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1.
Helicobacter ; 25(2): e12684, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32074664

RESUMO

BACKGROUND: Resistant Helicobacter pylori to commonly used antimicrobial agents are associated with severe upper gastrointestinal disorders. To provide an epidemiological picture of H pylori and characterize the resistance pattern and genetic variation of clinical isolates, stomach biopsies from patients with functional dyspepsia were evaluated in northeast of Iran. MATERIALS AND METHODS: In this study, 80 patients were recruited. Finally, fifty H pylori strains were isolated from antrum and corpus biopsies by culturing on Columbia agar. All strains were identified by standard laboratory procedures. Susceptibility testing of antibiotics was performed using minimum inhibitory concentration test. Allele-specific primer (ASP)-PCR of 23S rRNA which associated with clarithromycin resistance was done among resistant strains. Moreover, cagA gene and polymorphism in vacA were detected. Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was applied to investigate the genetic variations among all strains. RESULTS: Antibiotic resistance pattern of H pylori strains was as follows: 68% (34/50) to metronidazole, 50% (25/50) to rifampicin, 30% (15/50) to amoxicillin, 28% (14/50) to levofloxacin, 22% (11/50) to clarithromycin, and 16% (8/50) to tetracycline. Multidrug-resistant strains were observed in 19 strains (38%). ASP-PCR of 23S rRNA showed four strains had A2143G mutation, six strains had A2142G mutation, and one strain had a Wt+A2143G mutation. Amplification of virulence-associated genes revealed that cagA was present in 27 isolates (54%) and vacA in 36 isolates (72%). The most common genotype of H pylori was vacA s1am2 (40%) followed by vacA s2m2 (14%), vacA s1am1 (12%), vacA s1bm1 (4%), and vacA s1bm2 (2%). DNA fingerprinting pattern indicated a high heterogeneity among isolated strains. CONCLUSION: An alarming level of resistance to metronidazole and rifampicin and high heterogeneity among H pylori isolates highlighted the importance of continued monitoring of antimicrobial susceptibility and epidemiological surveillance of this pathogen.


Assuntos
Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Helicobacter , Helicobacter pylori , Virulência/genética , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Biópsia , Feminino , Variação Genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , RNA Ribossômico 23S/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Estômago/microbiologia
2.
Helicobacter ; 25(2): e12681, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32088936

RESUMO

BACKGROUND: Helicobacter pylori occupy a unique niche, located within the mucus layer lining the stomach, and attached to the apical surface of the gastric epithelium. As such, antibodies would be expected to play a major role in regulating infection and/or pathogenesis. However, experiments using antibody-deficient mice to study gastric helicobacter infection have yielded inconsistent results, although some pointed toward antibodies increasing colonization levels and decreasing gastritis severity. The variability in these studies is possibly due to their use of nonmatched wild-type controls. This current study presents the first evaluation of the role of antibodies in H pylori infection by comparing antibody-deficient mice with matched wild-type siblings. METHODS: Matched wild-type and antibody-deficient µMT mice were generated by heterozygous crossings. In two separate experiments, appropriately genotyped sibling littermates were infected with H pylori for 4 months and then sera and stomachs were collected. RESULTS: There was no difference in H pylori colonization levels between infected µMT mice and sibling wild-type controls. Similarly, there was no significant difference in the severity of gastritis between these groups of mice, although there was a trend toward less severe gastritis in µMT mice which was supported by a significantly lower IFNγ (Th1) gastric cytokine response. CONCLUSIONS: Comparing matched antibody-deficient and antibody-competent mice indicates that an antibody response does not influence H pylori colonization levels. Contrary to previous studies, these results suggest antibodies might have a minor pro-inflammatory effect by promoting gastric Th1 cytokines, although this did not translate to a significant effect on gastritis severity.


Assuntos
Anticorpos/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori , Animais , Citocinas/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Imunidade nas Mucosas , Camundongos , Camundongos Endogâmicos C57BL , Estômago/microbiologia , Estômago/patologia
4.
APMIS ; 128(1): 25-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31628820

RESUMO

Eradication failure of Helicobacter pylori infection could play a causal role in progression of gastric disorders. In this study, infection with H. pylori was followed in gastric biopsies of symptomatic adult patients at two phases during 1-year period. Analyses were done to show association of therapeutic regimens with the refractory infection, changes in sequence types (STs) and minimum inhibitory concentration (MIC) values, and progression of histopathological changes. Infection with H. pylori was confirmed in 32.3% (57/170) of the patients. Persistent infection with H. pylori was confirmed in 14 out of the 25 patients (56%) who participated at the second phase of the study. A difference between primary and secondary resistance rates to clarithromycin (49% vs 64.3%), metronidazole (76.36% vs 100%), and ciprofloxacin (45% vs 57.1%) was detected. Although the re-emerged strains in patients with refractory infection did not show alteration in STs, their MIC50 values showed twofold increases for clarithromycin and ciprofloxacin. While ciprofloxacin containing regimens were more successful, failure of metronidazole containing regimens was detected in 77% of the patients. Consequently, inappropriate medication has an impact on refractory H. pylori infection, which could cause to a rise in resistance levels to antibiotics and progression of pathological disorders.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Biópsia , Ciprofloxacino/farmacologia , Claritromicina/farmacologia , Feminino , Seguimentos , Técnicas Histológicas , Humanos , Concentração Inibidora 50 , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Estômago/microbiologia , Estômago/patologia
5.
Biomed Res Int ; 2019: 1450536, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886171

RESUMO

Background and Aim: As a worldwide infectious bacterium, H. pylori leads to stomach pathologies such as gastritis, peptic ulcer, gastric cancer, MALToma, and various extragastric manifestations. In our study, we aimed to investigate the association between serum vitamin B12 level and cytotoxin-associated gene-A (CagA) seropositivity, which is one of the virulence factors of Helicobacter pylori (H. pylori). Method: This study has been conducted on 289 patients who have met the inclusion criteria. Within these patients, 213 of them were H. pylori positive and 76 were negative. Vitamin B12 and CagA-IgG levels were assessed in consecutive dyspeptic patients undergoing upper endoscopy. Results: Out of 289 patients, 51.9% were women (n = 150) and H. pylori was detected in 213 (73.7%) patients. Histopathological evaluation with modified Sydney classification revealed lymphocyte infiltration in 66.8% (n = 193), activation in 46% (n = 133), metaplasia in 11.4% (n = 33), atrophy in 11.4% (n = 33), and lymphoid follicles in 21.1% (n = 61) of the patients. Within H. pylori-positive patients, the ratio of CagA positivity was 57.3% (n = 122). Low B12 vitamin level was significantly correlated with existence of H. pylori (p=0.02), CagA (p=0.002), lymphocyte (p=0.006), metaplasia (p=0.001), atrophy (p=0.001), and lymphoid follicles (p=0.006). Positivity of CagA has been detected to be statistically corelated with lymphocyte (p=0.001) and activation (p=0.005); however, the same relation was not present with atrophy (p=0.236). Conclusion: In conclusion, B12 deficiency was positively correlated with CagA positivity and gastric inflammatory activity.


Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Vitamina B 12/sangue , Adolescente , Adulto , Idoso , Antígenos de Bactérias/sangue , Atrofia/sangue , Atrofia/genética , Proteínas de Bactérias/sangue , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Fatores de Virulência , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/genética , Deficiência de Vitamina B 12/microbiologia , Adulto Jovem
6.
PLoS Negl Trop Dis ; 13(11): e0007799, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31682611

RESUMO

Development of gastric diseases such as gastritis, peptic ulcer and gastric cancer is often associated with several biotic and abiotic factors. Helicobacter pylori infection is such a well-known biotic factor. However, not all H. pylori-infected individuals develop gastric diseases and not all individuals with gastric diseases are infected with H. pylori. Therefore, it is possible that other gastric bacteria may contribute to the formation and progression of gastric disease. The aim of this study was to isolate prevalent gastric bacteria under microaerobic condition and identify them by 16S rRNA gene sequence analysis. Analysis of gastric biopsies showed infection of Mycobacterium abscessus (phylum Actinobacteria) to be highly prevalent in the stomachs of subjects included. Our data show that of 129 (67 male and 62 female) patients with gastric symptoms, 96 (51 male and 45 female) showed the presence of M. abscessus in stomach tissues. Infection of M. abscessus in gastric epithelium was further confirmed by imaging with acid fast staining, immunohistochemistry and immunofluorescence. Our imaging data strongly suggested that M. abscessus is an intracellular colonizer residing inside the gastric epithelial cells rather than in macrophages. Additionally, phylogenetic analysis of the mycobacterial hsp65 gene showed that the nearest match to the M. abscessus strains isolated from our study subjects is the M. abscessus strain ATCC 19977. Surprisingly, the subjects studied, the prevalence of M. abscessus infection in stomach is even higher than the prevalence of H. pylori infection. This, to the best of our knowledge, is the first study showing the colonization of M. abscessus in human gastric mucosa among patients with various gastric symptoms. This study could provide usher in a new opportunity to understand the role of less studied gastric bacteria in the development of gastric diseases.


Assuntos
Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Estômago/microbiologia , Adolescente , Adulto , Idoso , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , Biópsia , Chaperonina 60/classificação , Chaperonina 60/genética , Criança , Coinfecção , Células Epiteliais , Feminino , Mucosa Gástrica/microbiologia , Genes Bacterianos/genética , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium abscessus/genética , Mycobacterium abscessus/isolamento & purificação , Filogenia , Prevalência , RNA Ribossômico 16S/genética , Estômago/patologia , Adulto Jovem
7.
J Agric Food Chem ; 67(45): 12428-12440, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31668067

RESUMO

In the present study, the digestion and fermentation of blackberry polysaccharides (BBPs) with different molecular weights (Mw) were investigated. The results showed that the Mw decrease rates of BBP, BBP-8, BBP-16, and BBP-24 were 77.48, 69.61, 56.87, and 52.89%, respectively. The antioxidant and α-glucosidase inhibitory activities of BBPs were decreased under gastrointestinal condition, which might be due to the variation of Mw during digestion. The bile acid-binding ability of BBPs showed an Mw-dependent manner for higher Mw polysaccharides with higher viscosity. Through fermentation, the BBPs affected the ecosystem of the intestinal tract by promoting the production of short-chain fatty acids, lowering the pH of colon, and decreasing the ratio of Firmicutes to Bacteroidetes. All BBPs showed almost a similar modulation effect on the gut bacteria, but the lower Mw polysaccharide was more easily utilized by bacteria.


Assuntos
Extratos Vegetais/química , Extratos Vegetais/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Rubus/metabolismo , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Digestão , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Peso Molecular , Rubus/química , Estômago/microbiologia , Adulto Jovem
8.
Int J Mol Sci ; 20(18)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500233

RESUMO

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0-6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or ß-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42-. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.


Assuntos
Helicobacter pylori/fisiologia , Lipopolissacarídeos/metabolismo , Estômago/microbiologia , Fator Trefoil-1/metabolismo , Mucinas Gástricas/metabolismo , Glucosidases/farmacologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/química , Manosidases/farmacologia , Mucina-5AC/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica , Fator Trefoil-1/química , Tropismo
9.
Internist (Berl) ; 60(11): 1201-1208, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31511906

RESUMO

This article reports about a 73-year-old woman of Bosnian descent who presented with acute renal failure. A renal biopsy was diagnostic for a postinfect necrotizing and extracapillary proliferative glomerulonephritis. The patient reported a febrile infection fever 2 weeks previously. The diagnostics did not reveal any indications of an ongoing infection. The glomerulonephritis responded to treatment with systemic steroids. The patient was readmitted to hospital 6 weeeks later in a severely ill condition. A gastric biopsy revealed a Strongyloides stercoralis infestation. Due to the systemic steroid therapy the patient had developed a so-called hyperinfection syndrome and died despite treatment on the intensive care unit. This case illustrates the need for awareness of this rare parasitosis, particularly in patients from endemic areas. A likely causal relationship with the glomerulonephritis is discussed and an overview of the diagnostics, course of the disease and treatment of this parasitosis is given.


Assuntos
Lesão Renal Aguda/etiologia , Glomerulonefrite/tratamento farmacológico , Prednisolona/efeitos adversos , Esteroides/efeitos adversos , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/diagnóstico , Idoso , Animais , Antiparasitários/uso terapêutico , Evolução Fatal , Feminino , Glomerulonefrite/diagnóstico , Humanos , Ivermectina/uso terapêutico , Prednisolona/uso terapêutico , Esteroides/uso terapêutico , Estômago/microbiologia , Estômago/patologia , Estrongiloidíase/complicações , Estrongiloidíase/tratamento farmacológico
10.
BMC Gastroenterol ; 19(1): 140, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390989

RESUMO

BACKGROUND: Individuals can be infected with multiple strains of Helicobacter pylori. However, the differences among co-infecting strains have not been well analyzed yet. This study aimed to investigate whether the virulence factors and antibiotic resistance patterns of H. pylori differ between strains isolated from different locations of the stomach in the same patient. METHODS: H. pylori isolates were obtained from the antrum and body of the stomach. Genetic differences were examined by random amplified polymorphic DNA (RAPD) fingerprinting. Antibiotic resistance was assessed using the agar dilution method. Virulence factors were identified by polymerase chain reaction and DNA sequencing. RESULTS: Among 80 patients, co-infection by two H. pylori strains was detected in 10 patients. Among the 10 pairs of H. pylori strains, differences in antibiotic resistance patterns were detected in 7 pairs (clarithromycin, 1 patient; quinolone, 3 patients; metronidazole, 4 patients) and differences in virulence factors were detected in 5 pairs. The cagA virulence gene was detected in all 10 patients, and 2 patients had H. pylori strains with different EPIYA motifs. Differences in vacA genotypes were detected in 4 patients. CONCLUSIONS: Co-infection by two H. pylori strains was confirmed by RAPD fingerprinting. Frequently, two H. pylori strains obtained from a single host differed in their virulence factors and antibiotic resistance patterns. Co-infection by multiple H. pylori strains could undermine the success of eradication therapy and should be considered when interpreting the results of antimicrobial susceptibility tests.


Assuntos
Coinfecção/genética , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Estômago/microbiologia , Fatores de Virulência/genética , Antígenos de Bactérias , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , DNA Bacteriano , Genótipo , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Antro Pilórico/microbiologia , Técnica de Amplificação ao Acaso de DNA Polimórfico , Estudos Retrospectivos
11.
Lett Appl Microbiol ; 69(5): 325-332, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31454425

RESUMO

The aim of the research was to develop a galenical formulation for the combination of the three probiotic strains Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3 and Bifidobacterium bifidum MF 20/5 that would lead to the presence of a high amount of viable cells in the small intestine, the presumed site of action of these strains. This was tested in a validated, dynamic in vitro model of the stomach and small intestine (TIM-1), simulating human adults after intake of a meal. Experiments were performed both in the gastric compartment of the model, as well as in the complete system (stomach + small intestine). Survival of the strains in an unformulated probiotic powder after transit through the gastric compartment was 5·3% for the bifidobacteria and 1% for L. gasseri. After transit through the complete gastrointestinal tract, this dropped to 2% for bifidobacteria and 0·1% for Lactobacillus. After several rounds of optimization, an enteric-coated tablet was developed that increased the delivery of viable cells reaching the small intestine to 72% (gastric survival) for bifidobacteria, and 53% (gastric) for L. gasseri. Also survival in the small intestine increased by about an order of magnitude. The final galenical formulation was tested in two applications: adults and elderly, both of which have their own physiological parameters. These experiments corroborated the results obtained in the development phase of the project. In conclusion, the developed enteric coating led to a 20- to 40-fold increase in the delivery of viable cells to the small intestine. SIGNIFICANCE AND IMPACT OF THE STUDY: Predictive GI in vitro models are very helpful and reliable tools for the development of new galenical formula containing probiotics, and in the current example helped to deliver >10-fold higher numbers of viable cells to the small intestine, presumably leading to improved functionality of the strains.


Assuntos
Bifidobacterium/crescimento & desenvolvimento , Intestino Delgado/microbiologia , Lactobacillus/crescimento & desenvolvimento , Probióticos/química , Estômago/microbiologia , Adulto , Idoso , Composição de Medicamentos , Humanos , Viabilidade Microbiana , Comprimidos/química
12.
J Orthop Res ; 37(12): 2645-2654, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31317568

RESUMO

Percutaneous osseointegrated (OI) prostheses (POPs) are used to skeletally attach artificial limbs in amputees. While any permanent percutaneous interface is at risk of becoming infected by the resident microbiota colonizing the stoma, most of these patients remain infection-free. Avoidance of infection likely depends upon a mechanically and/or biologically stable skin-to-implant interface. The ultimate question remains, "why do some stomata become infected while others do not?" The answer might be found in the dynamic bacterial communities of the patient and within the stomal site itself. This study is an appendix to the first Food and Drug Administration approved prospective early feasibility study of OI prosthetic docking, in which, 10 transfemoral amputees were implanted with a unique POP device. In this analytical, longitudinal cohort study, each patient's skin and stomal microbiota were analyzed from the initial surgery to 1 year following the second-stage surgery. During each follow-up visit, three swab samples-stomal, device thigh skin and contralateral thigh skin-were obtained. DNA was extracted, and bacterial 16S ribosomal RNA (rRNA) genes were amplified and sequenced to profile microbial communities. The stomal microbiota were distinct from the microbiota on the adjacent thigh skin and the skin of the contralateral thigh, with a significantly increased abundance of Staphylococcus aureus within the stoma. Early on stomal microbiota were characterized by high diversity and high relative abundance of obligate anaerobes. Over time, the stomal microbiota shifted and stabilized in communities of lower diversity dominated by Streptococcus, Corynebacterium, and/or Staphylococcus spp. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2645-2654, 2019.


Assuntos
Microbioma Gastrointestinal , Osseointegração , Implantação de Prótese , Pele/microbiologia , Estômago/microbiologia , Humanos , Estudos Longitudinais , Estudos Prospectivos , Estomas Cirúrgicos/microbiologia
13.
Oncogene ; 38(37): 6461-6477, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31332288

RESUMO

Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.


Assuntos
Gastrite , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Infiltração de Neutrófilos , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Animais , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/patologia , Células Cultivadas , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/genética , Gastrite/imunologia , Gastrite/microbiologia , Gastrite/patologia , Células HL-60 , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos/genética , Neutrófilos/imunologia , Neutrófilos/metabolismo , Estômago/imunologia , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia
14.
Z Gastroenterol ; 57(7): 883-888, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31288284

RESUMO

Viruses and bacteria play central roles in gastrointestinal tumor development. This includes well-characterized contributions of Helicobacter pylori to gastric carcinoma and MALT lymphoma and of Hepatitis B and C virus infections to hepatocellular cancer. However, recent studies have demonstrated a much broader role of the microbiota in the regulation of cancer development. As such, it was shown that barrier defects and alterations in microbial community structure contribute to colorectal and hepatocellular cancer. Moreover, intriguing studies have highlighted the microbiota as a central regulator of the efficacy of systemic anti-tumor therapies. Here, we provide an overview of recent observations on the role of the microbiota in tumor development and the regulation of therapeutic anti-tumor responses and discuss the implications of these findings for clinical diagnostics and treatment.


Assuntos
Microbioma Gastrointestinal , Neoplasias Gastrointestinais/microbiologia , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B/microbiologia , Microbiota , Neoplasias Gástricas/microbiologia , Estômago/microbiologia , Infecções por Helicobacter , Humanos
15.
PLoS One ; 14(6): e0218274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31211818

RESUMO

Helicobacter pylori (H. pylori) is known to colonize gastric mucosa, induce inflammation, and alter gastric microbiota resulting in a spectrum of gastric diseases. Likewise, changes in gut microbiota have recently been linked with various metabolic and inflammatory diseases. While extensive number of studies were published examining the relationship between H. pylori and gastric microbiota, little is known about the impact of H. pylori on downstream gut microbiota. In this study, we performed 16 S rRNA and ITS2-based microbial profiling analysis of 60 stool samples from adult individuals. Remarkably, the gut microbiota of H. pylori infected individuals was shown to be increased of members belonging to Succinivibrio, Coriobacteriaceae, Enterococcaceae, and Rikenellaceae. Moreover, gut microbiota of H. pylori infected individuals was shown to have increased abundance of Candida glabrata and other unclassified Fungi. These results links possible role for H. pylori-associated changes in the gut microbiota in intestinal mucosal barrier disruption and early stage colorectal carcinoma deployment. Altogether, the identified differences in bacterial and fungal composition provides important information that may eventually lead to the development of novel biomarkers and more effective management strategies.


Assuntos
Microbioma Gastrointestinal/genética , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Inflamação/microbiologia , Adulto , Candida glabrata/genética , Enterococcaceae/genética , Face/microbiologia , Feminino , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Microbiota/genética , RNA Ribossômico 16S/genética , Estômago/microbiologia
16.
BMC Infect Dis ; 19(1): 546, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226948

RESUMO

BACKGROUND: The effectiveness of Helicobacter pylori first-line treatment has decreased drastically with the rise of strains resistant to clarithromycin. Therapy failure has also been described in patients with infections by strains with dissimilar antimicrobial susceptibilities. The present study aims to estimate the prevalence of resistance and heteroresistance to clarithromycin in H. pylori isolates from antrum and corpus of Colombian patients. METHODS: The study material included 126 isolates from antrum and corpus biopsies from 63 symptomatic patients over 18 years old who had a gastric endoscopy performed on them between June 2014 to August 2016. PCR amplification and sequencing of the H. pylori 23S rDNA gene was performed to determine the presence of mutations associated with clarithromycin resistance. Random amplified polymorphic DNA analysis was implemented in cases of resistance and heteroresistance. RESULTS: The overall frequency of resistance to clarithromycin was 38.1% (24/63 patients), of which 19 patients had resistant isolates in both stomach segments (14 with A2143G mutation and 5 with A2142G mutation), and 5 patients had a heteroresistant status. The remaining 61.9% (39/63 patients) presented only susceptible isolates. DNA fingerprinting analysis showed different patterns in 4/22 paired isolates. CONCLUSIONS: The high prevalence of H. pylori clarithromycin-resistance obtained (> 15%) constitutes an alert for gastroenterologists and suggests the need for reconsideration of the current eradication regimen for H. pylori in the studied population. The data show that heteroresistance status is an additional factor to be considered in the assessment of resistance. In consequence, it is advisable to examine at least two biopsies from different gastric segments.


Assuntos
Técnicas de Tipagem Bacteriana , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Colômbia/epidemiologia , Feminino , Genótipo , Técnicas de Genotipagem , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase/métodos , Prevalência , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Estômago/microbiologia , Estômago/patologia , Adulto Jovem
17.
J Forensic Sci ; 64(6): 1707-1719, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31170333

RESUMO

Multiple methods have been proposed to provide accurate time since death estimations, and recently, the discovery of bacterial community turnover during decomposition has shown itself to have predictable patterns that may prove useful. In this study, we demonstrate the use of metatranscriptomics from the postmortem microbiome to simultaneously obtain community structure and functional data across postmortem intervals (PMIs). We found that bacterial succession patterns reveal similar trends as detected through DNA analysis, such as increasing Clostridiaceae as decomposition occurs, strengthening the reliability of total RNA community analyses. We also provide one of the first analyses of RNA transcripts to characterize bacterial metabolic pathways during decomposition. We found distinct pathways, such as amino acid metabolism, to be strongly up-regulated with increasing PMIs. Elucidating the metabolic activity of postmortem microbial communities provides the first steps to discovering postmortem functional biomarkers since functional redundancy across bacteria may reduce host individual microbiome variability.


Assuntos
Fenômenos Fisiológicos Bacterianos , Mudanças Depois da Morte , RNA Bacteriano/análise , Animais , Medula Óssea/microbiologia , Clostridium perfringens/genética , Clostridium perfringens/fisiologia , Coração/microbiologia , Interações entre Hospedeiro e Microrganismos , Intestinos/microbiologia , Camundongos , Modelos Animais , Reação em Cadeia da Polimerase , RNA Ribossômico 16S , Staphylococcus aureus/genética , Staphylococcus aureus/fisiologia , Estômago/microbiologia
18.
Infect Immun ; 87(7)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31061142

RESUMO

Half of all humans harbor Helicobacter pylori in their stomachs. Helical cell shape is thought to facilitate H. pylori's ability to bore into the protective mucus layer in a corkscrew-like motion, thereby enhancing colonization of the stomach. H. pylori cell shape mutants show impaired colonization of the mouse stomach, highlighting the importance of cell shape in infection. To gain a deeper understanding of how helical cell morphology promotes host colonization by H. pylori, we used three-dimensional confocal microscopy to visualize the clinical isolate PMSS1 and an isogenic straight-rod mutant (Δcsd6) within thick longitudinal mouse stomach sections. We also performed volumetric image analysis to quantify the number of bacteria residing within corpus and antral glands in addition to measuring total CFU. We found that straight rods show attenuation during acute colonization of the stomach (1 day or 1 week postinfection) as measured by total CFU. Our quantitative imaging revealed that wild-type bacteria extensively colonized antral glands at 1 week postinfection, while csd6 mutants showed variable colonization of the antrum at this time point. During chronic infection (1 or 3 months postinfection), total CFU were highly variable but similar for wild-type and straight rods. Both wild-type and straight rods persisted and expanded in corpus glands during chronic infection. However, the straight rods showed reduced inflammation and disease progression. Thus, helical cell shape contributes to tissue interactions that promote inflammation during chronic infection, in addition to facilitating niche acquisition during acute infection.


Assuntos
Infecções por Helicobacter/microbiologia , Helicobacter pylori/citologia , Helicobacter pylori/crescimento & desenvolvimento , Estômago/patologia , Animais , Aderência Bacteriana , Doença Crônica , Feminino , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Humanos , Camundongos Endogâmicos C57BL , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Estômago/microbiologia
19.
Nat Microbiol ; 4(8): 1411-1423, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31110360

RESUMO

Helicobacter pylori infection is a proven carcinogen for gastric cancer. Its virulence factor vacuolating cytotoxin A (VacA) promotes more severe disease and gastric colonization. VacA, by an unknown mechanism, usurps lysosomal and autophagy pathways to generate a protected reservoir for H. pylori that confers bacterial survival in vitro. Here, we show the existence of a VacA-generated intracellular niche in vivo that protects the bacteria from antibiotic treatment and leads to infection recrudescence after therapy. Furthermore, we report that VacA targets the lysosomal calcium channel TRPML1 to disrupt endolysosomal trafficking and mediate these effects. Remarkably, H. pylori that lack toxigenic VacA colonize enlarged dysfunctional lysosomes in the gastric epithelium of trpml1-null mice, where they are protected from eradication therapy. Furthermore, a small molecule agonist directed against TRPML1 reversed the toxic effects of VacA on endolysosomal trafficking, culminating in the clearance of intracellular bacteria. These results suggest that TRPML1 may represent a therapeutic target for chronic H. pylori infection.


Assuntos
Proteínas de Bactérias/metabolismo , Cálcio/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Lisossomos/metabolismo , Canais de Receptores Transientes de Potencial/metabolismo , Animais , Antibacterianos/farmacologia , Autofagia , Canais de Cálcio/metabolismo , Modelos Animais de Doenças , Infecções por Helicobacter/patologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Viabilidade Microbiana , Transporte Proteico , Estômago/microbiologia , Estômago/patologia , Canais de Receptores Transientes de Potencial/genética
20.
Acta Med Indones ; 51(1): 34-41, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31073104

RESUMO

BACKGROUND: early detection of H. pylori is essential to prevent the development of infections into gastric malignancies. The coccoid form of H. pylori is difficult to detect either by culture or histopathology; however, it can be detected using molecular methods, such as real-time PCR. The study was expected to provide new information on the development of H. pylori detection. METHODS: a cross-sectional study was conducted at the Gastrointestinal Endoscopy Center of Cipto Mangunkusumo Hospital between October 2016 and August 2017. The sampling method used was consecutive sampling. Biopsy from gastric antrum and corpus were performed in 64 patients. We collected 2 specimens from each site to be examined using real-time PCR and histopathology. Initially, we conducted real-time PCR optimization followed by application of clinical samples from gastric biopsy. Data analysis using McNemar's χ2 and Kappa tests. RESULTS: the real-time PCR showed 25% positivity, while the positive proportion of histopathological examination was 14%. Real-time PCR has a sensitivity and specificity 88.9% dan 85.5%, respectively. The McNemar's χ2 test showed that there is significantly different (p=0.039) between the two tests; kappa value (p=0.561).  Conclusion: the real-time PCR examination is more sensitive than histopathology. This technique can improve diagnosis by 11% compared to histopathological examination.


Assuntos
Dispepsia/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/genética , RNA Ribossômico 16S/genética , Adulto , Idoso , Estudos Transversais , Feminino , Gastroscopia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Estômago/microbiologia , Estômago/patologia , Adulto Jovem
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