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1.
Front Microbiol ; 15: 1361626, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559357

RESUMO

Introduction: One of the biggest obstacles in diagnosing Implant-Associated Infections is the lack of infection criteria and standardized diagnostic methods. These infections present a wide range of symptoms, and their diagnosis can be hampered by the formation of microbial biofilms on the surface of implants. This study aimed to provide insight into the performance of sonication in the diagnosis of infections associated with Cardiac Implantable Electronic Devices, to help define a consensus on the algorithm for the microbial diagnosis of these infections. Methods: We carried out a systematic review with meta-analysis. The PRISMA methodology guidelines were followed, and an advanced search was carried out in PubMed and Web of Science, which enabled 8 articles to be included in the review, in which a meta-analysis was also carried out. QUADAS-2 was used to assess the risk of bias and effect measures were calculated to assess publication bias. Results: The overall sensitivity of the method was 0.823 (95% CI: 0.682-0.910) and the specificity was 0.632 (95% CI: 0.506-0.743). Discussion: These results suggest that sonication may offer advantages in diagnosing these infections. However, it is essential to approach these findings carefully and take into account the recommendations provided in the EHRA 2019 guidelines. This study highlights the importance of more effective diagnostic approaches for implantable medical device-associated infections to improve the quality of treatment and minimize the risks associated with these challenging medical conditions.

2.
Gut Microbes ; 16(1): 2325067, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38445660

RESUMO

The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes in the composition and metabolism of the mouse gut microbiota. We observed several taxonomic-level changes on day (D)7 post-infection, including a marked reduction in the abundance of members of the Lactobacillaceae and Bifidobacteriaceae families, and an increase in the abundance of Akkermansia muciniphila. On D14, perturbation persisted in some species. Functional scale analysis of metagenomic data revealed transient changes in several metabolic pathways, particularly those leading to the production of short-chain fatty acids (SCFAs), polyamines, and tryptophan metabolites. Quantitative targeted metabolomics analysis of the serum revealed changes in specific classes of gut microbiota metabolites, including SCFAs, trimethylamine, polyamines, and indole-containing tryptophan metabolites. A marked decrease in indole-3-propionic acid (IPA) blood level was observed on D7. Changes in microbiota-associated metabolites correlated with changes in taxon abundance and disease marker levels. In particular, IPA was positively correlated with some Lactobacillaceae and Bifidobacteriaceae species (Limosilactobacillus reuteri, Lactobacillus animalis) and negatively correlated with Bacteroidales bacterium M7, viral load, and inflammation markers. IPA supplementation in diseased animals reduced viral load and lowered local (lung) and systemic inflammation. Treatment of mice with antibiotics targeting IPA-producing bacteria before infection enhanced viral load and lung inflammation, an effect inhibited by IPA supplementation. The results of this integrated metagenomic-metabolomic analysis highlighted IPA as an important contributor to influenza outcomes and a potential biomarker of disease severity.


Assuntos
Actinobacteria , Microbioma Gastrointestinal , Influenza Humana , Humanos , Animais , Camundongos , Propionatos , Triptofano , Inflamação , Poliaminas
3.
RMD Open ; 9(1)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36963782

RESUMO

OBJECTIVE: To assess whether gut microbiota composition is associated with patient characteristics and may have predictive value on the response to TNF inhibitor (TNFi) treatment in axial spondyloarthritis (AxSpA). METHODS: The study involved 61 patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for AxSpA. All patients had active disease despite non-steroidal anti-inflammatory drugs intake and were eligible for treatment with a TNFi. At baseline, the mean Ankylosing Spondylitis Disease Activity Score was 2.9±1 and mean C reactive protein (CRP) level 9.7±11.4 mg/L. Bacterial 16S ribosomal RNA gene sequencing was performed on stool samples collected at baseline (month 0 (M0)) and 3 months after TNFi initiation (month 3 (M3)). Alpha and beta diversity metrics were calculated on the relative abundance of core operational taxonomic units (OTUs). RESULTS: The HLA-B27 status affected at least in part the global composition of faecal microbiota at M0 as well as the abundance/prevalence of several anaerobic bacteria in the families Oscillospiraceae, Lachnospiraceae and Bifidobacteriaceae. In contrast, smoking affected the global composition of faecal microbiota at both M0 and M3. The prevalence/abundance of seven bacterial OTUs at M0 was associated with response to TNFi treatment. One of the candidates, present only in non-responders, is the genus Sutterella, and the other six candidates are in the class Clostridia. CONCLUSIONS: Several SpA patients' characteristics modulate the composition of gut microbiota as did TNFi treatment. Moreover, the abundance/prevalence of seven OTUs at baseline may be used as a novel non-invasive index that predicts the response to TNFi with greater accuracy than HLA-B27 status, CRP level and measures of disease activity.


Assuntos
Microbioma Gastrointestinal , Espondilite Anquilosante , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Antígeno HLA-B27/genética , Resultado do Tratamento , Fator de Necrose Tumoral alfa , Espondilite Anquilosante/tratamento farmacológico
4.
Front Microbiol ; 13: 863777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531285

RESUMO

Bone and joint infections (BJIs) are complex infections that require precise microbiological documentation to optimize antibiotic therapy. Currently, diagnosis is based on microbiological culture, sometimes complemented by amplification and sequencing of the 16S rDNA gene. Clinical metagenomics (CMg), that is, the sequencing of the entire nucleic acids in a sample, was previously shown to identify bacteria not detected by conventional methods, but its actual contribution to the diagnosis remains to be assessed, especially with regard to 16S rDNA sequencing. In the present study, we tested the performance of CMg in 34 patients (94 samples) with suspected BJIs, as compared to culture and 16S rDNA sequencing. A total of 94 samples from 34 patients with suspicion of BJIs, recruited from two sites, were analyzed by (i) conventional culture, (ii) 16S rDNA sequencing (Sanger method), and (iii) CMg (Illumina Technology). Two negative controls were also sequenced by CMg for contamination assessment. Based on the sequencing results of negative controls, 414 out of 539 (76.7%) bacterial species detected by CMg were considered as contaminants and 125 (23.2%) as truly present. For monomicrobial infections (13 patients), the sensitivity of CMg was 83.3% as compared to culture, and 100% as compared to 16S rDNA. For polymicrobial infections (13 patients), the sensitivity of CMg was 50% compared to culture, and 100% compared to 16S rDNA. For samples negative in culture (8 patients, 21 samples), CMg detected 11 bacteria in 10 samples from 5 different patients. In 5/34 patients, CMg brought a microbiological diagnosis where conventional methods failed, and in 16/34 patients, CMg provided additional information. Finally, 99 antibiotic resistance genes were detected in 24 patients (56 samples). Provided sufficient genome coverage (87.5%), a correct inference of antibiotic susceptibility was achieved in 8/8 bacteria (100%). In conclusion, our study demonstrated that the CMg provides complementary and potentially valuable data to conventional methods of BJIs diagnosis.

5.
Fisioter. Bras ; 22(6): 809-823, Fevereiro 7, 2022.
Artigo em Português | LILACS | ID: biblio-1358267

RESUMO

A Síndrome da Fragilidade (SF) é a resposta do organismo do idoso frente ao aumento da vulnerabilidade a estressores que redundam em diminuição das reservas fisiológicas e desregulação de múltiplos sistemas. Aspectos sociais e emocionais podem potencializar essa vulnerabilidade, sendo a institucionalização do idoso um agente potencializador desse quadro. Objetivo: Estimar a prevalência da SF e caracterizar o perfil clínico e epidemiológico dos idosos institucionalizados de Pindamonhangaba/SP. Métodos: Trata-se de um estudo observacional transversal descritivo. Para tanto, foram incluídos 31 idosos de ambos os sexos, residentes em duas Instituições de Longa Permanência para Idosos (ILPI) do município de Pindamonhangaba/SP. A SF avalia: perda de peso não intencional, autorrelato de exaustão ou fadiga, diminuição da força muscular pela força de preensão palmar, lentidão na marcha e baixo nível de atividade física. Resultados: A prevalência da SF em idosos institucionalizados foi de 67,4%. Considerando os cinco itens que compõe a SF, a perda de peso não intencional esteve presente em 61,9% dos idosos, o autorrelato de exaustão ou fadiga em 66,6%, o baixo nível de atividade física em 66,6%, a lentidão na marcha em 71,4% e a diminuição da força de preensão palmar em 95,2%. A maior prevalência de idosos frágeis esteve entre os homens (41,9%), e as morbidades mais comuns foram: depressão (32,3%), hipertensão arterial sistêmica (38,7%), sintomas musculoesqueléticos (67,7%), alterações no equilíbrio (74,2%) e características sugestivas de alterações cognitivas (83,9%). Conclusão: A prevalência da SF entre os idosos do estudo foi alta com predomínio no sexo masculino. Destacou-se no perfil clínico, também, a alta prevalência, as características sugestivas de alterações cognitivas, a alteração do equilíbrio e risco de quedas e o sobrepeso ou obesidade. (AU)


Assuntos
Idoso , Idoso de 80 Anos ou mais , Exercício Físico , Depressão , Força Muscular , Instituição de Longa Permanência para Idosos , Hipertensão , Idoso Fragilizado , Fragilidade
6.
Gut Microbes ; 13(1): 1-19, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33685349

RESUMO

The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota's composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instrumental in understanding and controling COVID 19. We used a nonhuman primate model (the macaque), that recapitulates mild COVID-19 symptoms, to analyze the effects of a SARS-CoV-2 infection on dynamic changes of the gut microbiota. 16S rRNA gene profiling and analysis of ß diversity indicated significant changes in the composition of the gut microbiota with a peak at 10-13 days post-infection (dpi). Analysis of bacterial abundance correlation networks confirmed disruption of the bacterial community at 10-13 dpi. Some alterations in microbiota persisted after the resolution of the infection until day 26. Some changes in the relative bacterial taxon abundance associated with infectious parameters. Interestingly, the relative abundance of Acinetobacter (Proteobacteria) and some genera of the Ruminococcaceae family (Firmicutes) was positively correlated with the presence of SARS-CoV-2 in the upper respiratory tract. Targeted quantitative metabolomics indicated a drop in short-chain fatty acids (SCFAs) and changes in several bile acids and tryptophan metabolites in infected animals. The relative abundance of several taxa known to be SCFA producers (mostly from the Ruminococcaceae family) was negatively correlated with systemic inflammatory markers while the opposite correlation was seen with several members of the genus Streptococcus. Collectively, SARS-CoV-2 infection in a nonhuman primate is associated with changes in the gut microbiota's composition and functional activity.


Assuntos
COVID-19/microbiologia , Microbioma Gastrointestinal , Macaca/microbiologia , Macaca/virologia , Animais , Bactérias/classificação , Modelos Animais de Doenças , Fezes , Feminino , Metaboloma , RNA Ribossômico 16S/genética
7.
J Allergy Clin Immunol ; 147(4): 1296-1305.e6, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32926879

RESUMO

BACKGROUND: The links between microbial environmental exposures and asthma are well documented, but no study has combined deep sequencing results from pulmonary and indoor microbiomes of patients with asthma with spirometry, clinical, and endotype parameters. OBJECTIVE: The goal of this study was to investigate the links between indoor microbial exposures and pulmonary microbial communities and to document the role of microbial exposures on inflammatory and clinical outcomes of patients with severe asthma (SA). METHODS: A total of 55 patients with SA from the national Cohort of Bronchial Obstruction and Asthma cohort were enrolled for analyzing their indoor microbial flora through the use of electrostatic dust collectors (EDCs). Among these patients, 22 were able to produce sputum during "stable" or pulmonary "exacerbation" periods and had complete pairs of EDC and sputum samples, both collected and analyzed. We used amplicon targeted metagenomics to compare microbial communities from EDC and sputum samples of patients according to type 2 (T2)-asthma endotypes. RESULTS: Compared with patients with T2-low SA, patients with T2-high SA exhibited an increase in bacterial α-diversity and a decrease in fungal α-diversity of their indoor microbial florae, the latter being significantly correlated with fraction of exhaled nitric oxide levels. The ß-diversity of the EDC mycobiome clustered significantly according to T2 endotypes. Moreover, the proportion of fungal taxa in common between the sputum and EDC samples was significantly higher when patients exhibited acute exacerbation. CONCLUSION: These results illustrated, for the first time, a potential association between the indoor mycobiome and clinical features of patients with SA, which should renew interest in deciphering the interactions between indoor environment, fungi, and host in asthma.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Asma/microbiologia , Poeira/análise , Microbiota , Adulto , Idoso , DNA Bacteriano/análise , DNA Fúngico/análise , Monitoramento Ambiental , Feminino , Humanos , Masculino , Microbiota/genética , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Escarro/microbiologia
9.
Sci Total Environ ; 763: 142950, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33127155

RESUMO

Chlorinated ethenes (CEs) are most problematic pollutants in groundwater. Dehalogenating bacteria, and in particular organohalide-respiring bacteria (OHRB), can transform PCE to ethene under anaerobic conditions, and thus contribute to bioremediation of contaminated sites. Current approaches to characterize in situ biodegradation of CEs include hydrochemical analyses, quantification of the abundance of key species (e.g. Dehalococcoides mccartyi) and dehalogenase genes (pceA, vcrA, bvcA and tceA) involved in different steps of organohalide respiration (OHR) by qPCR, and compound-specific isotope analysis (CSIA) of CEs. Here we combined these approaches with sequencing of 16S rRNA gene amplicons to consider both OHRB and bacterial taxa involved in CE transformation at a multi-contaminated site. Integrated analysis of hydrogeochemical characteristics, gene abundances and bacterial diversity shows that bacterial diversity and OHRB mainly correlated with hydrogeochemical conditions, suggesting that pollutant exposure acts as a central driver of bacterial diversity. CSIA, abundances of four reductive dehalogenase encoding genes and the prevalence of Dehalococcoides highlighted sustained PCE, DCE and VC degradation in several wells of the polluted plume. These results suggest that bacterial taxa associated with OHR play an essential role in natural attenuation of CEs, and that representatives of taxa including Dehalobacterium and Desulfosporosinus co-occur with Dehalococcoides. Overall, our study emphasizes the benefits of combining several approaches to evaluate the interplay between the dynamics of bacterial diversity in CE-polluted plumes and in situ degradation of CEs, and to contribute to a more robust assessment of natural attenuation at multi-polluted sites.


Assuntos
Chloroflexi , Água Subterrânea , Poluentes Químicos da Água , Bactérias/genética , Biodegradação Ambiental , Chloroflexi/genética , Etilenos , Isótopos , RNA Ribossômico 16S/genética
10.
FASEB J ; 34(9): 12615-12633, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32729971

RESUMO

Although it is known that zinc has several beneficial roles in the context of gut inflammation, the underlying mechanisms have not been extensively characterized. Zinc (Zn) is known to be the primary physiological inducer of the expression of the metallothionein (MT) superfamily of small stress-responsive proteins. The expression of MTs in various tissues is induced or enhanced (including the gastrointestinal tract (GIT)) by a variety of stimuli, including infection and inflammation. However, the MTs' exact role in inflammation is still subject to debate. In order to establish whether or not MTs are the sole vectors in the Zn-based modulation of intestinal inflammation, we used transcriptomic and metagenomic approaches to assess the potential effect of dietary Zn, the mechanisms underlying the MTs' beneficial effects, and the induction of previously unidentified mediators. We found that the expression of endogenous MTs in the mouse GIT was stimulated by an optimized dietary supplementation with Zn. The protective effects of dietary supplementation with Zn were then evaluated in mouse models of chemically induced colitis. The potential contribution of MTs and other pathways was explored via transcriptomic analyses of the ileum and colon in Zn-treated mice. The microbiota's role was also assessed via fecal 16S rRNA sequencing. We found that high-dose dietary supplementation with Zn induced the expression of MT-encoding genes in the colon of healthy mice. We next demonstrated that the Zn diet significantly protected mice in the two models of induced colitis. When comparing Zn-treated and control mice, various genes were found to be differentially expressed in the colon and the ileum. Finally, we found that Zn supplementation did not modify the overall structure of the fecal microbiota, with the exception of (i) a significant increase in endogenous Clostridiaceae, and (ii) some subtle but specific changes at the family and genus levels. Our results emphasize the beneficial effects of excess dietary Zn on the prevention of colitis and inflammatory events in mouse models. The main underlying mechanisms were driven by the multifaceted roles of MTs and the other potential molecular mediators highlighted by our transcriptomic analyses although we cannot rule out contributions by other factors from the host and/or the microbiota.


Assuntos
Colite , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Metalotioneína/metabolismo , Transcriptoma , Zinco/farmacologia , Animais , Colite/tratamento farmacológico , Colite/metabolismo , Colite/microbiologia , Colo/efeitos dos fármacos , Colo/metabolismo , Suplementos Nutricionais , Fezes/microbiologia , Feminino , Íleo/efeitos dos fármacos , Íleo/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Zinco/administração & dosagem
11.
Cell Rep ; 30(9): 2934-2947.e6, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32130898

RESUMO

Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection.


Assuntos
Disbiose/microbiologia , Ácidos Graxos Voláteis/biossíntese , Trato Gastrointestinal/microbiologia , Influenza Humana/microbiologia , Pulmão/microbiologia , Infecções Pneumocócicas/complicações , Superinfecção/complicações , Superinfecção/microbiologia , Acetatos/farmacologia , Animais , Disbiose/complicações , Disbiose/virologia , Comportamento Alimentar , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Humanos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/patologia , Camundongos Endogâmicos C57BL , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/virologia , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Infecções Respiratórias/microbiologia
12.
São Paulo; s.n; 2020. 51 p. ilust, tabelas.
Tese em Português | LILACS, Inca | ID: biblio-1222802

RESUMO

Câncer de pulmão de não pequenas células (CPNPC) é o tipo mais frequente de câncer de pulmão, acometendo por volta de 85% à 90% de todos os cânceres de pulmão, sendo o tabagismo o fator de risco mais relevante para a doença. O sistema imune possui um papel importante na resposta antitumoral, porém, as células do tumor fazem uso de mecanismos para evadir da imunovigilância através de células imunossupressoras e produção de citocinas. A análise de células imunes e de citocinas pode auxiliar em um conhecimento mais abrangente do microambiente tumoral como um todo, permitindo um melhor entendimento da doença e a proposta de tratamentos que possam ser mais eficazes. Neste trabalho, foi avaliando o perfil imune sistêmico de pacientes com CPNPC, comparando pacientes não metastáticos (estágios I, II, III) e pacientes metastáticos (estágio IV). Nós avaliamos a frequência de células linfoides e mieloides por meio de citometria de fluxo, além das concentrações plasmáticas de citocinas por meio da análise multiplex a partir de amostras de sangue de pacientes coletadas antes do início do tratamento. Foram incluídos 39 pacientes com CPNPC, sendo 28 no grupo de metastáticos e 11 no grupo de não metastáticos. Foi possível verificar um aumento da frequência de monócitos inflamatórios no sangue de pacientes metastáticos, se comparados a pacientes não metastáticos, indicando um microambiente mais favorável ao desenvolvimento de metástase. Além disso, foram observados níveis mais elevados de monócitos não-clássicos, conhecidos como patrulhadores e das citocinas TRAIL E IL-1Ra em pacientes não metastáticos, indicando um microambiente mais protetor. Concluindo, este estudo propõe mecanismos imunológicos relacionados ao desenvolvimento de metástase para pacientes com CPNPC, sugerindo biomarcadores que podem auxiliar no prognóstico e acompanhamento desse grupo de pacientes


Non-small cell lung cancer (NSCLC) is the most common type of cancer among lung cancers, accounting for about 85% to 90% of cases, with smoking being the most relevant risk factor related to the disease. The immune system plays an important role in anti-tumoral response; however, tumor cells use mechanisms that allow escape from immune surveillance, such as the presence of immunosuppressive cells and production of inhibitory cytokines in the tumor microenvironment. Analyzing the immune cells and cytokines can be helpful to better understand the tumor microenvironment and diseases development allowing a more effective treatment. In this work it was determine the immune cells profile of patients with NSCLC, comparing non-metastatic (stages I, II and III) and metastatic (stage IV) patients. We evaluated the frequencies of lymphocytes and myeloid cells in patients using flow cytometry and plasmatic cytokines concentration cytokines using multiplex analysis in blood samples collected before treatment begins. It was including 39 NSCLC patients, of which 28 from the metastatic group and 11 from the non-metastatic group. There was an increase in inflammatory monocytes frequency in metastatic patients when compared to metastatic patients indicating a more favorable microenvironment for tumor metastasis. Moreover, it was found discovered a higher level of non-classic monocytes also known as patrolling monocytes, and TRAIL and IL-1Ra Cytokines in non-metastatic patients in compare with metastatic patients, indicating a more protective microenvironment. In conclusion, this study demonstrated immunological mechanisms related to metastasis in NSCLC patient suggesting helpful biomarker for prognosis and patient flow up


Assuntos
Humanos , Masculino , Feminino , Prognóstico , Biomarcadores Tumorais , Carcinoma de Pequenas Células do Pulmão , Microambiente Tumoral , Metástase Neoplásica
13.
Artigo em Inglês | MEDLINE | ID: mdl-31636067

RESUMO

Fluoroquinolone treatments induce dysbiosis of the intestinal microbiota, resulting in loss of resistance to colonization by exogenous bacteria such as Clostridioides difficile that may cause severe diarrhea in humans and lethal infection in hamsters. We show here that DAV131A, a charcoal-based adsorbent, decreases the intestinal levels of the fluoroquinolone antibiotics levofloxacin and ciprofloxacin in hamsters, protects their intestinal microbiota, and prevents lethal infection by C. difficile.


Assuntos
Carvão Vegetal/administração & dosagem , Clostridioides difficile , Infecções por Clostridium/prevenção & controle , Administração Oral , Adsorção , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Ciprofloxacina/efeitos adversos , Ciprofloxacina/farmacocinética , Clostridioides difficile/patogenicidade , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Disbiose/metabolismo , Disbiose/prevenção & controle , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/farmacocinética , Microbioma Gastrointestinal/efeitos dos fármacos , Levofloxacino/efeitos adversos , Levofloxacino/farmacocinética , Masculino , Mesocricetus
14.
Artigo em Inglês | MEDLINE | ID: mdl-31307985

RESUMO

Although the global deleterious impact of antibiotics on the intestinal microbiota is well known, temporal changes in microbial diversity during and after an antibiotic treatment are still poorly characterized. We used plasma and fecal samples collected frequently during treatment and up to one month after from 22 healthy volunteers assigned to a 5-day treatment by moxifloxacin (n = 14) or no intervention (n = 8). Moxifloxacin concentrations were measured in both plasma and feces, and bacterial diversity was determined in feces by 16S rRNA gene profiling and quantified using the Shannon index and number of operational taxonomic units (OTUs). Nonlinear mixed effect models were used to relate drug pharmacokinetics and bacterial diversity over time. Moxifloxacin reduced bacterial diversity in a concentration-dependent manner, with a median maximal loss of 27.5% of the Shannon index (minimum [min], 17.5; maximum [max], 27.7) and 47.4% of the number of OTUs (min, 30.4; max, 48.3). As a consequence of both the long fecal half-life of moxifloxacin and the susceptibility of the gut microbiota to moxifloxacin, bacterial diversity indices did not return to their pretreatment levels until days 16 and 21, respectively. Finally, the model characterized the effect of moxifloxacin on bacterial diversity biomarkers and provides a novel framework for analyzing antibiotic effects on the intestinal microbiome.


Assuntos
Antibacterianos/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Microbiota/efeitos dos fármacos , Microbiota/genética , Adulto , Bactérias/efeitos dos fármacos , Bactérias/genética , Fezes/microbiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina/uso terapêutico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodos , Adulto Jovem
15.
Front Microbiol ; 10: 89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809199

RESUMO

Microcosm experiments with CE-contaminated groundwater from a former industrial site were set-up to evaluate the relationships between biological CE dissipation, dehalogenase genes abundance and bacterial genera diversity. Impact of high concentrations of PCE on organohalide respiration was also evaluated. Complete or partial dechlorination of PCE, TCE, cis-DCE and VC was observed independently of the addition of a reducing agent (Na2S) or an electron donor (acetate). The addition of either 10 or 100 µM PCE had no effect on organohalide respiration. qPCR analysis of reductive dehalogenases genes (pceA, tceA, vcrA, and bvcA) indicated that the version of pceA gene found in the genus Dehalococcoides [hereafter named pceA(Dhc)] and vcrA gene increased in abundance by one order of magnitude during the first 10 days of incubation. The version of the pceA gene found, among others, in the genus Dehalobacter, Sulfurospirillum, Desulfuromonas, and Geobacter [hereafter named pceA(Dhb)] and bvcA gene showed very low abundance. The tceA gene was not detected throughout the experiment. The proportion of pceA(Dhc) or vcrA genes relative to the universal 16S ribosomal RNA (16S rRNA) gene increased by up to 6-fold upon completion of cis-DCE dissipation. Sequencing of 16S rRNA amplicons indicated that the abundance of Operational Taxonomic Units (OTUs) affiliated to dehalogenating genera Dehalococcoides, Sulfurospirillum, and Geobacter represented more than 20% sequence abundance in the microcosms. Among organohalide respiration associated genera, only abundance of Dehalococcoides spp. increased up to fourfold upon complete dissipation of PCE and cis-DCE, suggesting a major implication of Dehalococcoides in CEs organohalide respiration. The relative abundance of pceA and vcrA genes correlated with the occurrence of Dehalococcoides and with dissipation extent of PCE, cis-DCE and CV. A new type of dehalogenating Dehalococcoides sp. phylotype affiliated to the Pinellas group, and suggested to contain both pceA(Dhc) and vcrA genes, may be involved in organohalide respiration of CEs in groundwater of the study site. Overall, the results demonstrate in situ dechlorination potential of CE in the plume, and suggest that taxonomic and functional biomarkers in laboratory microcosms of contaminated groundwater following pollutant exposure can help predict bioremediation potential at contaminated industrial sites.

16.
Antiinfect Agents ; 16(2): 144-146, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30079296

RESUMO

BACKGROUND: Fascioliasis is a neglected tropical disease that affects poor people from poor and developing countries. In the world, it has been estimated that at least 2.6 million people are affected with this disease. The International agency for Research on Cancer, states that O. viverrini and C. sinensis, also liver flukes, are considered as definitive causes of cholangiocarcinoma. However, fascioliasis caused by F. hepatica has not been associated with cancer to date. There are not any known causative associations between this parasite and liver cancer (cholangiocarcinoma). METHODS: Chine Hamster Ovary (CHO) cells were treated with F. hepatica extracts and cell proliferation was assessed by using the indirect method for estimating cell number based on the mitochondrial activity with MTS cell proliferation reagent. We observed unexpected death of these cells when treated with F. hepatica extracts. RESULTS: We now hypothesize that this parasite could be used as a medically-important trematode pathogen in cancer therapy.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30061286

RESUMO

Antibiotic disruption of the intestinal microbiota favors colonization by Clostridium difficile Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis and quantified the link between this intensity and mortality. We administered either moxifloxacin (n = 70) or clindamycin (n = 60) to hamsters by subcutaneous injection from day 1 (D1) to D5 and challenged them with a C. difficile toxigenic strain at D3 Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D0 and D3 using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D16 We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time of C. difficile challenge and studied their capacity to predict subsequent death of the animals. Increasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis, and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (P < 10-5 for the change of Shannon index in moxifloxacin-treated animals and P < 10-9 in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the receiver operating curve (ROC) of 0.89 (95% confidence interval [CI], 0.82, 0.95) and 0.95 (0.90, 0.98), respectively. Altogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency on the DAV131A dose; mortality after C. difficile challenge was related to the intensity of dysbiosis in similar manners with the two antibiotics.


Assuntos
Antibacterianos/efeitos adversos , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/mortalidade , Disbiose/induzido quimicamente , Animais , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/patogenicidade , Cricetinae , Disbiose/mortalidade , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Mesocricetus , Moxifloxacina/uso terapêutico
19.
Int J Food Microbiol ; 238: 265-273, 2016 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-27710867

RESUMO

Surface-ripened cheeses host complex microbial communities responsible for the transformation of milk into cheese as well as the development of important properties in terms of texture, color and sensory perception. In this study, we used high-throughput amplicon sequencing to decipher the bacterial and fungal diversity of 60 cheeses belonging to 12 popular French cheese varieties. Using this approach, 76 bacterial and 44 fungal phylotypes were identified. Major differences were observed between rind and core samples and also according to cheese varieties and manufacturing processes. Occurrence analysis revealed the presence of widespread taxa as well as operational taxonomic units (OTUs) specific to one or several cheese varieties. Finally, we observed patterns specific to the cheese production facility, supporting the importance of indigenous microorganisms for the microbial assemblage of cheese microbiota.


Assuntos
Bactérias/classificação , Queijo/microbiologia , Fungos/classificação , Microbiota/genética , Animais , Bactérias/genética , Sequência de Bases , DNA Bacteriano/genética , DNA Fúngico/genética , DNA Intergênico/genética , França , Fungos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Leite/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
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