Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.550
Filtrar
1.
PLoS Pathog ; 16(3): e1008376, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214382

RESUMO

BACKGROUND: Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome (CVM) in the natural history of HR-HPV. METHODS: This study was nested within the placebo arm of the Costa Rica HPV Vaccine Trial that included women aged 18-25 years of age. Cervical samples from two visits of women with an incident HR-HPV infection (n = 273 women) were used to evaluate the prospective role of the CVM on the natural history of HR-HPV. We focus specifically on infection clearance, persistence, and progression to cervical intraepithelial neoplasia grade 2 and 3 (CIN2+). The CVM was characterized by amplification and sequencing the bacterial 16S V4 rRNA gene region and the fungal ITS1 region using an Illumina MiSeq platform. OTU clustering was performed using QIIME2. Functional groups were imputed using PICRUSt and statistical analyses were performed using R. RESULTS: At Visit 1 (V1) abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis (LDA)>4.0), whereas V1 Gardnerella was the dominant biomarker for HR-HPV progression (LDA>4.0). At visit 2 (V2), increased microbial Shannon diversity was significantly associated with progression to CIN2+ (p = 0.027). Multivariate mediation analysis revealed that the positive association of V1 Gardnerella with CIN2+ progression was due to the increased cervicovaginal diversity at V2 (p = 0.040). A full multivariate model of key components of the CVM showed significant protective effects via V1 genus Lactobacillus, OR = 0.41 (0.22-0.79), V1 fungal diversity, OR = 0.90 (0.82-1.00) and V1 functional Cell Motility pathway, OR = 0.75 (0.62-0.92), whereas V2 bacterial diversity, OR = 1.19 (1.03-1.38) was shown to be predictive of progression to CIN2+. CONCLUSION: This study demonstrates that features of the cervicovaginal microbiome are associated with HR-HPV progression in a prospective longitudinal cohort. The analyses indicated that the association of Gardnerella and progression to CIN2+ may actually be mediated by subsequent elevation of microbial diversity. Identified features of the microbiome associated with HR-HPV progression may be targets for therapeutic manipulation to prevent CIN2+. TRIAL REGISTRATION: ClinicalTrials.gov NCT00128661.


Assuntos
Neoplasia Intraepitelial Cervical , Colo do Útero , Gardnerella , Lactobacillus , Microbiota , Papillomaviridae/metabolismo , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Vagina , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/microbiologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/metabolismo , Colo do Útero/microbiologia , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Gardnerella/classificação , Gardnerella/genética , Gardnerella/metabolismo , Humanos , Lactobacillus/classificação , Lactobacillus/genética , Lactobacillus/metabolismo , Estudos Longitudinais , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/microbiologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vagina/metabolismo , Vagina/microbiologia , Vagina/patologia , Vagina/virologia
2.
Adv Exp Med Biol ; 1219: 77-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130694

RESUMO

Several aspects of the human physiology are controlled by the microbiota that plays a key role in health and disease. In fact, microbial dysbiosis is associated with numerous diseases, including several types of cancer such as colon, gastric, esophageal, pancreatic, laryngeal, breast and gallbladder carcinomas.Metabolic symbiosis between non-malignant cells and the resident microbita is crucial for the host homeostasis. However, cancer cells are able to repurpose the pre-existing metabolic symbiosis, being able to recycle those relations and also create novel metabolic symbiosis, leading to profound alterations on the local microenvironment.In here we will explore some of these symbiotic metabolic interactions between bacteria and non-malignant cells in two different contexts: colon and uterine cervix. The way malignant cells are able to recycle these normal interactions and also create novel types of symbiotic metabolic relations will also be discussed.The knowledge of these complex interactions and recycling mechanisms is of extreme importance for cancer treatment, as new therapeutic targets could be developed.


Assuntos
Bactérias/metabolismo , Células Epiteliais/metabolismo , Neoplasias/metabolismo , Neoplasias/microbiologia , Simbiose , Colo do Útero/citologia , Colo do Útero/metabolismo , Colo do Útero/microbiologia , Colo/citologia , Colo/metabolismo , Colo/microbiologia , Feminino , Humanos , Microbiota/fisiologia
3.
Nat Rev Urol ; 17(4): 232-250, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32071434

RESUMO

The female reproductive tract (FRT), similar to other mucosal sites, harbours a site-specific microbiome, which has an essential role in maintaining health and homeostasis. In the majority of women of reproductive age, the microbiota of the lower FRT (vagina and cervix) microenvironment is dominated by Lactobacillus species, which benefit the host through symbiotic relationships. By contrast, the upper FRT (uterus, Fallopian tubes and ovaries) might be sterile in healthy individuals or contain a low-biomass microbiome with a diverse mixture of microorganisms. When dysbiosis occurs, altered immune and metabolic signalling can affect hallmarks of cancer, including chronic inflammation, epithelial barrier breach, changes in cellular proliferation and apoptosis, genome instability, angiogenesis and metabolic dysregulation. These pathophysiological changes might lead to gynaecological cancer. Emerging evidence shows that genital dysbiosis and/or specific bacteria might have an active role in the development and/or progression and metastasis of gynaecological malignancies, such as cervical, endometrial and ovarian cancers, through direct and indirect mechanisms, including modulation of oestrogen metabolism. Cancer therapies might also alter microbiota at sites throughout the body. Reciprocally, microbiota composition can influence the efficacy and toxic effects of cancer therapies, as well as quality of life following cancer treatment. Modulation of the microbiome via probiotics or microbiota transplant might prove useful in improving responsiveness to cancer treatment and quality of life. Elucidating these complex host-microbiome interactions, including the crosstalk between distal and local sites, will translate into interventions for prevention, therapeutic efficacy and toxic effects to enhance health outcomes for women with gynaecological cancers.


Assuntos
Carcinogênese , Disbiose/microbiologia , Neoplasias dos Genitais Femininos/microbiologia , Genitália Feminina/microbiologia , Microbiota/fisiologia , Anti-Infecciosos/uso terapêutico , Bactérias Anaeróbias , Colo do Útero/microbiologia , Disbiose/metabolismo , Estrogênios/metabolismo , Tubas Uterinas/microbiologia , Feminino , Microbioma Gastrointestinal , Neoplasias dos Genitais Femininos/metabolismo , Neoplasias dos Genitais Femininos/prevenção & controle , Neoplasias dos Genitais Femininos/terapia , Genitália Feminina/metabolismo , Humanos , Lactobacillus , Ovário/microbiologia , Probióticos/uso terapêutico , Útero/microbiologia , Vagina/microbiologia
4.
PLoS Pathog ; 16(1): e1008236, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971984

RESUMO

Bacterial vaginosis (BV), a condition in which the vaginal microbiota consists of community of obligate and facultative anaerobes rather than dominated by a single species of Lactobacillus, affects ~30% of women in the US. Women with BV are at 60% increased risk for HIV acquisition and are 3-times more likely to transmit HIV to an uninfected partner. As cervicovaginal mucus (CVM) is the first line of defense against mucosal pathogens and the home of the resident vaginal microbiota, we hypothesized the barrier function of CVM to HIV may be diminished in BV. Here, we characterized CVM properties including pH, lactic acid content, and Nugent score to correlate with the microbiota community composition, which was confirmed by 16S rDNA sequencing on a subset of samples. We then quantified the mobility of fluorescently-labeled HIV virions and nanoparticles to characterize the structural and adhesive barrier properties of CVM. Our analyses included women with Nugent scores categorized as intermediate (4-6) and BV (7-10), women that were either symptomatic or asymptomatic, and a small group of women before and after antibiotic treatment for symptomatic BV. Overall, we found that HIV virions had significantly increased mobility in CVM from women with BV compared to CVM from women with Lactobacillus crispatus-dominant microbiota, regardless of whether symptoms were present. We confirmed using nanoparticles and scanning electron microscopy that the impaired barrier function was due to reduced adhesive barrier properties without an obvious degradation of the physical CVM pore structure. We further confirmed a similar increase in HIV mobility in CVM from women with Lactobacillus iners-dominant microbiota, the species most associated with transitions to BV and that persists after antibiotic treatment for BV. Our findings advance the understanding of the protective role of mucus and highlight the interplay between vaginal microbiota and the innate barrier function mucus.


Assuntos
Colo do Útero/microbiologia , Colo do Útero/virologia , Infecções por HIV/virologia , Vagina/microbiologia , Vagina/virologia , Vaginose Bacteriana/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , HIV-1/fisiologia , Humanos , Microbiota , Pessoa de Meia-Idade , Muco/microbiologia , Muco/virologia , Adulto Jovem
5.
PLoS One ; 15(1): e0224359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914129

RESUMO

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of ß-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1ß-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.


Assuntos
Disbiose/imunologia , Imunidade Inata/genética , Doenças Sexualmente Transmissíveis/imunologia , Vaginose Bacteriana/imunologia , Adolescente , Adulto , Biomarcadores/metabolismo , Colo do Útero/imunologia , Colo do Útero/microbiologia , Colo do Útero/patologia , Disbiose/epidemiologia , Disbiose/microbiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Estresse Oxidativo/imunologia , Gravidez , Infecções do Sistema Genital/epidemiologia , Infecções do Sistema Genital/imunologia , Inibidor Secretado de Peptidases Leucocitárias/imunologia , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Doenças Sexualmente Transmissíveis/epidemiologia , Doenças Sexualmente Transmissíveis/microbiologia , Uganda/epidemiologia , Vagina/imunologia , Vagina/microbiologia , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Zimbábue/epidemiologia
6.
Nat Commun ; 11(1): 199, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924800

RESUMO

Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth.


Assuntos
Colo do Útero/lesões , Inflamação/metabolismo , Complicações Infecciosas na Gravidez , Ureaplasma/metabolismo , Animais , Proliferação de Células , Colo do Útero/microbiologia , Colo do Útero/patologia , Citocinas , Modelos Animais de Doenças , Feminino , Humanos , Recém-Nascido , Camundongos , Camundongos Endogâmicos C57BL , Nonoxinol , Gravidez
7.
PLoS Pathog ; 15(12): e1008136, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31790511

RESUMO

Sexually transmitted infections are a critical public health issue. However, the mechanisms underlying sexually transmitted infections in women and the link between the infection mechanism and the wide range of clinical outcomes remain elusive due to a lack of research models mimicking human infection in vivo. We established a human cervical tissue explant model to mimic local Neisseria gonorrhoeae (GC) infections. We found that GC preferentially colonize the ectocervix by activating integrin-ß1, which inhibits epithelial shedding. GC selectively penetrate into the squamocolumnar junction (TZ) and endocervical epithelia by inducing ß-catenin phosphorylation, which leads to E-cadherin junction disassembly. Epithelial cells in various cervical regions differentially express carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), the host receptor for GC opacity-associated proteins (OpaCEA). Relatively high levels were detected on the luminal membrane of ecto/endocervical epithelial cells but very low levels intracellularly in TZ epithelial cells. CEACAM-OpaCEA interaction increased ecto/endocervical colonization and reduced endocervical penetration by increasing integrin-ß1 activation and inhibiting ß-catenin phosphorylation respectively, through CEACAM downstream signaling. Thus, the intrinsic properties of cervical epithelial cells and phase-variation of bacterial surface molecules both play a role in controlling GC infection mechanisms and infectivity, preferential colonization or penetration, potentially leading to asymptomatic or symptomatic infection.


Assuntos
Aderência Bacteriana/fisiologia , Colo do Útero/microbiologia , Gonorreia/microbiologia , Membrana Mucosa/microbiologia , Neisseria gonorrhoeae/patogenicidade , Colo do Útero/metabolismo , Feminino , Humanos , Membrana Mucosa/metabolismo , Técnicas de Cultura de Órgãos
9.
Integr Cancer Ther ; 18: 1534735419893063, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31833799

RESUMO

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders (Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 (P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.


Assuntos
Colo do Útero/microbiologia , Microbiota/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Lesões Intraepiteliais Escamosas/imunologia , Neoplasias do Colo do Útero/imunologia , Adulto , Colo do Útero/imunologia , Feminino , Papillomavirus Humano 16/imunologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/microbiologia , Lesões Intraepiteliais Escamosas/microbiologia , Neoplasias do Colo do Útero/microbiologia , Carga Viral/imunologia , Adulto Jovem
10.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 37(10): 661-667, dic. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-189594

RESUMO

La cervicitis es un cuadro de inflamación del cuello uterino. Suele ser causada por un agente infeccioso, generalmente de transmisión sexual. Frecuentemente es asintomática, y la infección silente puede originar complicaciones del tracto genital superior. Los síntomas suelen ser inespecíficos, y los más significativos son aumento del flujo vaginal y/o sangrado intermenstrual. Para su diagnóstico existen sistemas comerciales basados en técnicas moleculares que incluyen la casi totalidad de los patógenos conocidos asociados a cervicitis, aunque los cultivos no deben abandonarse por la necesidad de realizar estudios de sensibilidad a los antibióticos. Se recomienda iniciar un tratamiento empírico que incluya C.trachomatis y N. gonorrhoeae en el caso de mujeres con elevado riesgo de infección por dichos patógenos, sobre todo si el seguimiento no está asegurado o no se dispone de pruebas diagnósticas adecuadas. En mujeres con bajo riesgo el tratamiento deberá ajustarse a los resultados de las pruebas microbiológicas


Cervicitis is the inflammation of the cervix. It is usually caused by an infectious agent, usually sexually transmitted. Cervicitis is frequently asymptomatic and silent infection can cause complications of the upper genital tract. The symptoms are usually nonspecific, the most significant being an increase in vaginal discharge and/or intermenstrual bleeding. For its diagnosis, there are commercial systems based on molecular techniques that include almost all of the known pathogens associated with cervicitis, although cultures should not be abandoned due to the need to conduct studies of susceptibility to antibiotics. It is recommended to initiate an empirical antibiotic therapy that covers C.trachomatis and N. gonorrhoeae in the case of women at high risk of infection by these pathogens, especially if the follow-up is not assured or adequate diagnostic tests are not available. In women with low risk of sexually transmitted infection, antibiotic therapy should be adjusted to the results of the microbiological results


Assuntos
Humanos , Feminino , Cervicite Uterina/etiologia , Cervicite Uterina/diagnóstico , Doenças Sexualmente Transmissíveis/epidemiologia , Cervicite Uterina/terapia , Técnicas Microbiológicas/métodos , Colo do Útero/anatomia & histologia , Colo do Útero/microbiologia , Mycoplasma genitalium/isolamento & purificação , Herpes Simples/microbiologia
11.
Asian Pac J Cancer Prev ; 20(12): 3843-3847, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31870131

RESUMO

OBJECTIVE: High-risk human papillomavirus (HR HPV) was associated with the development of cervical cancer. Asymptomatic Chlamydia trachomatis (C. trachomatis) infection is the most common bacterial, sexually-transmitted infection. This study aimed to investigate the association of C. trachomatis in positive HR HPV and the cytological results from liquid-based cytology (LBC). METHODS: 150 residual LBC specimens were collected; all of which had undergone cytology and HPV testing by Cobas. The samples were established as C. trachomatis using real-time PCR (RT-PCR) with Cryptic F/Cryptic R primers. RESULTS: Of 150 positive HPV findings, the most common (72.7%, 109/150) were the 12 other HR HPVs (viz., 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). The cervical cytology of those positive HR HPVs were mostly negative (70.0%, 105/150).  The C. trachomatis infections in positive HR HPV were 16% (24/150) HPV. The analysis of the abnormal cytology revealed that 41.6% had C. trachomatis co-infection (C. trachomatis and HPV infection) viz., LSIL (20.8%), HSIL (12.5%), and ASC-US (8.3%). A comparison with positive HPV without C. trachomatis co-infection revealed that the highest prevalence was for LSIL, ASC-US, and HSIL (11.1%, 10.3%, and 6.4%, respectively). There was no difference between the abnormalities and negative cervical cytology with negative and positive C. trachomatis co-infection in HR HPV positive (p = 0.174). CONCLUSION: C. trachomatis infection was not significantly associated HR-HPV and abnormal cytology. This study confirms the increasing rate of C. trachomatis infection in asymptomatic women so routine screening for these infections has been suggested to (a) prevent complications such as the chronic pelvic pain associated with prolong infection and (b) reduce sexual transmission of the infection.


Assuntos
Colo do Útero/microbiologia , Colo do Útero/virologia , Infecções por Chlamydia/microbiologia , Coinfecção/complicações , Programas de Rastreamento/métodos , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Células Escamosas Atípicas do Colo do Útero/microbiologia , Células Escamosas Atípicas do Colo do Útero/virologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/microbiologia , Neoplasia Intraepitelial Cervical/virologia , Infecções por Chlamydia/complicações , Chlamydia trachomatis/isolamento & purificação , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Seguimentos , Humanos , Incidência , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Prognóstico , Fatores de Risco , Lesões Intraepiteliais Escamosas/diagnóstico , Lesões Intraepiteliais Escamosas/epidemiologia , Lesões Intraepiteliais Escamosas/microbiologia , Lesões Intraepiteliais Escamosas/virologia , Tailândia/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos
12.
PLoS One ; 14(11): e0224658, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31738795

RESUMO

The cervical microbiota constitutes an important protective barrier against the invasion of pathogenic microorganisms. A disruption of microbiota within the cervical milieu has been suggested to be a driving factor of sexually transmitted infections. These include Chlamydia trachomatis which frequently causes serious reproductive sequelae such as infertility in women. In this study, we profiled the cervical microbial composition of a population of 70 reproductive-age Malaysian women; among which 40 (57.1%) were diagnosed with genital C. trachomatis infection, and 30 (42.8%) without C. trachomatis infection. Our findings showed a distinct compositional difference between the cervical microbiota of C. trachomatis-infected subjects and subjects without C. trachomatis infection. Specifically, significant elevations of mostly strict and facultative anaerobes such as Streptococcus, Megasphaera, Prevotella, and Veillonella in the cervical microbiota of C. trachomatis-positive women were detected. The results from the current study highlights an interaction of C. trachomatis with the environmental microbiome in the endocervical region.


Assuntos
Colo do Útero/microbiologia , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/isolamento & purificação , Infertilidade/microbiologia , Microbiota/imunologia , Centros Médicos Acadêmicos , Adulto , Bactérias Anaeróbias/imunologia , Bactérias Anaeróbias/isolamento & purificação , Infecções por Chlamydia/complicações , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/patogenicidade , Estudos de Coortes , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Infertilidade/imunologia , Malásia , Metagenômica , Microbiota/genética , Ambulatório Hospitalar , RNA Ribossômico 16S/genética , Adulto Jovem
13.
mBio ; 10(5)2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641087

RESUMO

In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of d- and l-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of d-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject's age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and d-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition.IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.


Assuntos
Colo do Útero/metabolismo , Colo do Útero/microbiologia , Microbiota/genética , Vagina/metabolismo , Vagina/microbiologia , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Lactobacillus/genética , Lactobacillus/metabolismo , Lactobacillus crispatus/genética , Lactobacillus crispatus/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Gravidez , RNA Ribossômico 16S/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Adulto Jovem
14.
Reprod Biol Endocrinol ; 17(1): 85, 2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31656198

RESUMO

BACKGROUND: Voluntary control of fertility is of paramount importance to the modern society. But since the contraceptive methods available for women have their limitations such as urinary tract infections, allergies, cervical erosion and discomfort, a desperate need exists to develop safe methods. Vaginal contraceptives may be the answer to this problem, as these are the oldest ways of fertility regulation, practiced over the centuries. With minimal systemic involvement, these are also the safest. Natural substances blocking or impairing the sperm motility offer as valuable non-cytotoxic vaginal contraceptives. Antimicrobial peptides (AMPs) isolated from plants, animals and microorganisms are known to possess sperm immobilizing and spermicidal properties. Following this, in the quest for alternative means, we have cloned, over expressed and purified the recombinant sperm agglutinating factor (SAF) from Staphylococcus warneri, isolated from the cervix of a woman with unexplained infertility. METHODS: Genomic library of Staphylococcus warneri was generated in Escherichia coli using pSMART vector and screened for sperm agglutinating factor (SAF). The insert in sperm agglutinating transformant was sequenced and was found to express ribonucleotide-diphosphate reductase-α sub unit. The ORF was sub-cloned in pET28a vector, expressed and purified. The effect of rSAF on motility, viability, morphology, Mg++-dependent ATPase activity and acrosome status of human sperms was analyzed in vitro and contraceptive efficacy was evaluated in vivo in female BALB/c mice. RESULTS: The 80 kDa rSAF showed complete sperm agglutination, inhibited its Mg2+-ATPase activity, caused premature sperm acrosomal loss in vitro and mimicked the pattern in vivo showing 100% contraception in BALB/c mice resulting in prevention of pregnancy. The FITC labeled SAF was found to bind the entire surface of spermatozoa. Vaginal application and oral administration of rSAF to mice for 14 successive days did not demonstrate any significant change in vaginal cell morphology, organ weight and tissue histology of reproductive and non-reproductive organs and had no negative impact in the dermal and penile irritation tests. CONCLUSION: The Sperm Agglutinating Factor from Staphylococcus warneri, natural microflora of human cervix, showed extensive potential to be employed as a safe vaginal contraceptive.


Assuntos
Colo do Útero/microbiologia , Anticoncepcionais Femininos/farmacologia , Aglutinação Espermática/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos , Staphylococcus/metabolismo , Acrossomo/efeitos dos fármacos , Acrossomo/fisiologia , Animais , Anticoncepcionais Femininos/metabolismo , Feminino , Biblioteca Genômica , Humanos , Infertilidade Feminina , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Gravidez , Staphylococcus/genética
15.
New Microbiol ; 42(4): 237-239, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31609456

RESUMO

Alloscardovia omnicolens is a recently-reported microorganism with unknown pathogenic implications. It has been isolated in various clinical localizations but not in the endocervix. We isolated A. omnicolens in an endocervical sample from a 31-yr-old patient with preterm premature rupture of membranes (PPROM) in week 33+3 of pregnancy. The main risk of PPROM is prematurity and the possibility of developing infectious chorioamnionitis, which can be lethal for the mother and newborn. This is the first report of an association between A. omnicolens and PPROM, although its pathogenic role has not yet been elucidated.


Assuntos
Actinobacteria , Infecções por Bifidobacteriales , Corioamnionite , Ruptura Prematura de Membranas Fetais , Actinobacteria/fisiologia , Adulto , Antibacterianos/uso terapêutico , Infecções por Bifidobacteriales/complicações , Infecções por Bifidobacteriales/tratamento farmacológico , Infecções por Bifidobacteriales/microbiologia , Infecções por Bifidobacteriales/patologia , Colo do Útero/microbiologia , Corioamnionite/tratamento farmacológico , Corioamnionite/microbiologia , Feminino , Ruptura Prematura de Membranas Fetais/etiologia , Ruptura Prematura de Membranas Fetais/microbiologia , Idade Gestacional , Humanos , Gravidez , Nascimento Prematuro , Resultado do Tratamento
17.
Int J Nanomedicine ; 14: 5957-5976, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440052

RESUMO

Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.


Assuntos
Azitromicina/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Colo do Útero/microbiologia , Vagina/microbiologia , Animais , Antibacterianos/farmacologia , Azitromicina/farmacologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Chlamydia trachomatis/efeitos dos fármacos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Lipossomos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Plâncton/efeitos dos fármacos , Suínos
18.
mBio ; 10(4)2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409678

RESUMO

The mechanism(s) by which Lactobacillus-dominated cervicovaginal microbiota provide a barrier to Chlamydia trachomatis infection remain(s) unknown. Here we evaluate the impact of different Lactobacillus spp. identified via culture-independent metataxonomic analysis of C. trachomatis-infected women on C. trachomatis infection in a three-dimensional (3D) cervical epithelium model. Lactobacillus spp. that specifically produce d(-) lactic acid were associated with long-term protection against C. trachomatis infection, consistent with reduced protection associated with Lactobacillus iners, which does not produce this isoform, and with decreased epithelial cell proliferation, consistent with the observed prolonged protective effect. Transcriptomic analysis revealed that epigenetic modifications involving histone deacetylase-controlled pathways are integral to the cross talk between host and microbiota. These results highlight a fundamental mechanism whereby the cervicovaginal microbiota modulates host functions to protect against C. trachomatis infection.IMPORTANCE The vaginal microbiota is believed to protect women against Chlamydia trachomatis, the etiologic agent of the most prevalent sexually transmitted infection (STI) in developed countries. The mechanism underlying this protection has remained elusive. Here, we reveal the comprehensive strategy by which the cervicovaginal microbiota modulates host functions to protect against chlamydial infection, thereby providing a novel conceptual mechanistic understanding. Major implications of this work are that (i) the impact of the vaginal microbiota on the epithelium should be considered in future studies of chlamydial infection and other STIs and (ii) a fundamental understanding of the cervicovaginal microbiota's role in protection against STIs may enable the development of novel microbiome-based therapeutic strategies to protect women from infection and improve vaginal and cervical health.


Assuntos
Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/patogenicidade , Interações entre Hospedeiro e Microrganismos/fisiologia , Vagina/microbiologia , Movimento Celular , Proliferação de Células , Colo do Útero/microbiologia , Colo do Útero/patologia , Infecções por Chlamydia/prevenção & controle , Feminino , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/química , Ácido Láctico/metabolismo , Lactobacillus/classificação , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Microbiota , Estereoisomerismo , Transcriptoma , Vagina/química
19.
Pan Afr Med J ; 32: 163, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31303932

RESUMO

Tuberculosis of the cervix is rare and can mimick cervical cancer. Patients are paucisymptomatic and the disease is characterized by an insidious evolution, hence the delay in diagnosis. Common symptoms are non-specific contributing to therapeutic delay and increasing the risk of infertility which is perhaps inevitable. We report a case of tuberculosis of the cervix whose diagnosis given first wasn't obvious. Indeed, a patient was referred to our Department with suspected cervical cancer. Suspected diagnosis of cancer was then retained based on the presence of vaginal bleeding on contact and abdominopelvic CT scan results showing cervical cancer. Biopsy was indicated in order to confirm the diagnosis histologically. Anatomo-pathological examination objectified epitheliogigantocellular granuloma with caseous necrosis, supporting cervical tuberculosis. The other examinations were negative. The patient received TB treatment which led to healing. Diagnosis and treatment of tuberculosis of the cervix is often based on presumptive elements, hence the importance of anatomo-pathological examination.


Assuntos
Colo do Útero/patologia , Tuberculose dos Genitais Femininos/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Antituberculosos/administração & dosagem , Biópsia , Colo do Útero/microbiologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Tuberculose dos Genitais Femininos/tratamento farmacológico
20.
Rev Assoc Med Bras (1992) ; 65(6): 857-863, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340317

RESUMO

OBJECTIVE: To evaluate endocervical and vaginal environment changes in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A quasi-experimental study included sixty women who had an LNG-IUS inserted in the Family Planning Clinic of UNICAMP between April and November of 2016. Women in reproductive age, non-pregnant, without the use of antibiotics and contraceptives seeking for LNG-IUS insertion were selected for this study. All women were evaluated with regard to vaginal and endocervical pH, vaginal and endocervical Gram-stained bacterioscopy, and Pap-smear before and two months after LNG-IUS insertion. Clinical aspects such as cervical mucus, vaginal discharge, and cervical ectopy were also observed. RESULTS: After LNG-IUS insertion, there was an increase in the following parameters: endocervical pH>4.5 (p=0.02), endocervical neutrophil amount (p<0.0001), vaginal cytolysis (p=0.04). There was a decrease in vaginal discharge (p=0.01). No statistically significant changes were found in vaginal pH, neutrophils amount in the vaginal mucosa, vaginal discharge appearance, vaginal candidiasis, bacterial vaginosis, vaginal coccobacillary microbiota, cervical mucus appearance, or cervical ectopy size. CONCLUSIONS: Short-term LNG-IUS use did not increase vulvovaginal candidiasis or bacterial vaginosis, and led to diminished vaginal discharge. Notwithstanding, this device promoted reactional changes in the vaginal and endocervical environment, without modification on cervical ectopy size.


Assuntos
Colo do Útero/efeitos dos fármacos , Anticoncepcionais Femininos/efeitos adversos , Endométrio/efeitos dos fármacos , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Vagina/efeitos dos fármacos , Adolescente , Adulto , Colo do Útero/microbiologia , Endométrio/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Estatísticas não Paramétricas , Fatores de Tempo , Vagina/química , Vagina/microbiologia , Esfregaço Vaginal , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA