatment success) cost-effective regimens is suggested as well as details of regimens likely to be effective in India. H. pylori is just one of the health care problems faced in India, but one where all the resources are on hand to understand and solve it.

  16. Helicobacter pylori and autoimmune disease: Cause or bystander

    PubMed Central

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  17. Transmission of Helicobacter pylori: a role for food?

    PubMed Central

    van Duynhoven, Y. T.; de Jonge, R.

    2001-01-01

    Helicobacter pylori colonizes and grows in human gastric epithelial tissue and mucus. Its presence is associated with gastritis and there is substantial evidence that it causes peptic and duodenal ulcers and chronic gastritis. Since 1994, H. pylori has been classified as carcinogenic to humans. In industrialized countries, as many as 50% of adults are infected with the pathogen, while in the developing world, prevalence values of about 90% have been reported. As little is known about the mode of transmission, a literature search was carried out to determine whether food acts a reservoir or vehicle in the transmission of H. pylori. Although growth of the pathogen should be possible in the gastrointestinal tract of all warm-blooded animals, the human stomach is its only known reservoir. Under conditions where growth is not possible, H. pylori can enter a viable, but nonculturable state. H. pylori has been detected in such states in water, but not in food. Person-to-person contact is thought to be the most likely mode of transmission, and there is no direct evidence that food is involved in the transmission of H. pylori. PMID:11417041

  18. Diagnosis of Helicobacter pylori infection: Current options and developments

    PubMed Central

    Wang, Yao-Kuang; Kuo, Fu-Chen; Liu, Chung-Jung; Wu, Meng-Chieh; Shih, Hsiang-Yao; Wang, Sophie SW; Wu, Jeng-Yih; Kuo, Chao-Hung; Huang, Yao-Kang; Wu, Deng-Chyang

    2015-01-01

    Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes. PMID:26523098

  19. Helicobacter pylori and food products: a public health problem.

    PubMed

    Herrera, Anavella Gaitan

    2004-01-01

    Helicobacter pylori is a major human pathogen causing gastritis and chronic superficial infection (CSG). It colonizes the stomach of more than 50% of humans and causes disease. This microorganism is associated with the gastric antral epithelium in patients with active chronic gastritis, peptic (gastric) or duodenal ulcers, and gastric adenocarcinoma H. pylori is present in feces, sewage, and water but is killed by routine chlorination. Therefore, in developing countries, consumption of sewage-contaminated drinking water and vegetables may pose a risk; properly cooking foods and chlorinating water reduces the risk of transmitting H. pylori to humans. In South America the consumption of raw vegetables fertilized with human feces has been found to be a risk factor for infection, and consumption of water from a municipal supply has been suggested as a risk factor for children. Epidemiological studies have found that H. pylori organisms colonize the stomach and duodenum of humans and many animal species and family clusters; it is believed to be orally transmitted person to person. This transmission is the major, if not exclusive, source of infection.H. pylori has been detected in the mouth from dental plaque. Recent observations in persons infected with H. pylori caused to vomit or have diarrhea showed that an actively unwell person with these symptoms could spread H. pylori in the immediate vicinity by aerosol, splashing of vomitus, infected vomitus, and infected diarrhea. In summary, H. pylori is usually spread by the fecal-oral route but possibly also by the oral-oral route and the spread of contaminated secretions. Thus, in developing countries, individuals catch H. pylori at a very young age from other persons (children) in their environment. In developed countries, H. pylori is more difficult to acquire and is usually transmitted from one family member to another, possibly by the fecal-oral route, or by the oral-oral route, e.g., kissing, vomitus. On occasion

  20. Anti-Helicobacter pylori xanthones of Garcinia fusca.

    PubMed

    Nontakham, Jannarin; Charoenram, Napaporn; Upamai, Wanchalerm; Taweechotipatr, Malai; Suksamrarn, Sunit

    2014-08-01

    A new geranylated xanthone derivative, fuscaxanthone I (1), along with nine xanthones (2-9 and 11), a biphenyl (10) and three biflavonoids (12-14) were isolated from the roots of Garcinia fusca Pierre. Compounds 8, 10 and 11-14 were reported from this plant species for the first time. Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR and MS. The isolated compounds were evaluated for antibacterial activity against Helicobacter pylori. Cowaxanthone (5) and fukugiside (14) exhibited stronger inhibitory activity against H. pylori DMST reference strain at MICs 4.6 and 10.8 μM, respectively, than that of the control metronidazole. Isojacareubin (8) displayed the most potent activity against H. pylori HP40 clinical isolate with MIC 23.9 μM, which was approximately two times greater than that of the standard drug amoxicillin.

  1. Heme oxygenase-1 dysregulates macrophage polarization and the immune response to Helicobacter pylori.

    PubMed

    Gobert, Alain P; Verriere, Thomas; Asim, Mohammad; Barry, Daniel P; Piazuelo, M Blanca; de Sablet, Thibaut; Delgado, Alberto G; Bravo, Luis E; Correa, Pelayo; Peek, Richard M; Chaturvedi, Rupesh; Wilson, Keith T

    2014-09-15

    Helicobacter pylori incites a futile inflammatory response, which is the key feature of its immunopathogenesis. This leads to the ability of this bacterial pathogen to survive in the stomach and cause peptic ulcers and gastric cancer. Myeloid cells recruited to the gastric mucosa during H. pylori infection have been directly implicated in the modulation of host defense against the bacterium and gastric inflammation. Heme oxygenase-1 (HO-1) is an inducible enzyme that exhibits anti-inflammatory functions. Our aim was to analyze the induction and role of HO-1 in macrophages during H. pylori infection. We now show that phosphorylation of the H. pylori virulence factor cytotoxin-associated gene A (CagA) in macrophages results in expression of hmox-1, the gene encoding HO-1, through p38/NF (erythroid-derived 2)-like 2 signaling. Blocking phagocytosis prevented CagA phosphorylation and HO-1 induction. The expression of HO-1 was also increased in gastric mononuclear cells of human patients and macrophages of mice infected with cagA(+) H. pylori strains. Genetic ablation of hmox-1 in H. pylori-infected mice increased histologic gastritis, which was associated with enhanced M1/Th1/Th17 responses, decreased regulatory macrophage (Mreg) response, and reduced H. pylori colonization. Gastric macrophages of H. pylori-infected mice and macrophages infected in vitro with this bacterium showed an M1/Mreg mixed polarization type; deletion of hmox-1 or inhibition of HO-1 in macrophages caused an increased M1 and a decrease of Mreg phenotype. These data highlight a mechanism by which H. pylori impairs the immune response and favors its own survival via activation of macrophage HO-1.

  2. Biofilm and Helicobacter pylori: from environment to human host.

    PubMed

    García, Apolinaria; Salas-Jara, María José; Herrera, Carolina; González, Carlos

    2014-05-21

    Helicobacter pylori (H. pylori) is a Gram negative pathogen that selectively colonizes the human gastric epithelium. Over 50% of the world population is infected with H. pylori reaching up to 90% of infected individuals in developing countries. Nonetheless the increased impact upon public health care, its reservoir and the transmission pathway of the species has not been clearly established yet. Molecular studies allowed the detection of H. pylori in various aquatic environments, even forming biofilm in tap water distribution systems in several countries, suggesting a role of water as a possible reservoir of the pathogen. The persistence of human infection with H. pylori and the resistance of clinical isolates to commonly used antibiotics in eradication therapy have been related to the genetic variability of the species and its ability to develop biofilm, demonstrated both in vivo and in vitro experiments. Thus, during the last years, experimental work with this pathogen has been focused in the search for biofilm inhibitors and biofilm destabilizing agents. However, only two anti- H. pylori biofilm disrupting agents have been successfully used: Curcumin - a natural dye - and N-acetyl cysteine - a mucolytic agent used in respiratory diseases. The main goal of this review was to discuss the evidences available in the literature supporting the ability of H. pylori to form biofilm upon various surfaces in aquatic environments, both in vivo and in vitro. The results published and our own observations suggest that the ability of H. pylori to form biofilm may be important for surviving under stress conditions or in the spread of the infection among humans, mainly through natural water sources and water distribution systems.

  3. One week's anti-Helicobacter pylori treatment for duodenal ulcer.

    PubMed Central

    Logan, R P; Gummett, P A; Misiewicz, J J; Karim, Q N; Walker, M M; Baron, J H

    1994-01-01

    This open study tested whether eradication of Helicobacter pylori (H pylori) heals duodenal ulcers as well as decreasing recurrence. H pylori was detected in patients with endoscopic duodenal ulcers by histology, CLO-test, culture, and 13C-urea breath test (13C-UBT). Tripotassium dicitrato bismuthate (120 mg) and amoxycillin (500 mg) each four times daily, were given for seven days, with 400 mg metronidazole five times a day on days 5-7. The 13C-UBT was repeated immediately after treatment and endoscopy repeated within 21 days. After treatment unhealed ulcers were reinspected one month later and healed ulcers followed up by 13C-UBT alone for 12 months. Of 45 patients, 44 were available for follow up. Mean pretreatment excess delta 13CO2 excretion was 25.6 per mil, which fell to 2.4 per mil immediately after finishing treatment, indicating clearance of H pylori in every patient. At the second endoscopy (median interval 20 days from start of treatment) 33 of 44 (75%) duodenal ulcers had healed. Ten of the remaining 11 duodenal ulcers were smaller and those 10 healed in the next two weeks with no further treatment. Two patients' ulcers that initially healed with clearance of H pylori recurred three weeks later (both had metronidazole resistant H pylori). H pylori was eradicated in 28 of 44 (64%) patients (13C-UBT negative for median follow up 10.2 months). Overall 41 of 43 (93%, 95% confidence intervals 81%-99%) duodenal ulcers were healed at one month. This study suggests that one week of anti-H pylori triple treatment is effective in healing duodenal ulcers. PMID:8307442

  4. Relatedness of Helicobacter pylori populations to gastric carcinogenesis

    PubMed Central

    Dong, Quan-Jiang; Zhan, Shu-Hui; Wang, Li-Li; Xin, Yong-Ning; Jiang, Man; Xuan, Shi-Ying

    2012-01-01

    Helicobacter pylori (H. pylori) is a Gram-negative bacterium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrica1, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and possibly result from geographical separation of the bacterium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different populations of H. pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H. pylori. Further studies are indicated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals. PMID:23236231

  5. Age of the Association between Helicobacter pylori and Man

    PubMed Central

    Bond, Robert P.; Nieuwoudt, Martin; Soodyall, Himla; Schlebusch, Carina M.; Bernhöft, Steffi; Hale, James; Suerbaum, Sebastian; Mugisha, Lawrence; van der Merwe, Schalk W.; Achtman, Mark

    2012-01-01

    When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya. PMID:22589724

  6. Antibiotic resistance among Helicobacter pylori clinical isolates in Lima, Peru

    PubMed Central

    Boehnke, Kevin F; Valdivieso, Manuel; Bussalleu, Alejandro; Sexton, Rachael; Thompson, Kathryn C; Osorio, Soledad; Reyes, Italo Novoa; Crowley, John J; Baker, Laurence H; Xi, Chuanwu

    2017-01-01

    Objectives Gastric carcinoma is the most common cancer and cause of cancer mortality in Peru. Helicobacter pylori, a bacterium that colonizes the human stomach, is a Group 1 carcinogen due to its causal relationship to gastric carcinoma. While eradication of H. pylori can help prevent gastric cancer, characterizing regional antibiotic resistance patterns is necessary to determine targeted treatment for each region. Thus, we examined primary antibiotic resistance in clinical isolates of H. pylori in Lima, Peru. Materials and methods H. pylori strains were isolated from gastric biopsies of patients with histologically proven H. pylori infection. Primary antibiotic resistance among isolates was examined using E-test strips. Isolates were examined for the presence of the cagA pathogenicity island and the vacA m1/m2 alleles via polymerase chain reaction. Results Seventy-six isolates were recovered from gastric biopsies. Clinical isolates showed evidence of antibiotic resistance to 1 (27.6%, n=21/76), 2 (28.9%, n=22/76), or ≥3 antibiotics (40.8%). Of 76 isolates, eight (10.5%) were resistant to amoxicillin and clarithromycin, which are part of the standard triple therapy for H. pylori infection. No trends were seen between the presence of cagA, vacA m1, or vacA m2 and antibiotic resistance. Conclusion The rate of antibiotic resistance among H. pylori isolates in Lima, Peru, is higher than expected and presents cause for concern. To develop more targeted eradication therapies for H. pylori in Peru, more research is needed to better characterize antibiotic resistance among a larger number of clinical isolates prospectively. PMID:28331349

  7. Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery

    PubMed Central

    Yoon, Kichul; Kim, Nayoung; Kim, Jaeyeon; Lee, Jung Won; Lee, Hye Seung; Lee, Jong-Chan; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung Ho; Lee, Yoon Jin; Lee, Kyoung-Ho; Kim, Young-Hoon; Lee, Dong Ho

    2017-01-01

    Background/Aims Helicobacter pylori eradication is recommended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for “retesting” postoperative H. pylori status. Methods Patients who underwent curative gastrectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were assessed pre- and postoperatively. Results One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently positive for H. pylori, and 60 (42.9%) showed spontaneous negative conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group. Conclusions A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individuals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori. PMID:27840366

  8. Biofilm and Helicobacter pylori: From environment to human host

    PubMed Central

    García, Apolinaria; Salas-Jara, María José; Herrera, Carolina; González, Carlos

    2014-01-01

    Helicobacter pylori (H. pylori) is a Gram negative pathogen that selectively colonizes the human gastric epithelium. Over 50% of the world population is infected with H. pylori reaching up to 90% of infected individuals in developing countries. Nonetheless the increased impact upon public health care, its reservoir and the transmission pathway of the species has not been clearly established yet. Molecular studies allowed the detection of H. pylori in various aquatic environments, even forming biofilm in tap water distribution systems in several countries, suggesting a role of water as a possible reservoir of the pathogen. The persistence of human infection with H. pylori and the resistance of clinical isolates to commonly used antibiotics in eradication therapy have been related to the genetic variability of the species and its ability to develop biofilm, demonstrated both in vivo and in vitro experiments. Thus, during the last years, experimental work with this pathogen has been focused in the search for biofilm inhibitors and biofilm destabilizing agents. However, only two anti- H. pylori biofilm disrupting agents have been successfully used: Curcumin - a natural dye - and N-acetyl cysteine - a mucolytic agent used in respiratory diseases. The main goal of this review was to discuss the evidences available in the literature supporting the ability of H. pylori to form biofilm upon various surfaces in aquatic environments, both in vivo and in vitro. The results published and our own observations suggest that the ability of H. pylori to form biofilm may be important for surviving under stress conditions or in the spread of the infection among humans, mainly through natural water sources and water distribution systems. PMID:24914322

  9. Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors

    PubMed Central

    Al-Marhoon, Mohammed S.; Ouhtit, Allal; Al-Abri, Aisha O.; Venkiteswaran, Krishna P.; Al-Busaidi, Qassim; Mathew, Josephkunju; Al-Haddabi, Ibrahim; Shareef, Omar; Aquil, Shahid; Rahman, Khalid; Al-Hashmi, Intisar; Gupta, Ishita; Ganguly, Shyam S.

    2015-01-01

    Objectives To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa. Methods One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables. Results Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09–23.34, one-tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients. Conclusions This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa. PMID:26889133

  10. Anti-Helicobacter pylori activity of crude N-acetylneuraminic acid isolated from glycomacropeptide of whey

    PubMed Central

    Kim, Dong-Jae; Kang, Min-Jung; Choi, Jin-A; Na, Dae-Seung; Kim, Jin-Beom; Na, Chun-Soo

    2016-01-01

    Helicobacter pylori colonizes the gastric mucosa of about half of the world's population, causing chronic gastritis and gastric cancer. An increasing emergence of antibiotic-resistant H. pylori arouses demand on alternative non-antibiotic-based therapies. In this study, we freshly prepared crude N-acetylneuraminic acid obtained from glycomacropeptide (G-NANA) of whey through a neuraminidase-mediated reaction and evaluated its antibacterial ability against H. pylori and H. felis. Overnight cultures of the H. pylori were diluted with fresh media and different concentrations (1-150 mg/mL) of crude G-NANA were added directly to the culture tube. Bacterial growth was evaluated by measuring the optical density of the culture medium and the number of viable bacteria was determined by a direct count of the colony forming units (CFU) on agar plates. For the in vivo study, mice were orally infected with 100 µL (5×108 cfu/mL) of H. felis four times at a day's interval, accompanied by a daily administration of crude G-NANA or vehicle. A day after the last infection, the mice were daily administered the crude G-NANA (0, 75, and 300 mg/mL) for 10 days and euthanized. Their stomachs were collected and bacterial colonization was determined by quantitative real-time PCR. Crude G-NANA inhibited H. pylori's growth and reduced the number of viable bacteria in a dose-dependent manner. Furthermore, crude G-NANA inhibited bacterial colonization in the mice. These results showed that crude G-NANA has antibacterial activity against Helicobacter and demonstrated its therapeutic potential for the prevention of chronic gastritis and gastric carcinogenesis induced by Helicobacter infection in humans. PMID:27382378

  11. Pancreatic cancer: Helicobacter pylori colonization, N-nitrosamine exposures, and ABO blood group.

    PubMed

    Risch, Harvey A

    2012-01-01

    Thirty years of research with animal models has shown that pancreatic adenocarcinoma is induced by N-nitrosamine carcinogens, which damage DNA through adduct formation. Human risk factors for pancreatic cancer include gastric colonization by Helicobacter pylori, as well as dietary intake of those same N-nitrosamines or of nitrite which forms those N-nitrosamines in the stomach, and cigarette smoking which also contains those N-nitrosamines. Physiologic actions of H. pylori colonization enhance the carcinogenic effect of N-nitrosamines delivered by smoking or dietary sources. This effect is modulated by host inflammatory response to the organism, by various virulence and other properties of the Helicobacter itself, and by host-organism interactions. A recent genome-wide association study identified SNPs within the ABO 9q34 locus as statistically significantly associated with risk of pancreatic cancer. A number of recent and older studies going back 40 yr also support the ABO association. ABO-product antigens are expressed on gastrointestinal epithelium on which H. pylori binds, and ABO genotype is known to be associated with risks of duodenal and gastric ulcer and with risk of gastric cancer, conditions definitively related to Helicobacter colonization. We suspect that ABO genotype/phenotype status influences the behavior of H. pylori which in turn affects gastric and pancreatic secretory function, and these ultimately influence the pancreatic carcinogenicity of dietary- and smoking-related N-nitrosamine exposures, and thus risk of pancreatic cancer. Our study results on the interaction of ABO and H. pylori significantly confirm this hypothesis and together with other existing studies strongly implicate this organism in the disease etiology.

  12. The non-H pylori helicobacters: their expanding role in gastrointestinal and systemic diseases

    PubMed Central

    Fox, J G

    2002-01-01

    The number of species in the genus Helicobacter has rapidly expanded over the past decade. The genus now includes at least 24 formally named species as well as numerous other helicobacters awaiting formal naming. This review highlights the expanding role that other helicobacters, although not as well known as H pylori, play in gastrointestinal and systemic disease in humans. PMID:11788573

  13. Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

    PubMed Central

    Magalhães, Ana; Marcos-Pinto, Ricardo; Nairn, Alison V.; Rosa, Mitche dela; Ferreira, Rui M.; Junqueira-Neto, Susana; Freitas, Daniela; Gomes, Joana; Oliveira, Patrícia; Santos, Marta R.; Marcos, Nuno T.; Xiaogang, Wen; Figueiredo, Céu; Oliveira, Carla; Dinis-Ribeiro, Mário; Carneiro, Fátima; Moremen, Kelley W.; David, Leonor; Reis, Celso A.

    2015-01-01

    Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local proinflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity. PMID:26144047

  14. Lipopolysaccharide a virulence factor of Helicobacter pylori: effect of antiulcer agents.

    PubMed

    Piotrowski, J

    1998-03-01

    Helicobacter pylori plays a major role in the pathogenesis of gastric disease. The gastric epithelial integrity is compromised by the H. pylori cell wall lipopolysaccharide untoward effect on the gastric epithelial cell receptors interaction with proteins of extracellular matrix, glycoproteins of mucus coat, and bioactive peptides. These interactions cause the weakening of the mucus coat rendering the underying epithelium vulnerable to noxious luminal contents and disrupting the regulatory feedback of somatostatin and gastrin. Moreover, H. pylori lipopolysaccharide induces histologic lesions typical of acute gastritis and these changes are reflected in the increased epithelial cell apoptosis. These findings thus identify cell wall lipopolysaccharide as a virulent factor responsible for the H. pylori effect on gastric epithelium. The effect of antiulcer agents on the interference of lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding. In the case of somatostatin-receptor binding, sulglycotide followed by sucralfate and ebrotidine showed the most potency in of reversing the effect of H. pylori lipopolysaccharide. Thus these antiulcer agents have a great promise in the treatment gastric diseases associated with H. pylori infection.

  15. Mixed Infections of Helicobacter pylori Isolated from Patients with Gastrointestinal Diseases in Taiwan

    PubMed Central

    Huang, Ju-Chun; Chiang-Ni, Chuan; Li, Ju-Pi; Wu, Lii-Tzu; Wu, Hua-Shan; Sun, Yu-Chen; Lin, Mei-Ling; Lee, Ju-Fang

    2016-01-01

    Background. Persistent Helicobacter pylori infection may induce several upper gastrointestinal diseases. Two major virulence factors of H. pylori, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), are thought to be associated with the severity of disease progression. The distribution of vacA and cag-pathogenicity island (cag-PAI) alleles varies in H. pylori isolated from patients in different geographic regions. Aim. To assess the association between mixed infection of H. pylori clinical isolates from Taiwanese patients and the severity of gastrointestinal diseases. Methods. A total of 70 patients were enrolled in this study. Six distinct and well-separated colonies were isolated from each patient and 420 colonies were analyzed to determine the genotypes of virulence genes. Results. The prevalence of mixed infections of all H. pylori-infected patients was 28.6% (20/70). The rate of mixed infections in patients with duodenal ulcer (47.6%) was much higher than that with other gastrointestinal diseases (P < 0.05). Conclusions. H. pylori mixed infections show high genetic diversity that may enhance bacterial adaptation to the hostile environment of the stomach and contribute to disease development. PMID:27738429

  16. Refractory iron deficiency anemia and Helicobacter Pylori Infection in pediatrics: A review

    PubMed Central

    Gheibi, Sh; Farrokh-Eslamlou, HR; Noroozi, M; Pakniyat, A

    2015-01-01

    Background Since the discovery of Helicobacter pylori, several clinical reports have demonstrated that H. Pylori infection has emerged as a new cause of refractory iron stores in children. We carried out a systematic literature review to primarily evaluate the existing evidence on the association between childhood H. Pylori infection and iron deficiency anemia (IDA) and secondly, to investigate the beneficial effects of bacterium elimination. Material and Methods This review concerns important pediatric studies published from January 1991 to October 2014. Fourteen case reports and series of cases, 24 observational epidemiologic studies, seven uncontrolled trials, and 16 randomized clinical trials were included in the review. Results Although there are a few observational epidemiologic studies and some randomized trials mostly due to the potential confounders, most studies reported a positive association linking between H. Pylori infection and iron deficiency or iron deficiency anemia among children. In addition, it seems that elimination of H. Pylori infection induces beneficial effects on iron deficiency. Conclusions Since the evidence for the association of H. pylori eradication therapy and refractory childhood IDA is not enough and there are contrasting data about such association, future high quality and cohort researches are needed to determine the causal association. PMID:25914802

  17. Effects of prolonged chlorine exposures upon PCR detection of Helicobacter pylori DNA.

    EPA Science Inventory

    The effect of low doses of free chlorine on the detection by qPCR of Helicobacter pylori (H. pylori) cells by qPCR in tap water was monitored. H. pylori target sequences (within suspended, intact cells at densities of 102 to 103 cells /ml) were rendered undetectable by qPCR an...

  18. Immune Responses to "Helicobacter pylori" Infection in Children with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Douraghi, Masoumeh; Goudarzi, Hossein; Rostami, Mahmoud Nateghi; Nikmanesh, Bahram

    2012-01-01

    Infection with "Helicobacter pylori" was assessed through serum "H. pylori" IgG antibody in children with intellectual disabilities (ID). The sero-status of cytotoxin-associated gene A (CagA) was determined as a risk determinant for severe "H. pylori"-associated diseases. In total, 210 children with ID were included…

  19. Dietary prevention of Helicobacter pylori-associated gastric cancer with kimchi

    PubMed Central

    Han, Young-Min; Park, Kun Young; Lee, Don Haeng; Yoo, Joon-Hwan; Cho, Joo Young; Hahm, Ki-Baik

    2015-01-01

    To prove whether dietary intervention can prevent Helicobacter pylori-induced atrophic gastritis and gastric cancer, we developed cancer preventive kimchi (cpKimchi) through special recipe and administered to chronic H. pylori-initiated, high salt diet-promoted, gastric tumorigenesis mice model. H. pylori-infected C57BL/6 mice were administered with cpKimchi mixed in drinking water up to 36 weeks. Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively and explored underlying molecular changes to explain efficacies. Cancer preventive actions of anti-inflammation and anti-mutagenesis were compared between standard recipe kimchi (sKimchi) and special recipe cpKimchi in in vitro H. pylori-infected cell model. The erythematous and nodular changes, mucosal ulcerative and erosive lesions in the stomach were noted at 24th weeks, but cpKimchi administration significantly ameliorated. After 36th weeks, scattered nodular masses, some ulcers, and thin nodular gastric mucosa were noted in H. pylori-infected mice, whereas these gross lesions were significantly attenuated in cpKimchi group. On molecular analysis, significant expressions of COX-2 and IL-6, activated NF-κB and STAT3, increased apoptosis, and marked oxidative stresses were noted in H. pylori-infected group relevant to tumorigenesis, but these were all significantly attenuated in cpKimchi group. cpKimchi extracts imparted significant selective induction of apoptosis only in cancer cells, led to inhibition of H. pylori-induced proliferation, while no cytotoxicity through significant HO-1 induction in non-transformed gastric cells. In conclusion, daily dietary intake of cpKimchi can be an effective way either to rejuvenate H. pylori-atrophic gastritis or to prevent tumorigenesis supported with the concerted actions of anti-oxidative, anti-inflammatory, and anti-mutagenic mechanisms. PMID:26317548

  20. Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis.

    PubMed

    Lee, Inchul

    2014-06-07

    Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.

  1. Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis

    PubMed Central

    Lee, Inchul

    2014-01-01

    Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach. PMID:24914362

  2. Drug therapy for Helicobacter pylori infection: problems and pitfalls.

    PubMed

    Glupczynski, Y; Burette, A

    1990-12-01

    Antibacterial chemotherapy against Helicobacter pylori is currently being assessed by open or randomized controlled clinical studies for its efficacy in eradicating this bacterium from the stomach of patients with gastritis or gastroduodenal ulcer. Whereas there is presently no "optimal" agent and treatment scheme, the combination of some antibiotics (metronidazole, tinidazole, amoxicillin) with bismuth salts proves definitely superior in vivo to either of these agents administered alone. Several reasons have been proposed, to explain the clinical failure after treatment: insufficient concentration of active drugs in gastric mucus, instability of some agents at an acidic pH, inappropriate formulation of drug, insufficient duration of treatment, and variable compliance of patients. Recently, it has appeared from several clinical trials that H. pylori may rapidly acquire resistance to some antibiotics, and that this event might also account for clinical failure. A critical review of the literature on H. pylori treatment indicates that association of bismuth and antibiotics or of antibiotics alone both may efficiently reduce the risk of emergence of resistance and improve the therapeutic outcome. Guidelines of treatment are suggested in order to avoid the future misuse of antibiotics that would increase selection of antibiotic-resistant H. pylori and negatively affect the ecology of the gastric microflora. Likewise, an accurate definition of a subset of patients with H. pylori who really will require treatment needs to be rapidly established.

  3. Quinolone-containing therapies in the eradication of Helicobacter pylori.

    PubMed

    Chuah, Seng-Kee; Tai, Wei-Chen; Lee, Chen-Hsiang; Liang, Chih-Ming; Hu, Tsung-Hui

    2014-01-01

    Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to "rescue" therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

  4. Does Helicobacter pylori exhibit corkscrew motion while swimming?

    NASA Astrophysics Data System (ADS)

    Constantino, Maira; Hardcastle, Joseph; Bansil, Rama

    2015-03-01

    Helicobacter pylori is a spiral shaped bacterium associated with ulcers, gastric cancer, gastritis among other diseases. In order to colonize the harsh acidic environment of the stomach H. pylori has to go across the viscoelastic mucus layer of the stomach. Many studies have been conducted on the swimming of H. pylori in viscous media however none have taken into account the influence of cell-body shape on the trajectory. We present an experimental study of the effects of body shape in the swimming trajectory of H. pylori in viscous media by a quantitative analysis of the bacterium rotation and translation in gels using phase contrast microscopy and particle tracking techniques. Preliminary microscopic tracking measurements show very well defined helical trajectories in the spiral-shaped wild type H. pylori. These helical trajectories are not seen in rod-shaped mutants which sometimes display whirling motion about one end acting as a hinge. We will present an analysis of the different trajectories for bacteria swimming in media with different viscoelastic parameters. Supported by the National Science Foundation PHY PoLS.

  5. Chinese Helicobacter pylori vaccine: Solution for an old challenge?

    PubMed Central

    Talebi Bezmin Abadi, Amin; Lee, Yeong Yeh

    2016-01-01

    Helicobacter pylori (H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world’s population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class I carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase III study of an oral recombinant vaccine (Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children (6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge. PMID:27602242

  6. PCR Detection of Helicobacter pylori in Clinical Samples

    PubMed Central

    Rimbara, Emiko; Sasatsu, Masanori; Graham, David Y.

    2014-01-01

    Helicobacter pylori is an important pathogen whose primary niche is the human stomach. H. pylori is etio-logically associated with gastric inflammation (gastritis), peptic ulcer disease, and gastric cancer. Both noninvasive (e.g., urea breath and stool antigen tests) and invasive (gastric biopsy for histology, culture, or PCR) tests are used for diagnosis. PCR detection of H. pylori has been reported using a variety of clinical samples including gastric biopsy, gastric juice, saliva, dental plaque, and stools as well as environmental samples. Whenever possibly, noninvasive tests are preferred over invasive tests. H. pylori are excreted in the stool. Culture from stool is variable whereas stool antigen testing is widely used. Stool consists of a complicated mixture of commensal bacteria and chemicals and often includes inhibitors of PCR. Nevertheless, simple extraction methods are available to efficiently extract DNA from human stools and nested-PCR targeting the 23S rRNA gene have proven to be highly sensitive for the detection of H. pylori. Detection of clarithromycin susceptibility/resistance is important clinically and the mutation of the 23S rRNA gene responsible for resistance can also be detected using stool. This described method can be modified for other clinical samples such as gastric juice or biopsy material. PMID:23104297

  7. Review of Helicobacter pylori infection and chronic renal failure.

    PubMed

    Sugimoto, Mitsushige; Yamaoka, Yoshio

    2011-02-01

    Chronic renal failure patients receiving hemodialysis and continuous ambulatory peritoneal dialysis often encounter gastrointestinal troubles over their long treatment period. Helicobacter pylori infection has close association with development of peptic ulcer, gastric cancer and gastric lymphoma, and is thought to be one of the major risk factors for gastrointestinal troubles in dialysis patients. However, it is unclear whether H. pylori infection is directly associated with progression of renal dysfunction and prognosis of chronic renal failure patients. Recent consensus shows that the prevalence of H. pylori infection in chronic renal failure patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in hemodialysis patients, the prevalence of infection decreases as dialysis periods progressed, in particular within the first four years after the start of treatment. However, the chance of natural eradication becomes rare for patients receiving dialysis treatment for a long time. Moreover, chronic renal failure patients with H. pylori infection have a higher incidence of gastroduodenal diseases, and therefore, are recommended to receive eradication therapies, especially for those receiving treatment for a long time and with higher risks of complication. Intensive endoscopic check-ups for the prevention of gastrointestinal events and the discovery of peptic ulcer and neoplastic diseases at an early phase may be required.

  8. Role of gastritis pattern on Helicobacter pylori eradication.

    PubMed

    Zullo, Angelo; Severi, Carola; Vannella, Lucy; Hassan, Cesare; Sbrozzi-Vanni, Andrea; Annibale, Bruno

    2012-12-01

    Helicobacter pylori eradication rate following standard triple therapy is decreasing. Identification of predictive factors of therapy success would be useful for H. pylori management in clinical practice. This study aimed to evaluate the role of different gastritis patterns on the efficacy of the currently suggested 14-day triple therapy regimen. One-hundred and seventeen, consecutive, non-ulcer dyspeptic patients, with H. pylori infection diagnosed at endoscopy, were enrolled. All patients received a 14-day, triple therapy with lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g, all given twice daily. Bacterial eradication was assessed with (13)C-urea breath test 4-6 weeks after completion of therapy. H. pylori infection was cured in 70.1% at ITT analysis and 83.7% at PP analysis. The eradication rate tended to be lower in patients with corpus-predominant gastritis as compared to those with antral-predominant gastritis at both ITT (66.1 vs 74.5%) and PP (80.4 vs 87.2%) analyses. The multivariate analysis failed to identify factors associated with therapy success. However, 14-day triple therapy does not achieve acceptable H. pylori cure rate in Italy, and should be not recommended in clinical practice.

  9. Contemporary Diagnostic Strategies for the Detection of Helicobacter pylori Infection

    PubMed Central

    Elfant, Adam B.; Howden, Colin W.; Stollman, Neil

    2012-01-01

    Helicobacter pylori infection is highly prevalent, affecting approximately half of the world’s population. While the majority of infected individuals are asymptomatic, H. pylori infection is associated with certain diseases, including peptic ulcers (either duodenal or gastric), gastritis, and 2 malignancies—gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. Many of the epidemiologic associations between these diseases and H. pylori infection have been further validated by treatment studies, which show that effective eradication therapy correlates with a decreased risk of disease. A variety of testing strategies are used to detect H. pylori infection. Serologic techniques are widely available and inexpensive, but they are no longer preferred as they have low sensitivities and specificities, and they may show a positive result for a long period following effective therapy. The remaining testing methods are divided into 2 categories: invasive tests (which require endoscopy) and noninvasive tests. Noninvasive test methods such as the urea breath test and stool antigen test have gained popularity due to their high sensitivities and specificities. Further, both of these methods may be used to confirm the absence of infection following eradication therapy. Due to the increasing incidence of treatment failure (caused in part by antibiotic resistance), post-treatment testing is recommended to confirm H. pylori eradication. PMID:24847180

  10. Analysis of Helicobacter pylori genotypes in clinical gastric wash samples.

    PubMed

    Miyamoto, Shuichi; Watanabe, Yoshiyuki; Oikawa, Ritsuko; Ono, Shoko; Mabe, Katsuhiro; Kudo, Takahiko; Yamamoto, Hiroyuki; Itoh, Fumio; Kato, Mototsugu; Sakamoto, Naoya

    2016-08-01

    Helicobacter pylori is a key factor in the development of gastric cancer; indeed, clearance of H. pylori helps prevent gastric cancer. However, the relationship between gastric cancer and the abundance and diversity of H. pylori genotypes in the stomach remains unknown. Here, we present, for the first time, a quantitative analysis of H. pylori genotypes in gastric washes. A method was first developed to assess diversity and abundance by pyrosequencing and analysis of single nucleotide polymorphisms in 23S ribosomal RNA (rRNA), a gene associated with clarithromycin resistance. This method was then validated using arbitrarily mixed plasmids carrying 23S rRNA with single nucleotide polymorphisms. Multiple strains were detected in many of 34 clinical samples, with frequency 24.3 ± 24.2 and 26.3 ± 33.8 % for the A2143G and A2144G strains, respectively. Importantly, results obtained from gastric washes were similar to those obtained from biopsy samples. The method provides opportunities to investigate drug resistance in H. pylori and assess potential biomarkers of gastric cancer risk, and should thus be validated in large-scale clinical trials.

  11. [Animal models for the study of Helicobacter pylori infection].

    PubMed

    Miszczyk, Eliza; Walencka, Maria; Mikołajczyk-Chmiela, Magdalena

    2014-05-15

    The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma). Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural history of H. pylori infection. Preclinical investigations on animal models are an essential stage of research which enrich the knowledge on treatment and prevention strategies.

  12. Helicobacter pylori Stores Nickel To Aid Its Host Colonization

    PubMed Central

    Benoit, Stéphane L.; Miller, Erica F.

    2013-01-01

    The transition metal nickel (Ni) is critical for the pathogenicity of Helicobacter pylori. Indeed the element is a required component of two enzymes, hydrogenase and urease, that have been shown to be important for in vivo colonization of the host gastric mucosa. Urease accounts for up to 10% of the total cellular H. pylori protein content, and therefore the bacterial Ni demand is very high. H. pylori possess two small and abundant histidine-rich, Ni-binding proteins, Hpn and Hpn-like, whose physiological role in the host have not been investigated. In this study, special husbandry conditions were used to control Ni levels in the host (mouse), including the use of Ni-free versus Ni-supplemented food. The efficacy of each diet was confirmed by measuring the Ni concentrations in sera of mice fed with either diet. Colonization levels (based on rank tests) of the Δhpn Δhpn-like double mutants isolated from the mice provided Ni-deficient chow were statistically lower than those for mice given Ni in their diet. In contrast, H. pylori wild-type colonization levels were similar in both host groups (e.g., regardless of Ni levels). Our results indicate that the gastric pathogen H. pylori can utilize stored Ni via defined histidine-rich proteins to aid colonization of the host. PMID:23230291

  13. Endoscopic gastritis, serum pepsinogen assay, and Helicobacter pylori infection

    PubMed Central

    Lee, Sun-Young

    2016-01-01

    Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fundus, and thickened gastric folds are common endoscopic findings. The secreting ability of the gastric mucosa cells is usually intact in both noninfected and actively infected stomachs, and the intragastric condition becomes hyperacidic upon inflammation. Increased serum pepsinogen II concentration correlates well with active H. pylori infection, and also indicates an increased risk of diffuse-type gastric cancer. In chronic inactive H. pylori infection, metaplastic gastritis and atrophic gastritis extending from the antrum (closed-type chronic atrophic gastritis) toward the corpus (open-type chronic atrophic gastritis) are common endoscopic findings. The intragastric environment is hypoacidic and the risk of intestinal-type gastric cancer is increased in such conditions. Furthermore, there is a decrease in serum pepsinogen I concentration when the secreting ability of the gastric mucosa cells is damaged. Serologic and endoscopic changes that occur upon H. pylori infection are important findings for estimating the secreting ability of the gastric mucosa cells, and could be applied for the secondary prevention of gastric cancer. PMID:27604795

  14. Antimicrobial activity of Northwestern Mexican plants against Helicobacter pylori.

    PubMed

    Robles-Zepeda, Ramón E; Velázquez-Contreras, Carlos A; Garibay-Escobar, Adriana; Gálvez-Ruiz, Juan C; Ruiz-Bustos, Eduardo

    2011-10-01

    Helicobacter pylori is the major etiologic agent of such gastric disorders as chronic active gastritis and gastric carcinoma. Over the past few years, the appearance of antibiotic-resistant bacteria has led to the development of better treatments, such as the use of natural products. This study evaluated the anti-H. pylori activity of 17 Mexican plants used mainly in the northwestern part of Mexico (Sonora) for the empirical treatment of gastrointestinal disorders. The anti-H. pylori activity of methanolic extracts of the plants was determined by using the broth microdilution method. The 50% minimum inhibitory concentrations ranged from less than 200 to 400 μg/mL for Castella tortuosa, Amphipterygium adstringens, Ibervillea sonorae, Pscalium decompositum, Krameria erecta, Selaginella lepidophylla, Pimpinella anisum, Marrubium vulgare, Ambrosia confertiflora, and Couterea latiflora and were greater than 800 μg/mL for Byophyllum pinnatum, Tecoma stans linnaeus, Kohleria deppena, Jatropha cuneata, Chenopodium ambrosoides, and Taxodium macronatum. Only Equisetum gigantum showed no activity against H. pylori. This study suggests the important role that these plants may have in the treatment of gastrointestinal disorders caused by H. pylori. The findings set the groundwork for further characterization and elucidation of the active compounds responsible for such activity.

  15. Identification of Helicobacter pylori genes that contribute to stomach colonization.

    PubMed

    Baldwin, David N; Shepherd, Benjamin; Kraemer, Petra; Hall, Michael K; Sycuro, Laura K; Pinto-Santini, Delia M; Salama, Nina R

    2007-02-01

    Chronic infection of the human stomach by Helicobacter pylori leads to a variety of pathological sequelae, including peptic ulcer and gastric cancer, resulting in significant human morbidity and mortality. Several genes have been implicated in disease related to H. pylori infection, including the vacuolating cytotoxin and the cag pathogenicity island. Other factors important for the establishment and maintenance of infection include urease enzyme production, motility, iron uptake, and stress response. We utilized a C57BL/6 mouse infection model to query a collection of 2,400 transposon mutants in two different bacterial strain backgrounds for H. pylori genetic loci contributing to colonization of the stomach. Microarray-based tracking of transposon mutants allowed us to monitor the behavior of transposon insertions in 758 different gene loci. Of the loci measured, 223 (29%) had a predicted colonization defect. These included previously described H. pylori virulence genes, genes implicated in virulence in other pathogenic bacteria, and 81 hypothetical proteins. We have retested 10 previously uncharacterized candidate colonization gene loci by making independent null alleles and have confirmed their colonization phenotypes by using competition experiments and by determining the dose required for 50% infection. Of the genetic loci retested, 60% have strain-specific colonization defects, while 40% have phenotypes in both strain backgrounds for infection, highlighting the profound effect of H. pylori strain variation on the pathogenic potential of this organism.

  16. Recent Acquisition of Helicobacter pylori by Baka Pygmies

    PubMed Central

    Montano, Valeria; Maady, Ayas; Nkwescheu, Armand; Siri, Jose; Elamin, Wael F.; Falush, Daniel; Linz, Bodo; Achtman, Mark; Moodley, Yoshan; Suerbaum, Sebastian

    2013-01-01

    Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations

  17. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

    PubMed Central

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M.; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  18. Helicobacter pylori-negative Russell body gastritis: Case report

    PubMed Central

    Gobbo, Alessandro Del; Elli, Luca; Braidotti, Paola; Nuovo, Franca Di; Bosari, Silvano; Romagnoli, Solange

    2011-01-01

    Russell body gastritis is an unusual form of chronic gastritis characterized by the permeation of lamina propria by numerous plasma cells with eosinophilic cytoplasmic inclusions. Very few cases have been reported in the literature; the majority of which have shown Helicobacter Pylori (H. pylori) infection, thus suggesting a correlation between plasma cell presence and antigenic stimulation by H. pylori. We present a case of Russell body gastritis in a 78-year-old woman who was undergoing esophagogastroduodenoscopy for epigastric pain. Gastric biopsy of the gastroesophageal junction showed the presence of cells with periodic acid-Schiff-positive hyaline pink bodies. Giemsa staining for H. pylori infection was negative, as well as immunohistochemical detection. The cells with eosinophilic inclusions stained positive for CD138, CD79a, and κ and lambda light chains, which confirmed plasma cell origin. In particular, κ and lambda light chains showed a polyclonal origin and the patient was negative for immunological dyscrasia. The histological observations were confirmed by ultrastructural examination. The cases reported in the literature associated with H. pylori infection have shown regression of plasma cells after eradication of H. pylori. Nothing is known about the progression of H. pylori-negative cases. The unusual morphological appearance of this type of chronic gastritis should not be misinterpreted during routine examination, and it should be distinguished from other common forms of chronic gastritis. It is mandatory to exclude neoplastic diseases such as gastric carcinoma, lymphoma and plasmocytoma by immunohistochemistry and electron microscopy, which can help with differential diagnosis. The long-term effects of plasma cells hyperactivation are still unknown, because cases of gastric tumor that originated in patients affected by Russell body gastritis have not been described in the literature. We are of the opinion that these patients should be scheduled

  19. Helicobacter pylori-negative Russell body gastritis: case report.

    PubMed

    Del Gobbo, Alessandro; Elli, Luca; Braidotti, Paola; Di Nuovo, Franca; Bosari, Silvano; Romagnoli, Solange

    2011-03-07

    Russell body gastritis is an unusual form of chronic gastritis characterized by the permeation of lamina propria by numerous plasma cells with eosinophilic cytoplasmic inclusions. Very few cases have been reported in the literature; the majority of which have shown Helicobacter Pylori (H. pylori) infection, thus suggesting a correlation between plasma cell presence and antigenic stimulation by H. pylori. We present a case of Russell body gastritis in a 78-year-old woman who was undergoing esophagogastroduodenoscopy for epigastric pain. Gastric biopsy of the gastroesophageal junction showed the presence of cells with periodic acid-Schiff-positive hyaline pink bodies. Giemsa staining for H. pylori infection was negative, as well as immunohistochemical detection. The cells with eosinophilic inclusions stained positive for CD138, CD79a, and κ and lambda light chains, which confirmed plasma cell origin. In particular, κ and lambda light chains showed a polyclonal origin and the patient was negative for immunological dyscrasia. The histological observations were confirmed by ultrastructural examination. The cases reported in the literature associated with H. pylori infection have shown regression of plasma cells after eradication of H. pylori. Nothing is known about the progression of H. pylori-negative cases. The unusual morphological appearance of this type of chronic gastritis should not be misinterpreted during routine examination, and it should be distinguished from other common forms of chronic gastritis. It is mandatory to exclude neoplastic diseases such as gastric carcinoma, lymphoma and plasmocytoma by immunohistochemistry and electron microscopy, which can help with differential diagnosis. The long-term effects of plasma cells hyperactivation are still unknown, because cases of gastric tumor that originated in patients affected by Russell body gastritis have not been described in the literature. We are of the opinion that these patients should be scheduled

  20. Overview of the phytomedicine approaches against Helicobacter pylori

    PubMed Central

    Vale, Filipa F; Oleastro, Mónica

    2014-01-01

    Helicobacter pylori (H. pylori) successfully colonizes the human stomach of the majority of the human population. This infection always causes chronic gastritis, but may evolve to serious outcomes, such as peptic ulcer, gastric carcinoma or mucosa-associated lymphoid tissue lymphoma. H. pylori first line therapy recommended by the Maastricht-4 Consensus Report comprises the use of two antibiotics and a proton-pomp inhibitor, but in some regions failure associated with this treatment is already undesirable high. Indeed, treatment failure is one of the major problems associated with H. pylori infection and is mainly associated with bacterial antibiotic resistance. In order to counteract this situation, some effort has been allocated during the last years in the investigation of therapeutic alternatives beyond antibiotics. These include vaccines, probiotics, photodynamic inactivation and phage therapy, which are briefly revisited in this review. A particular focus on phytomedicine, also described as herbal therapy and botanical therapy, which consists in the use of plant extracts for medicinal purposes, is specifically addressed, namely considering its history, category of performed studies, tested compounds, active principle and mode of action. The herbs already experienced are highly diverse and usually selected from products with a long history of employment against diseases associated with H. pylori infection from each country own folk medicine. The studies demonstrated that many phytomedicine products have an anti-H. pylori activity and gastroprotective action. Although the mechanism of action is far from being completely understood, current knowledge correlates the beneficial action of herbs with inhibition of essential H. pylori enzymes, modulation of the host immune system and with attenuation of inflammation. PMID:24914319

  1. The Role of Helicobacter pylori in Laryngopharyngeal Reflux.

    PubMed

    Campbell, Ross; Kilty, Shaun J; Hutton, Brian; Bonaparte, James P

    2017-02-01

    Objective The primary objective was to determine the prevalence of Helicobacter pylori among patients with laryngopharyngeal reflux. The secondary objective was determining if H pylori eradication leads to greater symptom improvement in patients with laryngopharyngeal reflux as compared with standard proton pump inhibitor therapy alone. Data Sources EMBASE, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, World Health Organization International Clinical Trials Registry Platform, European Union Clinical Trials Register, Cochrane Library databases of clinical trials, and ClinicalTrials.gov. Review Methods A systematic review was performed of studies assessing the diagnosis or treatment of H pylori among patients with laryngopharyngeal reflux. Randomized controlled trials, cohort studies, case-control studies, and case series were included. A meta-analysis of prevalence data and assessment of heterogeneity was performed on relevant studies. Results Fourteen studies were analyzed in the review, with 13 eligible for the meta-analysis. We determined that the prevalence of H pylori among patients with laryngopharyngeal reflux was 43.9% (95% confidence interval, 32.1-56.5). The heterogeneity of studies was high, with an overall I(2) value of 92.3%. We were unable to quantitatively assess findings for our secondary outcome, since H pylori identification and treatment were not the primary focus of the majority of studies. Conclusion There is a high rate of H pylori infection among patients with laryngopharyngeal reflux. The infection rate in North America and Western Europe has not been adequately studied. There is insufficient evidence to make a recommendation regarding the testing and treatment of H pylori infection among patients with laryngopharyngeal reflux.

  2. The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer.

    PubMed

    Moss, Steven F

    2017-03-01

    Gastric cancer has long been recognized to be accompanied and preceded by chronic gastritis, lasting decades. Arguably, the most important development in our understanding of gastric cancer pathogenesis over the past 50 years has been the realization that, for most cases of gastric cancer, Helicobacter pylori is the cause of the underlying gastritis. Gastritis can promote gastric carcinogenesis, typically via the Correa cascade of atrophic gastritis, intestinal metaplasia, and dysplasia. Nested case-control studies have shown that H pylori infection increases the risk of gastric cancer significantly, both of the intestinal and diffuse subtypes, and that H pylori is responsible for approximately 90% of the world's burden of noncardia gastric cancer. Based largely on randomized studies in high gastric cancer prevalence regions in East Asia, it appears that primary and tertiary intervention to eradicate H pylori can halve the risk of gastric cancer. Some public health authorities now are starting screening and treatment programs to reduce the burden of gastric cancer in these high-risk areas. However, there is currently much less enthusiasm for initiating similar attempts in the United States. This is partially because gastric cancer is a relatively less frequent cause of cancer in the United States, and in addition there are concerns about theoretical downsides of H pylori eradication, principally because of the consistent inverse relationship noted between H pylori and esophageal adenocarcinoma. Nevertheless, establishing a link between chronic H pylori infection and gastric cancer has led to novel insights into cancer biology, the gastrointestinal microbiome, and on individual and population-based gastric cancer prevention strategies.

  3. [Gastrointestinal giardiasis associated with Helicobacter pylori].

    PubMed

    Isaeva, G Sh; Efimova, N G

    2010-01-01

    The study involved 160 patients with chronic cholecystitis associated with chronic gastroduodenitis. Obtaining biopsy specimens of gastric mucosa and bile samples allowed to compare the microbial picture and the morphological structure of gastric mucosa in the same patient, to identify patterns of colonization of the stomach, 12 duodenal ulcer and gall bladder various microorganisms. At cytological examination was detected in the gall bladder G. lamblia in 47.5 +/- 3.95% of cases in the stomach--in 29.09 +/- 6.12% of cases. The frequency of H. pylori detection in biopsy of gastric mucosa amounted to 98.18 +/- 1.8% of cases, in 12-duodenum--93.75 +/- 1.9%, in the gall bladder--to 54.38 +/- 3.94%, in the bile duct--in 54.38 +/- 3.94%. It was found strict association between the detection of H. pylori and G. lamblia in the stomach--100% of H. pylori-infection combined with giardiasis. Morphological changes of gastric mucosa in the form of lymphoid infiltration detected mainly in the mixed-infection H. pylori and G. lamblia.

  4. Helicobacter pylori inhibits the cleavage of TRAF1 via a CagA-dependent mechanism

    PubMed Central

    Wan, Xiu-Kun; Yuan, Sheng-Ling; Wang, Yan-Chun; Tao, Hao-Xia; Jiang, Wei; Guan, Zhang-Yan; Cao, Cheng; Liu, Chun-Jie

    2016-01-01

    AIM To study the impact on cleavage of tumor necrosis factor receptor-associated factor 1 (TRAF1) regulated by Helicobacter pylori (H. pylori). METHODS Cleavage of TRAF1 was detected by western blotting in the human gastric cancer cell line AGS following treatment with an apoptosis inducer. Cleavage of TRAF1 mediated by caspase was examined in vitro using specific caspase inhibitors. The effect of the COOH-terminal TRAF1 fragment on gastric cell apoptosis during H. pylori infection was measured using flow cytometry. The impact of H. pylori infection on TRAF1 cleavage was detected in the presence of apoptosis inducer. The roles of H. pylori virulence factors that may regulate TRAF1 cleavage were analyzed using isogenic cagA-, vacA- and cagE-null mutants. RESULTS TRAF1 was found to be cleaved in AGS cells treated with the apoptosis inducer, and caspase-8 was the major caspase involved in the cleavage of TRAF1. The COOH-terminal TRAF1 fragment significantly induced cell apoptosis (P < 0.05) as well as promoted H. pylori-induced cell apoptosis (P < 0.05). H. pylori infection was found to significantly inhibit the cleavage of TRAF1 and to inhibit the activation of caspase-8 in the presence of the apoptosis inducer at specific infection times and different cell/bacteria ratios. We also found that the effects of cagE- and cagA-null mutants on the inhibition of TRAF1 cleavage and activation of caspase-8 were significantly attenuated, compared with wild-type H. pylori, in the presence of the apoptosis inducer, showing that the virulence factor CagA was mainly involved in the inhibition of TRAF1 cleavage. CONCLUSION H. pylori infection significantly inhibits the cleavage of TRAF1 via a CagA-dependent mechanism, which would increase the relative amounts of full-length TRAF1 and exert an antiapoptotic effect on H. pylori-infected cells. PMID:28082808

  5. Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA

    PubMed Central

    Shimoda, Asako; Ueda, Koji; Nishiumi, Shin; Murata-Kamiya, Naoko; Mukai, Sada-atsu; Sawada, Shin-ichi; Azuma, Takeshi; Hatakeyama, Masanori; Akiyoshi, Kazunari

    2016-01-01

    CagA, encoded by cytotoxin-associated gene A (cagA), is a major virulence factor of Helicobacter pylori, a gastric pathogen involved in the development of upper gastrointestinal diseases. Infection with cagA-positive H. pylori may also be associated with diseases outside the stomach, although the mechanisms through which H. pylori infection promotes extragastric diseases remain unknown. Here, we report that CagA is present in serum-derived extracellular vesicles, known as exosomes, in patients infected with cagA-positive H. pylori (n = 4). We also found that gastric epithelial cells inducibly expressing CagA secrete exosomes containing CagA. Addition of purified CagA-containing exosomes to gastric epithelial cells induced an elongated cell shape, indicating that the exosomes deliver functional CagA into cells. These findings indicated that exosomes secreted from CagA-expressing gastric epithelial cells may enter into circulation, delivering CagA to distant organs and tissues. Thus, CagA-containing exosomes may be involved in the development of extragastric disorders associated with cagA-positive H. pylori infection. PMID:26739388

  6. Helicobacter pylori in gastroduodenal diseases: rapid identification by endoscopic brush cytology.

    PubMed

    De Francesco, F; Nicòtina, P A; Picciotto, M; Martines, F; Ferlazzo, G; d'Aquino, A

    1993-08-01

    Previous reports showed Helicobacter pylori (H. pylori) in type B gastritis-affected stomachs. This study was carried out to compare H. pylori staining effectiveness on biopsy to brush cytology. Tissue and brush parallel samples of gastric mucosa with abnormal or normal appearances were examined: 57.6% H. pylori-positive pieces from the antrum and 19.2% from the body were found, versus 65.3% and 25% H. pylori-positive brush smears, respectively. H. pylori resembling organisms were mainly related to chronic and acute antral inflammations and were often associated with higher amounts of round-shaped cocco-bacteria. In addition, H. pylori direct stain on brushing is proposed as the most rapid and reliable method for the routine diagnosis of Helicobacter pylori infection, in both ulcer or nonulcer gastritis.

  7. Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters.

    PubMed

    Dangtakot, Rungtiwa; Pinlaor, Somchai; Itthitaetrakool, Upsornsawan; Chaidee, Apisit; Chomvarin, Chariya; Sangka, Arunnee; Wilailuckana, Chotechana; Pinlaor, Porntip

    2017-04-01

    Persistent infection with Opisthorchis viverrini causes hepatobiliary abnormalities, predisposing infected individuals to cholangiocarcinoma (CCA). In addition, Helicobacter pylori is highly prevalent in most countries and is a possible risk factor for CCA; however, its role in enhancing hepatobiliary abnormality is unclear. Here, we investigated the effects of coinfection with H. pylori and O. viverrini on hepatobiliary abnormality. Hamsters were divided into four groups: (i) normal, (ii) H. pylori infected (HP), (iii) O. viverrini infected (OV), and (iv) O. viverrini and H. pylori infected (OV+HP). At 6 months postinfection, PCR and immunohistochemistry were used to test for the presence of H. pylori in the stomach, gallbladder, and liver. In the liver, H. pylori was detected in the following order: OV+HP, 5 of 8 (62.5%); HP, 2 of 5 (40%); OV, 2 of 8 (25%). H. pylori was not detected in normal (control) liver tissues. Coinfection induced the most severe hepatobiliary abnormalities, including periductal fibrosis, cholangitis, and bile duct hyperplasia, leading to a significantly decreased survival rate of experimental animals. The greatest thickness of periductal fibrosis was associated with a significant increase in fibrogenesis markers (expression of alpha smooth muscle actin and transforming growth factor beta). Quantitative reverse transcription-PCR revealed that the highest expression levels of genes for proinflammatory cytokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) were also observed in the OV+HP group. These results suggest that coinfection with H. pylori and O. viverrini increased the severity of hepatobiliary abnormalities to a greater extent than either single infection did.

  8. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.

  9. Onset of Ulcerative Colitis after Helicobacter pylori Eradication Therapy: A Case Report

    PubMed Central

    Chiba, Mitsuro; Tsuji, Tsuyotoshi; Takahashi, Kenichi; Komatsu, Masafumi; Sugawara, Takeshi; Ono, Iwao

    2016-01-01

    In Japan, Helicobacter pylori eradication has been approved since 2013 for treatment of H pylori-induced chronic gastritis, in an attempt to reduce the prevalence of gastric cancer, a leading cancer in Japan. H pylori infection affects more than 50% of the world’s population. H pylori eradication therapy is generally safe. To our knowledge, no case of newly diagnosed ulcerative colitis occurring immediately after H pylori eradication therapy has previously been reported. A 63-year-old man received a diagnosis of chronic gastritis and H pylori infection. In early March 2014, primary H pylori eradication therapy was initiated; lansoprazole, amoxicillin, and clarithromycin were administered for 1 week. Beginning on the fourth day, he had watery diarrhea twice a day. From the 11th day, bloody stools and watery diarrhea increased to 6 times a day. Colonoscopy, performed on the 40th day after termination of drug therapy, revealed diffuse inflammation in the distal aspect of the colon, with histologic findings consistent with ulcerative colitis. He was admitted to the hospital and was provided with a semivegetarian diet and metronidazole. He noticed a gradual decrease in the amount of blood in his feces then a disappearance of the blood. A fecal occult blood test on the 11th hospital day recorded 337 ng/mL. Fecal occult blood test is not indicated during macroscopic bloody stool but is indicated after disappearance of bloody stool. Therefore, he achieved clinical remission by the 11th hospital day. He was in remission on discharge. New onset of ulcerative colitis should be added to a list of adverse events of H pylori eradication therapy. PMID:27043835

  10. Modification of Helicobacter pylori peptidoglycan enhances NOD1 activation and promotes cancer of the stomach

    DOE PAGES

    Suarez, Giovanni; Romero-Gallo, Judith; Piazuelo, M. Blanca; ...

    2015-03-02

    Helicobacter pylori is the strongest known risk factor for gastric carcinogenesis. One cancer-linked locus is the cag pathogenicity island, which translocates components of peptidoglycan (PGN) into host cells. NOD1 is an intracellular immune receptor that senses PGN from Gram-negative bacteria and responds by inducing autophagy and activating NF-κB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering PGN structure. We previously demonstrated that the H. pylori cag+ strain 7.13 rapidly induces gastric cancer in Mongolian gerbils. Using 2D-DIGE and mass spectrometry, we identified a novel mutation within the gene encoding the peptidoglycan deacetylase PgdA; therefore,more » we sought to define the role of H. pylori PgdA in NOD1-dependent activation of NF-κB, inflammation, and cancer. Co-culture of H. pylori strain 7.13 or its pgdA$-$ isogenic mutant with AGS gastric epithelial cells or HEK293 epithelial cells expressing a NF-κB reporter revealed that pgdA inactivation significantly decreased NOD1-dependent NF-κB activation and autophagy. Infection of Mongolian gerbils with an H. pylori pgdA$-$ mutant strain led to significantly decreased levels of inflammation and malignant lesions in the stomach; however, pre-activation of NOD1 prior to bacterial challenge reciprocally suppressed inflammation and cancer in response to wild-type H. pylori. Expression of NOD1 differs in human gastric cancer specimens compared to non-cancer samples harvested from the same patients. In conclusion, these results indicate that PGN deacetylation plays an important role in modulating host inflammatory responses to H. pylori, allowing the bacteria to persist and induce carcinogenic consequences in the gastric niche.« less

  11. Helicobacter pylori virulence factors affecting gastric proton pump expression and acid secretion.

    PubMed

    Hammond, Charles E; Beeson, Craig; Suarez, Giovanni; Peek, Richard M; Backert, Steffen; Smolka, Adam J

    2015-08-01

    Acute Helicobacter pylori infection of gastric epithelial cells and human gastric biopsies represses H,K-ATPase α subunit (HKα) gene expression and inhibits acid secretion, causing transient hypochlorhydria and supporting gastric H. pylori colonization. Infection by H. pylori strains deficient in the cag pathogenicity island (cag PAI) genes cagL, cagE, or cagM, which do not transfer CagA into host cells or induce interleukin-8 secretion, does not inhibit HKα expression, nor does a cagA-deficient strain that induces IL-8. To test the hypothesis that virulence factors other than those mediating CagA translocation or IL-8 induction participate in HKα repression by activating NF-κB, AGS cells transfected with HKα promoter-Luc reporter constructs containing an intact or mutated NF-κB binding site were infected with wild-type H. pylori strain 7.13, isogenic mutants lacking cag PAI genes responsible for CagA translocation and/or IL-8 induction (cagA, cagζ, cagε, cagZ, and cagβ), or deficient in genes encoding two peptidoglycan hydrolases (slt and cagγ). H. pylori-induced AGS cell HKα promoter activities, translocated CagA, and IL-8 secretion were measured by luminometry, immunoblotting, and ELISA, respectively. Human gastric biopsy acid secretion was measured by microphysiometry. Taken together, the data showed that HKα repression is independent of IL-8 expression, and that CagA translocation together with H. pylori transglycosylases encoded by slt and cagγ participate in NF-κB-dependent HKα repression and acid inhibition. The findings are significant because H. pylori factors other than CagA and IL-8 secretion are now implicated in transient hypochlorhydria which facilitates gastric colonization and potential triggering of epithelial progression to neoplasia.

  12. The number of Foxp3-positive regulatory T cells is increased in Helicobacter pylori gastritis and gastric cancer.

    PubMed

    Jang, Tae Jung

    2010-01-15

    Helicobacter pylori (H. pylori) colonization induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. Recent studies have shown that CD4(+) CD25(+) Foxp3-positive regulatory T cells (Tregs) suppress the immune response to H. pylori. Persistent H. pylori-associated gastritis is closely associated with gastric carcinogenesis. We investigated the number of Tregs in the context of H. pylori colonization in chronic gastritis, examined the relationship between it and histopathological findings and compared it with that of gastric dysplasia and adenocarcinoma. This study was based on the analysis of gastric biopsy specimens from 126 cases of H. pylori-associated gastritis, 16 cases of H. pylori-negative gastritis, 17 cases of gastric dysplasia, and 25 cases of gastric adenocarcinoma. The number of Tregs was elevated in H. pylori-associated gastritis, where it was positively correlated with the grade of chronic inflammation and the number of lymphoid follicles. It was significantly elevated in adenocarcinomas compared to chronic gastritis and gastric dysplasia. In summary, the number of Tregs is increased in H. pylori-associated gastritis and gastric cancer.

  13. [Clinical analysis of unsuccessful Helicobacter pylori eradication].

    PubMed

    Szadkowski, Aleksander; Chojnacki, Jan; Klupińska, Grazyna; Wojtuń, Stanisław

    2004-01-01

    Numerous medical reports claim that the effectiveness of H. pylori therapy decreases. The aim of the study was the analysis of the reasons of this phenomenon on own material. The study included 437 subjects, aged 19-64 years with chronic gastritis with H. pylori infection. All patients were subjected to: endoscopy, fast urease test, breath test (UBT-13C) and antibody titer in IgG class was determined. In the case of ineffective therapy bacteriological examination was performed. In the first stage of the therapy pantoprazol (2 x 40 mg) and amoxicillin (2 x 1000 mg) with metronidazol (2 x 500 mg) were applied in 282 subjects for 7 days (group I), amoxicillin with clarithromycin (2 x 500 mg) in 182 subjects (group II) and clarithromycin with metronidazol in 43 subjects (group III). After 6 weeks negative breath test was observed on average in 65.68% without significant differences between the groups. Ineffective therapy was more frequent in subjects over 45 years of age with high intensity of H. pylori colonization and earlier treated with antibiotics due to other reasons; such differences were not observed dependently on the antibody titer. In the second stage of the therapy pantoprazol was still administered but antibacterial drugs were changed among the groups. From among 150 subjects eradication was obtained in 117 (78.0%). In 33 subjects with ineffective therapy bacteriological examination of gastric bioptates confirmed antibiotic resistance in 75.76%. It results from the study that the applied therapy, consistent with current recommendations of the experts, does not ensure H. pylori eradication in part of the patients, what points to the necessity of searching for other effective antibiotics.

  14. Helicobacter pylori γ-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance

    PubMed Central

    Oertli, Mathias; Noben, Manuel; Engler, Daniela B.; Semper, Raphaela P.; Reuter, Sebastian; Maxeiner, Joachim; Gerhard, Markus; Taube, Christian; Müller, Anne

    2013-01-01

    Infection with the gastric bacterial pathogen Helicobacter pylori is typically contracted in early childhood and often persists for decades. The immunomodulatory properties of H. pylori that allow it to colonize humans persistently are believed to also account for H. pylori’s protective effects against allergic and chronic inflammatory diseases. H. pylori infection efficiently reprograms dendritic cells (DCs) toward a tolerogenic phenotype and induces regulatory T cells (Tregs) with highly suppressive activity in models of allergen-induced asthma. We show here that two H. pylori virulence determinants, the γ-glutamyl transpeptidase GGT and the vacuolating cytotoxin VacA, contribute critically and nonredundantly to H. pylori’s tolerizing effects on murine DCs in vitro and in vivo. The tolerance-promoting effects of both factors are independent of their described suppressive activity on T cells. Isogenic H. pylori mutants lacking either GGT or VacA are incapable of preventing LPS-induced DC maturation and fail to drive DC tolerization as assessed by induction of Treg properties in cocultured naive T cells. The Δggt and ΔvacA mutants colonize mice at significantly reduced levels, induce stronger T-helper 1 (Th1) and T-helper 17 (Th17) responses, and/or trigger more severe gastric pathology. Both factors promote the efficient induction of Tregs in vivo, and VacA is required to prevent allergen-induced asthma. The defects of the Δggt mutant in vitro and in vivo are phenocopied by pharmacological inhibition of the transpeptidase activity of GGT in all readouts. In conclusion, our results reveal the molecular players and mechanistic basis for H. pylori-induced immunomodulation, promoting persistent infection and conferring protection against allergic asthma. PMID:23382221

  15. Creation of a new synthetic medium for culturing Helicobacter pylori.

    PubMed

    Vartanova, N O; Arzumanyan, V G; Serdyuk, O A; Temper, R M

    2005-05-01

    We developed a scheme of consecutive replacement of complex components of a known Brucella medium containing peptones and blood with simple analogs and created a synthetic medium for Helicobacter pylori culturing. H. pylori cells require hemic iron for their growth; an appreciable increment in biomass was ensured by hemoglobin, but not simpler hemocontaining compounds (hemin and cytochrome C). Glutamine (20 g/liter) was used as the main nitrogen-containing component, and other amino acids were added in trace amounts. Adhesion was provided by adding agarose gel (0.1%) also promoting the increase in biomass. The proposed medium of a certain chemical composition differs from the known foreign analogs by the presence of hemocontaining component (hemoglobin), short period of exponential growth, and appreciable accumulation of cell protein.

  16. Helicobacter pylori identification: a diagnostic/confirmatory method for evaluation.

    PubMed

    Mesquita, B; Gonçalves, M J; Pacheco, P; Lopes, J; Salazar, F; Relvas, M; Coelho, C; Pacheco, J J; Velazco, C

    2014-09-01

    The Helicobacter pylori extra gastric reservoir is probably the oral cavity. In order to evaluate the presence of this bacterium in patients with periodontitis and suspicious microbial cultures, saliva was collected from these and non-periodontitis subjects. PCRs targeting 16S rRNA gene and a 860 bp specific region were performed, and digested with the restriction enzyme DdeI. We observed that the PCR-RFLP approach augments the accuracy from 26.2 % (16/61), found in the PCR-based results, to 42.6 % (26/61), which is an excellent indicator for the establishment of this low-cost procedure as a diagnostic/confirmatory method for H. pylori evaluation.

  17. Evolution of Brunner gland hamartoma associated with Helicobacter pylori infection.

    PubMed

    Kurella, Ravi R; Ancha, Hanumantha R; Hussain, Sanam; Lightfoot, Stan A; Harty, Richard

    2008-06-01

    The pathogenesis of Brunner gland hamartoma of the duodenum is unknown. This case report describes the chronology of the development of Brunner gland hamartoma from Brunner gland hyperplasia over a 12-year interval. The study subject, a 64-year-old man with chronic iron deficiency anemia, underwent serial upper endoscopies during this period. Repeated endoscopies demonstrated the evolution of Brunner gland hyperplasia, as manifest endoscopically by a submucosal mass, to a pedunculated polyp with histologic features of Brunner gland hamartoma. The duodenal polypoid mass was removed by snare polypectomy. The patient also had a chronic Helicobacter pylori infection of the stomach. This report details the time-dependent evolution of Brunner gland hyperplasia to hamartoma in association with chronic gastric H. pylori infection.

  18. Characteristics of clinical Helicobacter pylori strains from Ecuador.

    PubMed

    Debets-Ossenkopp, Yvette J; Reyes, Germán; Mulder, Janet; aan de Stegge, Birgit M; Peters, José T A M; Savelkoul, Paul H M; Tanca, J; Peña, Amado S; Vandenbroucke-Grauls, Christina M J E

    2003-01-01

    In Ecuador, Helicobacter pylori infections are highly prevalent. A total of 42 H. pylori clinical isolates from 86 patients attending the outpatient clinic of the gastroenterology department of the university hospital of Guayaquil in Ecuador were characterized. Their susceptibility, and cagA and vacA status were determined. Resistance to metronidazole and clarithromycin was found in 80.9% and 9.5% of strains, respectively. Neither amoxicillin- nor tetracycline-resistant strains were found. The most prevalent genotype was the cagA(+), vacA s1b,m1 type. This genotype was associated with gastric cancer and peptic ulcer. Typing by random amplified polymorphic DNA showed no genetic relationship among the strains.

  19. Helicobacter pylori treatment: Still a work in progress.

    PubMed

    Senatore, Frank J; Wilmot, Jonathan; Birk, John W

    2016-01-01

    Helicobacter pylori is a common worldwide bacterium, possessing adaptability that has created difficulty achieving eradication. While the standard treatment was thought to be triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin, growing rates of treatment failure and antibiotic resistance have stimulated research into novel regimens. Quadruple therapy with bismuth has been compared for both first- and second-line treatments, but eradication still has not reached expected goals. Innovative regimens including sequential and concomitant therapy, as well as the introduction of new antibiotics into previous treatment schedules, have shown promising improvements in eradication rates. We discuss and compare these unique regimens, reviewing the current literature to deduce those which are most likely to provide the highest success in curing H. pylori infection.

  20. Phenotypic and Molecular Antimicrobial Susceptibility of Helicobacter pylori.

    PubMed

    Chen, Derrick; Cunningham, Scott A; Cole, Nicolynn C; Kohner, Peggy C; Mandrekar, Jayawant N; Patel, Robin

    2017-04-01

    Failure to eradicate Helicobacter pylori infection is often a result of antimicrobial resistance, which for clarithromycin is typically mediated by specific point mutations in the 23S rRNA gene. The purpose of this study was to define current patterns of antimicrobial susceptibility in H. pylori isolates derived primarily from the United States and to survey them for the presence of point mutations in the 23S rRNA gene and assess the ability of these mutations to predict phenotypic clarithromycin susceptibility. Antimicrobial susceptibility testing was performed using agar dilution on 413 H. pylori isolates submitted to Mayo Medical Laboratories for susceptibility testing. For a subset of these isolates, a 150-bp segment of the 23S rRNA gene was sequenced. A total of 1,970 MICs were reported over the 4-year study period. The rate of clarithromycin resistance was high (70.4%), and elevated MICs were frequently observed for metronidazole (82.4% of isolates had an MIC of >8 μg/ml) and ciprofloxacin (53.5% of isolates had an MIC of >1 μg/ml). A total of 111 archived H. pylori isolates underwent 23S rRNA gene sequencing; we found 95% concordance between genotypes and phenotypes (P = 0.9802). Resistance to clarithromycin was most commonly due to an A2143G mutation (82%), followed by A2142G (14%) and A2142C (4%) mutations. Clinical H. pylori isolates derived primarily from the United States demonstrated a high rate of clarithromycin resistance and elevated metronidazole and ciprofloxacin MICs. The relative distribution of point mutations at positions 2143 and 2142 in the 23S rRNA gene in clarithromycin-resistant H. pylori was similar to that reported from other parts of the world; these mutations predict phenotypic resistance to clarithromycin.

  1. Helicobacter pylori eradication as a preventive tool against gastric cancer.

    PubMed

    Hamajima, Nobuyuki; Goto, Yasuyuki; Nishio, Kazuko; Tanaka, Daisuke; Kawai, Sayo; Sakakibara, Hisataka; Kondo, Takaaki

    2004-01-01

    Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

  2. Multiple Acid Sensors Control Helicobacter pylori Colonization of the Stomach

    PubMed Central

    Huang, Julie Y.; Goers Sweeney, Emily; Guillemin, Karen

    2017-01-01

    Helicobacter pylori’s ability to respond to environmental cues in the stomach is integral to its survival. By directly visualizing H. pylori swimming behavior when encountering a microscopic gradient consisting of the repellent acid and attractant urea, we found that H. pylori is able to simultaneously detect both signals, and its response depends on the magnitudes of the individual signals. By testing for the bacteria’s response to a pure acid gradient, we discovered that the chemoreceptors TlpA and TlpD are each independent acid sensors. They enable H. pylori to respond to and escape from increases in hydrogen ion concentration near 100 nanomolar. TlpD also mediates attraction to basic pH, a response dampened by another chemoreceptor TlpB. H. pylori mutants lacking both TlpA and TlpD (ΔtlpAD) are unable to sense acid and are defective in establishing colonization in the murine stomach. However, blocking acid production in the stomach with omeprazole rescues ΔtlpAD’s colonization defect. We used 3D confocal microscopy to determine how acid blockade affects the distribution of H. pylori in the stomach. We found that stomach acid controls not only the overall bacterial density, but also the microscopic distribution of bacteria that colonize the epithelium deep in the gastric glands. In omeprazole treated animals, bacterial abundance is increased in the antral glands, and gland colonization range is extended to the corpus. Our findings indicate that H. pylori has evolved at least two independent receptors capable of detecting acid gradients, allowing not only survival in the stomach, but also controlling the interaction of the bacteria with the epithelium. PMID:28103315

  3. Eradicating Helicobacter pylori and symptoms of non-ulcer dyspepsia.

    PubMed Central

    Patchett, S; Beattie, S; Leen, E; Keane, C; O'Morain, C

    1991-01-01

    OBJECTIVE--To examine the effect of eradication of Helicobacter pylori on symptoms of non-ulcer dyspepsia. DESIGN--Four week prospective study. SETTING--One hospital outpatient and endoscopy department. PATIENTS--90 adults with persistent symptoms typical of non-ulcer dyspepsia but no clinical or endoscopic evidence of other peptic, biliary, pancreatic, or malignant disease; all had histological and microbiological evidence of infection with H pylori. 83 patients completed the treatment regimen. INTERVENTION--Colloidal bismuth subcitrate 120 mg four times a day for four weeks (27 patients); metronidazole 400 mg and amoxycillin 500 mg each three times a day for one week (27); and bismuth subcitrate 120 mg four times a day for four weeks, metronidazole 400 mg three times a day for one week, plus amoxycillin 500 mg three times a day for the first week (29). MAIN OUTCOME MEASURES--Change in symptom scores determined with questionnaire; histological evidence of gastritis and microbiological evidence of presence of H pylori in biopsy specimens. RESULTS--Overall, H pylori was eradicated in 41 (49%) patients. Although gastritis scores improved significantly in only patients in whom H pylori had been eradicated (from 1.56 to 0.61, p less than 0.01 v from 1.83 to 1.07, p = 0.52) mean symptom scores after treatment were similar in patients in whom H pylori had or had not been eradicated (3.0 v 2.3, NS). Similarly the mean symptom score improved whether or not gastritis improved (2.8 v 3.1 respectively, p = 0.72). The observations were similar for treatment groups analysed individually. CONCLUSION--Antral infection with the organism does not seem to have an important aetiological role in non-ulcer dyspepsia short term. PMID:1747644

  4. Helicobacter pylori infection in women with Hashimoto thyroiditis

    PubMed Central

    Shmuely, Haim; Shimon, Ilan; Gitter, Limor Azulay

    2016-01-01

    Abstract An association between Helicobacter pylori (H pylori) infection as environmental risk factors for Hashimoto thyroiditis (HT) has been reported. We investigated this hypothesis in women in which HT is more common. Serum immunoglobulin G antibodies against H pylori (enzyme-linked immunosorbent assay), CagA protein (Western blot assay), circulating antibodies to thyroid antigens, mainly thyroperoxidase (TPOAbs) and thyroglobulin (TgAbs), were tested in 101 females with HT and 111 non-HT control women without a history of autoimmune disease. Thyroid function, socioeconomic status at childhood, and family history of thyroid malfunction were also studied. Forty-seven HT women (46.5%) tested seropositive for H pylori versus 48 controls (43.2%; P = 0.63). The prevalence of anti-CagA antibodies was 21.3% in HT-infected patients and 31.2% in infected controls (P = 0.352). Women with HT were older than the controls at a significance level of 0.03, and higher prevalence of hypothyroidism (69% vs 13.5%, respectively) and family history of thyroid malfunction (59% vs 34%, respectively) (P < 0.001 in both). Body mass index, diaphragmatic hernia, peptic ulcer, heartburn, use of proton pump inhibitors, childhood socioeconomic background, and crowding index showed no significant difference between HT-positive or negative individuals. Multivariate analysis demonstrated that H pylori seropositivity was not associated with HT (odds ratio 1.15, 95% confidence interval 0.57–1.83, P = 0.95) and that family thyroid malfunction was independently associated with an increased risk of HT (odds ratio 3.39, 95% confidence interval 1.86–6.18, P < 0.001). No association was found between H pylori infection and HT in women. Family history of thyroid malfunction is a risk factor for HT. PMID:27442635

  5. Loose ends in the eradication of Helicobacter pylori infection

    PubMed Central

    Silva, Marco; Gaspar, Rui; Morais, Rui; Ramalho, Rosa; Macedo, Guilherme; Santos-Antunes, João

    2016-01-01

    Abstract The eradication of Helicobacter pylori is essential for prevention and treatment of various conditions associated with this infection. However, its effectiveness is limited and influenced by factors linked to the bacteria and the host. In particular, influence of the biotype, smoking, diabetes mellitus, and previous treatment failure in eradication is understudied. Our center proposed to evaluate these aspects in a real life cohort by applying a questionnaire with demographic and lifestyle variables in patients who consecutively underwent urease breath test after the eradication therapy. PMID:28191542

  6. TRPM2 ion channels regulate macrophage polarization and gastric inflammation during Helicobacter pylori infection.

    PubMed

    Beceiro, S; Radin, J N; Chatuvedi, R; Piazuelo, M B; Horvarth, D J; Cortado, H; Gu, Y; Dixon, B; Gu, C; Lange, I; Koomoa, D-Lt; Wilson, K T; Algood, H M S; Partida-Sánchez, S

    2017-03-01

    Calcium signaling in phagocytes is essential for cellular activation, migration, and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection. We show that Trpm2(-)/(-) mice, when chronically infected with H. pylori, exhibit increased gastric inflammation and decreased bacterial colonization compared with wild-type (WT) mice. The absence of TRPM2 triggers greater macrophage production of inflammatory mediators and promotes classically activated macrophage M1 polarization in response to H. pylori. TRPM2-deficient macrophages upon H. pylori stimulation are unable to control intracellular calcium levels, which results in calcium overloading. Furthermore, increased intracellular calcium in TRPM2(-)/(-) macrophages enhanced mitogen-activated protein kinase and NADPH-oxidase activities, compared with WT macrophages. Our data suggest that augmented production of ROS and inflammatory cytokines with TRPM2 deletion regulates oxidative stress in macrophages and consequently decreases H. pylori gastric colonization while increasing inflammation in the gastric mucosa.

  7. Fermented Foods: Are They Tasty Medicines for Helicobacter pylori Associated Peptic Ulcer and Gastric Cancer?

    PubMed Central

    Nair, Mydhily R. B.; Chouhan, Deepak; Sen Gupta, Sourav; Chattopadhyay, Santanu

    2016-01-01

    More than a million people die every year due to gastric cancer and peptic ulcer. Helicobacter pylori infection in stomach is the most important reason for these diseases. Interestingly, only 10–20% of the H. pylori infected individuals suffer from these gastric diseases and rest of the infected individuals remain asymptomatic. The genotypes of H. pylori, host genetic background, lifestyle including smoking and diet may determine clinical outcomes. People from different geographical regions have different food habits, which also include several unique fermented products of plant and animal origins. When consumed raw, the fermented foods bring in fresh inocula of microbes to gastrointestinal tract and several strains of these microbes, like Lactobacillus and Saccharomyces are known probiotics. In vitro and in vivo experiments as well as clinical trials suggest that several probiotics have anti-H. pylori effects. Here we discuss the possibility of using natural probiotics present in traditional fermented food and beverages to obtain protection against H. pylori induced gastric diseases. PMID:27504109

  8. Helicobacter pylori eradication as prevention against chronic peptic ulcer disease in children.

    PubMed

    Maciorkowska, E; Kaczmarski, M; Skowrońska, J; Cieśla, J M; Chrzanowska, U; Olejnik, B T; Sacharewicz, A; Ryszczuk, E

    2005-01-01

    The changes caused by Helicobacter pylori are a slow, progressing inflammatory process developing from several to dozen years. H. pylori infection leads to an inflammatory response in the gastric mucosa with granulocyte infiltrates in an acute form of the inflammation, and lymphocytes, plasmatic, macrophages and eosinophils in a chronic form inducing the development of gastric and duodenal ulcers and gastric cancer in some patients. The frequency and the type of morphological changes in the gastric mucosa were analyzed in children with positive IgG against H. pylori and the incidence of gastric and duodenal ulcers in family members of children examined was evaluated in our study. Gastritis was reported in 68.8% of children with positive IgG against H. pylori. Gastric ulcer was confirmed in 37.1% of families of children included in the study. Duodenal ulcers were found in 22.9% of families. The results obtained, indicate the usefulness of long-term observation and clinical follow-up of children with chronic gastritis of H. pylori ethiology taking into consideration bacterium eradication as prophylaxis of peptic ulceration.

  9. Comparison of the nucleic acids of helical and coccoid forms of Helicobacter pylori.

    PubMed Central

    Narikawa, S; Kawai, S; Aoshima, H; Kawamata, O; Kawaguchi, R; Hikiji, K; Kato, M; Iino, S; Mizushima, Y

    1997-01-01

    The nucleic acids of the helical and coccoid forms of Helicobacter pylori were studied to determine if the coccoid forms are "viable (capable of growing) but nonculturable." Using a reference strain (NCTC 11638) and five clinical strains, the nucleic acid contents, DNA integrity, and results of PCR and reverse transcription-PCR (RT-PCR) were compared for helical H. pylori and coccoid forms induced using glycochenodeoxycholic acid or bismuth citrate. The DNA and RNA contents of the coccoid forms were respectively 6.8- and 8.1-fold lower than those of helical H. pylori after 3 days of induction and 11.5- and 14.7-fold lower after 7 days. Agarose gel electrophoresis of DNA extracted from the coccoid forms after 3 days of induction showed a smear pattern indicating DNA cleavage, whereas DNA from helical H. pylori showed a single band with a high molecular mass. After 12 days of induction, all RNA samples from 100% coccoid cultures were negative for the mRNA of urease A or the 26-kDa species-specific protein by RT-PCR. However, most RNA samples obtained after 3 or 7 days of induction were positive at low levels despite the lack of recovery from these cultures. These results suggest that the coccoid form of H. pylori has impaired genomic DNA and is in the process of cellular degeneration, thus being still alive but nonincreasable. PMID:9144365

  10. TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection

    PubMed Central

    Beceiro, Susana; Radin, Jana N.; Chatuvedi, Rupesh; Piazuelo, M. Blanca; Horvarth, Dennis J.; Cortado, Hanna; Gu, Yuanzheng; Dixon, Beverly; Gu, Chen; Lange, Ingo; Koomoa, Dana-Lynn T.; Wilson, Keith T.; Scott Algood, Holly M.; Partida-Sánchez, Santiago

    2016-01-01

    Calcium signaling in phagocytes is essential for cellular activation, migration and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate-) oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection. We show that Trpm2−/− mice, when chronically infected with H. pylori, exhibit increased gastric inflammation and decreased bacterial colonization compared with WT mice. The absence of TRPM2 triggers greater macrophage production of inflammatory mediators and promotes classically activated macrophage M1 polarization in response to H. pylori. TRPM2-deficient macrophages upon H. pylori stimulation are unable to control intracellular calcium levels, which results in calcium overloading. Furthermore, increased intracellular calcium in TRPM2−/− macrophages enhanced MAPK and NADPH oxidase activities, compared to WT macrophages. Our data suggest that augmented production of ROS and inflammatory cytokines with TRPM2 deletion regulates oxidative stress in macrophages, and consequently, decreases H. pylori gastric colonization while increasing inflammation in the gastric mucosa. PMID:27435104

  11. Immunomodulatory Effects of Psyllium Extract on Helicobacter pylori Interaction With Gastric Epithelial Cells.

    PubMed

    Yakoob, Javed; Jafri, Wasim; Mehmood, Malik Hassan; Abbas, Zaigham; Tariq, Kanwal

    2016-10-01

    Natural plant product Psyllium has anti-inflammatory activity that can modulate the function of cytokines. We determined the effect of Psyllium husk extract on interleukin (IL)-8 and NF-κB secretion by gastric epithelial cells in response to Helicobacter pylori Human gastric adenocarcinoma cell line (AGS) cells were pretreated with Psyllium extract in different concentrations before H pylori infection. Cell culture supernatant was analyzed for IL-8 and NF-κB by ELISA. RNA from cells was used for real-time polymerase chain reaction for messenger RNA expression of IL-8. Psyllium extract 5 and 10 μg/mL markedly (P < .001) lowered basal IL-8 by 64.71% and 74.51%, respectively, and H pylori-stimulated IL-8 was also (P < .001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10 μg/mL also reduced (P < .0001) cagA-positive H pylori-induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced (P = .0001) NF-κB in response to H pylori strains confirming its role as an anti-inflammatory agent.

  12. Fermented Foods: Are They Tasty Medicines for Helicobacter pylori Associated Peptic Ulcer and Gastric Cancer?

    PubMed

    Nair, Mydhily R B; Chouhan, Deepak; Sen Gupta, Sourav; Chattopadhyay, Santanu

    2016-01-01

    More than a million people die every year due to gastric cancer and peptic ulcer. Helicobacter pylori infection in stomach is the most important reason for these diseases. Interestingly, only 10-20% of the H. pylori infected individuals suffer from these gastric diseases and rest of the infected individuals remain asymptomatic. The genotypes of H. pylori, host genetic background, lifestyle including smoking and diet may determine clinical outcomes. People from different geographical regions have different food habits, which also include several unique fermented products of plant and animal origins. When consumed raw, the fermented foods bring in fresh inocula of microbes to gastrointestinal tract and several strains of these microbes, like Lactobacillus and Saccharomyces are known probiotics. In vitro and in vivo experiments as well as clinical trials suggest that several probiotics have anti-H. pylori effects. Here we discuss the possibility of using natural probiotics present in traditional fermented food and beverages to obtain protection against H. pylori induced gastric diseases.

  13. Attempts to enhance the eradication rate of Helicobacter pylori infection

    PubMed Central

    Bang, Chang Seok; Baik, Gwang Ho

    2014-01-01

    Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates. Knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen. In addition, adverse effect profiles of therapeutic regimens are important and must be addressed to enhance compliance rates. Various methods of enhancing the eradication rates of Helicobacter pylori (H. pylori) have been investigated, including changing combinations or durations of established drugs, adding adjuvant drugs, or development of new molecules or agents. Bismuth-containing quadruple, sequential, concomitant, and levofloxacin-based triple therapies are replacing the long-standing standard of the triple regimen. Despite the encouraging results of these regimens, individualized approaches like treatment after antibiotics resistance test or CYP2C19 genotyping would be the mainstream of future therapy. Because scientific, economic, and technical problems make these advance therapies unfit for widespread use, future development for H. pylori therapy should be directed to overcome individualized antibiotic resistance. Although various novel regimens and additive agents have indicated favorable outcomes, more studies or validations are needed to become a mainstream H. pylori therapy. PMID:24833855

  14. Population screening and treatment of Helicobacter pylori infection.

    PubMed

    O'Connor, Anthony; O'Morain, Colm A; Ford, Alexander C

    2017-04-01

    Helicobacter pylori is an important human pathogen, associated with a substantial burden from both malignant and non-malignant diseases. The bacterium is classed as a human carcinogen, being strongly linked with gastric cancer, the third most common cause of cancer death worldwide and is also associated with common conditions such as dyspepsia and peptic ulcer. Eradication of H. pylori reduces the incidence of gastric cancer and peptic ulcer, as well as the prevalence and costs of managing dyspepsia. Economic analyses suggest that eradication of H. pylori as a means of controlling gastric cancer is cost-effective in high-risk populations. Even in populations at low risk of gastric cancer, there might be other benefits arising from screening and treatment, owing to the effects on non-malignant upper gastrointestinal diseases. However, public health authorities have been slow to consider the benefits of population-based screening and treatment as a means of reducing the morbidity and mortality associated with the infection. There are also concerns about widespread use of eradication therapy, including antimicrobial resistance and a rise in the prevalence of diseases that are negatively associated with H. pylori, such as GERD, Barrett oesophagus, asthma and obesity. This Review summarizes these issues.

  15. Cooperation of Gastric Mononuclear Phagocytes with Helicobacter pylori during Colonization.

    PubMed

    Viladomiu, Monica; Bassaganya-Riera, Josep; Tubau-Juni, Nuria; Kronsteiner, Barbara; Leber, Andrew; Philipson, Casandra W; Zoccoli-Rodriguez, Victoria; Hontecillas, Raquel

    2017-03-06

    Helicobacter pylori, the dominant member of the human gastric microbiota, elicits immunoregulatory responses implicated in protective versus pathological outcomes. To evaluate the role of macrophages during infection, we employed a system with a shifted proinflammatory macrophage phenotype by deleting PPARγ in myeloid cells and found a 5- to 10-fold decrease in gastric bacterial loads. Higher levels of colonization in wild-type mice were associated with increased presence of mononuclear phagocytes and in particular with the accumulation of CD11b(+)F4/80(hi)CD64(+)CX3CR1(+) macrophages in the gastric lamina propria. Depletion of phagocytic cells by clodronate liposomes in wild-type mice resulted in a reduction of gastric H. pylori colonization compared with nontreated mice. PPARγ-deficient and macrophage-depleted mice presented decreased IL-10-mediated myeloid and T cell regulatory responses soon after infection. IL-10 neutralization during H. pylori infection led to increased IL-17-mediated responses and increased neutrophil accumulation at the gastric mucosa. In conclusion, we report the induction of IL-10-driven regulatory responses mediated by CD11b(+)F4/80(hi)CD64(+)CX3CR1(+) mononuclear phagocytes that contribute to maintaining high levels of H. pylori loads in the stomach by modulating effector T cell responses at the gastric mucosa.

  16. Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas.

    PubMed

    Thorell, Kaisa; Yahara, Koji; Berthenet, Elvire; Lawson, Daniel J; Mikhail, Jane; Kato, Ikuko; Mendez, Alfonso; Rizzato, Cosmeri; Bravo, María Mercedes; Suzuki, Rumiko; Yamaoka, Yoshio; Torres, Javier; Sheppard, Samuel K; Falush, Daniel

    2017-02-01

    For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.

  17. Structural Insight into Polymorphic ABO Glycan Binding by Helicobacter pylori

    PubMed Central

    Moonens, Kristof; Gideonsson, Pär; Subedi, Suresh; Bugaytsova, Jeanna; Romaõ, Ema; Mendez, Melissa; Nordén, Jenny; Fallah, Mahsa; Rakhimova, Lena; Shevtsova, Anna; Lahmann, Martina; Castaldo, Gaetano; Brännström, Kristoffer; Coppens, Fanny; Lo, Alvin W.; Ny, Tor; Solnick, Jay V.; Vandenbussche, Guy; Oscarson, Stefan; Hammarström, Lennart; Arnqvist, Anna; Berg, Douglas E.; Muyldermans, Serge; Borén, Thomas; Remaut, Han

    2016-01-01

    Summary The Helicobacter pylori adhesin BabA binds mucosal ABO/Leb blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Leb binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Leb-expressing mice, providing perspectives on possible H. pylori eradication therapies. PMID:26764597

  18. Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori.

    PubMed

    Cosme, A; Montes, M; Martos, M; Gil, I; Mendarte, U; Salicio, Y; Piñeiro, L; Recasens, M T; Ibarra, B; Sarasqueta, C; Bujanda, L

    2013-04-01

    The rate of eradication of Helicobacter pylori with standard triple therapy using omeprazole, amoxicillin and clarithromycin (OAC) is unacceptable in populations with high rates of clarithromycin resistance (15-20%). The aim of this study was to compare the efficacy of 10-day OAC therapy as the first-line treatment in patients diagnosed by culture with antimicrobial susceptibility or diagnosed by a (13) C-labelled urea breath test (UBT) without antimicrobial susceptibility in an area where the clarithromycin resistance rate was 15-20%. This was a retrospective cohort study of 266 patients, recruited consecutively throughout 2008. A total of 247 H. pylori-infected patients received antibiotic therapy (221 received the 10-day OAC therapy and 26 received other regimens) of which 134 patients were diagnosed by culture of gastric samples followed by antimicrobial susceptibility testing and 113 were diagnosed by UBT. In all patients, the eradication of H. pylori was checked by UBT. The cost of eradication by 10-day OAC treatment was assessed in each patient. The success rate of 10-day OAC therapy in patients diagnosed by culture and by UBT was 88% (103/117) and 49% (51/104), respectively (p <0.0005). The treatment was also more cost-effective in the former of these two groups (€571 versus €666). To perform culture and antimicrobial susceptibility of the H. pylori isolates was a more successful and cost effective strategy than empirical 10-day OAC treatment in populations with high rates of resistance to clarithromycin.

  19. A Novel Reduction Strategy of Clarithromycin Resistance in Helicobacter pylori

    PubMed Central

    Tadjrobehkar, Omid; Abdollahi, Hamid

    2014-01-01

    Background: Antibiotic resistance is a major therapeutic problem in patients infected with Helicobacter pylori. H. pylori clarithromycin resistant mutants have been evolved during antibiotic therapy, this is mainly due to 23s rRNA point mutations. Objectives: In the present study, we investigated anti-mutational features of four traditionally Iranian medicinal plants on three local isolated H. pylori strains. Materials and Methods: In this study clarithromycin resistance was used as a mutation indicator. Frequencies of such mutations in the presence and absence of plant extracts were evaluated. Mutation incidence was evaluated by Luria Delbruck fluctuation assay. Results: The mean mutation frequency in H. pylori isolates was 27 × 10-9 which decreased at the presence of Mirtus communis, Teucrium polium, Achillea millefolium and Thymus vulgaris of plant extract, this amount was 97.4%, 95.2%, 63.7% and 19.6% respectively. Moreover, A-to-G transition at 2143 position (A2143G) was detected by PCR-sequencing as major point mutation causing clarithromycin resistant mutants. Conclusions: The efficacy of these plant extracts in prohibiting resistance showed considerable results. This finding should be considered to use plant extracts with antibiotics to develop more effective eradication regimens. PMID:25741431

  20. Chemotactic response of Helicobacter pylori to human plasma and bile.

    PubMed

    Worku, Mulugeta L; Karim, Q Najma; Spencer, John; Sidebotham, Ramon L

    2004-08-01

    To clarify further the role of chemotaxis in Helicobacter pylori colonization, the in vitro bacterium response to human plasma and bile (secretions containing chemoeffector compounds that are present in the gastric mucus layer) was examined. Human plasma, after dilution to 1 % (v/v) with buffer, was found to be a chemoattractant for the motile bacillus. Human gall-bladder bile, after dilution to 2 % (v/v) with buffer, was found to be a chemorepellent, but did not cause the motility of the bacillus to be diminished after prolonged exposure. The basis of the chemoattractant effect of plasma was explored by examining how urea and 12 amino acids found in plasma affected the taxis of H. pylori. Urea and the amino acids histidine, glutamine, glycine and arginine were the strongest chemoattractants. Other amino acids were chemoattractants, with the exceptions of aspartic and glutamic acids, which were chemorepellents. The basis of the chemorepellent effect of bile was explored by examining how the six most abundant conjugated bile acids in human bile affected the taxis of H. pylori. All the bile acids were chemorepellents, with the greatest effects being demonstrated by taurocholic and taurodeoxycholic acids. The implications of these findings for H. pylori colonization of gastric epithelium are discussed.

  1. Approach to Helicobacter pylori infection in geriatric population.

    PubMed

    Cizginer, Sevdenur; Ordulu, Zehra; Kadayifci, Abdurrahman

    2014-08-06

    The prevalence of Helicobacter pylori (H. pylori) infection and its complications increase with age. The majority of infected individuals remain asymptomatic throughout the life but 10%-20% develops peptic ulcer disease and 1% gastric malignancies. The incidence of ulcers and their complications are more common in the older population resulting in higher hospitalization and mortality rates. The increased use of medications causing gastric mucosal damage and the decreased secretion of protective prostaglandins in elderly are major factors increasing gastric mucosal sensitivity to the destructive effects of H. pylori. Due to higher prevalence of gastrointestinal (GI) malignancies, upper GI endoscopy is mostly preferred in elderly for the diagnosis of infection. Therefore, "endoscopy and treat" strategy may be more appropriate instead of "test and treat" strategy for dyspeptic patients in older age. Urea breath test and stool antigen test can be used for control of eradication, except for special cases requiring follow-up with endoscopy. The indications for treatment and suggested eradication regimens are similar with other age groups; however, the eradication failure may be a more significant problem due to high antibiotic resistance and low compliance rate in elderly. Multidrug usage and drug interactions should always be considered before starting the treatment. This paper reviews briefly the epidemiology, diagnosis, disease manifestations, and treatment options of H. pylori in the geriatric population.

  2. Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas

    PubMed Central

    Mikhail, Jane; Kato, Ikuko; Suzuki, Rumiko; Yamaoka, Yoshio; Sheppard, Samuel K.; Falush, Daniel

    2017-01-01

    For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations. PMID:28231283

  3. Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori.

    PubMed

    Moonens, Kristof; Gideonsson, Pär; Subedi, Suresh; Bugaytsova, Jeanna; Romaõ, Ema; Mendez, Melissa; Nordén, Jenny; Fallah, Mahsa; Rakhimova, Lena; Shevtsova, Anna; Lahmann, Martina; Castaldo, Gaetano; Brännström, Kristoffer; Coppens, Fanny; Lo, Alvin W; Ny, Tor; Solnick, Jay V; Vandenbussche, Guy; Oscarson, Stefan; Hammarström, Lennart; Arnqvist, Anna; Berg, Douglas E; Muyldermans, Serge; Borén, Thomas; Remaut, Han

    2016-01-13

    The Helicobacter pylori adhesin BabA binds mucosal ABO/Le(b) blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

  4. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori.

    PubMed

    Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

    2014-07-28

    Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world's population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections.

  5. Helicobacter pylori eradication therapy: A review of current trends.

    PubMed

    Olokoba, A B; Obateru, O A; Bojuwoye, M O

    2013-01-01

    Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.

  6. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

    PubMed Central

    Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

    2014-01-01

    Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections. PMID:25071326

  7. Helicobacter pylori virulence factors as tools to study human migrations.

    PubMed

    Queiroz, Dulciene Maria de Magalhães; Cunha, Roberto Penna de Almeida; Saraiva, Ivan Euclides Borges; Rocha, Andreia Maria Camargos

    2010-12-15

    Helicobacter pylori is one of the most common infections worldwide. In most individuals it consists in a lifelong host-pathogen relationship without consequences, but in some subjects it is associated with peptic ulcer disease and gastric cancer. Polymorphism in genes that code bacterial virulence factors, cagA and vacA, are independently associated with the infection severe outcomes and are geographically diverse. In the last decade, accumulated knowledge allowed to characterize typical H. pylori strain patterns for all the major human populations; patterns that can be used to study the origin of specific human groups. Thus, the presence or absence of cagA, cagA EPIYA genotypes, and vacA subtypes can be used as tools to study not only the geographic origin of specific human populations, but also to identify markers of historical contact between different ethnicities. We report here a study including a set of native Amazon Amerindians that had supposedly been some, but little, contact with European Brazilian colonizer and/or African slaves. They harbor H. pylori strains in a mixed pattern with Asian and Iberian Peninsula characteristics. It is possible that this finding represents H. pylori recombination upon short contact between human groups. Alternatively, it could be due to a founder effect from a small cluster of Asian origin native Americans.

  8. Nickel trafficking system responsible for urease maturation in Helicobacter pylori.

    PubMed

    Ge, Rui-Guang; Wang, Dong-Xian; Hao, Ming-Cong; Sun, Xue-Song

    2013-12-07

    Helicobacter pylori (H. pylori) is a common human pathogen responsible for various gastric diseases. This bacterium relies on the production of urease and hydrogenase to inhabit the acidic environment of the stomach. Nickel is an essential cofactor for urease and hydrogenase. H. pylori has to uptake sufficient nickel ions for the maturation of urease, and on the other way, to prevent the toxic effects of excessive nickel ions. Therefore, H. pylori has to strike a delicate balance between the import of nickel ions, its efficient intracellular storage, and delivery to nickel-dependent metalloenzymes when required. The assembly and maturation of the urease enzyme is a complex and timely ordered process, requiring various regulatory, uptake, chaperone and accessory proteins. In this review, we focus on several nickel trafficking proteins involved in urease maturation: NikR, NixA, HypAB, UreEFGH, HspA, Hpn and Hpnl. The work will deepen our understanding of how this pathogenic bacterium adapts to severe habitant environments in the host.

  9. Alternative therapies for Helicobacter pylori: probiotics and phytomedicine.

    PubMed

    Vítor, Jorge M B; Vale, Filipa F

    2011-11-01

    Helicobacter pylori is a common human pathogen infecting about 30% of children and 60% of adults worldwide and is responsible for diseases such as gastritis, peptic ulcer and gastric cancer. Treatment against H. pylori is based on the use of antibiotics, but therapy failure can be higher than 20% and is essentially due to an increase in the prevalence of antibiotic-resistant bacteria, which has led to the search for alternative therapies. In this review, we discuss alternative therapies for H. pylori, mainly phytotherapy and probiotics. Probiotics are live organisms or produced substances that are orally administrated, usually in addition to conventional antibiotic therapy. They may modulate the human microbiota and promote health, prevent antibiotic side effects, stimulate the immune response and directly compete with pathogenic bacteria. Phytomedicine consists of the use of plant extracts as medicines or health-promoting agents, but in most cases the molecular mode of action of the active ingredients of these herbal extracts is unknown. Possible mechanisms include inhibition of H. pylori urease enzyme, disruption of bacterial cell membrane, and modulation of the host immune system. Other alternative therapies are also reviewed.

  10. Rapid improvement of Henoch-Schonlein purpura associated with the treatment of Helicobacter pylori infection

    PubMed Central

    Ulas, Turgay; Tursun, Irfan; Dal, Mehmet Sinan; Eren, Mehmet Ali; Buyukhatipoglu, Hakan

    2012-01-01

    Helicobacter pylori (H. pylori) are one of the most common bacterial infections, seen in humans, worldwide and their possible relationships to different diseases are a focus of attention nowadays. H. pylori may cause some extra intestinal manifestations some of which are dermatological conditions, including Henoch-Schönlein purpura (HSP), chronic urticaria and atopic dermatitis. We describe a 49-year-old man who presented with HSP triggered by gastric H. pylori infection. Treatment of H. Pylori infection was accompanied by prompt resolution of the gastrointestinal manifestations and purpuric rashes. These findings suggest a causative role for H. pylori in the occurrence of HSP. PMID:23833587

  11. Prevalence of Helicobacter pylori Infection in Samples of Gastric Biopsies

    PubMed Central

    Trindade, Leda Maria Delmondes Freitas; Menezes, Lania Barreto de Oliveira; de Souza Neta, Adozina Marques; Leite Rolemberg, Paulo Candido; Souza, Lais Dantas; Barreto, Ikaro Daniel de Carvalho; Meurer, Luise

    2017-01-01

    Background Helicobacter pylori (H. pylori) infection affects about 50% of the world population and its association with environmental factors and host properties is involved in gastric carcinogenesis. The study aimed to estimate the prevalence of H. pylori in samples of gastric mucosa biopsies, correlate the presence of the bacteria in the sample with the variables age, sex and origin, to identify the types of lesions found in patients with H. pylori, and to evaluate the association of the lesions with the region of the gastric mucosa. Methods A cross-sectional, retrospective study was carried out in Aracaju, Sergipe, Brazil, from January 2013 to December 2015. A total of 45,206 gastric mucosal biopsies were obtained from patients submitted to upper gastrointestinal endoscopy. Of the reports evaluated, 12,909 met the inclusion criteria since they presented the patient’s demographic data as well as the histopathological characteristics of gastric mucosal regions and positivity for H. pylori. Data were analyzed by IBM SPSS Statistic 20 and subjected to descriptive analyses (categorical variables) and inferential (Pearson’s Qui-square and linear association tests) and multiple correspondence analyses. Significance level adopted 5%. Results Of the total of 12,909 (28.6%) reports evaluated, 67% (8,647) came from urban areas and 64.5% (8,320) were female. The mean age (standard deviation (SD)) was 43 years, ranging from 8 to 100 years, prevailing between 21 and 60 years. Among the types of gastric mucosa analyzed, 95.5% (12,322) were of the antral mucosa. The absence of glandular atrophy, the mild infection intensity for H. pylori, the absence of metaplasia, the presence of foveolar hyperplasia and lymphoid follicles were statistically significant (P < 0.001) in this region. In the fundic region, the evidence of fibrinoleucocytic crust and lymphoid follicles was significant (P < 0.001). There was no evidence of associated ulcerated lesions or significant relationship

  12. Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway.

    PubMed

    Maeda, Masahiro; Moro, Hiroshi; Ushijima, Toshikazu

    2017-03-01

    Multiple pathogenic mechanisms by which Helicobacter pylori infection induces gastric cancer have been established in the last two decades. In particular, aberrant DNA methylation is induced in multiple driver genes, which inactivates them. Methylation profiles in gastric cancer are associated with specific subtypes, such as microsatellite instability. Recent comprehensive and integrated analyses showed that many cancer-related pathways are more frequently altered by aberrant DNA methylation than by mutations. Aberrant DNA methylation can even be present in noncancerous gastric mucosae, producing an "epigenetic field for cancerization." Mechanistically, H. pylori-induced chronic inflammation, but not H. pylori itself, plays a direct role in the induction of aberrant DNA methylation. The expression of three inflammation-related genes, Il1b, Nos2, and Tnf, is highly associated with the induction of aberrant DNA methylation. Importantly, the degree of accumulated aberrant DNA methylation is strongly correlated with gastric cancer risk. A recent multicenter prospective cohort study demonstrated the utility of epigenetic cancer risk diagnosis for metachronous gastric cancer. Suppression of aberrant DNA methylation by a demethylating agent was shown to inhibit gastric cancer development in an animal model. Induction of aberrant DNA methylation is the major pathway by which H. pylori infection induces gastric cancer, and this can be utilized for translational opportunities.

  13. Structure-based inhibitors exhibit differential activities against Helicobacter pylori and Escherichia coli undecaprenyl pyrophosphate synthases.

    PubMed

    Kuo, Chih-Jung; Guo, Rey-Ting; Lu, I-Lin; Liu, Hun-Ge; Wu, Su-Ying; Ko, Tzu-Ping; Wang, Andrew H-J; Liang, Po-Huang

    2008-01-01

    Helicobacter pylori colonizes the human gastric epithelium and causes diseases such as gastritis, peptic ulcers, and stomach cancer. Undecaprenyl pyrophosphate synthase (UPPS), which catalyzes consecutive condensation reactions of farnesyl pyrophosphate with eight isopentenyl pyrophosphate to form lipid carrier for bacterial peptidoglycan biosynthesis, represents a potential target for developing new antibiotics. In this study, we solved the crystal structure of H. pylori UPPS and performed virtual screening of inhibitors from a library of 58,635 compounds. Two hits were found to exhibit differential activities against Helicobacter pylori and Escherichia coli UPPS, giving the possibility of developing antibiotics specially targeting pathogenic H. pylori without killing the intestinal E. coli.

  14. Detection of Helicobacter pylori and fecal indicator bacteria in five North American rivers.

    USGS Publications Warehouse

    Voytek, M.A.; Ashen, J.B.; Fogarty, L.R.; Kirshtein, J.D.; Landa, E.R.

    2005-01-01

    This study examines the use of fecal indicator bacteria (FIB) as a predictor of the presence of Helicobacter spp. A combination of standard culture and molecular techniques were used to detect and quantify FIB, Helicobacter spp. and H. pylori from five North American rivers of different size and with different land use characteristics. Primers designed to amplify genes specific to Helicobacter spp. and H. pylori were evaluated for their efficacy in detection and quantification in environmental samples. Helicobacter spp. were detected in 18/33 (55%) of river samples. H. pylori was detected in 11/33 (33%) of river samples. FIB were found in 32/33 (96%) of river samples. When FIB abundance exceeded USEPA water quality standards for single samples, Helicobacter or H. pylori were detected in 7/15 (47%) cases. No numerical correlation was found between the presence of FIB and either Helicobacter spp. or H. pylori. This suggests that the presence of FIB will be of limited use for detection of Helicobacter spp. or H. pylori by public health agencies.

  15. Symptomatic infantile Helicobacter pylori gastritis infection in indigenous African infants: a case series.

    PubMed

    Malande, Oliver Ombeva

    2014-01-01

    Helicobacter pylori gastritis infection rate increases with age. Higher rates have however been reported among young people in the developing countries of the world. The infection however has rarely been reported in infants, especially in Africa. This case series describes three cases of Helicobacter pylori gastritis infection as diagnosed in three infants. The goal is to raise the suspicion index of medical practitioners about the possibility of this this infection among infants who present with suggestive symptoms. On three separate occasions in 2012 and 2013, three ill, indigenous, black African female infants aged 4, 6 and 7 months, were brought to hospital with symptoms ranging from fever, refusal to feed, diarrhoea, restlessness, vomiting and irritability. In each case, systemic examination findings were unremarkable. After several laboratory investigations, each infant was found to have Helicobacter pylori infection following positive blood antibody (using Tell Me Fast H. Pylori antibody serum and Plasma test manufactured by Biocan Diagnostics Canada) and fecal HpSA ImmunoCardSTAT antigen tests. Repeat stool antigen test was negative in each case after completion of the recommended triple therapy. Helicobacter pylori infection has been rarely reported among infants. This case series highlights the need for health care providers to have a high index of suspicion so that infants with suggestive symptoms, especially in settings with high Helicobacter pylori colonization prevalence can be evaluated for Helicobacter pylori gastritis infection.

  16. EGFR tyrosine kinase inhibitory peptide attenuates Helicobacter pylori-mediated hyper-proliferation in AGS enteric epithelial cells

    SciTech Connect

    Himaya, S.W.A.; Dewapriya, Pradeep; Kim, Se-Kwon

    2013-06-15

    Helicobacter pylori infection is one of the most critical causes of stomach cancer. The current study was conducted to explore the protective effects of an isolated active peptide H-P-6 (Pro-Gln-Pro-Lys-Val-Leu-Asp-Ser) from microbial hydrolysates of Chlamydomonas sp. against H. pylori-induced carcinogenesis. The peptide H-P-6 has effectively suppressed H. pylori-induced hyper-proliferation and migration of gastric epithelial cells (AGS). However, the peptide did not inhibit the viability of the bacteria or invasion into AGS cells. Therefore, the effect of the peptide on regulating H. pylori-induced molecular signaling was investigated. The results indicated that H. pylori activates the EGFR tyrosine kinase signaling and nuclear translocation of the β-catenin. The EGFR activation has led to the up-regulation of PI3K/Akt signaling pathway. Moreover, the nuclear translocation levels of β-catenin were significantly increased as a result of Akt mediated down-regulation of GSK3/β protein levels in the cytoplasm. Both of these consequences have resulted in increased expression of cell survival and migration related genes such as c-Myc, cyclin-D, MMP-2 and matrilysin. Interestingly, the isolated peptide potently inhibited H. pylori-mediated EGFR activation and thereby down-regulated the subsequent P13K/Akt signaling leading to β-catenin nuclear translocation. The effect of the peptide was confirmed with the use of EGFR tyrosine kinase inhibitor AG1487 and molecular docking studies. Collectively this study identifies a potent peptide which regulates the H. pylori-induced hyper-proliferation and migration of AGS cells at molecular level. - Highlights: • Chlamydomonas sp. derived peptide H-P-6 inhibits H. pylori-induced pathogenesis. • H-P-6 suppresses H. pylori-induced hyper-proliferation and migration of AGS cells. • The peptide inhibits H. pylori-induced EGFR activation.

  17. Helicobacter pylori and the BMP pathway regulate CDX2 and SOX2 expression in gastric cells.

    PubMed

    Camilo, Vânia; Barros, Rita; Sousa, Sofia; Magalhães, Ana Maria; Lopes, Teresa; Mário Santos, António; Pereira, Teresa; Figueiredo, Céu; David, Leonor; Almeida, Raquel

    2012-10-01

    Helicobacter pylori infection is the main risk factor for intestinal metaplasia (IM) and gastric cancer development. IM is a pre-neoplastic lesion, induced by the transcription factor CDX2, where the gastric mucosa is converted to an intestinal phenotype. We previously demonstrated that key elements of the bone morphogenetic protein (BMP) pathway co-localize with CDX2 in IM and upregulate CDX2 expression in gastric cell lines. These observations, together with the hypothesis that CDX2 could be repressed by SOX2, led us to test whether H. pylori, through BMPs, SOX2 and CDX2 could participate in a molecular network critical for the development of IM. AGS cells with and without SMAD4 knock-down were co-cultured with H. pylori or BMP2 to assess the expression of BMP pathway members as well as CDX2 and SOX2 by qPCR and western blot. Proximity ligation assay (PLA) was also performed to evaluate SMAD proteins interaction. Immunohistochemistry and western blot were performed in gastric samples from mice infected with Helicobacter spp. to measure Smad4, pSmad1/5/8, Cdx2 and Sox2 expression in vivo. Increased expression and activity of the BMP pathway accompanied by CDX2 upregulation and SOX2 downregulation were observed in AGS cells co-cultured with H. pylori or BMP2. These effects were impaired by downregulation of the BMP pathway. Finally, infected mice present BMP pathway upregulation, focal Cdx2 expression and decreased Sox2. These results provide a novel link between H. pylori infection and the BMP pathway in the regulation of intestinal and gastric-specific genes that might be relevant for gastric IM.

  18. Diagnosis of Helicobacter pylori: What should be the gold standard?

    PubMed Central

    Patel, Saurabh Kumar; Pratap, Chandra Bhan; Jain, Ashok Kumar; Gulati, Anil Kumar; Nath, Gopal

    2014-01-01

    Since the discovery of Helicobacter pylori (H. pylori) in 1983, numerous detection methods for the presence of the bacterium have been developed. Each one of them has been associated with advantages and disadvantages. Noninvasive tests such as serology, 13C urea breath test (UBT) and stool antigen tests are usually preferred by the clinicians. Serology has its own limitation especially in endemic areas while 13C UBT is technically very demanding. The stool antigen detection method, although specific, is usually associated with poor sensitivity. The 13C UBT is believed to be specific, but with present revelation of the fact that stomach is colonized by many other urease producing bacteria makes it questionable. Histology, culture, rapid urease test and polymerase chain reaction (PCR) are the tests which are carried out on antral biopsies collected by invasive means. Histology has been proposed to be very sensitive and specific but the question is how by simply looking the morphology of the bacteria in the microscope, one can claim that the curved bacterium is exclusively H. pylori. Rapid urease test (RUT), the doctor’s test, is also challenged because the presence of other urease producing bacteria in the stomach cannot be denied. Moreover, RUT has been reported with poor sensitivity specially, when density of the bacterium is low. Isolation of H. pylori is essential to investigate its growth requirements, antibiotic susceptibility testing, studying virulence factor to develop vaccine and many more explorations. It has also got several disadvantages i.e., special condition for transporting, media, incubation and few days waiting for the colonies to appear, apart from the speed essentially needed to process the specimens. Till date, majority of the microbiological laboratories in the world are not equipped and trained to isolate such fastidious bacterium. The option left is PCR methods to detect H. pylori’s DNA in gastric mucosa, gastric juice, saliva, dental

  19. Helicobacter pylori infection modulates the expression of miRNAs associated with DNA mismatch repair pathway.

    PubMed

    Santos, Juliana C; Brianti, Mitsue T; Almeida, Victor R; Ortega, Manoela M; Fischer, Wolfgang; Haas, Rainer; Matheu, Ander; Ribeiro, Marcelo L

    2017-04-01

    Genetic and epigenetic inactivation of DNA mismatch repair (MMR) genes might lead to modifications in cancer-related gene expression and cancer development. Recently, it has been shown that the infection by Helicobacter pylori, the major causative agent of gastric cancer, induces DNA damage and inhibits MMR DNA repair. Also, it has been reported that microRNAs (miRs) have an important role in regulating genomic stability and MMR DNA repair. Thus, the aim of this study was to identify miRs regulating MMR pathway in H. pylori-associated gastric carcinogenesis. To address this question, a gastric epithelial cell line and AGS cancer gastric cells were infected with several H. pylori strains. MMR gene expression and miRs correlating with H. pylori strain infection were evaluated. The results showed that H. pylori infection significantly down-regulated the expression of all selected MMR genes. Also, H. pylori infection modulated the expression of several miRs (including miR-150-5p, miR-155-5p, and miR-3163), after 4, 8, and 12 h of infection. Computational prediction of candidate miRs and their predicted MMR targeting sites were obtained from TargetScan, mirDB, and MetaCore. The generated data indicated that the selected miRs (miR-150-5p, miR-155-5p, and miR-3163) could possibly target and modulate MMR genes (POLD3, MSH2, and MSH3, respectively). The target validation was performed using mimics and luciferase gene reporter assays. Briefly, this study shows that H. pylori impairs MMR DNA repair pathway and identifies miRs that regulate MMR gene expression in gastric cancer. © 2016 Wiley Periodicals, Inc.

  20. Partial characterization of a cell proliferation-inhibiting protein produced by Helicobacter pylori.

    PubMed Central

    Knipp, U; Birkholz, S; Kaup, W; Opferkuch, W

    1996-01-01

    Despite the induction of an immunological reaction, Helicobacter pylori-associated gastritis is a chronic disease, suggesting that this microbe can evade the host immune defense. Previous studies by our group showed that H. pylori suppresses the in vitro proliferative response of human mononuclear cells to mitogens and antigens. Here we demonstrate that the antiproliferative activity of H. pylori also affects the proliferation of various mammalian cell lines (U937, Jurkat, AGS, Kato-3, HEP-2, and P388D1). This effect is detectable in the first 16 h of incubation and maximal between 24 and 48 h. In addition, the presence of H. pylori significantly diminished the protein synthesis of cells in the first 6 h of incubation, comparable to the results with cycloheximide and diphtheria toxin. The urease enzyme, the cagA gene product, and the vacuolizing cytotoxin of H. pylori were excluded as causative agents of the antiproliferative effect by using isogenic knockout mutant strains. The inhibitory effect was not due to a lytic activity of this bacterium. The results reported here indicate that the responsible factor is a protein with an apparent native molecular mass of 100 +/- 10 kDa. Our work implicates the presence of a protein factor in H. pylori (termed PIP [for proliferation-inhibiting protein]) with antiproliferative activity for mammalian cells, including immunocompetent and epithelial cells. Thus, it is reasonable to presume that this property may contribute to the pathogenesis of H. pylori-induced diseases. It may be involved on the one hand in immune response evasion and on the other hand in the suppression of epithelial repair mechanisms. PMID:8751889

  1. Galectin-3 Plays an Important Role in Innate Immunity to Gastric Infection by Helicobacter pylori.

    PubMed

    Park, Ah-Mee; Hagiwara, Satoru; Hsu, Daniel K; Liu, Fu-Tong; Yoshie, Osamu

    2016-04-01

    We studied the role of galectin-3 (Gal3) in gastric infection by Helicobacter pylori We first demonstrated that Gal3 was selectively expressed by gastric surface epithelial cells and abundantly secreted into the surface mucus layer. We next inoculated H. pylori Sydney strain 1 into wild-type (WT) and Gal3-deficient mice using a stomach tube. At 2 weeks postinoculation, the bacterial cells were mostly trapped within the surface mucus layer in WT mice. In sharp contrast, they infiltrated deep into the gastric glands in Gal3-deficient mice. Bacterial loads in the gastric tissues were also much higher in Gal3-deficient mice than in WT mice. At 6 months postinoculation,H. pylori had successfully colonized within the gastric glands of both WT and Gal3-deficient mice, although the bacterial loads were still higher in the latter. Furthermore, large lymphoid clusters mostly consisting of B cells were frequently observed in the gastric submucosa of Gal3-deficient mice.In vitro, peritoneal macrophages from Gal3-deficient mice were inefficient in killing engulfed H. pylori Furthermore, recombinant Gal3 not only induced rapid aggregation of H. pylori but also exerted a potent bactericidal effect on H. pylori as revealed by propidium iodide uptake and a morphological shift from spiral to coccoid form. However, a minor fraction of bacterial cells, probably transient phase variants of Gal3-binding sugar moieties, escaped killing by Gal3. Collectively, our data demonstrate that Gal3 plays an important role in innate immunity to infection and colonization of H. pylori.

  2. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

    PubMed Central

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C.; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G.

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world’s population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6–9 weeks of age, and were necropsied at 27–29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use

  3. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    PubMed

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp

  4. Environmental Exposures Are Important Risk Factors for Infection Toxoplasma gondii and Helicobacter pylori

    EPA Science Inventory

    Background: An estimated 70% of Americans suffer chronic infections. Helicobacter pylori and Toxoplasma gondii affect an estimated 35% and 15% of Americans, respectively. Despite their heavy burden, environmental transmission of these infections is not well understood. Object...

  5. Control of gene expression in Helicobacter pylori using the Tet repressor

    PubMed Central

    McClain, Mark S.; Duncan, Stacy S.; Gaddy, Jennifer A.; Cover, Timothy L.

    2013-01-01

    The lack of a versatile system to control gene expression in Helicobacter pylori has hampered efforts to study H. pylori physiology and pathogenesis. To overcome these limitations, we evaluated the utility of an inducible system based on the well-characterized Tet repressor (TetR) and Tet operator (tetO). As validation of this system, we introduced three copies of tetO into the promoter region upstream of the cagUT operon (encoding two virulence factors required for function of the H. pylori Cag type IV secretion system) and expressed tetR by introducing a codon-optimized gene into the chromosomal ureA locus. Introduction of the tetO copies upstream of cagUT did not disrupt promoter activity, as determined by immunoblotting for CagT. The subsequent introduction of tetR, however, did repress CagT synthesis. Production of CagT was restored when strains were cultured in the presence of the inducer, anhydrotetracycline. To demonstrate one potential application of this new tool, we analyzed the function of the Cag type IV secretion system. When the modified H. pylori strains were co-cultured with AGS cells, activity of the Cag type IV secretion system was dependent on the presence of anhydrotetracycline as evidenced by inducer-dependent induction of IL-8 secretion, CagA translocation, and appearance of type IV secretion system pili at the bacteria-host interface. These studies demonstrate the effectiveness of the tetR-tetO system to control gene expression in H. pylori and provide an improved system for studying H. pylori physiology and pathogenesis. PMID:24113399

  6. [Is dental plaque a normal Helicobacter pylori reservoir?].

    PubMed

    Améndola, R; Roldán, C D; Morgade, L; Solagna, A; Lineado, A; Musi, A O; Valero, J; Zerbo, O; Kogan, Z; Ferro, F E; Schenone, L; Corti, R

    1998-01-01

    The mechanisms of transmission and reservoir of Helicobacter pylori is still unclear; even it has been suggested that dental plaque could be the bacterial reservoir and one important factor in the reinfection. The aim of the study was to evaluate the prevalence of Helicobacter pylori in dental plaque in 20 patients with non ulcer dyspepsia (12 females, 7 males; mean age 40.5 years) and antral infection; and to establish the presence of bacteria in dental plaque and gastric mucosa after eradication. Gastric colonization in all of them was confirmed by five samples (three of antrum and two of body) with Giemsa conventional technique, clotest and culture. When clotest was positive in gastric mucosa, we performed the scrape of dental plaque and sending the material for culture. All patients were treated with a scheme of seven days with one protom pump inhibitor and two antibiotics. After four weeks all the patients were controlled with endoscopy and culture of dental plaque to confirm eradication. Dental plaque culture was positive in 1/20 patients (5%), and this results was similar to developed countries, using as detection method culture or polymerase chain reaction (PCR).

  7. Salty food intake and risk of Helicobacter pylori infection.

    PubMed

    Tsugane, S; Tei, Y; Takahashi, T; Watanabe, S; Sugano, K

    1994-05-01

    To clarify the risk factors for Helicobacter pylori infection, which is considered to play an etiologic role in atrophic gastritis, duodenal ulcer and gastric cancer, various parameters including diet and socioeconomic characteristics were compared between H. pylori-infected and non-infected men. In a cross-sectional study of 634 men aged 40 to 49 years selected randomly from five areas with different rates of gastric cancer mortality, 474 of 628 men evaluated were positive for IgG antibody against H. pylori. After logistic regression analysis adjusted for area, the results showed a significant association between frequent intake of pickled vegetables and prevalence of H. pylori antibody (odds ratios against men who consume < 1 day/week 1.19 for 1-2 days/week, 1.92 for 3-4 days/week, 1.90 for 5-7 days/week; P for trend = 0.02). Daily consumption of miso soup was also associated with an increased risk (odds ratio against non-daily consumer = 1.60, 95% confidence interval = 1.03-2.49). Occupation, number of siblings, education, smoking and alcohol drinking, and other dietary habits were not significantly associated with the prevalence of infection in this population. Although there are limitations in a cross-sectional study such as this, consumption of salty foods appears to increase the risk of H. pylori infection, which could be a marker of salty food intake or an intermediate risk factor in the etiologic sequence between salty food intake and gastric cancer.

  8. “Rescue” regimens after Helicobacter pylori treatment failure

    PubMed Central

    Gisbert, Javier P

    2008-01-01

    Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a clarithromycin-based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender. PMID:18803350

  9. High antibiotic resistance rate: A difficult issue for Helicobacter pylori eradication treatment.

    PubMed

    Zhang, Mei

    2015-12-28

    Helicobacter pylori (H. pylori) infection is associated with a variety of upper gastrointestinal diseases, including gastric cancer. With the wide application of antibiotics in H. pylori eradication treatment, drug-resistant strains of H. pylori are increasing. H. pylori eradication treatment failure affects the outcome of a variety of diseases of the upper gastrointestinal tract. Therefore, antibiotic resistance that affects H. pylori eradication treatment is a challenging situation for clinicians. The ideal H. pylori eradication therapy should be safe, effective, simple, and economical. The eradication rate of triple antibiotic therapy is currently less than 80% in most parts of the world. Antibiotic resistance is the main reason for treatment failure, therefore the standard triple regimen is no longer suitable as a first-line treatment in most regions. H. pylori eradication treatment may fail for a number of reasons, including H. pylori strain factors, host factors, environmental factors, and inappropriate treatment.

  10. Characterization of the low-pH responses of Helicobacter pylori using genomic DNA arrays.

    PubMed

    Allan, E; Clayton, C L; McLaren, A; Wallace, D M; Wren, B W

    2001-08-01

    Helicobacter pylori is unique among bacterial pathogens in its ability to persist in the acidic environment of the human stomach. To identify H. pylori genes responsive to low pH, the authors assembled a high-density array of PCR-amplified random genomic DNA. Hybridization of radiolabelled cDNA probes, prepared using total RNA from bacteria exposed to buffer at either pH 4.0 or pH 7.0, allowed both qualitative and quantitative information on differential gene expression to be obtained. A previously described low-pH-induced gene, cagA, was identified together with several novel genes that may have relevance to the survival and persistence of H. pylori in the gastric environment. These include genes encoding enzymes involved in LPS and phospholipid synthesis and secF, encoding a component of the protein export machinery. A hypothetical protein unique to H. pylori (HP0681) was also found to be acid induced. Genes down-regulated at pH 4.0 include those encoding a sugar nucleotide biosynthesis protein, a flagellar protein and an outer-membrane protein. Differential gene expression was confirmed by total RNA slot-blot hybridization.

  11. Functional association between the Helicobacter pylori virulence factors VacA and CagA.

    PubMed

    Argent, Richard H; Thomas, Rachael J; Letley, Darren P; Rittig, Michael G; Hardie, Kim R; Atherton, John C

    2008-02-01

    The Helicobacter pylori virulence factors CagA and VacA are implicated in the development of gastroduodenal diseases. Most strains possessing CagA also possess the more virulent vacuolating form of VacA. This study assessed the significance of possession of both virulence factors in terms of their effect on gastric epithelial cells, using a set of minimally passaged, isogenic VacA, CagA and CagE mutants in H. pylori strains 60190 and 84-183. The cagA and cagE mutants were found to significantly increase VacA-induced vacuolation of epithelial cells, and the vacA mutants significantly increased CagA-induced cellular elongations, compared with wild-type strains, indicating that CagA reduces vacuolation and VacA reduces hummingbird formation. Although epithelial cells incubated with the wild-type H. pylori strains may display both vacuolation and hummingbird formation, it was found that (i) hummingbird length was significantly reduced in vacuolated cells compared with those without vacuolation; (ii) the number of vacuoles was significantly reduced in vacuolated cells with hummingbird formation compared with those without hummingbirds; and (iii) cells displaying extensive vacuolation did not subsequently form hummingbirds and vice versa. VacA did not affect the phosphorylation of CagA. These data show that VacA and CagA downregulate each other's effects on epithelial cells, potentially allowing H. pylori interaction with cells whilst avoiding excessive cellular damage.

  12. Helicobacter pylori and gastric cancer: a state of the art review.

    PubMed

    Ishaq, Sauid; Nunn, Lois

    2015-01-01

    Gastric cancer is the third most common cause of cancer-related death in the world. It is now well- established that Helicobacter pylori infection predispose individuals toward gastric adenocarcinoma later in life. It has since been classified as a class I carcinogen by the World Health Organization. Research suggests that the oncogenic effects of Helicobacter pylori can occur through a variety of mechanisms, including the indirect inflammatory effects of Helicobacter pylori on the gastric mucosa and the direct epigenetic effects of Helicobacter pylori on individual cells. Whilst infected with Helicobacter pylori, a combination of environmental and host-dependent factors determines the likelihood of developing gastric cancer. Controversy remains regarding the effects of eradication of Helicobacter pylori on the prevention of further progression of gastric lesions and the possibility for regression of atrophic gastritis. The aim of this review is to synthesis different elements that contribute to the step-wise progression of normal gastric mucosa to gastric adenocarcinoma. This review helps clinicians to better identify those infected individuals who are at high risk of developing gastric cancer and implement the necessary investigations and treatment.

  13. Antibacterial actions of fatty acids and monoglycerides against Helicobacter pylori.

    PubMed

    Sun, Cynthia Q; O'Connor, Charmian J; Roberton, Anthony M

    2003-05-15

    The bactericidal potencies of saturated and unsaturated fatty acids (FAs) and monoglycerides (MGs) against Helicobacter pylori were determined following short incubations with freshly harvested cells over a range of pHs. FAs and their derivatives with an equivalent-carbon number of 12 were the most potent: lauric acid had a minimum bactericidal concentration (MBC) at pH 7.4 of 1 mM, myristoleic and linolenic acid were the most potent unsaturated FAs (MBCs of 0.5 mM, pH 7.4), and monolaurin was the most potent MG (MBC 0.5 mM). Potencies of saturated FAs were increased sharply by lowering pH, and a decrease of only 0.5 pH units can cause a change from non-lethal to lethal conditions. Conversely, the bactericidal action of monolaurin was not pH-dependent. The bactericidal potencies of unsaturated FAs increased with degree of unsaturation. When more than one FA or FA plus MGs were present, their combined action was additive. Urea and endogenous urease did not protect H. pylori from the bactericidal action of FAs. These results suggest that H. pylori present in the stomach contents (but not necessarily within the mucus barrier) should be rapidly killed by the millimolar concentrations of FAs and MGs that are produced by pre-intestinal lipase(s) acting on suitable triglycerides such as milk fat.

  14. CYP2C19 polymorphism influences Helicobacter pylori eradication

    PubMed Central

    Kuo, Chao-Hung; Lu, Chien-Yu; Shih, Hsiang-Yao; Liu, Chung-Jung; Wu, Meng-Chieh; Hu, Huang-Ming; Hsu, Wen-Hung; Yu, Fang-Jung; Wu, Deng-Chyang; Kuo, Fu-Chen

    2014-01-01

    The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1β- 511 polymorphism) would be also under consideration. PMID:25473155

  15. [First line therapy for Helicobacter pylori eradication in France].

    PubMed

    Dupas, Jean-Louis

    2003-03-01

    The available results of triple therapy for the eradication of Helicobacter pylori (H. pylori), as recommended in European countries--i.e. combination of proton pump inhibitor (PPI) and two antibiotics among amoxicillin, clarithromycin, metronidazole for 7 days--lead to rates of failure of about 30%. Several clinical studies have been recently conducted to distinguish factors influencing effectiveness of therapy and to evaluate results of new regimens. Comparative trials have demonstrated the equivalence of omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, rabeprazole 20 mg and esomeprazole 20 mg, twice daily in these 7-days triple therapies. Efficacy of treatment is not affected by metronidazole resistance (44% in France) when amoxicillin-clarithromycin-based triple therapy is prescribed. The impact of clarithromycin resistance (14%) is much more important with failure of eradication in all cases treated by clarithromycin-based triple therapy. The eradication rate could be slightly improved by increasing the dose of clarithromycin but with more frequent side effects. To prolong the duration treatment improve also slightly the cure rate with a gain of less than 10%, but with an increasing rate of side effects. To date, the PPI-based triple therapies, as recommended in France, have not to be modified. The treatment of H. pylori infection has to be globally considered, with a first-line treatment leading to eradication in 70% of patients and a second-line treatment needed for the resting 30% of patients.

  16. Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

    PubMed Central

    Noh, Hye-Ji; Koh, Hong Bum; Kim, Hee-Kyoung; Cho, Hyang Hyun

    2017-01-01

    BACKGROUND/OBJECTIVES Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-1β and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention. PMID:28194260

  17. The Role of PPARγ in Helicobacter pylori Infection and Gastric Carcinogenesis

    PubMed Central

    Lee, Jong-Min; Kim, Sung Soo; Cho, Young-Seok

    2012-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγ plays an important role in gastric mucosal injury due to Helicobacter pylori (H. pylori). As H. pylori infection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγ in H. pylori infection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγ in H. pylori infection and its related gastric carcinogenesis. PMID:22936949

  18. [Kyoto global consensus report for treatment of Helicobacter pylori and its implications for China].