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PROVIDER: PRJNA321729 | ENA |
REPOSITORIES: ENA
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Project description:Vaginal microbiome in a high risk PTB cohort
| PRJNA300860 | ENA
Project description:<p>Preterm birth is the leading cause of neonatal morbidity and mortality. A failure to predict and understand the causes of preterm birth have limited effective interventions and therapeutics. From a cohort of 2,000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Modern and innovative Bayesian modeling of vaginal microbiota identified features of these communities associated with PTB. Seven bacterial taxa were shown to have relative abundances significantly associated with an increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of β-defensins significantly decreased the risk of sPTB associated with the vaginal microbiota in an ethnicity-dependent manner. These findings hold promise for the development of novel diagnostics that could more accurately identify women at risk for sPTB early in pregnancy and offer new therapeutic strategies that would include immune modulators and microbiome-based therapeutics to reduce this significant health burden.</p>
| phs001739 | dbGaP
Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
2011-10-24 | E-MEXP-2958 | biostudies-arrayexpress
Project description:Preterm birth (PTB) is defined as childbirth occurring at less than 37 completed weeks or 259 days of gestation. Premature babies have higher rates of cerebral palsy, sensory deficits, learning disabilities and respiratory illnesses that extend into adulthood. This lifelong morbidity results in high economic and social costs to families and communities. PTB is a syndrome initiated by multiple mechanisms, including infection or inflammation, uteroplacental ischaemia or haemorrhage, uterine overdistension, stress, and other immunologically mediated processes. Identifying and monitoring molecular signals in easily accessible body fluids that can diagnose or predict the risk of preterm labor in pregnant women will reduce or prevent PTBs. A number of studies reported the identification of putative biomarkers for PTB including protein, miRNA and hormone from different body fluids such as serum/plasma, cervical vaginal fluid, saliva and amniotic fluids. These putative biomarkers identified can largely be grouped into three main functional categories: inflammatory related molecules, placenta or fetal derived molecules and stress related molecules. In the past few years next generation sequencing (NGS) has become the major platform for miRNA analysis especially with body fluids. However, studies have shown significant sequence bias among different small RNA library preparation protocols. We have modified the small RNA library construction protocol which greatly reduces the sequence bias and increase miRNA coverage in sample. We also adapted a newly developed size exclusion chromatography (SEC) based EV purification protocol which can provide cleaner EVs compared to other methods. We are using these improved approaches to gain more reliable profile of circulating RNA in body fluid as well as its associated EVs. With these new approaches, we explore the possibility of using specific circulating miRNAs, specifically those encapsulated in EVs, as a noninvasive biomarker for PTB by comparing the miRNA profiles in maternal plasma, EV and EV-depleted plasma between individuals who had a spontaneous preterm birth and uncomplicated pregnancies.
2018-03-19 | GSE106224 | GEO
Project description:Preterm birth (PTB), defined as birth at less than 37 weeks of gestation, is a major determinant of neonatal mortality and morbidity. Early diagnosis of the PTB followed by protective treatments is essential to reduce neonatal adverse outcomes. However, due to the redundant nature of clinical conditions with other diseases, PTB-associated clinical parameters are poor predictors of the PTB. It has been thus needed to identify molecular biomarkers with high accuracy in diagnosis of PTB. Here, we performed mRNA sequencing analysis of PTB patients and full-term birth (FTB) controls in Korean population and identified differentially expressed genes (DEGs) between PTB and FTB, as well as cellular pathways represented by the DEGs. By integrating two previous gene expression profiles generated from different ethnic groups, we then identified the core T-cell activation pathway associated with the PTB, which was shared among all previous datasets, and selected the three representative DEGs (CYLD, TFRC, and RIPK2) of the core pathway as biomarker candidates for the PTB. We finally confirmed the dysregulations of the biomarker candidates and the core T-cell activation pathway in an independent cohort. Our results suggest that CYLD, TFRC, and RIPK2 can serve as reliable biomarkers for the PTB.
2021-04-06 | GSE148402 | GEO
Project description:Preterm birth (PTB) is a leading global cause of infant mortality. Risk factors include genetics, lifestyle choices and infection. Understanding the mechanism of PTB could aid the development of novel approaches to prevent PTB. This study aimed to investigate the metabolic biomarkers of PTB in early pregnancy and the association of significant metabolites with participant genotypes. Maternal sera collected at 16 and 20 weeks of gestation, from women who previously experienced PTB (high-risk) and women who did not (low-risk controls), were analysed using 1H nuclear magnetic resonance (NMR) metabolomics and genome-wide screening microarray. ANOVA and probabilistic neural network (PNN) modelling were performed on the spectral bins. Metabolomics genome-wide association (MGWAS) of the spectral bins and genotype data from the same participants was applied to determine potential metabolite-gene pathways. Phenylalanine, acetate and lactate metabolite differences between PTB cases and controls were obtained by ANOVA and PNN showed strong prediction at week 20 (AUC = 0.89). MGWAS identified several metabolite bins with strong genetic associations. Cis-eQTL analysis highlighted TRAF1 (involved in the inflammatory pathway) local to a non-coding SNP associated with lactate at week 20 of gestation. MGWAS of a well-defined cohort of participants highlighted a lactate-TRAF1 relationship that could potentially contribute to PTB.
2023-05-24 | MTBLS1990 | MetaboLights
Project description:The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.
2019-10-17 | GSE138971 | GEO
Project description:Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55-0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.
2022-11-21 | MTBLS702 | MetaboLights
Project description:Background: While the luminal microbiome composition in the human cervicovaginal tract has been defined, the presence and impact of tissue-adherent ectocervical microbiota remain incompletely understood. Studies of luminal and tissue-associated bacteria in the gastrointestinal tract suggest that they may have distinct roles in health and disease. Here, we performed a multi-omics characterization of paired luminal and tissue samples collected from a clinically well-characterized cohort of Kenyan women. Results: We identified a tissue-adherent bacterial microbiome, with a higher alpha diversity than the luminal microbiome, in which dominant genera overall included Gardnerella and Lactobacillus, followed by Prevotella, Atopobium, and Sneathia. About half of the L. iners dominated luminal samples had a corresponding Gardnerella dominated tissue microbiome. Broadly, the tissue-adherent microbiome was associated with fewer differentially expressed host genes than the luminal microbiome. Gene set enrichment analysis revealed that L. crispatus-dominated tissue-adherent communities were associated with protein translation and antimicrobial activity, whereas a highly diverse microbiome was associated with epithelial remodeling and pro-inflammatory pathways. Communities dominated by L. iners and Gardnerella were associated with low host transcriptional activity. Tissue-adherent microbiomes dominated by Lactobacillus and Gardnerella correlated with host protein profiles associated with epithelial barrier stability, and with a more pro-inflammatory profile for the Gardnerella-dominated microbiome group. Tissue samples with a highly diverse composition had a protein profile representing cell proliferation and pro-inflammatory activity. Conclusion: We identified ectocervical tissue-adherent bacterial communities in all study participants. These communities were distinct from cervicovaginal luminal microbiota in a significant proportion of individuals. This difference could possibly explain that L. iners dominant luminal communities have a high probability of transitioning to high diverse bacterial communities including high abundance of Gardnerella. By performing integrative multi-omics analyses we further revealed that bacterial communities at both sites correlated with distinct host gene expression and protein levels. The tissue-adherent bacterial community is similar to vaginal biofilms that significantly impact women’s reproductive and sexual health.
2023-02-10 | GSE194276 | GEO