• Helicobacter pylori
• bibliometric analysis
• treatment
• vaccine
• visualization

• Helicobacter pylori
• animal models
• vaccine

• Helicobacter Infections/prevention & control
• Helicobacter Infections/microbiology
• Helicobacter Infections/immunology
• Animals
• Bacterial Vaccines/immunology
• Helicobacter pylori/immunology
• Disease Models, Animal
• Humans

• Project for high and talent of Science and Technology Innovation in Jiangxi "Double-Thousand Talents Program of Jiangxi Province"
• National Innovation and Entrepreneurship Training Program for college students
• Natural Science Foundation of Jiangxi Province
• Training Plan for Academic and Technical Leaders of Major Disciplines in Jiangxi Province-Youth Talent Project
• National Natural Science Foundation of China

• Helicobacter pylori
• gastric cancer
• gastritis
• genomics
• hpEastAsia
• spore vectored vaccine

• Humans
• Male
• Female
• Mice
• Animals
• Helicobacter pylori
• Helicobacter Infections/microbiology
• Mice, Inbred C57BL
• Mice, Inbred ICR
• Genotype
• Genomics
• Asia, Southeastern/epidemiology
• Vaccines

• MR/R026262/1 Medical Research Council

• Mice
• Animals
• Humans
• Helicobacter pylori
• Helicobacter Infections/drug therapy
• Helicobacter Infections/prevention & control
• Mice, Inbred C57BL
• Lactobacillus
• Gastric Mucosa/pathology
• Stomach Diseases
• Probiotics

• ATP
• Helicobacter pylori
• VacA
• mitochondria
• mitochondrial dynamics
• mitochondrial dysfunction
• mitochondrial fission
• mitochondrial transmembrane potential
• oxidative phosphorylation
• vacuolating cytotoxin

• R01 AI045928 NIAID NIH HHS
• R21 AI117497 NIAID NIH HHS
• R56 AI045928 NIAID NIH HHS

• Castanea sativa Mill.
• Helicobacter pylori
• castalagin
• chestnut
• ellagitannins
• gastritis
• tannins

• Progetto Eccellenza Ministry of Education, Universities and Research

• Leishmania (Viannia) panamensis
• cutaneous leishmaniasis
• forward vaccinology
• immunopathology
• mouse model
• vaccine

• Bioengineering
• Brain development modeling
• Cerebral organoids
• Human pluripotent stem cells
• Neurodegeneration

• Brain
• Humans
• Induced Pluripotent Stem Cells
• Nervous System Diseases/metabolism
• Pluripotent Stem Cells/metabolism

• A549 Cells
• ADAM17 Protein/genetics
• Animals
• Carrier Proteins/genetics
• Child
• Child, Preschool
• Citrobacter rodentium/pathogenicity
• Colitis/genetics
• Cytokines/genetics
• Enterobacteriaceae Infections/genetics
• Female
• HEK293 Cells
• Humans
• Infant, Newborn
• Macrophages/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Mutation/genetics
• Primary Immunodeficiency Diseases/genetics
• Pseudomonas Infections/genetics
• Pseudomonas aeruginosa/pathogenicity
• Signal Transduction/genetics

• ZIA AI000769 Intramural NIH HHS

• Antibiotic resistance
• Antimicrobial photodynamic therapy (aPDT)
• Benzylidene cyclopentanone photosensitizers (BCP photosensitizers)
• Helicobacter pylori
• Human gastric epithelial cell

• Helicobacter pylori
• NuoD
• complex I inhibitor
• thienopyridine

• C57BL/6 mice
• Colonization
• Gastric cancer
• Gastric mucosa
• Gastritis
• Helicobacter pylori
• Mouse model
• Peptic ulcer
• Urease

• JSNZ
• Staphylococcus aureus
• dirty mouse
• host adaptation
• humanized mice
• microbiome
• mouse models
• mouse-adapted
• vaccine
• wildling

• Animals
• Disease Models, Animal
• Gastrointestinal Microbiome
• Host Microbial Interactions
• Host Specificity
• Humans
• Mice
• Staphylococcal Infections/microbiology
• Staphylococcus aureus/pathogenicity
• Staphylococcus aureus/physiology

• 03ZZ0806B InfectControl2020-inVAC
• GRK1870/1 Deutsche Forschungsgemeinschaft (DFG)
• ESF/14-BMA55-0037/16 European Social Fund, Card-ii-Omics

• GASTRIC CANCER
• GASTRIC METAPLASIA
• GASTRITIS

• Antibodies
• Autoantibodies
• Autoimmunity
• Infection
• Scleroderma

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Bacterial/metabolism
• Antigens, Bacterial/immunology
• Cohort Studies
• Epitopes/immunology
• Female
• Helicobacter Infections/immunology
• Helicobacter pylori/physiology
• Humans
• Immunity, Humoral
• Male
• Middle Aged
• Scleroderma, Systemic/immunology

Helicobacter pylori infection has been identified as a major cause of peptic ulcer diseases, including gastric and duodenal ulcers, gastritis, chronic and gastric carcinoma, and even gastric lymphoma. In vitro studies using Western blotting analysis, hemagglutination test, adherence inhibition assays, and immunocytochemical staining revealed that the 49.6-kDa subunit pili protein of H. pylori was considered an immunogenic protein. This study aimed to develop a serological diagnostic test using 49.6 kDa for detecting antibodies against H. pylori proteins in an early phase of the infection.

An in-house immunochromatographic test (ICT) kit was developed and used to test a panel of sera sample obtained from a randomly selected symptomatic patient, in which 40 sera were H. pylori positive and 40 sera were H. pylori negative.

The results showed that ICT with 49.6 kDa as an antigen was highly sensitive and specific for detecting anti-H. pylori immunoglobulin G antibodies in human serum, with a high negative predictive value.

The developed test could be used to exclude H. pylori infection in symptomatic patients.

• 49.6-kDa pili protein
• Helicobacter pylori
• immunochromatographic test

• H. pylori-naïve subjects
• Helicobacter pylori
• immune response
• vaccination
• vaccine development

• Crystal structure
• Epithelial–mesenchymal transition
• Helicobacter pylori
• Lipoprotein

• Helicobacter pylori
• chemoprevention
• chronic atrophic gastritis
• eradication
• intestinal metaplasia

• Antibacterial susceptibility
• Antibiotics
• Fluorescence
• In vivo animal infection models
• Phenotypic heterogeneity
• Raman spectroscopy
• Single-cell level methods

One of the major toxins secreted by H. pylori is the Vacuolating cytotoxin A (VacA) named after its ability to induce the formation of “vacuole”-like membrane vesicles in the cytoplasm of gastric cells. VacA has been associated with the disruption of mitochondrial functions, stimulation of apoptosis, blockade of T cell proliferation and promotion of regulatory T cells, thereby making it a promising vaccine target. Immunity to bacterial virulence factors is well known to protect humans against bacterial infections; hence, detoxified VacA has been evaluated as a vaccine antigen. Our short review summarizes the pre-clinical and clinical data that have been published on the use of VacA in the development of the H. pylori vaccine.

• H. pylori
• VacA
• vaccine

The VacA toxin secreted by Helicobacter pylori enhances the ability of the bacteria to colonize the stomach and contributes to the pathogenesis of gastric adenocarcinoma and peptic ulcer disease. The amino acid sequence and structure of VacA are unrelated to corresponding features of other known bacterial toxins. VacA is classified as a pore-forming toxin, and many of its effects on host cells are attributed to formation of channels in intracellular sites. The most extensively studied VacA activity is its capacity to stimulate vacuole formation, but the toxin has many additional effects on host cells. Multiple cell types are susceptible to VacA, including gastric epithelial cells, parietal cells, T cells, and other types of immune cells. This review focuses on the wide range of VacA actions that are detectable in vitro, as well as actions of VacA in vivo that are relevant for H. pylori colonization of the stomach and development of gastric disease.

• autotransporter
• bacterial toxins
• gastric cancer
• type V secretion
• vacuolating toxin

• Animals
• Bacterial Proteins/chemistry
• Bacterial Proteins/genetics
• Bacterial Proteins/toxicity
• Bacterial Toxins/chemistry
• Bacterial Toxins/genetics
• Bacterial Toxins/toxicity
• Helicobacter pylori/genetics
• Helicobacter pylori/metabolism
• Humans
• Ion Channels/metabolism
• Protein Conformation
• Transcription, Genetic

• T32 GM008320 NIGMS NIH HHS
• R25 GM062459 NIGMS NIH HHS
• P01 CA116087 NCI NIH HHS
• I01 BX000627 BLRD VA
• R01 AI118932 NIAID NIH HHS
• R01 AI039657 NIAID NIH HHS

• Cancer
• Clinical trials
• Helicobacter pylori
• Inflammation
• Vaccine

AIM: To explore whether recombinant human lactoferrin (rhLF) plus triple therapy can increase the rate of Helicobacter pylori(H. pylori) eradication, reduce gastric mucosal inflammation, and inhibit vacuolating cytotoxin (VacA) mRNA expression.

METHODS: One hundred and ninety-two H. pylori ATCC43504 infected Babl/c mice with gastritis were randomly divided into four groups: A (rhLF+standard triple therapy), B (rhLF alone), C (standard triple therapy alone), and D (saline). H. pyloricolonization of the gastric mucosa was assessed by silver staining. Gastric mucosal inflammation was assessed by HE staining. Tumor necrosis factor (TNF)-α content was determined by ELISA. VacA mRNA expression was detected by RT-PCR.

RESULTS: Compared with group D, the rate of H. pylori colonization and gastric mucosal inflammation score decreased significantly in groups A, B, and C (P < 0.05). Compared with groups B and C, the rate of H. pylori colonization and gastric mucosal inflammation score decreased significantly in group A (P < 0.05). rhLF plus standard triple therapy significantly decreased gastric TNF-α content (28.64 pg/mL ± 12.07 pg/mL vs 300.16 pg/mL ± 59.1 pg/mL, 54.96 pg/mL ± 15.02 pg/mL, 503.25 pg/mL ± 1.35 pg/mL, P < 0.01) and VacA mRNA expression (P < 0.01) compared with groups B, C and D.

CONCLUSION: rhLF combined with triple therapy can improve H. pylori eradication rate, reduce gastric mucosal inflammation possibly by inhibiting proinflammatory factor release, and effectively inhibit VacA mRNA expression.

• Recombinant human lactoferrin
• Helicobacter pylori infection
• Tumor necrosis factor-alpha
• Vacuolating cytotoxin

To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU) in Korean patients.

Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included 72 non-uveitis patients and 35 age- and sex-matched healthy controls in the study.

Of the 106 patients with AAU, 41 (38.7%) were HLA-B27-positive, and 45 (42.5%) were seropositive for H. pylori. Patients with HLA-B27-positive AAU had a significantly lower prevalence of H. pylori seropositivity compared to those with HLA-B27-negative AAU and healthy controls (24.4% vs. 53.8%, p = 0.003; 24.4% vs. 57.1%, p = 0.004, respectively). In the non-uveitis group, however, HLA-B27-positive patients exhibited similar H. pylori seropositivity prevalence to HLA-B27-negative patients and healthy controls (45.5% vs. 55.7%, p = 0.529; 45.5% vs. 57.1%, p = 0.497, respectively). In multivariate analysis, a low prevalence of H. pylori seropositivity was significantly associated with HLA-B27-positive AAU (odds ratio = 0.340, 95% confidence interval 0.135–0.855, p = 0.022).

Our results suggest an inverse association between H. pylori seropositivity and HLA-B27-positive AAU. Further investigation of this association is needed, given the low prevalence of H. pylori seropositivity observed in patients with HLA-B27-positive AAU.

• Acute Disease
• Adult
• Asian People
• Demography
• Female
• HLA-B27 Antigen/metabolism
• Helicobacter pylori/physiology
• Humans
• Logistic Models
• Male
• Middle Aged
• Uveitis, Anterior/blood
• Uveitis, Anterior/microbiology

The lesions induced by Helicobacter pylori in a candidate animal model should always be examined thoroughly. The resemblance of these lesions to those observed in humans can indicate whether the usage of this model will contribute to the understanding of the various pathogenic mechanisms involved in the development of human H. pylori-associated diseases.

The aim of this study was to perform a histopathological and bacteriological evaluation of gastric lesions based on H. pylori and Helicobacter-like organisms (HLOs) in cats.

The present study was carried out on 28 cat’s (13 male and 15 female cases) gastric mucosae, which were tested by bacteriological and histopathological methods. Biochemical tests such as catalase, oxidase and urease were utilized in addition to Gram and Giemsa staining.

This research demonstrated that solely one case of H. pylori was isolated by gastric mucosal culture. Microscopically, the infected stomachs by HLOs comprised a mild to severe diffuse lymphoplasmacytic infiltration into the subglandular and gastric mucosa. Lymphoid follicles were also marked, particularly within pyloric tissues and mostly in displaced mucosal glands. For 75% of the gastritis cases, both HLOs and rapid urease tests were positive, whereas 83% of cases were more than one-year-old with gastritis. Furthermore, 75% of cats indicated gastritis, though 25% encompassed no gastritis; hence 20% had negative results for the rapid urease test and 25% for the Giemsa staining test. Such results may indicate that cats without gastritis were considered as free of HLOs pathogenic bacteria.

These results suggest that most cases of gastritis were located in the antral region. Additionally, the isolation of H. pylori from domestic cats raises the possibility of zoonotic characteristics for the slightly pathogen; therefore transmission occurs from cats to human and vice versa.

• Cat Diseases
• Helicobacter pylori
• Mucous Membrane

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.

• Helicobacter pylori
• Vaccine
• Immune response
• Peptic ulcer
• Gastric cancer

• Anti-Bacterial Agents/therapeutic use
• Bacterial Proteins/genetics
• CD4-Positive T-Lymphocytes/immunology
• Gastritis/immunology
• Gastritis/microbiology
• Gastrointestinal Tract/immunology
• Gastrointestinal Tract/microbiology
• Helicobacter Infections/immunology
• Helicobacter pylori
• Humans
• Immunity, Innate
• Immunoglobulin A/immunology
• Immunoglobulin G/immunology
• Inflammation/immunology
• Inflammation/microbiology
• Peptic Ulcer/immunology
• Peptic Ulcer/microbiology
• Stomach/immunology
• Stomach/microbiology

Helicobacter pylori, a gram-negative bacterial pathogen that expresses a strong urease activity, is associated with the development of gastroduodenal disease. Urease B subunit, one of the two structural subunits of urease, was expressed in E. coli BL21 (DE3) strain. The objective of this study was to evaluate the effects of Helicobacter pylori urease B subunit on the immune responses in mice by subcutaneous immunization.

The mice were immunized and boosted with Helicobacter pylori urease B subunit antigen subcutaneously three times with 2-wk intervals between the immunizations and boosters. The mice in the control group were immunized with PBS. The adjuvant group received PBS containing complete/incomplete freund’s adjuvant identical to antigen group without Helicobacter pylori urease B subunit antigen. Four weeks after the final booster, all the mice were sacrificed. Blood was collected on d 0, 14, 28 and 56 before immunization, booster and sacrifice, respectively. Immediately after sacrifice, gastric liquid and spleen were collected for antibody and cytokine analyses.

Urease B subunit increased the concentrations of serum and gastric anti-urease B antigen specific IgG, and the levels of interleukin-4 and interferon-γ in splenocytes of the mice (P < 0.05).

This study demonstrated that recombinant urease B subunit can induce systemic and local immune responses in mice by subcutaneous immunization, which might be used as the effective component of vaccine against Helicobacter pylori.

• Helicobacter felis
• Helicobacter pylori
• diet
• gerbils
• mice

• Animals
• Ascorbic Acid/administration & dosage
• Developing Countries
• Diet
• Dietary Fats/administration & dosage
• Disease Models, Animal
• Folic Acid/administration & dosage
• Gerbillinae
• Helicobacter Infections/complications
• Helicobacter Infections/physiopathology
• Helicobacter pylori
• Humans
• Mice
• Salts/administration & dosage
• Stomach Neoplasms/etiology
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/physiopathology

• P01 CA028842 NCI NIH HHS
• R01 CA093405 NCI NIH HHS
• P01CA026731 NCI NIH HHS
• R01CA093405 NCI NIH HHS
• P30ES002109 NIEHS NIH HHS
• P30 ES002109 NIEHS NIH HHS
• P01 CA026731 NCI NIH HHS
• P01CA028842 NCI NIH HHS

Objective. Helicobacter pylori provokes a host of immune alterations upon colonizing the gastric mucosa. Design. We report 22 individuals with confirmed Helicobacter pylori infection who were also managed for the concurrent elevation of immunoglobulin free light chain (kappa and lambda) levels. Result. Of the 22 patients, 15 patients (68.2%) had elevated free light chain levels: 6 patients (40%) had only kappa chain elevation, 2 patients (13.3%) had only lambda chain elevation, and 7 patients (46.7%) had both kappa and lambda chain elevation. Twenty out of the 22 patients (90.9%) were microbiologically confirmed cured with 3 patients being lost to follow-up for repeat levels. Of the 3 patients who were lost to follow-up, 1 patient had only kappa chain elevation, 1 patient had only lambda chain elevation, and 1 patient had both kappa and lambda chain elevation. For those who were cured (19 patients), 5 patients with kappa elevation had normalized values, 4 patients with lambda elevation had normalized values, and 2 patients with combined kappa and lambda elevation had normalized values. For 6 out of the 19 patients, the light chain levels remained elevated. Conclusion. We speculate that the Helicobacter pylori infection disrupts the immunoglobulin system with potential implications being discussed below.

• Helicobacter pylori
• dyspepsia
• gastric cancer
• vaccine

• 14-3-3 Isoforms
• Diethylnitrosamine
• Gastric cancer
• Gulo(−/−) mice
• Helicobacter pylori
• Proteome analysis

Listeria monocytogenes (Lm) is an invasive foodborne pathogen that leads to severe central nervous system and maternal-fetal infections. Lm ability to actively cross the intestinal barrier is one of its key pathogenic properties. Lm crosses the intestinal epithelium upon the interaction of its surface protein internalin (InlA) with its host receptor E-cadherin (Ecad). InlA-Ecad interaction is species-specific, does not occur in wild-type mice, but does in transgenic mice expressing human Ecad and knock-in mice expressing humanized mouse Ecad. To study listeriosis in wild-type mice, InlA has been “murinized” to interact with mouse Ecad. Here, we demonstrate that, unexpectedly, murinized InlA (InlA^m) mediates not only Ecad-dependent internalization, but also N-cadherin-dependent internalization. Consequently, InlA^m-expressing Lm targets not only goblet cells expressing luminally-accessible Ecad, as does Lm in humanized mice, but also targets villous M cells, which express luminally-accessible N-cadherin. This aberrant Lm portal of entry results in enhanced innate immune responses and intestinal barrier damage, both of which are not observed in wild-type Lm-infected humanized mice. Murinization of InlA therefore not only extends the host range of Lm, but also broadens its receptor repertoire, providing Lm with artifactual pathogenic properties. These results challenge the relevance of using InlA^m-expressing Lm to study human listeriosis and in vivo host responses to this human pathogen.

Co-evolution of microbes with their hosts can select stringently specific host-microbe interactions at the cell, tissue and species levels. Listeria monocytogenes (Lm) is a foodborne pathogen that causes a deadly systemic infection in humans. Lm crosses the intestinal epithelium upon the interaction of its surface protein InlA with E-cadherin (Ecad). InlA-Ecad interaction is species-specific, does not occur in wild-type mice, but does in transgenic mice expressing human Ecad and knock-in mice expressing humanized mouse Ecad. To study listeriosis in wild-type mice, InlA has been “murinized” to interact with mouse Ecad. Here, we demonstrate that in addition to interacting with mouse Ecad, InlA^m also uses N-cadherin as a receptor, whereas InlA does not. This artifactual InlA^m-N-cadherin interaction promotes bacterial translocation across villous M cells, a cell type which is not targeted by InlA-expressing bacteria. This leads to intestinal inflammation and intestinal barrier damage, both of which are not seen in humans and humanized mouse models permissive to InlA-Ecad interaction. These results challenge the relevance of using InlA^m-expressing Lm as a model to study human listeriosis and host responses to this pathogen. They also illustrate that caution must be exercised before using “murinized” pathogens to study human infectious diseases.

• Animals
• Bacterial Proteins/genetics
• Bacterial Proteins/metabolism
• Cadherins/biosynthesis
• Cadherins/genetics
• Disease Models, Animal
• Female
• Humans
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/pathology
• Listeria monocytogenes/genetics
• Listeria monocytogenes/metabolism
• Listeria monocytogenes/pathogenicity
• Listeriosis/genetics
• Listeriosis/metabolism
• Listeriosis/pathology
• Mice
• Mice, Transgenic

The risk of Helicobacter pylori infection is highest in childhood, but the colonization process of the stomach mucosa is poorly understood. We used anesthetized Mongolian gerbils to study the initial stages of H. pylori colonization. Prandial and postprandial gastric conditions characteristic of humans of different ages were simulated. The fraction of bacteria that reached the deep mucus layer varied strongly with the modelled postprandial conditions. Colonization success was weak with fast gastric reacidification typical of adults. The efficiency of deep mucus entry was also low with a slow pH decrease as seen in pH profiles simulating the situation in babies. Initial colonization was most efficient under conditions simulating the postprandial reacidification and pepsin activation profiles in young children. In conclusion, initial H. pylori colonization depends on age-related gastric physiology, providing evidence from an in vivo infection model that suggests an explanation why the bacterium is predominantly acquired in early childhood.