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1.
N Engl J Med ; 382(20): 1906-1915, 2020 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-32402161

RESUMEN

BACKGROUND: Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence suggests the need for new treatments to prevent recurrent bacterial vaginosis. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of Lactobacillus crispatus CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. Women 18 to 45 years of age who had received a diagnosis of bacterial vaginosis and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered Lactin-V or placebo for 11 weeks; follow-up occurred through week 24. The primary outcome was the percentage of women who had a recurrence of bacterial vaginosis by week 12. RESULTS: A total of 228 women underwent randomization: 152 to the Lactin-V group and 76 to the placebo group; of these participants, 88% in the Lactin-V group and 84% in the placebo group could be evaluated for the primary outcome. In the intention-to-treat population, recurrence of bacterial vaginosis by week 12 occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (risk ratio after multiple imputation for missing responses, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P = 0.01). The risk ratio for recurrence by week 24 (also calculated with multiple imputation for missing responses) was 0.73 (95% CI, 0.54 to 0.92). At the 12-week visit, L. crispatus CTV-05 was detected in 79% of participants in the Lactin-V group. The percentage of participants who had at least one adverse event related to Lactin-V or placebo by week 24 did not differ significantly between the groups. The percentage of participants with local or systemic adverse events was similar in the two groups. CONCLUSIONS: The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02766023.).


Asunto(s)
Antibacterianos/administración & dosificación , Lactobacillus crispatus/fisiología , Vagina/microbiología , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/prevención & control , Administración Intravaginal , Adolescente , Adulto , Antibacterianos/efectos adversos , Antibiosis , Método Doble Ciego , Femenino , Geles , Humanos , Incidencia , Lactobacillus crispatus/aislamiento & purificación , Metronidazol/uso terapéutico , Persona de Mediana Edad , Prevención Secundaria , Vaginosis Bacteriana/epidemiología , Adulto Joven
2.
Ceska Gynekol ; 85(1): 67-70, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32414287

RESUMEN

OBJECTIVE: To summarize current knowledge regarding Lactobacillus crispatus-dominated vaginal microbiota in pregnancy, as well as an association between the presence of Lactobacillus crispatus-dominated vaginal microbiota and pregnancy complications. DESIGN: Review. SETTING: Department of Obstetrics and Gynecology, University Hospital Hradec Kralove. MATERIAL AND METHODOLOGY: In this review, the results from literature available about the presence of L. crispatus-dominated microbiota in pregnancy are summarized. RESULTS: Pregnant women with Lactobacillus crispatus-dominated vaginal microbiota is very common in pregnancy and it is associated with a lower risk of preterm delivery. CONCLUSION: Lactobacillus crispatus-dominated vaginal microbiota represents an optimal vaginal microbiota in pregnancy.


Asunto(s)
Lactobacillus crispatus/aislamiento & purificación , Microbiota , Nacimiento Prematuro/microbiología , Vagina/microbiología , Femenino , Humanos , Recién Nacido , Trabajo de Parto Prematuro/microbiología , Embarazo
3.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-32276519

RESUMEN

Lactic acid bacteria can act as reservoirs of antibiotic resistance genes that can be ultimately transferred to pathogens. The present work reports on the minimum inhibitory concentration (MIC) of 16 antibiotics to 25 LAB isolates of five Lactobacillus and one Bifidobacterium species from the human vagina. Acquired resistances were detected to kanamycin, streptomycin, chloramphenicol, gentamicin, and ampicillin. A PCR analysis of lactobacilli failed to identify genetic determinants involved in any of these resistances. Surprisingly, a tet(W) gene was detected by PCR in two Bifidobacterium bifidum strains, although they proved to be tetracycline-susceptible. In agreement with the PCR results, no acquired genes were identified in the genome of any of the Lactobacillus spp. strains sequenced. A genome analysis of B. bifidum VA07-1AN showed an insertion of two guanines in the middle of tet(W) interrupting the open reading frame. By growing the strain in the presence of tetracycline, stable tetracycline-resistant variants were obtained. An amino acid substitution in the ribosomal protein S12 (K43R) was further identified as the most likely cause of VA07-1AN being streptomycin resistance. The results of this work expand our knowledge of the resistance profiles of vaginal LAB and provide evidence for the genetic basis of some acquired resistances.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Lactobacillales/fisiología , Polimorfismo Genético , Vagina/microbiología , Bifidobacterium bifidum/efectos de los fármacos , Bifidobacterium bifidum/genética , Bifidobacterium bifidum/fisiología , Femenino , Humanos , Lactobacillales/efectos de los fármacos , Lactobacillales/genética , Lactobacillus/efectos de los fármacos , Lactobacillus/genética , Lactobacillus/fisiología , Tetraciclina/farmacología
4.
BMC Infect Dis ; 20(1): 302, 2020 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-32321444

RESUMEN

BACKGROUND: Estimates of Group B Streptococcus (GBS) disease burden, antimicrobial susceptibility, and serotypes in pregnant women are limited for many resource-limited countries including Kenya. These data are required to inform recommendations for prophylaxis and treatment of infections due to GBS. METHODS: We evaluated the prevalence, antimicrobial susceptibility patterns, serotypes, and risk factors associated with rectovaginal GBS colonization among pregnant women receiving antenatal care at Kenyatta National Hospital (KNH) between August and November 2017. Consenting pregnant women between 12 and 40 weeks of gestation were enrolled. Interview-administered questionnaires were used to assess risk factors associated with GBS colonization. An anorectal swab and a lower vaginal swab were collected and cultured on Granada agar for GBS isolation. Positive colonies were tested for antimicrobial susceptibility to penicillin G, ampicillin, vancomycin, and clindamycin using the disk diffusion method. Serotyping was performed by latex agglutination. Logistic regression was used to identify factors associated with GBS colonization. RESULTS: A total of 292 women were enrolled. Median age was 30 years (Interquartile range {IQR} 26-35) and a median gestational age of 35 weeks (IQR 30-37). Overall GBS was identified in 60/292 (20.5%) of participants. Among the positive isolates, resistance was detected for penicillin G in 42/58 (72.4%) isolates, ampicillin in 32/58 (55.2%) isolates, clindamycin in 14/46 (30.4%) isolates, and vancomycin in 14/58 (24.1%) isolates. All ten GBS serotypes were isolated, and 37/53 (69.8%) of GBS positive participants were colonized by more than one serotype. None of the risk factors was associated with GBS colonization. CONCLUSION: The prevalence of GBS colonization was high among antenatal women at KNH. In addition, a high proportion of GBS isolates were resistant to commonly prescribed intrapartum antibiotics. Hence, other measures like GBS vaccination is a potentially useful approaches to GBS prevention and control in this population. Screening of pregnant mothers for GBS colonization should be introduced and antimicrobial susceptibility test performed on GBS positive samples to guide antibiotic prophylaxis.


Asunto(s)
Pruebas de Sensibilidad Microbiana , Complicaciones Infecciosas del Embarazo/epidemiología , Recto/microbiología , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/clasificación , Streptococcus agalactiae/aislamiento & purificación , Vagina/microbiología , Adulto , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Estudios Transversales , Femenino , Humanos , Kenia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/microbiología , Prevalencia , Factores de Riesgo , Serogrupo , Serotipificación , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/efectos de los fármacos
5.
BMC Infect Dis ; 20(1): 201, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-32143598

RESUMEN

BACKGROUND: Melioidosis is a potentially life-threatening infection caused by the Gram-negative bacterium Burkholderia pseudomallei. Melioidosis is difficult to diagnose due to its diverse clinical manifestations, which often delays administration of appropriate antibiotic therapy. CASE PRESENTATION: Melioidosis is uncommon in pregnancy but both spontaneous abortion and neonatal melioidosis have been reported. We report a case of bacteraemic melioidosis in a young woman with a subsequent spontaneous abortion, with B. pseudomallei cultured from a high vaginal swab as well as blood. CONCLUSION: It remains unclear in this and previously reported cases as to whether the maternal melioidosis was sexually transmitted.


Asunto(s)
Melioidosis/diagnóstico , Enfermedades Bacterianas de Transmisión Sexual/diagnóstico , Aborto Espontáneo , Adulto , Antibacterianos/uso terapéutico , Burkholderia pseudomallei/aislamiento & purificación , Femenino , Humanos , Melioidosis/tratamiento farmacológico , Melioidosis/microbiología , Embarazo , Enfermedades Bacterianas de Transmisión Sexual/tratamiento farmacológico , Enfermedades Bacterianas de Transmisión Sexual/microbiología , Vagina/microbiología
6.
PLoS One ; 15(3): e0229586, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32134931

RESUMEN

BACKGROUND: The ECHO trial has relieved apprehension about intramuscular depot medroxyprogesterone acetate (DMPA-IM), however it is still important to understand how DMPA-IM affects the vaginal environment. We sought to describe how DMPA-IM initiation influences vaginal bacteria associated with HIV acquisition in postpartum women. METHODS: Vaginal swabs were collected for Nugent score determination and taxon-specific quantitative PCR of eight bacteria. Enrollment occurred at contraceptive initiation (DMPA-IM or non-hormonal contraception (non-HC)) and repeat vaginal swabs were collected after three months. Generalized estimating equations were used to estimate changes in Nugent score, total bacterial load, and taxa concentrations among contraceptive groups. RESULTS: Women who chose DMPA-IM (n = 33) were more likely to be married (97%vs.67%) and have resumed intercourse since delivery (52%vs.29%) compared to women who chose non-HC (n = 21). After three months, significant decreases in the concentrations of Sneathia species, Mycoplasma hominis, and Parvimonas species Type 1 were seen among non-HC users, however concentrations remained stable among DMPA-IM users; contraceptive method was associated with significantly different changes in M. hominis concentration between groups (p = 0.010). CONCLUSIONS: Our findings suggest that postpartum use of DMPA-IM and non-HC may have differential impacts on the vaginal concentrations of some bacteria that have previously been associated with HIV acquisition.


Asunto(s)
Infecciones Bacterianas/microbiología , Anticonceptivos Femeninos/administración & dosificación , Acetato de Medroxiprogesterona/administración & dosificación , Vagina/microbiología , Adulto , África , Bacterias/crecimiento & desarrollo , Anticoncepción/métodos , Femenino , Humanos , Periodo Posparto , Estudios Prospectivos , Adulto Joven
7.
PLoS Pathog ; 16(3): e1008376, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32214382

RESUMEN

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.


Asunto(s)
Neoplasia Intraepitelial Cervical , Cuello del Útero , Gardnerella , Lactobacillus , Microbiota , Papillomaviridae/metabolismo , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Vagina , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/microbiología , Neoplasia Intraepitelial Cervical/patología , Neoplasia Intraepitelial Cervical/virología , Cuello del Útero/metabolismo , Cuello del Útero/microbiología , Cuello del Útero/patología , Cuello del Útero/virología , Femenino , Gardnerella/clasificación , Gardnerella/genética , Gardnerella/metabolismo , Humanos , Lactobacillus/clasificación , Lactobacillus/genética , Lactobacillus/metabolismo , Estudios Longitudinales , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/microbiología , Infecciones por Papillomavirus/patología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/microbiología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Vagina/metabolismo , Vagina/microbiología , Vagina/patología , Vagina/virología
8.
PLoS One ; 15(3): e0230170, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32163469

RESUMEN

Treatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiota, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. In this study we used healthy rats, which are a common animal model for sexual function, however the rat vaginal microbiome is understudied. Thus this study also sought to examine the composition of the rat vaginal microbiota. Treatment rats (n = 5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n = 4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Analysis of 16S rRNA gene sequences was used to characterize the rat vaginal microbiota in baseline samples and determine the effect of stimulation. We found that the rat vaginal microbiota is dominated by Proteobacteria, Firmicutes, and Actinobacteria, which changed in relative abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear in these healthy rats, some Treatment animals had less alteration in microbiota composition between sequential samples than Control animals, suggesting that stimulation may help stabilize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.


Asunto(s)
Ciclo Estral/fisiología , Nervio Pudendo/fisiología , Roedores/microbiología , Vagina/microbiología , Vagina/fisiología , Animales , Nivel de Alerta/fisiología , Bacterias/genética , Estimulación Eléctrica/métodos , Femenino , Microbiota/genética , ARN Ribosómico 16S/genética , Ratas , Ratas Sprague-Dawley
9.
BMC Infect Dis ; 20(1): 98, 2020 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-32005177

RESUMEN

BACKGROUND: Potentially pathogenic bacteria that colonise the lower genital tract of women in labour can be passed to the baby during birth. While many babies become colonised with these bacteria after delivery, a few develop neonatal infections. The lower genital tract is a reservoir for potential pathogens and a source of infection for neonates. We determined the prevalence of vaginal colonisation of potentially pathogenic bacteria among women in labour in Central Uganda and identified potential risk factors associated with this colonisation. METHODS: We conducted a cross sectional study at three primary health care facilities and collected vaginal swabs from HIV-1 negative women in labour. Specimens were cultured on different selective microbiological media, and biochemical tests were used to classify bacterial isolates on the species level. Multivariable logistic regression analyses were used to estimate the association between relevant exposures and colonisation with potentially pathogenic bacteria. RESULTS: We recruited 1472 women in labour whose mean age was 24.6 years (standard deviation [SD] 4.9). Of these, 955 (64.9%; 95% Confidence Interval [CI] 62.4, 67%) were vaginally colonised with at least one potentially pathogenic bacterial species. The most commonly isolated species were Escherichia coli (n = 508; 34.5%), Klebsiella pneumoniae (n = 144; 9.8%) and Staphylococcus aureus (n = 121; 8.2%). Results from exploratory multivariable regression analyses indicated that having had ≥5 previous pregnancies (adjusted odds ratio [aOR] 0.59; 95% CI 0.35, 0.97) or being ≥30 years old (aOR 1.52; 95% CI 1.03, 2.23) could be associated with vaginal colonisation with any potentially pathogenic bacteria, as well as with vaginal colonisation with S. aureus (aOR 0.33; 95% CI 0.12, 0.88, and aOR 2.17; 95% CI 1.17, 4.00, respectively). Possession of domestic animals in a household (aOR 0.57; 95% CI 0.35, 0.92) could be associated with vaginal colonisation with E. coli. CONCLUSIONS: Two-thirds of HIV-1 negative women in labour were vaginally colonised by potentially pathogenic bacteria, mainly E. coli, K. pneumoniae, and S. aureus.


Asunto(s)
Infecciones por Escherichia coli/epidemiología , Infecciones por Klebsiella/epidemiología , Complicaciones Infecciosas del Embarazo/microbiología , Infecciones Estafilocócicas/epidemiología , Vagina/microbiología , Adulto , Estudios Transversales , Femenino , Seropositividad para VIH/epidemiología , Humanos , Trabajo de Parto , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Atención Primaria de Salud , Factores de Riesgo , Uganda/epidemiología , Adulto Joven
10.
Life Sci ; 246: 117413, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32035929

RESUMEN

Cervical cancer is the second common cancer and the third leading cause of cancer deaths among women in less developed countries. It has been indicated that changes in vaginal microbiome play an important role in the occurrence and development of cervical cancer. However, studies have shown that probiotics play an effective role in fighting cancer by affecting pathogenic bacteria, inducing cancer cells apoptosis, and other anticancer activities. Therefore, the purpose of the present study is reviewing the anticancer effect of cervicovaginal bacteria and their potential for cervical cancer treatment.


Asunto(s)
Bacterias , Neoplasias del Cuello Uterino/terapia , Toxinas Bacterianas/uso terapéutico , Femenino , Humanos , Inmunoterapia/métodos , Microbiota , Probióticos , Vagina/microbiología
11.
Life Sci ; 248: 117444, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32084433

RESUMEN

AIMS: Nonhuman primates have been used to investigate pathogenic mechanisms and evaluate immune responses following Chlamydia trachomatis inoculation. This study aimed to systemically profile antibody responses to C. trachomatis infection in nonhuman primates. MATERIALS AND METHODS: Sera were obtained from 4 pig-tailed and 8 long-tailed macaques which were intravaginally or ocularly infected with live C. trachomatis organisms, and analyzed by C. trachomatis proteome array of antigens. KEY FINDINGS: The sera from 12 macaques recognized total 172 C. trachomatis antigens. While 84 antigens were recognized by pig-tailed macaques intravaginally infected with serovar D strain, 125 antigens were recognized by long-tailed macaques ocularly infected with serovar A, and 37 antigens were recognized by both. Ocular inoculation with virulent A2497 strain induced antibodies to more antigens. Among the antigens uniquely recognized by A2497 strain infected macaques, outer membrane complex B antigen (OmcB) induced robust antibody response. Although macaques infected by less virulent A/HAR-13 strain failed to develop antibodies to OmcB, reinfection by A2497 strain induced high levels of antibodies to OmcB. SIGNIFICANCE: Proteome array has revealed a correlation of chlamydial infection invasiveness with chlamydial antigen immunogenicity, and identified antibody responses to OmcB potentially as biomarkers for invasive infection with C. trachomatis.


Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Antígenos Bacterianos/sangre , Infecciones por Chlamydia/inmunología , Chlamydia trachomatis/inmunología , Infecciones del Sistema Genital/inmunología , Tracoma/inmunología , Animales , Anticuerpos Antibacterianos/clasificación , Antígenos Bacterianos/clasificación , Proteínas de la Membrana Bacteriana Externa/sangre , Infecciones por Chlamydia/sangre , Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/patogenicidad , Ojo/inmunología , Ojo/microbiología , Femenino , Sueros Inmunes/química , Macaca fascicularis , Macaca nemestrina , Masculino , Análisis por Matrices de Proteínas , Proteoma/química , Proteoma/inmunología , Infecciones del Sistema Genital/sangre , Infecciones del Sistema Genital/microbiología , Tracoma/sangre , Tracoma/microbiología , Vagina/inmunología , Vagina/microbiología
12.
Nat Rev Urol ; 17(4): 232-250, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32071434

RESUMEN

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.


Asunto(s)
Carcinogénesis , Disbiosis/microbiología , Neoplasias de los Genitales Femeninos/microbiología , Genitales Femeninos/microbiología , Microbiota/fisiología , Antiinfecciosos/uso terapéutico , Bacterias Anaerobias , Cuello del Útero/microbiología , Disbiosis/metabolismo , Estrógenos/metabolismo , Trompas Uterinas/microbiología , Femenino , Microbioma Gastrointestinal , Neoplasias de los Genitales Femeninos/metabolismo , Neoplasias de los Genitales Femeninos/prevención & control , Neoplasias de los Genitales Femeninos/terapia , Genitales Femeninos/metabolismo , Humanos , Lactobacillus , Ovario/microbiología , Probióticos/uso terapéutico , Útero/microbiología , Vagina/microbiología
13.
Nat Commun ; 11(1): 940, 2020 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-32103005

RESUMEN

Analysis of metagenomic and metatranscriptomic data is complicated and typically requires extensive computational resources. Leveraging a curated reference database of genes encoded by members of the target microbiome can make these analyses more tractable. In this study, we assemble a comprehensive human vaginal non-redundant gene catalog (VIRGO) that includes 0.95 million non-redundant genes. The gene catalog is functionally and taxonomically annotated. We also construct a vaginal orthologous groups (VOG) from VIRGO. The gene-centric design of VIRGO and VOG provides an easily accessible tool to comprehensively characterize the structure and function of vaginal metagenome and metatranscriptome datasets. To highlight the utility of VIRGO, we analyze 1,507 additional vaginal metagenomes, and identify a high degree of intraspecies diversity within and across vaginal microbiota. VIRGO offers a convenient reference database and toolkit that will facilitate a more in-depth understanding of the role of vaginal microorganisms in women's health and reproductive outcomes.


Asunto(s)
Bacterias/clasificación , Bacterias/genética , Microbiota/genética , Transcriptoma/genética , Vagina/microbiología , Bacterias/aislamiento & purificación , Femenino , Perfilación de la Expresión Génica , Biblioteca de Genes , Humanos , Metagenoma/genética , ARN Ribosómico 16S/genética
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 60-66, 2020 Jan.
Artículo en Chino | MEDLINE | ID: mdl-31950791

RESUMEN

Objective: To optimize the preparation parameters of the new silk birth-canal microecology transporter (BMT) for transferring the symbiotic bacteria of the birth canal efficiently. Methods: Birth canal microbial samples of 30 full term pregnant women at admission were collected as the control group (NC, n=30). The experimental group included 18 pregnant women terminated by Cesarean section, who were divided into 6 sub-groups (M1-M6, n=3) to complete the transfer tests of the birth-canal microecology. The new silk BMT was processed in the sterile liquid of the different osmotic pressure with the different immersion depth, and was placed in the vagina of the pregnant women for 1 h before sealed. All extracted DNA specimens were amplified in the V3-V4 region of the 16S rDNA, and were sequenced by Illumina Hiseq2500. Microbial diversity analysis was performed by Mothur, QIIME, Lefse and Metastat. Welch's t-test and Anosim nonparametric test were used to compare the difference between groups. Results: The new silk BMT with 70% immersion depth could be fully covered by the solution, and had good solution preserving and adhesion. The subjects had no foreign body sensation with satisfied experience. Both of the microbes on the new BMT and the control group were lactobacillus as the dominant bacteria genus. The microbial diversity and bacteria constitution in the new BMT was similar to the control group in the condition of 0.45% NaCl solution and 70% immersion depth, and there was no significant difference between the two groups ( P>0.05). Conclusion: The new silk BMT can transfer the symbiotic microbes of the birth canal efficiently, and the optimal preparation parameters were 0.45% hypotonic saline solution and 70% immersion depth.


Asunto(s)
Técnicas Microbiológicas , Microbiota , Seda , Vagina , Bacterias/clasificación , Biodiversidad , Cesárea , Femenino , Humanos , Lactobacillus/fisiología , Técnicas Microbiológicas/métodos , Microbiota/fisiología , Embarazo , Vagina/microbiología
15.
PLoS Pathog ; 16(1): e1008236, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31971984

RESUMEN

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.


Asunto(s)
Cuello del Útero/microbiología , Cuello del Útero/virología , Infecciones por VIH/virología , Vagina/microbiología , Vagina/virología , Vaginosis Bacteriana/microbiología , Adulto , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Coinfección/microbiología , Coinfección/virología , Femenino , VIH-1/fisiología , Humanos , Microbiota , Persona de Mediana Edad , Moco/microbiología , Moco/virología , Adulto Joven
16.
Ann Clin Microbiol Antimicrob ; 19(1): 5, 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31992328

RESUMEN

Recurrent vulvovaginal infections (RVVI) has not only become an epidemiological and clinical problem but also include large social and psychological consequences. Understanding the mechanisms of both commensalism and pathogenesis are necessary for the development of efficient diagnosis and treatment strategies for these enigmatic vaginal infections. Through this review, an attempt has been made to analyze vaginal microbiota (VMB) from scratch and to provide an update on its current understanding in relation to health and common RVVI i.e. bacterial vaginosis, vulvovaginal candidiaisis and Trichomoniasis, making the present review first of its kind. For this, potentially relevant studies were retrieved from data sources and critical analysis of the literature was made. Though, culture-independent methods have greatly unfolded the mystery regarding vaginal bacterial microbiome, there are only a few studies regarding the composition and diversity of vaginal mycobiome and different Trichomonas vaginalis strains. This scenario suggests a need of further studies based on comparative genomics of RVVI pathogens to improve our perceptive of RVVI pathogenesis that is still not clear (Fig. 5). Besides this, the review details the rationale for Lactobacilli dominance and changes that occur in healthy VMB throughout a women's life. Moreover, the list of possible agents continues to expand and new species recognised in both health and VVI are updated in this review. The review concludes with the controversies challenging the widely accepted dogma i.e. "VMB dominated with Lactobacilli is healthier than a diverse VMB". These controversies, over the past decade, have complicated the definition of vaginal health and vaginal infections with no definite conclusion. Thus, further studies on newly recognised microbial agents may reveal answers to these controversies. Conversely, VMB of women could be an answer but it is not enough to just look at the microbiology. We have to look at the woman itself, as VMB which is fine for one woman may be troublesome for others. These differences in women's response to the same VMB may be determined by a permutation of behavioural, cultural, genetic and various other anonymous factors, exploration of which may lead to proper definition of vaginal health and disease.


Asunto(s)
Candidiasis Vulvovaginal , Microbiota , Vaginitis por Trichomonas , Vagina/microbiología , Vaginosis Bacteriana , Biopelículas/crecimiento & desarrollo , Candida/aislamiento & purificación , Candida/metabolismo , Candida albicans/aislamiento & purificación , Candida albicans/metabolismo , Candidiasis Vulvovaginal/microbiología , Candidiasis Vulvovaginal/patología , Candidiasis Vulvovaginal/transmisión , Coinfección/microbiología , Coinfección/parasitología , Femenino , Gardnerella vaginalis/aislamiento & purificación , Interacciones Microbiota-Huesped , Humanos , Lactobacillus/aislamiento & purificación , Lactobacillus/metabolismo , Interacciones Microbianas , Microbiota/fisiología , Recurrencia , Vaginitis por Trichomonas/parasitología , Vaginitis por Trichomonas/patología , Vaginitis por Trichomonas/transmisión , Trichomonas vaginalis/aislamiento & purificación , Trichomonas vaginalis/metabolismo , Vagina/parasitología , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/patología , Vaginosis Bacteriana/transmisión , Factores de Virulencia/metabolismo
17.
PLoS One ; 15(1): e0224359, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31914129

RESUMEN

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.


Asunto(s)
Disbiosis/inmunología , Inmunidad Innata/genética , Enfermedades de Transmisión Sexual/inmunología , Vaginosis Bacteriana/inmunología , Adolescente , Adulto , Biomarcadores/metabolismo , Cuello del Útero/inmunología , Cuello del Útero/microbiología , Cuello del Útero/patología , Disbiosis/epidemiología , Disbiosis/microbiología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Molécula 1 de Adhesión Intercelular/inmunología , Molécula 1 de Adhesión Intercelular/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/inmunología , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Estrés Oxidativo/inmunología , Embarazo , Infecciones del Sistema Genital/epidemiología , Infecciones del Sistema Genital/inmunología , Inhibidor Secretorio de Peptidasas Leucocitarias/inmunología , Inhibidor Secretorio de Peptidasas Leucocitarias/metabolismo , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/microbiología , Uganda/epidemiología , Vagina/inmunología , Vagina/microbiología , Vaginosis Bacteriana/epidemiología , Vaginosis Bacteriana/microbiología , Factor A de Crecimiento Endotelial Vascular/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Zimbabwe/epidemiología
18.
BMC Infect Dis ; 20(1): 35, 2020 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-31931732

RESUMEN

BACKGROUND: Streptococcus agalctiae (Group B Streptococcus, GBS) is a perinatal pathogen and a leading cause of neonatal infections worldwide. Serotype, sequence type, clonality, antibiotic resistance genes and surface protein profiles of GBS are scarce in Ethiopia, a reason that this study was planned to investigate. . METHODS: Sixteen colonizing GBS isolates obtained from recto-vaginal swabs of pregnant women and body surfaces of newborns were further analyzed. Minimum inhibitory concentration (MIC) test, and whole genome sequence (WGS) methods were done for antibiotic susceptibility test, and molecular characterization of the isolates. RESULTS: All the GBS isolates analyzed were belonged to four capsular serotypes: II, 11/16(68.8%), V, 3/16(18.8%), Ia and VI each with 1/16(6.3%) and five sequence type (ST-2, ST-10, ST-14, ST-569 and ST-933). Sequence type-10 was the most predominant ST followed by ST-569. The five STs were grouped into the four clonal complexes (CC - 1, CC-10, CC-19, and CC-23). Different surface proteins and pili families such as ALP1, ALPHA, ALP23, PI-1 / PI-2A1, PI-1 / PI-2B, and Srr1 were detected from WGS data. All isolates were found to be susceptible to the tested antibiotics except for tetracycline in MIC and WGS test methods used. Tetracycline resistant determinant genes such as TETM and TETL / TETM combination were identified. CONCLUSION: Further studies on serotype and molecular epidemiology will provide a comprehensive data of the GBS capsular serotype and clones available in Ethiopia.


Asunto(s)
Epidemiología Molecular/métodos , Complicaciones Infecciosas del Embarazo/epidemiología , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/genética , Streptococcus agalactiae/aislamiento & purificación , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Etiopía/epidemiología , Femenino , Hospitales Especializados , Hospitales Universitarios , Humanos , Recién Nacido , Pruebas de Sensibilidad Microbiana , Filogenia , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Prevalencia , Recto/microbiología , Serogrupo , Infecciones Estreptocócicas/tratamiento farmacológico , Tetraciclina/uso terapéutico , Vagina/microbiología , Secuenciación Completa del Genoma
19.
Am J Obstet Gynecol ; 222(2): 154.e1-154.e10, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31421123

RESUMEN

BACKGROUND: Although the vaginal and urinary microbiomes have been increasingly well-characterized in health and disease, few have described the relationship between these neighboring environments. Elucidating this relationship has implications for understanding how manipulation of the vaginal microbiome may affect the urinary microbiome and treatment of common urinary conditions. OBJECTIVE: To describe the relationship between urinary and vaginal microbiomes using 16S rRNA gene sequencing. We hypothesized that the composition of the urinary and vaginal microbiomes would be significantly associated, with similarities in predominant taxa. STUDY DESIGN: This multicenter study collected vaginal swabs and catheterized urine samples from 186 women with mixed urinary incontinence enrolled in a parent study and 84 similarly aged controls. Investigators decided a priori that if vaginal and/or urinary microbiomes differed between continent and incontinent women, the groups would be analyzed separately; if similar, samples from continent and incontinent women would be pooled and analyzed together. A central laboratory sequenced variable regions 1-3 (v1-3) and characterized bacteria to the genus level. Operational taxonomic unit abundance was described for paired vaginal and urine samples. Pearson's correlation characterized the relationship between individual operational taxonomic units of paired samples. Canonical correlation analysis evaluated the association between clinical variables (including mixed urinary incontinence and control status) and vaginal and urinary operational taxonomic units, using the Canonical correlation analysis function in the Vegan package (R version 3.5). Linear discriminant analysis effect size was used to find taxa that discriminated between vaginal and urinary samples. RESULTS: Urinary and vaginal samples were collected from 212 women (mean age 53±11 years) and results from 197 paired samples were available for analysis. As operational taxonomic units in mixed urinary incontinence and control samples were related in canonical correlation analysis and since taxa did not discriminate between mixed urinary incontinence or controls in either vagina or urine, mixed urinary incontinence and control samples were pooled for further analysis. Canonical correlation analysis of vaginal and urinary samples indicated that that 60 of the 100 most abundant operational taxonomic units in the samples largely overlapped. Lactobacillus was the most abundant genus in both urine and vagina (contributing on average 53% to an individual's urine sample and 64% to an individual's vaginal sample) (Pearson correlation r=0.53). Although less abundant than Lactobacillus, other bacteria with high Pearson correlation coefficients also commonly found in vagina and urine included: Gardnerella (r=0.70), Prevotella (r=0.64), and Ureaplasma (r=0.50). Linear discriminant analysis effect size analysis identified Tepidimonas and Flavobacterium as bacteria that distinguished the urinary environment for both mixed urinary incontinence and controls as these bacteria were absent in the vagina (Tepidimonas effect size 2.38, P<.001, Flavobacterium effect size 2.15, P<.001). Although Lactobacillus was the most abundant bacteria in both urine and vagina, it was more abundant in the vagina (linear discriminant analysis effect size effect size 2.72, P<.001). CONCLUSION: Significant associations between vaginal and urinary microbiomes were demonstrated, with Lactobacillus being predominant in both urine and vagina. Abundance of other bacteria also correlated highly between the vagina and urine. This inter-relatedness has implications for studying manipulation of the urogenital microbiome in treating conditions such as urgency urinary incontinence and urinary tract infections.


Asunto(s)
Microbiota/genética , Sistema Urinario/microbiología , Orina/microbiología , Vagina/microbiología , Adulto , Burkholderiales , Estudios de Casos y Controles , Clostridiales , Análisis Discriminante , Escherichia , Femenino , Flavobacterium , Gardnerella , Humanos , Lactobacillus , Modelos Lineales , Persona de Mediana Edad , Prevotella , ARN Ribosómico 16S/análisis , Streptococcus , Ureaplasma , Incontinencia Urinaria
20.
Can J Microbiol ; 66(1): 1-10, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31526326

RESUMEN

Much is made of the need to translate scientific research into improved care of people or other life forms. Grant applications invariably start with the extent of a problem and end by claiming that their work will or could result in making an impact. In truth, very few projects ever lead to translation at the level of the host, nor was that really their intent. For those who are focused on applied science, there are many ways to reach the desired goal, sometimes through serendipity or by logical stepwise progress. The following paper will provide personal insight into the stages, pitfalls, and ultimate assessment of relevance in the context of using probiotic lactobacilli for human health and other applications.


Asunto(s)
Lactobacillus/fisiología , Probióticos/farmacología , Probióticos/uso terapéutico , Suplementos Dietéticos , Desarrollo de Medicamentos , Femenino , Enfermedades Urogenitales Femeninas/prevención & control , Enfermedades Urogenitales Femeninas/terapia , Humanos , Investigación en Medicina Traslacional , Vagina/microbiología , Vagina/fisiología
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