Vaginal microbiome as a tool for prediction of chorioamnionitis in preterm labor: a pilot study.
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ABSTRACT:
SUBMITTER: Urushiyama D
PROVIDER: S-EPMC8460623 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Vaginal microbiome as a tool for prediction of chorioamnionitis in preterm labor: a pilot study.
Urushiyama Daichi D Ohnishi Eriko E Suda Wataru W Kurakazu Masamitsu M Kiyoshima Chihiro C Hirakawa Toyofumi T Miyata Kohei K Yotsumoto Fusanori F Nabeshima Kazuki K Setoue Takashi T Nagamitsu Shinichiro S Hattori Masahira M Hata Kenichiro K Miyamoto Shingo S
Scientific reports 20210923 1
Intra-amniotic infection (IAI) is a major cause of preterm birth with a poor perinatal prognosis. We aimed to determine whether analyzing vaginal microbiota can evaluate the risk of chorioamnionitis (CAM) in preterm labor cases. Vaginal discharge samples were collected from 83 pregnant women admitted for preterm labor. Based on Blanc's classification, the participants were divided into CAM (stage ≥ II; n = 46) and non-CAM (stage ≤ I; n = 37) groups. The 16S rDNA amplicons (V1-V2) from vaginal sa ...[more]
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| S-EPMC5933090 | biostudies-literature
Project description:The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.
| S-EPMC6750801 | biostudies-literature
Project description:ObjectiveChorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA.MethodsGestational age-, birth weight-, delivery mode- and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers with or without HCA were enrolled from an observational study. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine samples non-invasively collected in the first 24 hours of life. Univariate analysis, partial least square discriminant analysis (PLS-DA) and its associated variable importance in projection (VIP) score were performed. The most affected metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA).ResultsFifteen cases (mean GA 30.2 ± 3.8 weeks, mean BW 1415 ± 471.9 grams) and 30 controls (mean GA 30.2 ± 2.9 weeks, mean BW 1426 ± 569.8 grams) were enrolled. Following univariate analysis, 29 metabolites had a significantly different concentration between cases and controls. The supervised PLS-DA model confirmed a separation between the two groups. Only gluconic acid, an oxidation product of glucose, was higher in cases than in controls. All other VIP metabolites were more abundant in the control group. Glutamate metabolism, mitochondrial electron transport chain, citric acid cycle, galactose metabolism, and fructose and mannose degradation metabolism were the most significantly altered pathways (P < 0.01).ConclusionsFor the first time, urinary metabolomics was able to discriminate neonates born to mothers with and without HCA. The identification of specifically altered metabolic pathways may be helpful in understanding metabolic derangement following chorioamnionitis.
| S-EPMC5718427 | biostudies-literature
Project description:Endometriosis remains a challenge to understand and to diagnose. This is an observational cross-sectional pilot study to characterize the gut and vaginal microbiome profiles among endometriosis patients and control subjects without the disease and to explore their potential use as a less-invasive diagnostic tool for endometriosis. Overall, 59 women were included, n = 35 with endometriosis and n = 24 controls. Rectal and vaginal samples were collected in two different periods of the menstrual cycle from all subjects. Gut and vaginal microbiomes from patients with different rASRM (revised American Society for Reproductive Medicine) endometriosis stages and controls were analyzed. Illumina sequencing libraries were constructed using a two-step 16S rRNA gene PCR amplicon approach. Correlations of 16S rRNA gene amplicon data with clinical metadata were conducted using a random forest-based machine-learning classification analysis. Distribution of vaginal CSTs (community state types) significantly differed between follicular and menstrual phases of the menstrual cycle (p = 0.021, Fisher's exact test). Vaginal and rectal microbiome profiles and their association to severity of endometriosis (according to rASRM stages) were evaluated. Classification models built with machine-learning methods on the microbiota composition during follicular and menstrual phases of the cycle were built, and it was possible to accurately predict rASRM stages 1-2 verses rASRM stages 3-4 endometriosis. The feature contributing the most to this prediction was an OTU (operational taxonomic unit) from the genus Anaerococcus. Gut and vaginal microbiomes of women with endometriosis have been investigated. Our findings suggest for the first time that vaginal microbiome may predict stage of disease when endometriosis is present.
| S-EPMC7539818 | biostudies-literature
Project description:BackgroundPreterm labor is one of the leading causes of perinatal death and is currently considered a syndrome with many causes. One of the most important causes of preterm birth is ascending infection from bacterial vaginosis. Chlorhexidine has proven to be effective against bacterial vaginosis and against bacterial biofilms without affecting gestation.ObjectiveWe aimed to evaluate the effectiveness of a universal primary prevention strategy for preterm birth using intravaginal chlorhexidine applied before 16 weeks (Preterm Labor Prevention Using Vaginal Antiseptics study).Study designWe performed a prospective observational study with 2 cohorts of pregnant women that were assigned either to prevention of preterm birth by means of intravaginal chlorhexidine (Cum Laude Chlorhexidine, chlorhexidine digluconate 0.2%) before 16 weeks (n=413), or to no treatment following the usual hospital protocol (n=704). Primary outcomes were the incidence of spontaneous preterm birth before 34 and 37 weeks; the incidence of preterm birth before 34 and 37 weeks, including inductions for premature rupture of membranes; and the incidence of preterm birth before 34 and 37 weeks, including any indication for termination of pregnancy. Both cohorts were compared using Mann-Whitney and Fisher tests. Finally, a multivariable analysis, including the odds ratio was performed, adjusting for clinical parameters, to evaluate the importance of the different determinants in the prediction of preterm birth.ResultsIn pregnancies treated with chlorhexidine, the incidences of spontaneous preterm birth; preterm birth, including induction for premature rupture of membranas; and preterm birth, including any indication for termination of pregnancy were at 34 and 37 weeks: 0% and 0%, 0.24% and 1.69, and 2.90% and 3.15%, respectively; whereas in nontreated pregnancies, these incidences were 9% and 11%, 12% and 23%, and 35% and 43%, respectively. According to the multivariable analysis, the incidence of preterm birth among women treated with chlorhexidine before 16 weeks was halved (Odds ratio, 0.52; P<.05).ConclusionUniversal treatment with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth, especially before 34 weeks.
| S-EPMC10724831 | biostudies-literature
Project description:Previous studies have investigated the associations between the vaginal microbiome and preterm birth, with the aim of determining whether differences in community patterns meaningfully alter risk and could therefore be the target of intervention. We report on vaginal microbial analysis of a nested case-control subset of the Pregnancy, Infection, and Nutrition (PIN) Study, including 464 White women (375 term birth and 89 spontaneous preterm birth, sPTB) and 360 Black women (276 term birth and 84 sPTB). We found that the microbiome of Black women has higher alpha-diversity, higher abundance of Lactobacillus iners, and lower abundance of Lactobacillus crispatus. However, among women who douche, there were no significant differences in microbiome by race. The sPTB-associated microbiome exhibited a lower abundance of L. crispatus, while alpha diversity and L. iners were not significantly associated with sPTB. For each order of magnitude increase in the normalized relative abundance of L. crispatus, multivariable adjusted odds of sPTB decreased by approximately 20% (odds ratio, 0.81; 95% confidence interval, 0.70, 0.94). When we considered the impact of douching, associations between the microbiome and sPTB were limited to women who do not douche. We also observed strong intercorrelations between a range of maternal factors, including poverty, education, marital status, age, douching, and race, with microbiome effect sizes in the range of 1.8 to 5.2% in univariate models. Therefore, race may simply be a proxy for other socially driven factors that differentiate microbiome community structures. Future work will continue to refine reliable microbial biomarkers for preterm birth across diverse cohorts. IMPORTANCE Approximately 10% of all pregnancies in the United States end in preterm birth, and over 14% of pregnancies end in preterm birth among Black women. Knowledge on the associations between vaginal microbiome and preterm birth is important for understanding the potential cause and assessing risk of preterm birth. Our study is one of the largest studies performed to date to investigate the associations between vaginal microbiome and spontaneous preterm birth (sPTB), with stratified design for Black and White women. We found that the vaginal microbiome was different between Black and White women. The vaginal microbiome was associated with sPTB, and a lower abundance of L. crispatus increased the risk of sPTB independent of racial differences in microbial community structures. Furthermore, we also found that vaginal douching obscured the associations between vaginal microbiome, race, and preterm birth, suggesting that vaginal douching is an important factor to consider in future studies.
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Project description:BackgroundDespite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions.ObjectiveTo characterize vaginal microbial community characteristics in a large, predominantly African-American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth.Study designThis is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term.ResultsA total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African-American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness, diversity, and evenness during pregnancy (P < .01). This change occurred between the first and second trimesters. Within-subject comparisons across pregnancy showed that preterm birth is associated with increased vaginal microbiome instability compared to term birth. No distinct taxa were associated with preterm birth.ConclusionIn a predominantly African-American population, a significant decrease of vaginal microbial community richness and diversity is associated with preterm birth. The timing of this suppression appears early in pregnancy, between the first and second trimesters, suggesting that early gestation may be an ecologically important time for events that ordain subsequent term and preterm birth outcomes.
| S-EPMC5581228 | biostudies-literature
Project description:Reproductive tract infection is a major initiator of preterm birth (PTB). The objective of this prospective cohort study of 88 participants was to determine whether PTB correlates with the vaginal microbiome during pregnancy. Total DNA was purified from posterior vaginal fornix swabs during gestation. The 16S ribosomal RNA gene was amplified using polymerase chain reaction primers, followed by chain-termination sequencing. Bacteria were identified by comparing contig consensus sequences with the Ribosomal Database Project. Dichotomous responses were summarized via proportions and continuous variables via means ± standard deviation. Mean Shannon Diversity index differed by Welch t test (P = .00016) between caucasians with PTB and term gestation. Species diversity was greatest among African Americans (P = .0045). Change in microbiome/Lactobacillus content and presence of putative novel/noxious bacteria did not correlate with PTB. We conclude that uncultured vaginal bacteria play an important role in PTB and race/ethnicity and sampling location are important determinants of the vaginal microbiome.
| S-EPMC3857766 | biostudies-literature
Project description:Background: Preterm delivery (PTD) represents an important public health and therapeutic challenge. Despite the reported link between the composition of vaginal microbiome and PTD, previous studies were inconsistent in their conclusions and utilized non-uniform designs. We performed an independent case-control study carried out on the Slovenian population, where we re-evaluated the role of the vaginal microbiome in PTD. Methods: Vaginal microbiomes of pregnant women who delivered preterm were compared to those delivered at term to examine differences in the microbial richness, diversity, and differential abundance of specific taxa. We obtained vaginal swab samples from 155 Caucasian women who were classified as either term (≥380/7 weeks, n = 107) or preterm (≤366/7 weeks, n = 48) in exclusion of any other medical or obstetric conditions. The vaginal microbiomes of these women were characterized by 16S ribosomal RNA (rRNA) gene sequencing of the V3-V4 region on the MiSeq platform. Results: Women who experienced PTD had a higher microbial richness (Chao1, P = 0.011) and alpha diversity (Shannon, P = 0.00059) than women with term deliveries. We report that overall vaginal microbial community composition (beta-diversity) was significantly different by delivery gestational age category (P WeightedUnifrac < 0.001). Women who delivered preterm had decreased Lactobacilli spp. abundance as well as increased abundance of Gardnerella and other bacterial vaginosis (BV) and aerobic vaginitis (AV) associated genera including Atopobium, Sneathia, Gemella, Megasphaera, Dorea, Streptococcus, and Escherichia/Shigella. Conclusions: In the present study, we provide further evidence that vaginal microbiome composition is associated with PTD.
| S-EPMC6746969 | biostudies-literature
Project description:In recent decades, preterm birth (PTB) has become a significant research focus in the healthcare field, as it is a leading cause of neonatal mortality worldwide. Using five independent study cohorts including 1290 vaginal samples from 561 pregnant women who delivered at term (n = 1029) or prematurely (n = 261), we analysed vaginal metagenomics data for precise microbiome structure characterization. Then, a deep neural network (DNN) was trained to predict term birth (TB) and PTB with an accuracy of 84.10% and an area under the receiver operating characteristic curve (AUROC) of 0.875 ± 0.11. During a benchmarking process, we demonstrated that our DL model outperformed seven currently used machine learning algorithms. Finally, our results indicate that overall diversity of the vaginal microbiota should be taken in account to predict PTB and not specific species. This artificial-intelligence based strategy should be highly helpful for clinicians in predicting preterm birth risk, allowing personalized assistance to address various health issues. DeepMPTB is open source and free for academic use. It is licensed under a GNU Affero General Public License 3.0 and is available at https://deepmptb.streamlit.app/ . Source code is available at https://github.com/oschakoory/DeepMPTB and can be easily installed using Docker ( https://www.docker.com/ ).
| S-EPMC10865581 | biostudies-literature