scholarly journals Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women

2017 ◽  
Vol 114 (37) ◽  
pp. 9966-9971 ◽  
Author(s):  
Benjamin J. Callahan ◽  
Daniel B. DiGiulio ◽  
Daniela S. Aliaga Goltsman ◽  
Christine L. Sun ◽  
Elizabeth K. Costello ◽  
...  
Keyword(s):  
Preterm Birth ◽  
High Risk ◽  
High Resolution ◽  
Neonatal Morbidity ◽  
16S Rrna Gene Sequencing ◽  
Vaginal Microbiota ◽  
Low Risk ◽  
Gardnerella Vaginalis ◽  
Rrna Gene ◽  
Taxonomic Assignment

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Previous studies have suggested that the maternal vaginal microbiota contributes to the pathophysiology of PTB, but conflicting results in recent years have raised doubts. We conducted a study of PTB compared with term birth in two cohorts of pregnant women: one predominantly Caucasian (n = 39) at low risk for PTB, the second predominantly African American and at high-risk (n = 96). We profiled the taxonomic composition of 2,179 vaginal swabs collected prospectively and weekly during gestation using 16S rRNA gene sequencing. Previously proposed associations between PTB and lower Lactobacillus and higher Gardnerella abundances replicated in the low-risk cohort, but not in the high-risk cohort. High-resolution bioinformatics enabled taxonomic assignment to the species and subspecies levels, revealing that Lactobacillus crispatus was associated with low risk of PTB in both cohorts, while Lactobacillus iners was not, and that a subspecies clade of Gardnerella vaginalis explained the genus association with PTB. Patterns of cooccurrence between L. crispatus and Gardnerella were highly exclusive, while Gardnerella and L. iners often coexisted at high frequencies. We argue that the vaginal microbiota is better represented by the quantitative frequencies of these key taxa than by classifying communities into five community state types. Our findings extend and corroborate the association between the vaginal microbiota and PTB, demonstrate the benefits of high-resolution statistical bioinformatics in clinical microbiome studies, and suggest that previous conflicting results may reflect the different risk profile of women of black race.

scholarly journals Recovery of Vaginal Microbiota after Standard Treatment for Bacterial Vaginosis Infection: An Observational Study

2020 ◽  
Vol 8 (6) ◽  
pp. 875
Author(s):  
Liisa Lehtoranta ◽  
Ashley A. Hibberd ◽  
Jenni Reimari ◽  
Jouni Junnila ◽  
Nicolas Yeung ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Antibiotic Treatment ◽  
16S Rrna Gene Sequencing ◽  
Antibiotic Use ◽  
Vaginal Microbiota ◽  
Gardnerella Vaginalis ◽  
Rrna Gene ◽  
Sequencing Analysis ◽  
Healthy Women ◽  
Before And After

Vaginal microbiota dysbiosis and bacterial vaginosis (BV) affect negatively women’s health. Understanding vaginal microbiota fluctuations in BV during and after antibiotic treatment would facilitate accurate decision-making on the treatment regimen, avoid unnecessary antibiotic use, and potentially mitigate recurrence. We investigated vaginal microbiota composition of 30 women with BV before and after 5-day metronidazole treatment and compared the results with 30 healthy women. Vaginal microbiota was assessed by Nugent score and analyzed by 16S rRNA gene sequencing in swabs on baseline Day 1, and on Day 8 and 15, after completion of antibiotic treatment by women with BV. Prior to antibiotic treatment (Day 1), BV-positive women were dominated by Lactobacillus iners (25.8%), Prevotella timonensis/bivia (18.0%), and Gardnerella vaginalis (14.6%), whereas healthy women were dominated by L. iners (37.5%) and Lactobacillus crispatus/acidophilus (19.2%). On Day 8, L. iners abundance increased in BV-treated women being significantly higher compared with healthy women (67.8% vs. 37.5%, p = 0.049). On Day 15, the relative abundance of all microbial taxa was similar between the groups. Vaginal microbiota of women with BV shifted to resemble that of healthy controls after metronidazole. Sequencing analysis provides more in-depth understanding of changes in vaginal microbiota. The role of L. iners in vaginal health and dysbiosis requires further investigations.

scholarly journals Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome

2021 ◽  
Author(s):  
William F Kindschuh ◽  
Federico Baldini ◽  
Martin C Liu ◽  
Kristen D Gerson ◽  
Jingqui Liao ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Black Women ◽  
Neonatal Morbidity ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Vaginal Microbiome ◽  
Spontaneous Preterm Birth ◽  
Potential Risk Factors ◽  
Rrna Gene Sequencing ◽  
Singleton Pregnancies

Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet both its prevention and early risk stratification are limited. The vaginal microbiome has been associated with PTB risk, possibly via metabolic or other interactions with its host. Here, we performed untargeted metabolomics on 232 vaginal samples, in which we have previously profiled the microbiota using 16S rRNA gene sequencing. Samples were collected at 20-24 weeks of gestation from women with singleton pregnancies, of which 80 delivered spontaneously before 37 weeks of gestation. We find that the vaginal metabolome correlates with the microbiome and separates into six clusters, three of which are associated with spontaneous preterm birth (sPTB) in Black women. Furthermore, while we identify five metabolites that associate with sPTB, another five associate with sPTB only when stratifying by race. We identify multiple microbial correlations with metabolites associated with sPTB, including intriguing correlations between vaginal bacteria that are considered sub-optimal and metabolites that were enriched in women who delivered at term. We propose that several sPTB-associated metabolites may be exogenous, and investigate another using metabolic models. Notably, we use machine learning models to predict sPTB risk using metabolite levels, weeks to months in advance, with high accuracy. We show that these predictions are more accurate than microbiome-based and maternal covariates-based models. Altogether, our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.

scholarly journals Combination of Immune and Viral Factors Distinguishes Low-Risk versus High-Risk HIV-1 Disease Progression in HLA-B*5701 Subjects

2012 ◽  
Vol 86 (18) ◽  
pp. 9802-9816 ◽  
Author(s):  
Melissa M. Norström ◽  
Marcus Buggert ◽  
Johanna Tauriainen ◽  
Wendy Hartogensis ◽  
Mattia C. Prosperi ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
High Resolution ◽  
Disease Progression ◽  
T Cell Responses ◽  
Low Risk ◽  
Early Infection ◽  
Cell Responses ◽  
Cell Counts ◽  
Hiv 1

HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although rates can vary within this group. Underlying mechanisms are not fully understood but likely involve both immunological and virological dynamics. The present study investigated HIV-1in vivoevolution and epitope-specific CD8+T cell responses in six HLA-B*5701 patients who had not received antiretroviral treatment, monitored from early infection for up to 7 years. The subjects were classified as high-risk progressors (HRPs) or low-risk progressors (LRPs) based on baseline CD4+T cell counts. Dynamics of HIV-1 Gag p24 evolution and multifunctional CD8+T cell responses were evaluated by high-resolution phylogenetic analysis and polychromatic flow cytometry, respectively. In all subjects, substitutions occurred more frequently in flanking regions than in HLA-B*5701-restricted epitopes. In LRPs, p24 sequence diversity was significantly lower; sequences exhibited a higher degree of homoplasy and more constrained mutational patterns than HRPs. The HIV-1 intrahost evolutionary rate was also lower in LRPs and followed a strict molecular clock, suggesting neutral genetic drift rather than positive selection. Additionally, polyfunctional CD8+T cell responses, particularly to TW10 and QW9 epitopes, were more robust in LRPs, who also showed significantly higher interleukin-2 (IL-2) production in early infection. Overall, the findings indicate that HLA-B*5701 patients with higher CD4 counts at baseline have a lower risk of HIV-1 disease progression because of the interplay between specific HLA-linked immune responses and the rate and mode of viral evolution. The study highlights the power of a multidisciplinary approach, integrating high-resolution evolutionary and immunological data, to understand mechanisms underlying HIV-1 pathogenesis.

scholarly journals Variations in cervico-vaginal microbiota among HPV-positive and HPV-negative asymptomatic women in Peru

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hugo Carrillo-Ng ◽  
Lorena Becerra-Goicochea ◽  
Yordi Tarazona-Castro ◽  
Luis Pinillos-Vilca ◽  
Luis J. del Valle ◽  
...  
Keyword(s):  
High Risk ◽  
Vaginal Microbiota ◽  
Low Risk ◽  
Asymptomatic Women

Abstract Objective To characterize the cervicovaginal microbiota of HPV-positive and HPV-negative asymptomatic Peruvian women, by identifying the presence of 13 representative bacteria genus. Results A total of 100 HPV-positive and 100 HPV-negative women were matched by age for comparison of microbiota. The following bacteria were more frequently identified in HPV-positive patients compared to HPV-negative: Eubacterium (68 vs 32%), Actinobacteria (46 vs 33%), Fusobacterium (11 vs 6%) and Bacteroides (20 vs 13%). A comparison between high-risk and low-risk genotypes was performed and differences were found in the detection of Actinobacteria (50 vs 33.33%), Bifidobacterium (50 vs 20.83%) and Enterococcus (50 vs 29.17%).

scholarly journals 424: Uterocervical angle does not predict spontaneous preterm birth in either a low-risk or high-risk group: A prospective study

2018 ◽  
Vol 218 (1) ◽  
pp. S258
Author(s):  
Courtney Olson-Chen ◽  
Kam Szlachetka ◽  
Dzhamala Gilmandyar ◽  
Erica Faske ◽  
Elizabeth Fountaine ◽  
...  
Keyword(s):  
Preterm Birth ◽  
High Risk ◽  
Prospective Study ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Spontaneous Preterm Birth ◽  
Group A ◽  
A Prospective Study

scholarly journals Effect of oral consumption of capsules containing Lactobacillus paracasei LPC-S01 on the vaginal microbiota of healthy adult women: a randomized, placebo-controlled, double-blind crossover study

2020 ◽  
Vol 96 (6) ◽  
Author(s):  
Ranjan Koirala ◽  
Giorgio Gargari ◽  
Stefania Arioli ◽  
Valentina Taverniti ◽  
Walter Fiore ◽  
...  
Keyword(s):  
Daily Intake ◽  
Vaginal Microbiota ◽  
Lactobacillus Paracasei ◽  
Gardnerella Vaginalis ◽  
Taxonomic Structure ◽  
Rrna Gene ◽  
Vaginal Mucosa ◽  
Adult Women ◽  
Oral Consumption ◽  
Vaginal Swabs

ABSTRACT Oral consumption of probiotics is practical and can be an effective solution to preserve vaginal eubiosis. Here, we studied the ability of orally administered Lactobacillus paracasei LPC-S01 (DSM 26760) to affect the composition of the vaginal microbiota and colonize the vaginal mucosa in nondiseased adult women. A total of 40 volunteers took oral probiotic (24 billion CFU) or placebo capsules daily for 4 weeks, and after a 4-week washout, they switched to placebo or probiotic capsules according to the crossover design. A total of 23 volunteers completed the study according to the protocol. Before and after capsule ingestion, vaginal swabs were collected for qPCR quantification to detect L. paracasei LPC-S01 and for 16S rRNA gene sequencing. Vaginal swabs were grouped according to their bacterial taxonomic structure into nine community state types (CSTs), four of which were dominated by lactobacilli. Lactobacillus paracasei LPC-S01 was detected in the vagina of two participants. Statistical modeling (including linear mixed-effects model analysis) demonstrated that daily intake of probiotic capsules reduced the relative abundance of Gardnerella spp. Quantitative PCR with Gardnerella vaginalis primers confirmed this result. Considering the pathogenic nature of G. vaginalis, these results suggest a potential positive effect of this probiotic capsule on the vaginal microbial ecosystem.

scholarly journals Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e035186 ◽  
Author(s):  
Erica M Lokken ◽  
Kishorchandra Mandaliya ◽  
Sujatha Srinivasan ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Umbilical Cord ◽  
Bacterial Species ◽  
Vaginal Microbiota ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Rrna Gene ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

IntroductionBacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria present around conception may lead to SPTB by compromising the protective effects of cervical mucus, colonising the endometrial surface before fetal membrane development, and causing low-level inflammation in the decidua, placenta and fetal membranes. This protocol describes a prospective case-cohort study addressing this hypothesis.Methods and analysisHIV-seronegative Kenyan women with fertility intent are followed from preconception through pregnancy, delivery and early postpartum. Participants provide monthly vaginal specimens during the preconception period for vaginal microbiota assessment. Estimated date of delivery is determined by last menstrual period and first trimester obstetrical ultrasound. After delivery, a swab is collected from between the fetal membranes. Placenta and umbilical cord samples are collected for histopathology. Broad-range 16S rRNA gene PCR and deep sequencing of preconception vaginal specimens will assess species richness and diversity in women with SPTB versus term delivery. Concentrations of key bacterial species will be compared using quantitative PCR (qPCR). Taxon-directed qPCR will also be used to quantify bacteria from fetal membrane samples and evaluate the association between bacterial concentrations and histopathological evidence of inflammation in the fetal membranes, placenta and umbilical cord.Ethics and disseminationThis study was approved by ethics committees at Kenyatta National Hospital and the University of Washington. Results will be disseminated to clinicians at study sites and partner institutions, presented at conferences and published in peer-reviewed journals. The findings of this study could shift the paradigm for thinking about the mechanisms linking vaginal microbiota and prematurity by focusing attention on the preconception vaginal microbiota as a mediator of SPTB.

scholarly journals The Nasopharyngeal, Ruminal, and Vaginal Microbiota and the Core Taxa Shared across These Microbiomes in Virgin Yearling Heifers Exposed to Divergent In Utero Nutrition during Their First Trimester of Gestation and in Pregnant Beef Heifers in Response to Mineral Supplementation

2021 ◽  
Vol 9 (10) ◽  
pp. 2011
Author(s):  
Samat Amat ◽  
Devin B. Holman ◽  
Kaycie Schmidt ◽  
Ana Clara B. Menezes ◽  
Friederike Baumgaertner ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Average Daily Gain ◽  
Methanogenic Archaea ◽  
16S Rrna Gene Sequencing ◽  
First Trimester ◽  
Vaginal Microbiota ◽  
Rrna Gene ◽  
Beef Heifers ◽  
Β Diversity ◽  
Significant Difference

In the present study, we evaluated whether the nasopharyngeal, ruminal, and vaginal microbiota would diverge (1) in virgin yearling beef heifers (9 months old) due to the maternal restricted gain during the first trimester of gestation; and (2) in pregnant beef heifers in response to the vitamin and mineral (VTM) supplementation during the first 6 months of pregnancy. As a secondary objective, using the microbiota data obtained from these two cohorts of beef heifers managed at the same location and sampled at the same time, we performed a holistic assessment of the microbial ecology residing within the respiratory, gastrointestinal, and reproductive tract of cattle. Our 16S rRNA gene sequencing results revealed that both α and β-diversity of the nasopharyngeal, ruminal and vaginal microbiota did not differ between virgin heifers raised from dams exposed to either a low gain (targeted average daily gain of 0.28 kg/d, n = 22) or a moderate gain treatment (0.79 kg/d, n = 23) during the first 84 days of gestation. Only in the vaginal microbiota were there relatively abundant genera that were affected by maternal rate of gain during early gestation. Whilst there was no significant difference in community structure and diversity in any of the three microbiota between pregnant heifers received no VTM (n = 15) and VTM supplemented (n = 17) diets, the VTM supplementation resulted in subtle compositional alterations in the nasopharyngeal and ruminal microbiota. Although the nasopharyngeal, ruminal, and vaginal microbiota were clearly distinct, a total of 41 OTUs, including methanogenic archaea, were identified as core taxa shared across the respiratory, gastrointestinal, and reproductive tracts of both virgin and pregnant heifers.

scholarly journals Comparison of Female Genital Tract Cytokine and Microbiota Signatures Induced by Initiation of Intramuscular DMPA and NET-EN Hormonal Contraceptives - a Prospective Cohort Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Smritee Dabee ◽  
Ramla F. Tanko ◽  
Bryan P. Brown ◽  
Rubina Bunjun ◽  
Christina Balle ◽  
...  
Keyword(s):  
High Risk ◽  
Genital Tract ◽  
Cohort Analysis ◽  
Female Genital Tract ◽  
Vaginal Microbiota ◽  
African Women ◽  
Hormonal Contraceptives ◽  
Rrna Gene ◽  
Female Genital

BackgroundCervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although in-vitro data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives.MethodsWe collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis.ResultsCytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota.ConclusionsBoth DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs.

scholarly journals Distinction Between Vaginal and Cervical Microbiota in High-risk Human Papilloma Virus Infected Women in China

2020 ◽  
Author(s):  
Zhan Zhang ◽  
Ting Li ◽  
Dai Zhang ◽  
Xiaonan Zong ◽  
Huihui Bai ◽  
...  
Keyword(s):  
High Risk ◽  
Human Papilloma Virus ◽  
Chinese Women ◽  
Variable Region ◽  
Vaginal Microbiota ◽  
Rrna Gene ◽  
Papilloma Virus ◽  
Next Generation Sequencing Technology ◽  
History Of ◽  
High Risk Hpv

Abstract Background: High-risk human papilloma virus (hrHPV) is regarded as the main causal factor of cervical precancer and cancer when persistent infection is left untreated. Previous studies have declared that HPV is associated with microecological environment of lower genital tract but haven’t discriminate vaginal microbiota from that of cervix. Objective: To analyze the distinction between vaginal and cervical microbiota in high-risk HPV(+) Chinese women. Methods: One hundred participants were recruited including 20 healthy women with HPV (-), 32 with other hrHPV (+), 38 subjects with HPV16/18 (+) and 10 with cervical carcinoma, demographics of whom were collected and analyzed. Vaginal and cervical microbiota were separately tested through next-generation sequencing technology (NGS) targeting the variable region (V3-V4) of bacterial ribosome 16S rRNA gene. Results: 1. Analysis of demographics demonstrated that hrHPV infected women tend to be accustomed to vaginal douching (p =0.001), show more frequent usage of sanitary pads (p =0.007), have more sex partners (p =0.047), be more sexually active (p =0.025), have more diverse ways of contraception (p =0.001) and history of vaginitis (p =0.002). 2. NGS identified microbial diversity of cervical microbiota was much higher than that of vagina with significantly increased Proteobacteria and decreased Lactobacillus. Variation of cervical microbiota of hrHPV(+) subjects partly similar to vaginal microbiota but had its unique features. Sphingomonas of α-Proteobacteria, almost invisible in the vagina, was more frequent at normal cervix whereas decreased remarkably at hrHPV(+) cervix. Reversely, γ-Proteobacteria showed a significant positive correlation with HPV16/18 and cervical cancer. BV related anaerobes like Gardnerella, Prevotella, Atopobium and Sneathia showed similar changes in both vaginal and cervical microbiota of hrHPV(+) women and did not exhibit cervical specificity. Conclusions: Cervical microbiota has its uniqueness from that of vagina in bacterial communities presenting a higher proportion of Proteobacteria, of which Sphingomonas is potentially predictive of a health guardian of hrHPV while Pseudomonas the opposite.

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