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1.
Maternal H. pylori is associated with differential fecal microbiota in infants born by vaginal delivery.
Hernandez, CD, Shin, H, Troncoso, PA, Vera, MH, Villagran, AA, Rodriguez-Rivera, SM, Ortiz, MA, Serrano, CA, Borzutzky, A, Dominguez-Bello, MG, et al
Scientific reports. 2020;(1):7305
Abstract
Helicobacter pylori colonization may affect the mucosal immune system through modification of microbiota composition and their interactions with the host. We hypothesized that maternal H. pylori status affects the maternal intestinal microbiota of both mother and newborn. In this study, we determine the structure of the fecal microbiota in mothers and neonates according to maternal H. pylori status and delivery mode. We included 22 mothers and H. pylori infection was determined by fecal antigen test. Eleven mothers (50%) were H. pylori-positive (7 delivering vaginally and 4 by C-section), and 11 were negative (6 delivering vaginally and 5 by C-section). Stool samples were obtained from mothers and infants and the fecal DNA was sequenced. The fecal microbiota from mothers and their babies differed by the maternal H. pylori status, only in vaginal birth, not in C-section delivery. All 22 infants tested negative for fecal H. pylori at 15 days of age, but those born vaginally -and not those by C-section- showed differences in the infant microbiota by maternal H. pylori status (PERMANOVA, p = 0.01), with higher abundance of Enterobacteriaceae and Veillonella, in those born to H. pylori-positive mothers. In conclusion, the structure of the infant fecal microbiota is affected by the maternal H. pylori status only in infants born vaginally, suggesting that the effect could be mediated by labor and birth exposures.
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2.
Helicobacter pylori and hematological disorders.
Santambrogio, E, Orsucci, L
Minerva gastroenterologica e dietologica. 2019;(3):204-213
Abstract
Helicobacter pylori (H. pylori) is one of the most common worldwide infections, which can affect both adults and children. The prevalence of this bacterium is variable in different countries, depending on various hygienic and socioeconomic conditions and living customs. The major damaged tissues of the infection are in the upper gastrointestinal tract, causing gastritis, gastric and duodenal ulcer and gastrointestinal malignancy. Nevertheless, other disorders are associated with this pathogen, including several hematological diseases, such as iron deficiency anemia, immune thrombocytopenia and vitamin B12 deficiency. A huge of data in literature support these associations, enough to recognize them in the last Maastricht V/Florence Consensus Report by European Study Group. The pathogenic mechanisms underlying the linkage between H. pylori and these hematological disorders are not clearly identified, but certainly the good hematological response reaches after eradication therapy confirm a central role of the bacterium in this scenario. Instead, the pathogenic mechanisms of H. pylori infection, which lead to the occurrence of mucosa-associated lymphoid tissue (MALT) lymphoma are clearer and more consolidated; so much that nowadays eradication therapy alone represents the only treatment in this disorder, when localized and with a concomitant H. pylori infection. This review focuses on the hematologic diseases related to H. pylori, particularly on iron deficiency anemia, vitamin B12 deficiency, immune thrombocytopenia and gastric MALT lymphoma.
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3.
Biological properties and pathogenicity factors of Helicobacter pylori.
Isaeva, GS, Fagoonee, S
Minerva gastroenterologica e dietologica. 2018;(3):255-266
Abstract
The unexpected discovery of Helicobacter pylori (H. pylori) has revolutionised the history of microbiology as well as of gastroenterology in the last 30 years, with an invaluable benefit for millions of persons worldwide. The confirmation that this Gram-negative spiral bacterium could live in the stomach has rendered out-of-date the concept of inhospitality of micro-organisms in the gastric environment, after a long history of unheard reports on the presence of spiral bacteria in the stomach. The pathogenicity of H. pylori depends on its ability to colonize as well as the capability to survive in the harsh gastric environment. This is possible by a coevolution between the pathogen itself and the host. Any perturbation of this equilibrium disrupts the host-pathogen interaction, promoting the pathological effects. H. pylori has a wide range of pathogenicity factors, in particular cytotoxins, enzymes of aggression, and factors providing protection against human defense systems. The most well-characterized cytotoxins contributing to epithelial cell damage are the vacuolating cytotoxin A (VacA) and the cytotoxin-associated gene A (CagA). Only detailed knowledge of the microbiology and genomics of H. pylori infection will allow a vaccine to be produced. Today, we know that H. pylori induces strong humoral and cellular immune responses, but these are incapable of eliminating the bacterium, raising doubts about the possibility of developing an effective vaccine easily. This review highlights microbiological findings concerning H. pylori infection, focusing on colonization, survival and pathogenicity.
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4.
Designing an efficient multi-epitope oral vaccine against Helicobacter pylori using immunoinformatics and structural vaccinology approaches.
Nezafat, N, Eslami, M, Negahdaripour, M, Rahbar, MR, Ghasemi, Y
Molecular bioSystems. 2017;(4):699-713
Abstract
Helicobacter pylori is the cunning bacterium that can live in the stomachs of many people without any symptoms, but gradually can lead to gastric cancer. Due to various obstacles, which are related to anti-H. pylori antibiotic therapy, recently developing an anti-H. pylori vaccine has attracted more attention. In this study, different immunoinformatics and computational vaccinology approaches were employed to design an efficient multi-epitope oral vaccine against H. pylori. Our multi-epitope vaccine is composed of heat labile enterotoxin IIc B (LT-IIc) that is used as a mucosal adjuvant to enhance vaccine immunogenicity for oral immunization, cartilage oligomeric matrix protein (COMP) to increase vaccine stability in acidic pH of gut, one experimentally protective antigen, OipA, and two hypothetical protective antigens, HP0487 and HP0906, and "CTGKSC" peptide motif that target epithelial microfold cells (M cells) to enhance vaccine uptake from the gut barrier. All the aforesaid segments were joined to each other by proper linkers. The vaccine construct was modeled, validated, and refined by different programs to achieve a high-quality 3D structure. The resulting high-quality model was applied for conformational B-cell epitopes selection and docking analyses with a toll-like receptor 2 (TLR2). Moreover, molecular dynamics studies demonstrated that the protein-TLR2 docked model was stable during simulation time. We believe that our vaccine candidate can induce mucosal sIgA and IgG antibodies, and Th1/Th2/Th17-mediated protective immunity that are crucial for eradicating H. pylori infection. In sum, the computational results suggest that our newly designed vaccine could serve as a promising anti-H. pylori vaccine candidate.
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5.
Current status of Helicobacter pylori association with haematological and cardiovascular diseases: A mini review.
Muhammad, JS, Zaidi, SF, Saeed, SA, Ishaq, M
JPMA. The Journal of the Pakistan Medical Association. 2017;(6):907-911
Abstract
Helicobacter pylori infection is considered the most commonly prevalent gastrointestinal pathogen where it manages to survive despite the hostile environment of human stomach, leading to various gastric diseases including gastric cancer. Due to the chronic inflammatory state induced by H. pylori and its interaction with host immune system have diverted researchers to investigate its correlation with systemic diseases outside of the gastrointestinal tract. This literature review was done to explore the association of H. pylori infection with haematological and cardiovascular diseases. We used medical subject heading (MeSH) terms "Helicobacter pylori" with "inflammation," "haematological diseases," "coronary heart diseases" or "vascular diseases" to search PubMed database. All relevant studies identified from 2005 to 2015 were included. As many of the studies are small-scale or showed weak association, further studies are needed to address the role of H. pylori in pathogenesis of haematological and cardiovascular diseases.
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6.
Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection.
Alam, M, Deng, X, Philipson, C, Bassaganya-Riera, J, Bisset, K, Carbo, A, Eubank, S, Hontecillas, R, Hoops, S, Mei, Y, et al
PloS one. 2015;(9):e0136139
Abstract
Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close "neighborhood" of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa.
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7.
Review: prospects for the use of extracts and polysaccharides from marine algae to prevent and treat the diseases caused by Helicobacter pylori.
Besednova, NN, Zaporozhets, TS, Somova, LM, Kuznetsova, TA
Helicobacter. 2015;(2):89-97
Abstract
Helicobacter pylori possesses a broad spectrum of pathogenic factors that allow it to survive and colonize the gastric mucosa, and thus, the pathogenetic targets, which have the same diversity, require search for and the development of alternative, effective, and innocuous means for the eradication of H. pylori. In recent years, fucoidans have been extensively studied due to the numerous interesting biological activities, including the anti-adhesive, anti-oxidative, antitoxic, immunomodulatory, anticoagulant, and anti-infection effects. This review summarizes the data on the effects of extracts and sulfated polysaccharides of marine algae, mainly fucoidans, on pathogenic targets in Helicobacter infection. The pathogenetic targets for therapeutic agents after H. pylori infection, such as flagellas, urease, and other enzymes, including adhesins, cytotoxin A (VacA), phospholipase, and L-8, are characterized here. The main target for the sulfated polysaccharides of seaweed is cell receptors of the gastric mucosa. This review presents the published data about the pleiotropic anti-inflammatory effects of polysaccharides on the gastric mucosa. It is known that fucoidan and other sulfated polysaccharides from algae have anti-ulcer effects, prevent the adhesion of H. pylori to, and reduce the formation of biofilm. The authors speculate that the effect of sulfated polysaccharides on the infectious process caused by H. pylori is related to their action on innate and adaptive immunity cells, and also anti-oxidant and antitoxic potential. Presented in the review are materials indicated for the study of extracts and sulfated polysaccharides from seaweed during H. pylori infection, as these compounds are characterized by multimodality actions. Based on the analysis of literary materials in recent years, the authors concluded that fucoidan can be attributed to the generation of new candidates to create drugs intended for the inclusion in the scheme of eradication therapy of H. pylori infection.
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8.
Overview of the phytomedicine approaches against Helicobacter pylori.
Vale, FF, Oleastro, M
World journal of gastroenterology. 2014;(19):5594-609
Abstract
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.
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9.
Alternative therapies for Helicobacter pylori: probiotics and phytomedicine.
Vítor, JM, Vale, FF
FEMS immunology and medical microbiology. 2011;(2):153-64
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Abstract
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.
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10.
[The role of Helicobacter pylori infection in hematological diseases - a review].
Sato, K, Ozawa, K
Gan to kagaku ryoho. Cancer & chemotherapy. 2011;(3):358-61
Abstract
Helicobacter pylori (H. pylori) infection has been known to be the most closely associated with extra-gastrointestinal diseases. Above all, the association between H. pylori and hematological diseases, including immune thrombocytopenic purpura ( ITP), gastric MALT lymphoma and iron deficiency anemia (IDA) has been focused. Although the molecular mechanisms have not yet been fully understood, H. pylori eradication resulted in high response rates without major adverse effects. We focus here on a comprehensive review of the current literature of ITP, gastric MALT lymphoma and IDA.