Affective symptoms in pregnancy are associated with the vaginal microbiome.

BACKGROUND: Composition of the vaginal microbiome in pregnancy is associated with adverse maternal, obstetric, and child health outcomes. Therefore, identifying sources of individual differences in the vaginal microbiome is of considerable clinical and public health interest. The current study tested the hypothesis that vaginal microbiome composition during pregnancy is associated with an individual's experience of affective symptoms and stress exposure. METHODS: Data were based on a prospective longitudinal study of a medically healthy community sample of 275 mother-infant pairs. Affective symptoms and stress exposure and select measures of associated biomarkers (diurnal salivary cortisol, serum measures of sex hormones) were collected at each trimester; self-report, clinical, and medical records were used to collect detailed data on socio-demographic factors and health behavior, including diet and sleep. Vaginal microbiome samples were collected in the third trimester (34-40 weeks) and characterized by 16S rRNA sequencing. Identified taxa were clustered into three community clusters (CC1-3) based on dissimilarity of vaginal microbiota composition. RESULTS: Results indicate that depressive symptoms during pregnancy were reliably associated with individual taxa and CC3 in the third trimester. Prediction of functional potential from 16S taxonomy revealed a differential abundance of metabolic pathways in CC1-3 and individual taxa, including biosynthetic pathways for serotonin and dopamine. We did not find robust evidence linking symptom- and stress-related biomarkers and CCs. CONCLUSIONS: Our results provide further evidence of how prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem that may be important for understanding maternal and child health outcomes.

Impact of postsurgical vaginal microbiome on high-risk HPV infection and recurrence risk in patients with cervical cancer and intraepithelial neoplasia: A retrospective study.

Purpose: This study aimed to determine the effect of postsurgical vaginal microbiome (VM) on high-risk human papillomavirus (hrHPV) infection and the risk of disease recurrence in patients surgically treated for cervical cancer (CC) or intraepithelial neoplasia (CIN). Methods: 207 women who underwent surgical treatment for CC or CIN at the Department of Gynecologic Oncology of the First Affiliated Hospital of University of Science and Technology of China from November 2016 to October 2023 were included. The patients' clinical data, including age, surgical modality, and diagnosis at time of index surgery, were collected retrospectively and analyzed. Associations between postsurgical VM indices, hrHPV infection, cervical cytology, and recurrence were also evaluated. Results: Patient age, surgical modality (whether complete excision of the cervix was performed), and diagnosis at time of index surgery (cervical dysplasia vs. cervical carcinoma) showed no significant association with postsurgical hrHPV infection, cervical cytology, or disease recurrence. However, postsurgical VM imbalance was significantly associated with hrHPV infection status (OR = 4.640, 95 % CI = 2.085-10.460, P < 0.001), abnormal cervical cytology (OR = 3.994, 95 % CI = 1.154-13.826, P = 0.020), and disease recurrence (OR = 3.789, 95 % CI = 1.091-13.154, P = 0.026). Among the specific VM indices, a vaginal pH above 4.5 (OR = 4.570, 95 % CI = 1.640-12.690, P = 0.002), a lactobacilli proportion below 50 % (OR = 3.938, 95 % CI = 1.299-11.934, P = 0.010), and the presence of aerobic vaginitis (AV, OR = 2.425, 95 % CI = 0.996-5.901, P = 0.046) were risk factors for postsurgical recurrence. Conclusion: Postsurgical VM imbalance, especially abnormal indices, such as a pH above 4.5, a lactobacilli proportion below 50 %, and the presence of AV, was associated with an increased risk of postsurgical recurrence in patients who underwent surgical treatment for CIN and CC. Monitoring and potentially intervening in the VM may improve the prognosis of these patients.

Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections.

The healthy cervicovaginal microbiota is dominated by various Lactobacillus species, which support a condition of eubiosis. Among their many functions, vaginal lactobacilli contribute to the maintenance of an acidic pH, produce antimicrobial compounds, and modulate the host immune response to protect against vaginal bacterial and fungal infections. Increasing evidence suggests that these beneficial bacteria may also confer protection against sexually transmitted infections (STIs) caused by viruses such as human papillomavirus (HPV), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Viral STIs pose a substantial public health burden globally, causing a range of infectious diseases with potentially severe consequences. Understanding the molecular mechanisms by which lactobacilli exert their protective effects against viral STIs is paramount for the development of novel preventive and therapeutic strategies. This review aims to provide more recent insights into the intricate interactions between lactobacilli and viral STIs, exploring their impact on the vaginal microenvironment, host immune response, viral infectivity and pathogenesis, and highlighting their potential implications for public health interventions and clinical management strategies.

Effect of Waiting Period on Initial Adverse Vaginal Microbiome Composition in IVF-ICSI Patients.

Background/Objectives: In this observational prospective cohort study, conducted at the Fertility Centre of the University Hospital, Duesseldorf Germany, the spontaneous reversal capacity and the effect of waiting time on an adverse vaginal microbiome profile in subfertile patients were investigated. Methods: Vaginal swabs of 76 patients were obtained before starting a fertility treatment using a commercially available test to perform a microbiome analysis. Patients with a favorable microbiome profile ("medium" or "high profile") according to the manufacturer's algorithm proceeded with the fertility treatment. Patients with an unfavorable microbiome profile ("low profile") postponed their fertility treatment and were sampled up to four times in each successive cycle or until a shift to a more favorable profile was detected. Results: Initially, 54/76 subjects had a high or medium profile and 23/76 had a low profile. Within 3 months, 75% of patients with an initial low profile shifted to a more favorable profile (7/23 dropouts). The presence of Lactobacillus crispatus in the initial sample was associated with a higher likelihood of a spontaneous shift to a more favorable profile. Conclusions: The vaginal microbiome is subject to strong fluctuations. Even an unfavorable microbiome profile can develop into a favorable microbiome profile within a few months without treatment.

Is there an association between vaginal microbiome community state types and diversity and preterm birth: A non-systematic literature review.

Worldwide, preterm birth (PTB) is a significant cause of neonatal mortality and morbidity. Surprisingly, the rate of PTB in the United States is among the top 10 nations in the world, comparable to those of the Democratic Republic of the Congo, Bangladesh, India, and Nigeria. However, there is no predictive biomarker or understanding of the mechanisms of PTB. Recent evidence suggests that the vaginal microbiome can be clustered into Community State Types (CST) and is altered in various obstetrical syndromes. The review aimed to summarize multiple studies on the vaginal microbiome and PTB and identify a particular microbe or CST associated with PTB. We hypothesized that there exists a specific microorganism that, when dominant within the vaginal microbiome, is protective against PTB. We hypothesized that the absence of a particular microbe or CST is a risk factor for PTB. To answer this question, we reviewed the current literature aiming to identify such a microorganism or a group of microorganisms. Our results indicate that no particular microbe or CST can be implicated in PTB. However, the review suggests that an increase in alpha and beta diversity of the vaginal microbiome can be predictive and involved in the pathogenesis of PTB.

Vaginal microbiota stability over 18 months in young student women in France.

PURPOSE: Non-optimal vaginal microbiota lacking lactobacilli and comprising a wide array of anaerobic bacteria, typified by community state type (CST) IV, have been associated with adverse gynecological and pregnancy outcomes. Here, we investigate the stability of the vaginal microbiota sampled every 6 months over 18 months and how samples distantly collected combined with exposures could provide insight on future microbiota compositional changes. METHODS: Vaginal microbiota dynamics were analyzed in 241 female students aged 18-24 years and negative for Chlamydia trachomatis and Neisseria gonorrhoeae. The vaginal microbiota was characterized using 16S rRNA gene amplicon sequencing and assigned to CSTs. Vaginal microbiota longitudinal profiles were determined through hierarchical clustering. RESULTS: At baseline, 11.2% of participants had a CST IV, 40.5% a CST I (Lactobacillus crispatus-dominated), and 38.1% a CST III (Lactobacillus iners-dominated). A total of 345 CST transitions were observed over the study period. Pain during sexual intercourse was associated with a higher probability of transition from CST III to CST IV, while self-reported yeast infection was associated with a higher probability of transition from CST IV to CST I. Over the study period, 32.0% participants displayed a stable CST trajectory. Composition of the vaginal microbiota of a single sample predicted with good accuracy the CST trajectory over the following 18 months. CONCLUSION: Vaginal longitudinal CST patterns over 18 months could be clustered into three main groups of trajectories. Performing molecular characterization at a single time point could contribute to improved preventive care and optimization of young women's reproductive and sexual health. CLINICALTRIALS: gov Identifier: NCT02904811. Registration date: September 19, 2016.

Synbiotics in patients at risk for spontaneous preterm birth: protocol for a multi-centre, double-blind, randomised placebo-controlled trial (PRIORI).

BACKGROUND: Prematurity remains one of the main causes of neonatal morbidity and mortality. Approximately two thirds of preterm births are spontaneous, i.e. secondary to preterm labour, preterm prelabour rupture of membranes (PPROM) or cervical insufficiency. Etiologically, the vaginal microbiome plays an important role in spontaneous preterm birth (sPTB). Vaginal dysbiosis and bacterial vaginosis are well-known risk factors for ascending lower genital tract infections and sPTB, while a Lactobacillus crispatus-dominated vaginal microbiome is associated with term deliveries. Synbiotics may help to achieve and/or maintain a normal, Lactobacillus-dominated vaginal microbiome. METHODS: We will perform a multi-centre, double-blind, randomised, placebo-controlled trial. Women aged 18 years or older with a singleton pregnancy are eligible for inclusion at 80/7-106/7 weeks gestational age if they have one or more of the following risk factors for sPTB: previous sPTB at 240/7-356/7 weeks, prior PPROM before 360/7 weeks, or spontaneous pregnancy loss at 140/7-236/7 weeks of gestation. Exclusion criteria are multiple gestation, cervix conisation, inflammatory bowel disease, uterine anomaly, and the use of pro-/pre-/synbiotics. Patients will be randomised to oral synbiotics or placebo, starting before 11 weeks of gestation until delivery. The oral synbiotic consists of eight Lactobacillus species (including L. crispatus) and prebiotics. The primary outcome is the gestational age at delivery. Vaginal microbiome analysis once per trimester (at approximately 9, 20, and 30 weeks) and delivery will be performed using metataxonomic sequencing (16S rRNA gene) and microbial culture. Secondary outcomes include PPROM, the use of antibiotics, antenatal admission information, and neonatal outcomes. DISCUSSION: This study will evaluate the effect of oral synbiotics on the vaginal microbiome during pregnancy in a high-risk population and correlate the microbial changes with the gestational age at delivery and relevant pregnancy outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05966649. Registered on April 5, 2024.

A Metagenomics Pipeline to Characterize Self-Collected Vaginal Microbiome Samples.

Vaginitis is a widespread issue for women worldwide, yet current diagnostic tools are lacking. Bacterial vaginosis (BV) is the most prevalent type of vaginitis, found in 10-50% of reproductive-aged women. Current diagnostic methods for BV rely on clinical criteria, microscopy, or the detection of a few microbes by qPCR. However, many vaginal infections lack a single etiological agent and are characterized by changes in the vaginal microbiome community structure (e.g., BV is defined as a loss of protective lactobacilli resulting in an overgrowth of anaerobic bacteria). Shotgun metagenomic sequencing provides a comprehensive view of all the organisms present in the vaginal microbiome (VMB), allowing for a better understanding of all potential etiologies. Here, we describe a robust VMB metagenomics sequencing test with a sensitivity of 93.1%, a specificity of 90%, a negative predictive value of 93.4%, and a positive predictive value of 89.6% certified by Clinical Laboratory Improvement Amendments (CLIA), the College of American Pathologist (CAP), and the Clinical Laboratory Evaluation Program (CLEP). We sequenced over 7000 human vaginal samples with this pipeline and described general findings and comparisons to US census data.

The In Vivo Effect of Water-Based Lubricants on the Vaginal Microbiome of Women from Varying Age Groups: Exploratory Analysis of a Randomized Controlled Trial.

Vaginal mucosa undergoes physiological changes across the lifespan, such as increased pH and reduced natural lubrication which are known to impact vaginal commensal microorganisms, hence increasing the chances of vaginal infections. An improved understanding of vaginal microbiome composition in different age groups and the effect of social behaviors, such as the use of personal lubricants, could facilitate the development of new strategies to maintain good vaginal health. The objective of this study was to assess the effect of water-based lubricants on the human vaginal microbiome. Fifty females from three age groups (18-29, 30-44, and 45-65 years) with mild-to-moderate vaginal dryness were randomized to one of five lubricants (four of which were formulated to meet expert guidance on osmolality and pH). Subjects entered the study at tolerance or treatment phase (vaginal intercourse minimum once a week using assigned lubricant). Four vaginal swabs per participant were sampled during pre-("baseline"), post-first ("2 h", "24 h") and post-last ("4 weeks") lubricant application to assess bacterial and fungal diversity via amplicon sequencing. Vaginal pH and relative humidity were measured at baseline, 2 h, and 24 h post-lubricant application. Relative bacteriome abundance was statistically compared between timepoints for each lubricant group. Vaginal moisture, age, BMI, and pH were correlated with bacteriome relative abundance. Lactobacilli and Gardnerella sp. Were predominant across participants. Repeated lubricant application did not significantly alter the vaginal bacteriome during 4 weeks of product use (p > 0.05) when measured by relative abundance and alpha-diversity index. Bacteriome diversity and abundance differed significantly between age groups at baseline whereas lactobacilli relative abundance was negatively associated with age and vaginal pH.

A Cross-Sectional Comparative Study of Vaginal Microbiota and Spontaneous Abortion at a Tertiary Care Hospital in North Karnataka, India.

OBJECTIVE: To compare the vaginal microbiome in women who have undergone spontaneous abortion with a gestational age of less than 20 weeks to that of women who have a continued pregnancy of the same gestational age. DESIGN: Cross-sectional comparative research design. SETTING: The study was conducted in a tertiary care hospital of North Karnataka, India. In this rural area, many women lack awareness of prenatal care and women's health information. Given rising rates of spontaneous abortion, studying the impact of the vaginal microbiome on pregnancy outcomes is crucial for raising local awareness. PARTICIPANTS: Two hundred women; 100 experienced spontaneous abortion within 20 weeks' gestation, and 100 maintained pregnancy with the same gestational age. MEASURES: Vaginal swab was used to detect participants' vaginal microbiota. DNA was extracted from the vaginal samples; the 16S ribosomal RNA sequencing method was used to identify the organisms present. RESULTS: A pathogen detection rate of 13.15% (n = 200 women) was found in vaginal cultures. The percentages of bacterial detection in women who had spontaneous abortion and those whose pregnancies continued were 19.9% and 7.9%, respectively (p < .05). Compared to women who sustained their pregnancy, women who experienced spontaneous abortion had five common species: Escherichia coli (48%), Enterococcus faecalis (28%), Enterococcus faecium (12%), Pseudomonas fluorescens (7%), and Pseudomonas cedrina (5%); the most prevalent species among those with sustained pregnancy were Lactobacillus iners (58%), Lactobacillus crispatus (32 %), and E. coli (10%; p < .05). CONCLUSION: The vaginal microbiomes of women with spontaneous abortion were more varied and irregularly distributed with bacteria. The bacteria identified could affect a woman's pregnancy outcome and perhaps be associated with spontaneous abortion. It is vital for nurses to provide education to women who are in the fertile period regarding prenatal screening, sexually transmitted infections, and perineal care.