Untangling Associations of Microbiomes of Pregnancy and Preterm Birth.

This review illuminates the complex interplay between various maternal microbiomes and their influence on preterm birth (PTB), a driving and persistent contributor to neonatal morbidity and mortality. Here, we examine the dynamics of oral, gastrointestinal (gut), placental, and vaginal microbiomes, dissecting their roles in the pathogenesis of PTB. Importantly, focusing on the vaginal microbiome and PTB, the review highlights (1) a protective role of Lactobacillus species; (2) an increased risk with select anaerobes; and (3) the influence of social health determinants on the composition of vaginal microbial communities.

Spatiotemporal patterns of the pregnancy microbiome and links to reproductive disorders.

The microbiome of females undergoes extensive remodeling during pregnancy, which is likely to have an impact on the health of both mothers and offspring. Nevertheless, large-scale integrated investigations characterizing microbiome dynamics across key body habitats are lacking. Here, we performed an extensive meta-analysis that compiles and analyzes microbiome profiles from  >10,000 samples across the gut, vagina, and oral cavity of pregnant women from diverse geographical regions. We have unveiled unexpected variations in the taxonomic, functional, and ecological characteristics of microbial communities throughout the course of pregnancy. The gut microbiota showed distinct trajectories between Western and non-Western populations. The vagina microbiota exhibited fluctuating transitions at the genus level across gestation, while the oral microbiota remained relatively stable. We also identified distinctive microbial signatures associated with prevalent pregnancy-related disorders, including opposite variations in the oral and gut microbiota of patients with gestational diabetes and disrupted microbial networks in preterm birth. This study establishes a comprehensive atlas of the pregnancy microbiome by integrating multidimensional datasets and offers foundational insights into the intricate interplay between microbes and host factors that underlie reproductive health.

Profiling of vaginal Lactobacillus jensenii isolated from preterm and full-term pregnancies reveals strain-specific factors relating to host interaction.

Each year, 15 million infants are born preterm (<37 weeks gestation), representing the leading cause of mortality for children under the age of five. Whilst there is no single cause, factors such as maternal genetics, environmental interactions, and the vaginal microbiome have been associated with an increased risk of preterm birth. Previous studies show that a vaginal microbiota dominated by Lactobacillus is, in contrast to communities containing a mixture of genera, associated with full-term birth. However, this binary principle does not fully consider more nuanced interactions between bacterial strains and the host. Here, through a combination of analyses involving genome-sequenced isolates and strain-resolved metagenomics, we identify that L. jensenii strains from preterm pregnancies are phylogenetically distinct from strains from full-term pregnancies. Detailed analysis reveals several genetic signatures that distinguish preterm birth strains, including genes predicted to be involved in cell wall synthesis, and lactate and acetate metabolism. Notably, we identify a distinct gene cluster involved in cell surface protein synthesis in our preterm strains, and profiling the prevalence of this gene cluster in publicly available genomes revealed it to be predominantly present in the preterm-associated clade. This study contributes to the ongoing search for molecular biomarkers linked to preterm birth and opens up new avenues for exploring strain-level variations and mechanisms that may contribute to preterm birth.

The Vaginal Microbiota of Pregnant Women Varies with Gestational Age, Maternal Age, and Parity.

The composition of the vaginal microbiota is heavily influenced by pregnancy and may factor into pregnancy complications, including spontaneous preterm birth. However, results among studies have been inconsistent due, in part, to variation in sample sizes and ethnicity. Thus, an association between the vaginal microbiota and preterm labor continues to be debated. Yet, before assessing associations between the composition of the vaginal microbiota and preterm labor, a robust and in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required. Here, we report a large longitudinal study (n = 474 women, 1,862 vaginal samples) of a predominantly African-American cohort-a population that experiences a relatively high rate of pregnancy complications-evaluating associations between individual identity, gestational age, and other maternal characteristics with the composition of the vaginal microbiota throughout gestation resulting in term delivery. The principal factors influencing the composition of the vaginal microbiota in pregnancy are individual identity and gestational age at sampling. Other factors are maternal age, parity, obesity, and self-reported Cannabis use. The general pattern across gestation is for the vaginal microbiota to remain or transition to a state of Lactobacillus dominance. This pattern can be modified by maternal parity and obesity. Regardless, network analyses reveal dynamic associations among specific bacterial taxa within the vaginal ecosystem, which shift throughout the course of pregnancy. This study provides a robust foundational understanding of the vaginal microbiota in pregnancy and sets the stage for further investigation of this microbiota in obstetrical disease. IMPORTANCE There is debate regarding links between the vaginal microbiota and pregnancy complications, especially spontaneous preterm birth. Inconsistencies in results among studies are likely due to differences in sample sizes and cohort ethnicity. Ethnicity is a complicating factor because, although all bacterial taxa commonly inhabiting the vagina are present among all ethnicities, the frequencies of these taxa vary among ethnicities. Therefore, an in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required prior to evaluating associations between the vaginal microbiota and obstetrical disease. This initial investigation is a large longitudinal study of the vaginal microbiota throughout gestation resulting in a term delivery in a predominantly African-American cohort, a population that experiences disproportionally negative maternal-fetal health outcomes. It establishes the magnitude of associations between maternal characteristics, such as age, parity, body mass index, and self-reported Cannabis use, on the vaginal microbiota in pregnancy.

Effects of emergency/nonemergency cervical cerclage on the vaginal microbiome of pregnant women with cervical incompetence.

Background: Evaluation of the therapeutic effects of cerclage on preterm birth (PTB) caused by cervical incompetence remains challenging. The vaginal microbiome is associated with preterm births. Thus, this study aimed to analyse the vaginal microbiota of patients with cervical incompetence, explore the relationship between the composition of the vaginal microbiota before cervical cerclage and at term delivery, and assess the effect of cervical cerclage on the vaginal microbiota. Methods: Patients (n = 30) underwent cerclage performed by the same surgical team. Vaginal swabs were obtained pre-surgery and seven days post-surgery. A gestational age-matched cohort of healthy pregnant women (n = 20) (no particular abnormality during pregnancy, delivery at term) was used as the control group and sampled during a comparable pregnancy. All collected vaginal swabs were analysed by 16S rRNA gene sequencing. Results: When comparing the healthy control and cervical cerclage groups, the enriched microorganism in the healthy controls was G. Scardovia, and the enriched microorganism of the cerclage was G. Streptococcus. α diversity was significantly increased in patients who received cerclage with preterm delivery compared with those with full-term delivery, and the enriched microorganism was F. Enterococcus. A comparison before and after nonemergency cerclage suggested that the enriched microorganisms were G. Lactobacillus and F. Lactobacillaceae before surgery. After nonemergency cerclage, the enriched microorganisms were F. Enterobacteriaceae and C. Gammaproteobacteria. Vaginal microbiota diversity significantly increased, and the proportion of women with Lactobacillus spp.-depleted microbiomes increased after emergency cerclage. Significant differences in ß diversity were found between the groups. Before the emergency cerclage, the enriched microorganisms were G. Lactobacillus, O. Alteromonadales, and P. Firmicutes. After emergency cerclage, the enriched microorganisms were P. Actinobacteria, C. Actinobacteria, P. Proteobacteria, F. Bifidobacteriaceae, O. Bifidobacteriales, G. Gardnerella, and G. Veillonella. Conclusion: Cerclage (particularly emergency cerclage) may alter the vaginal microbiota by increasing microbiota diversity, decreasing vaginal Lactobacillus abundance, and increasing the abundance of pathogenic bacteria that are not conducive to pregnancy maintenance, thereby affecting surgical efficacy. Therefore, the role of the vaginal microbiome should be considered when developing treatment strategies for pregnant women with cervical incompetence. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2100046305.

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

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.

Vaginal Microbiota and Pregnancy Outcomes of Patients with Conization Histories.

Background: One of the major risks of preterm birth is a history of conization. However, the risk of infection due to this procedure is still not well known. Using next-generation sequencing, we aimed to reveal the influence of conization on vaginal microbiota in the following pregnancy, and their relationship between spontaneous preterm birth (sPTB). Methods: We conducted a prospective cohort study including 133 pregnant patients, of whom 25 had conization histories and 108 did not. Vaginal microbiome samples were collected using swabs by an obstetrician upon inclusion in the first trimester and during delivery. V1-V2 of the 16S rRNA gene were amplified and analyzed to identify the bacteria. Results: The conization group had a significantly lower delivery week (34 weeks vs. 36 weeks, p = 0.003) and higher sPTB rate (64% vs. 8.3%, p ≤ 0.001) than the control group. In the conization group, alpha (Chao 1, p = 0.02; phylogenetic diversity whole tree, p = 0.04) and beta diversity (permutational multivariate analysis of variance test, p = 0.04) of the vaginal microbiota was significantly higher during delivery in patients who delivered preterm than in those who delivered term. Community-state type IV in the first trimester was significantly associated with sPTB (overall odds ratio 3.80, 95% confidence interval 1.33-10.8, p = 0.01). Conclusions: Conization is a risk factor for sPTB. Increased risk of sPTB in patients after conization may belong to the vulnerable defense mechanism, due to the shortened cervix and decreased cervical mucus.

Vaginal microbiota in women with spontaneous preterm labor versus those with term labor in Kenya: a case control study.

BACKGROUND: Preterm birth is a global problem with about 12% of births in sub-Saharan Africa occurring before 37 weeks of gestation. Several studies have explored a potential association between vaginal microbiota and preterm birth, and some have found an association while others have not. We performed a study designed to determine whether there is an association with vaginal microbiota and/or placental microbiota and preterm birth in an African setting. METHODS: Women presenting to the study hospital in labor with a gestational age of 26 to 36 weeks plus six days were prospectively enrolled in a study of the microbiota in preterm labor along with controls matched for age and parity. A vaginal sample was collected at the time of presentation to the hospital in active labor. In addition, a placental sample was collected when available. Libraries were constructed using PCR primers to amplify the V6/V7/V8 variable regions of the 16S rRNA gene, followed by sequencing with an Illumina MiSeq machine and analysis using QIIME2 2022.2. RESULTS: Forty-nine women presenting with preterm labor and their controls were enrolled in the study of which 23 matched case-control pairs had sufficient sequence data for comparison. Lactobacillus was identified in all subjects, ranging in abundance from < 1% to > 99%, with Lactobacillus iners and Lactobacillus crispatus the most common species. Over half of the vaginal samples contained Gardnerella and/or Prevotella; both species were associated with preterm birth in previous studies. However, we found no significant difference in composition between mothers with preterm and those with full-term deliveries, with both groups showing roughly equal representation of different Lactobacillus species and dysbiosis-associated genera. Placental samples generally had poor DNA recovery, with a mix of probable sequencing artifacts, contamination, and bacteria acquired during passage through the birth canal. However, several placental samples showed strong evidence for the presence of Streptococcus species, which are known to infect the placenta. CONCLUSIONS: The current study showed no association of preterm birth with composition of the vaginal community. It does provide important information on the range of sequence types in African women and supports other data suggesting that women of African ancestry have an increased frequency of non-Lactobacillus types, but without evidence of associated adverse outcomes.

Streptococcus agalactiae cadD alleviates metal stress and promotes intracellular survival in macrophages and ascending infection during pregnancy.

Perinatal infection with Streptococcus agalactiae, or Group B Streptococcus (GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional analyses of GBS-macrophage co-cultures reveal enhanced expression of a gene encoding a putative metal resistance determinant, cadD. Deletion of cadD reduces GBS survival in macrophages, metal efflux, and resistance to metal toxicity. In a mouse model of ascending infection during pregnancy, the ΔcadD strain displays attenuated bacterial burden, inflammation, and cytokine production in gestational tissues. Furthermore, depletion of host macrophages alters cytokine expression and decreases GBS invasion in a cadD-dependent fashion. Our results indicate that GBS cadD plays an important role in metal detoxification, which promotes immune evasion and bacterial proliferation in the pregnant host.

Oral cleaning habits and the copy number of periodontal bacteria in pregnant women and its correlation with birth outcomes: an epidemiological study in Mibilizi, Rwanda.

BACKGROUND: Since 1996, many studies have reported that periodontal disease during pregnancy may be a risk factor for preterm birth and low birth weight; however, in Africa, periodontal disease is considered a non-high-priority disease. In addition, there are few dental facilities in rural Rwanda; thus, the oral condition of pregnant women has not been investigated. The objective of this study was to assess the tooth brushing habits of pregnant women in rural Rwanda and evaluate whether periodontal bacteria in the oral cavity of pregnant women are related to birth outcomes or oral cleaning habits. METHODS: A questionnaire survey and saliva collection were conducted for pregnant women in the catchment area population of Mibilizi Hospital located in the western part of Rwanda. Real-time PCR was performed to quantitatively detect total bacteria and 4 species of periodontal bacteria. The relationship of the copy number of each bacterium and birth outcomes or oral cleaning habits was statistically analyzed. RESULTS: Among the participants, high copy numbers of total bacteria, Tannerella forsythia, and Treponema denticola were correlated with lower birth weight (p = 0.0032, 0.0212, 0.0288, respectively). The sex ratio at birth was higher in women who had high copy numbers of Porphyromonas gingivalis and T. denticola during pregnancy (p = 0.0268, 0.0043). Furthermore, regarding the correlation between oral cleaning habits and the amount of bacteria, the more frequently teeth were brushed, the lower the level of P. gingivalis (p = 0.0061); the more frequently the brush was replaced, the lower the levels of P. gingivalis and T. forsythia (p = 0.0153, 0.0029). CONCLUSIONS: This study suggested that improving tooth brushing habits may reduce the risk of periodontal disease among pregnant women in rural Rwanda. It also indicated that the amount of bacteria is associated with various birth outcomes according to the bacterial species. Both access to dental clinics and the oral cleaning habits of pregnant women should be important considerations in efforts to alleviate reproductive-related outcomes in rural Africa.

Periodontal disease is known to cause many complications. For instance, pregnant women with periodontal disease are at increased risk of preterm birth and delivering low-birth-weight infants. However, the importance of oral care during pregnancy is not an important consideration in rural Africa, where preterm birth rates and low-birth-weight rates are particularly high. Moreover, even the oral hygiene status of pregnant women has not been assessed in such areas. In this study, we focused on the amount of periodontal bacteria that cause periodontal disease and investigated the relationship between the amount of bacteria and birth outcomes. Our findings indicate that tooth brushing guidance for pregnant women and improved access to dental clinics in rural Africa may contribute to reduced rates of preterm birth and low birth weight.

Pathogenic microbe detection in placental tissues supports placental pathobiome association with preterm birth risk in Pakistani women: A brief snapshot.

Preterm birth (PTB) poses great risk to neonatal health in Pakistan with few tertiary health care facilities. Role of intrauterine microbiome in maintaining healthy pregnancy has been highlighted. However, there is ongoing debate whether a true placental microbiome exist. We analyzed placental and vaginal microbiome through V3-V4 16srRNA sequencing and observed increased abundance of proteobacteria, with concomitant decline in the firmicutes population in preterm vagina. Simplistic placental microflora included many environmental microbes with PTB placenta carrying pathogenic microbes like ureaplasma and mycoplasma species. We observed contribution of environmental, vaginal and skin contamination in term versus pathobiome signatures in preterm placenta.

Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth.

Ureaplasma and Prevotella infections are well-known bacteria associated with preterm birth. However, with the development of metagenome sequencing techniques, it has been found that not all Ureaplasma and Prevotella colonizations cause preterm birth. The purpose of this study was to determine the association between Ureaplasma and Prevotella colonization with the induction of preterm birth even in the presence of Lactobacillus. In this matched case-control study, a total of 203 pregnant Korean women were selected and their cervicovaginal fluid samples were collected during mid-pregnancy. The microbiome profiles of the cervicovaginal fluid were analyzed using 16S rRNA gene amplification. Sequencing data were processed using QIIME1.9.1. Statistical analyses were performed using R software, and microbiome analysis was performed using the MicrobiomeAnalyst and Calypso software. A positive correlation between Ureaplasma and other genera was highly related to preterm birth, but interestingly, there was a negative correlation with Lactobacillus and term birth, with the same pattern observed with Prevotella. Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth, although Ureaplasma and Prevotella are associated with preterm birth. Balanced colonization between Lactobacillus and Ureaplasma and Prevotella is important to prevent preterm birth.

Vaginal Microbiota Is Stable and Mainly Dominated by Lactobacillus at Third Trimester of Pregnancy and Active Childbirth: A Longitudinal Study of Ten Mexican Women.

In healthy women at reproductive age, the vaginal microbiota is mainly dominated by Lactobacillus bacteria during pregnancy and non-pregnancy stages. However, little is known about longitudinal changes within the vaginal microbiota composition from the third trimester of pregnancy to childbirth in healthy women. Thus, we conducted an exploratory longitudinal study of vaginal microbiota composition of 10 Mexican pregnant women, sampling from the same volunteer at two-time points: third trimester of pregnancy and active childbirth. Vaginal bacterial microbiota was characterized by V3-16S rDNA libraries by high-throughput sequencing and bioinformatics methods. Out of ten, vaginal microbiota from eight women was dominated by the Lactobacillus genus at both time points, whereas the other two women showed vaginal microbiota composition with high abundance of genera Gardnerella, Prevotella, and members of the Atopobiaceae family, without any preterm birth correlation. Importantly, we found no statistically significant differences in relative abundances, absolute reads count, alpha and beta diversity between the third trimester of pregnancy, and active childbirth time points. However, compared to the third trimester of pregnancy, we observed a trend with higher absolute reads counts for Gardnerella, Faecalibaculum, Ileibacterium, and Lactococcus genus at active childbirth and lower absolute reads count of Lactobacillus genus. Our results suggest that the vaginal microbiota composition is stable, and Lactobacillus genus is the dominant taxa in Mexican women's vagina at the third trimester of pregnancy and childbirth.

Abnormal vaginal flora correlates with pregnancy outcomes: A retrospective study from 737 pregnant women.

OBJECTIVE: Abnormal vaginal flora (AVF) is a common cause of vulvovaginal symptoms in women. This study aims to investigate the prevalence of AVF in pregnant women and assess associations between diverse AVF subtypes and pregnancy outcomes. METHODS: This study retrospectively collected clinical data of pregnant women who had vaginal flora tests (VFT) between January 2015 and December 2018 in the First Affiliated Hospital of Xi'an Jiaotong University. AVF were defined into different subtypes according to the results of VFT, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), aerobic bacteria (AV), cytolytic vaginosis (CV), and trichomoniasis. Pregnancy outcomes included gestational age at delivery, preterm birth (PTB), premature rupture of membranes (PROM), and infant birth weight. Student's t-test and Fisher's exact test was used for analyses using SPSS 22.0. P < 0.05 was considered as statistical significance. RESULTS: A total of 737 pregnant women were included in this study. Pregnant women in AVF group suffered more PROM than women in normal vaginal flora (NVF) group (18.8% [33/176] vs 10.6% [32/302], P = 0.012); pregnant women with BV (31.3% [5/16] vs 10.6% [32/302], P = 0.018) and mixed vaginitis (55.6% [5/9] vs 10.6% [32/302], P = 0.001) had higher PROM rates than women in the NVF group. In addition, pregnant women in NVF and AVF groups had similar PTB rates (5.0% [15/302] vs 3.5% [32/302], P = 0.38). CONCLUSIONS: AVF, including BV and Mixed vaginitis, augments PROM risk in pregnant women, demonstrating the need for vaginal flora examination during pregnancy.

Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response.

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1ß and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.

Variation of the Vaginal Microbiome During and After Pregnancy in Chinese Women.

A comprehensive profiling of the vaginal microbial communities and their variability enables an accurate description of the microbiome in women. However, there is a lack of studies available on Chinese women. In the present study, the composition of the vaginal microbiota during pregnancy and the 6-week postpartum period of 454 Chinese women was characterized by sequencing the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The vaginal microbiome showed variations during pregnancy and the postpartum period based on the abortion history, hypertensive disorders, delivery mode, and maternal age. Co-variation of 22 bacterial taxa, including the Lactobacillus genus and two of its species, may account for the common characteristics of the vaginal microbiome under scenarios of different medical histories and pregnancy outcomes. In contrast, discriminant bacterial species were significantly different between women who had preterm birth (PTB) with and without premature rupture of membranes (PROM), and the community state type (CST) IV-A without any predominant Lactobacillus species in the microbiota was more prevalent during pregnancy in the PROM-PTB cases, suggesting that specific bacterial species could be considered to distinguish between different types of PTB. By providing data on Chinese women, this study will enrich the knowledge of the human microbiome and contribute to a better understanding of the association between the vaginal microbiome and reproductive health.

A non-optimal cervicovaginal microbiota in pregnancy is associated with a distinct metabolomic signature among non-Hispanic Black individuals.

Biomechanical and molecular processes of premature cervical remodeling preceding spontaneous preterm birth (sPTB) likely result from interactions between the cervicovaginal microbiota and host immune responses. A non-optimal cervicovaginal microbiota confers increased risk of sPTB. The cervicovaginal space is metabolically active in pregancy; microbiota can produce, modify, and degrade metabolites within this ecosystem. We establish that cervicovaginal metabolomic output clusters by microbial community in pregnancy among Black individuals, revealing increased metabolism within the amino acid and dipeptide pathways as hallmarks of a non-optimal microbiota. Few differences were detected in metabolomic profiles when stratified by birth outcome. The study raises the possibility that metabolites could distinguish women with greater risk of sPTB among those with similar cervicovaginal microbiota, and that metabolites within the amino acid and carbohydrate pathways may play a role in this distinction.

Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth.

The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.

Complex species and strain ecology of the vaginal microbiome from pregnancy to postpartum and association with preterm birth.

BACKGROUND: Lactobacillus was described as a keystone bacterial taxon in the human vagina over 100 years ago. Using metagenomics, we and others have characterized lactobacilli and other vaginal taxa across health and disease states, including pregnancy. While shifts in community membership have been resolved at the genus/species level, strain dynamics remain poorly characterized. METHODS: We performed a metagenomic analysis of the complex ecology of the vaginal econiche during and after pregnancy in a large U.S. based longitudinal cohort of women who were initially sampled in the third trimester of pregnancy, then validated key findings in a second cohort of women initially sampled in the second trimester of pregnancy. FINDINGS: First, we resolved microbial species and strains, interrogated their co-occurrence patterns, and probed the relationship between keystone species and preterm birth outcomes. Second, to determine the role of human heredity in shaping vaginal microbial ecology in relation to preterm birth, we performed a mtDNA-bacterial species association analysis. Finally, we explored the clinical utility of metagenomics in detection and co-occurrence patterns for the pathobiont Group B Streptococcus (causative bacterium of invasive neonatal sepsis). CONCLUSIONS: Our highly refined resolutions of the vaginal ecology during and post-pregnancy provide insights into not only structural and functional community dynamics, but highlight the capacity of metagenomics to reveal finer aspects of the vaginal microbial ecologic framework. FUNDING: NIH-NINR R01NR014792, NIH-NICHD R01HD091731, NIH National Children's Study Formative Research, Burroughs Wellcome Fund Preterm Birth Initiative, March of Dimes Preterm Birth Research Initiative, NIH-NIGMS (K12GM084897, T32GM007330, T32GM088129).

Probiotic lactobacilli in formulas and hygiene products for the health of the urogenital tract.

Lactobacilli are the predominant microorganisms of the healthy human vagina. A novel alternative for the prevention and treatment of female urogenital tract infections (UGTI) is the inclusion of these microorganisms as active pharmaceutical ingredients in probiotic formulas, and more recently in female hygienic products. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host." A list of requirements must be considered during the development of probiotic product/formula for the female urogenital tract (UGT). This review aims to resume the requirements, probiotic characteristics, and clinical trial applied to determine the effect of probiotic and potentially probiotic strains on different woman's physiological and pathological conditions, and in preterm birth prevention. A revision of female hygienic products available in the world market is included, together with novel studies applying nanotechnology for Lactobacillus incorporation in hygienic products. Further studies and well-designed clinical trials are urgently required to complement the current knowledge and applications of probiotics in the female UGT. The use of probiotic formulas and products will improve and restore the ecological equilibrium of the UGT microbiome to prevent and treat UGTI in women under different conditions.