Vaginitis Research Articles

Gartner\'s Duct Cyst in Recurrent Vaginal Infection: A Case Report

Gartner\'s Duct Cyst in Recurrent Vaginal Infection: A Case Report

Multiplex antimicrobial activities of the self-assembled amphiphilic polypeptide β nanofiber KF-5 against vaginal pathogens

BackgroundVaginal infections caused by multidrug-resistant pathogens such as Candida albicans and Gardnerella spp. represent a significant health challenge. Current treatments often fail because of resistance and toxicity. This study aimed to synthesize and characterize a novel amphiphilic polypeptide, KF-5, and evaluate its antibacterial and antifungal activities, biocompatibility, and potential mechanisms of action.ResultsThe KF-5 peptide was synthesized via solid-phase peptide synthesis and self-assembled into nanostructures with filamentous and hydrogel-like configurations. Characterization by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) confirmed the unique nanostructural properties of KF-5. KF-5 (125, 250, or 500 µg/ml) demonstrated potent antibacterial and antifungal activities, with significant inhibitory effects on drug-resistant Candida albicans and Gardnerella spp. (P < 0.05). In vitro assays revealed that 500 µg/ml KF-5 disrupted microbial cell membranes, increased membrane permeability, and induced lipid oxidation, leading to cell death (P < 0.05). Cytotoxicity tests revealed minimal toxicity in human vaginal epithelial cells, keratinocytes, and macrophages, with over 95% viability at high concentrations. Molecular dynamics simulations indicated that KF-5 interacts with phospholipid bilayers through electrostatic interactions, causing membrane disruption. In vivo studies using a mouse model of vaginal infection revealed that 0.5, 1, and 2 mg/ml KF-5 significantly reduced fungal burden and inflammation, and histological analysis confirmed the restoration of vaginal mucosal integrity (P < 0.01). Compared with conventional antifungal treatments such as miconazole, KF-5 exhibited superior efficacy (P < 0.01).ConclusionsKF-5 demonstrates significant potential as a safe and effective antimicrobial agent for treating vaginal infections. Its ability to disrupt microbial membranes while maintaining biocompatibility with human cells highlights its potential for clinical application. These findings provide a foundation for further development of KF-5 as a therapeutic option for combating drug-resistant infections.

Regulate the Risk Factors of Pseudomonas aeruginosa by some of Sigma Factor Genes

In this research, a study was conducted isolating and identification of Pseudomonas aeruginosa bacteria from clinical samples from various pathological conditions such as burns , otitis media , urinary tract infection , wounds, eye infection, blood infection, catheter infection, throat , vaginal infection and surgical. The present study includes 313 samples collected from patients who attend Alsader Medical City and Al- Hakim General Hospital during the period extended From September 2023 to December 2023 ( men and women ) with age groups between (1 -77) years. The identification of bacterial isolates were detected by classical and molecular technique (PCR), were the frequency among males 163 (52.07% ) was more than that in female 150 (47.92). The samples distribution is made according age group , it appears high for the following high (15.97) and (12.77) with group (16-30) years of male and female respectively . The results revealed that 57/313 specimens of the total number of samples are Pseudomonas aeruginosa by identified according to their morphological, physiological and biochemical properties. Also with molecular identification by using four primers wre the results showed 16S rRNA gene was detected in 57/57 (100%) P. aeruginosa isolates , the Las biofilm gene was detected in 43/57 (75.43%) , the algD gene was detected in 41/57 (71.92%) and 41/57 samples show positive results with the oprL gene. Six types of antibiotics were also tested to determine the resistance of the samples to them.

Perinatal and Demographic Risk Factors Associated with Autism Spectrum Disorder: A National Survey of Potential Predictors and Severity.

INTRODUCTION: This study investigates autism spectrum disorders (ASD) in Greece, focusing on estimating prevalence and identifying regional disparities in children aged 4 to 7 years. MATERIALS AND METHODS: Utilizing a quantitative, descriptive, and exploratory methodology, the research employed a structured questionnaire to gather extensive maternal and child health data. RESULTS: The sample consisted of 517 mothers of children diagnosed with ASD from all over Greece, contributing to a nuanced understanding of ASD predictors. This study aims to elucidate the role of prenatal factors in the likelihood of an ASD diagnosis and their impact on the subsequent functionality of children with ASD. The study identified significant predictors of lower functionality in children with ASD, including higher maternal age, delayed ASD diagnosis, lower family income, and higher birth order. Prenatal health issues, such as vaginal bleeding and infections, also influenced functional outcomes. Notably, a family history of neurological or psychiatric conditions appeared protective. DISCUSSION: The regression model demonstrated robust predictive power, underscoring the complexity of genetic, environmental, and socioeconomic factors in ASD development. The findings advocate for early diagnosis and intervention, systematic screening, and addressing socioeconomic disparities to improve functional outcomes. The results support evidence-based service development and policy adjustments to enhance early identification, intervention, and rehabilitation for children with ASD. CONCLUSIONS: Establishing standardized case-recording procedures and an ASD register at national and regional levels is recommended for systematic monitoring and resource evaluation.

Vaginal lactobacilli produce anti-inflammatory β-carboline compounds.

The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV). We have identified that Lactobacillus crispatus, a key vaginal bacterial species, produces a family of β-carboline compounds with anti-inflammatory activity. These compounds suppress nuclear factor κB (NF-κB) and interferon (IFN) signaling downstream of multiple pattern recognition receptors in primary human cells and significantly dampen type I IFN receptor (IFNAR) activation in monocytes. Topical application of an anti-inflammatory β-carboline compound, perlolyrine, was sufficient to significantly reduce vaginal inflammation in a mouse model of genital herpes infection. These compounds are enriched in cervicovaginal lavage (CVL) of healthy people compared with people with BV. This study identifies a family of compounds by which vaginal lactobacilli mediate host immune homeostasis and highlights a potential therapeutic avenue for vaginal inflammation.

Assessing the Effectiveness of Wet Mount and PCR Methods in Diagnosing Trichomonas vaginalis Infections in Endocervical and Urine samples

Trichomonas vaginalis is the cause of trichomonas’s infection, which is referred to be the global sexually transmitted disease (STD) worldwide. This parasite primarily spreads through sexual activity, though it can also spread through intimate. Vaginal inflammation in females causes a variety of clinical symptoms, such as a profusion of greenish-yellow, frothy, foul-smelling discharge, valvar enlargement, itching, and punctate erythematous lesions of the cervix, commonly referred to as "strawberry cervix." There are numerous scenarios in which women may be sick but not exhibit any symptoms. The purpose of the current study is to compare the diagnostic efficacy of polymerase chain reaction (PCR) and wet mount preparation for detecting T. vaginalis in various sample types, including endocervical discharge, endocervical swabs, and urine, of 300 female patients (married and single), ages ranging from 15 to 62, who were referred to Dohuk Maternity Hospital, Shariya Camp, either inside or outside of Dohuk city. Based on the clinical symptoms of the patients, the diagnosis of parasite infection was validated by microscopically confirming the infection in the laboratory using two methods: PCR and direct wet mount preparation. The study findings demonstrated, out of 240 samples, 61 (25.4%) at Dohuk Maternity Hospital and 15 (25%) out of 60 samples in Shariya Camp were contaminated with T. vaginalis. Of the 300 samples, 74 (24.6%) had wet mount preparation infection, and 75 (25.0%) had PCR infection. In the current study, 42 single women had 10 (23.8%) and 258 married women had 66 (25.5%) infected. The age range of 15 to 25 had a higher infection rate (32.8%).

Endowed Polyphenols in Advanced Delivery Systems for Vaginal Infections

Endowed Polyphenols in Advanced Delivery Systems for Vaginal Infections

Microbiological studies on Escherichia coli and Klebsiella pneumoniae causing vaginal and urinary tract inflammation; prevalence, antibiotics-resistance and natural products susceptibility

Great efforts have been made for controlling multidrug-resistant bacteria (MDR). The antibacterial activity of natural products is an effective strategy due to its beneficial effects on human health. This study focused on the isolation, identification, studying the prevalence and the susceptibility of Escherichia coli and Klebsiella spp. to some natural products. After isolation, the isolates primarily identified using biochemical and API tests. Then, the antibiotic susceptibility test was done to reveal the most antibiotics resistant isolates before further identification of Escherichia coli and Klebsiella pneumoniae using phoA and gyrA genes, respectively. Furthermore, the sensitivity of the most antibiotics resistant isolates to apple cider vinegar (ACV), garlic oil (GO), coconut oil (CNO), tea tree oil (TTO), and lavender oil (LO) was estimated. All tested extracts especially ACV and TTO showed good antibacterial activity against MRD selected isolates. Statistical analysis indicated that there was significant difference in ACV and TTO antibacterial response between Escherichia coli and Klebsiella pneumoniae whereas there was no significant difference between natural products activity when tested against Escherichia coli and Klebsiella pneumoniae seperatly. GC-MS spectroscopy analysis revealed the most prominent active constituents present in tested ACV and TTO. Analyzing the 16S rRNA sequence confirmed the two most MRD pathogenic isolates that showed sensitivity to ACV and TTO were Escherichia coli MS1 and Klebsiella pneumoniae MS47, respectively. Essential oils tea tree and apple cider vinegar showed good antibacterial activities against antibiotics-resistant Escherichia coli and Klebsiella pneumoniae causing vaginal and urinary tract inflammation.

B-117 Rapid Classification of Cleanliness Grades of Vaginal Discharge through Computational Analysis of SERS Spectra via Variational Auto-Encoder Model And Long Short-Term Memory Networks

Abstract Background Classification of cleanliness grades of vaginal discharge plays a pivotal role in clinical laboratories, serving as indicators for the presence of various vaginal infections such as bacterial vaginosis and candidal vulvovaginitis, etc. The conventional method for assessing vaginal discharge cleanliness involves manual microscopy, a technique susceptible to variations based on the examiner's expertise and subjective judgment, hindering the attainment of swift and accurate diagnoses. Methods This study introduces a novel approach by integrating Surface-Enhanced Raman Spectroscopy (SERS) with a deep learning algorithm for the rapid classification of vaginal discharge cleanliness grades. The proposed classification method combines the Variational Auto-Encoder (VAE) and Long Short-Term Memory (LSTM) to process SERS spectra. The quality of the training data is assessed using the signal-to-noise ratio (SNR) as a standard indicator. Results The application of the VAE-LSTM algorithm significantly enhances classification performance, providing swift and accurate results while reducing the required time. Comparative analyses with various classical machine learning algorithms and evaluation metrics reveal the superior predictive capability and time efficiency of the VAE-LSTM algorithm, demonstrating 100% accuracy and a fitting time of 2 seconds. Blind testing of SERS spectra collected from unknown patients further validates the reliability of the proposed method. Conclusions This study presents a promising and practical approach for the rapid classification of vaginal discharge cleanliness grades. The integration of the SERS technique with the VAE-LSTM algorithm not only ensures accuracy and efficiency in clinical diagnosis but also lays the foundation for advancements in non-invasive diagnostic technologies in gynecological healthcare.

Vaginal Tritrichomonas foetus infection in mice as an in vivo model for drug development against Trichomonas vaginalis.

Trichomonas vaginalis is the causative agent of the common sexually transmitted disease, trichomoniasis, which affects more than a hundred million people worldwide. Metronidazole and tinidazole, agents belonging to the 5-nitroheterocyclic class of antimicrobials, are most often used to treat infection, but increased resistance has been reported and adverse effects of these drugs can be significant. Consequently, an urgent need exists for the development of novel drug entities against trichomoniasis. Critical for antimicrobial drug development is the demonstration of in vivo efficacy. Murine models of vaginal T. vaginalis infection are unreliable for unknown reasons. Meanwhile, murine infections with the related bovine pathogen, Tritrichomonas foetus, tend to be more robust, although susceptibility to different antimicrobials might differ from T. vaginalis. Here, we explored the utility of T. foetus infection as a surrogate model for drug development against T. vaginalis. Four different T. foetus strains caused robust vaginal infection in young mice, while none of four diverse T. vaginalis strains did. Comparison of drug susceptibility profiles revealed that T. foetus and T. vaginalis were similarly susceptible to a range of 5-nitroheterocyclic and gold(I) compounds. By comparison, proteasome inhibitors were 10- to 15-fold less active against T. foetus than T. vaginalis, although one of the proteasome inhibitors, bortezomib, had low micromolar activity or better against multiple strains of both trichomonads. Different strains of T. foetus were used to demonstrate the utility of the murine vaginal infection models for in vivo efficacy testing, including for bortezomib and a gold(I) compound. The differences in susceptibility to proteasome inhibitors may be partially explained by differences in the proteasome subunit sequences between the two trichomonads, although the functional relevance of the proteasome was similar in both organisms. These findings indicate that T. foetus can serve as a reliable surrogate model for T. vaginalis in vitro and in murine infections in vivo, but caution must be exercised for specific drug classes with targets, such as the proteasome, that may display genetic divergence between the trichomonads.

Identifying changes in vaginal fluid using SERS: Advancing diagnosis of vulvovaginal candidiasis

Vaginal infections, medically termed vaginitis, encompass a spectrum of symptomatic presentations arising from disturbances within the vaginal microflora. The conventional diagnostic approach relies on microscopic examination of wet preparation of vaginal discharge, considered the ‘gold standard’ in clinical practice. Complementary to this, culture-based methodologies are often employed to reinforce diagnostic accuracy. However, challenges such as subjectivity in result interpretation, resource-intensive requirements regarding skilled personnel, and reagent utilization underscore the need for alternative diagnostic strategies.In this article, we demonstrate surface-enhanced Raman spectroscopy (SERS) and partial least squares regression (PLSR) techniques to elucidate the molecular signatures present in vaginal fluids, accounting for various influencing factors, including disruptions in the natural microflora, vaginal irrigation practices, and contraceptive usage. Furthermore, we investigated the spectral manifestations associated with vulvovaginal candidiasis (VVC) relative to control samples. Each clinical specimen underwent meticulous characterization encompassing microbial composition, pH levels, purity, and other pertinent parameters.Our findings unveil significant associations between extraneous inflammatory factors such as vaginal irrigation and diminished sample purity with alterations in SERS signals. Conversely, the day of the menstrual cycle phase exhibits negligible influence on spectral profiles. Notably, VVC samples demonstrated diverse spectral responses correlating with the abundance of pathogenic bacteria. These explorations hold promise in paving the path towards developing a novel intrinsic framework for the diagnosis of vaginitis.

Fetomaternal outcomes in vaginal discharge during pregnancy: A prospective comparative study

Background: Vaginal discharge (VD) is a common symptom in women during the reproductive period, especially during pregnancy. Pathological VD during pregnancy is an important public health concern because it has a sociopsychological impact on women and influences fetomaternal outcomes. Aims and Objectives: The study aims to estimate the prevalence of pathological discharge in pregnant women. The study also focuses on the demographic profile and various risk factors associated with pathological VDs and their consequences on fetal and maternal health. Materials and Methods: A prospective observational study was conducted in the Department of Obstetrics and Gynecology in a tertiary care center in Northern India. A total of 150 pregnant women with complaints of VD in the second and third trimesters with confirmation on speculum examination were recruited and evaluated for the etiology of discharge. Patients were followed until delivery and data regarding fetomaternal outcomes was collected. Results: The prevalence of pathological VD among enrolled women was 39.33% and various etiologies were candidiasis (15.33%), bacterial vaginosis (10.66%), aerobic vaginitis (8.67%), and trichomoniasis (4.67%). These infections were significantly related to pre-term delivery and pre-term pre-labor rupture of membranes. Furthermore, the incidence of prematurity, and low birth weight neonates requiring neonatal intensive care unit care was significantly high in babies born to mothers with pathological VD. Conclusion: Vaginal infections affect both maternal and neonatal health, thus, increasing the likelihood of poor perinatal outcomes. Hence, we propose that routine screening for pathological VD for all pregnant women should be introduced into standard antenatal care.

The association between lifestyle factors and the composition of the vaginal microbiota: a review.

The vaginal microbiota offers valuable insights into women's sexual health and the risk of developing sexually transmitted infections (STIs) and bacterial vaginosis. Despite the public health implications of changes in the vaginal environment, existing data on this topic remain sparse. Following the PRISMA statement guidelines, we consulted five bibliographic databases, focusing on five main daily habits and behaviors. We included only studies published up to October 2023, investigating the influence of personal hygiene, sexual behaviors, hormonal contraception, smoking, alcohol consumption, and psychosocial stress on the vaginal microbiota using next-generation sequencing. Based on our inclusion criteria, we incorporated 37 studies into this review. Hormonal contraception and personal hygiene were found to promote eubiosis of the vaginal microbiota. In contrast, sexual behaviors, smoking, alcohol consumption, and psychosocial stress were associated with an increased susceptibility to bacterial vaginosis, STIs, and severe pelvic inflammatory diseases due to a modified vaginal microbiota. Black ethnicity emerged as a confounding factor, with this population showing unstable vaginal microbiota. Oral contraception and a stable male sexual partner were found to favor Lactobacillus colonization, acting as a protective factor. Conversely, non-hormonal contraception and unprotected or non-penile/vaginal sexual activity increased the incidence of vaginal inflammation and bacterial vaginosis by disturbing the vaginal microbiota and reducing Lactobacillus abundance. Daily habits and lifestyle can influence the composition of the vaginal microbiota, thereby affecting vaginal health. Disturbances in the vaginal microbiota could be associated factors for STIs and vaginosis. Therefore, prioritizing more appropriate management of the vaginal microbiota is crucial.

Research progress of hydrogels in the prevention of pelvic inflammatory disease

AbstractPelvic inflammatory disease (PID) is a critical global health concern with the potential to lead to adverse outcomes, including infertility and chronic pelvic pain. Since PID is often caused by ascending vaginal infections or urinary tract infections, understanding the treatment of both is critical to preventing PID. Meanwhile, the emergence of drug‐resistant and persistently infected strains poses a growing challenge. This review discusses current clinical treatments for the prevention of PID from the physiologic basis of PID, as well as summarizes the advantages and research progress of hydrogels in the prevention of PID. In contrast to conventional treatments, hydrogels serve as excellent vehicles for vaginal drug delivery, maintaining the presence of the drug at the target site and controlling its release. In the context of urinary tract infections (UTIs), hydrogels are employed primarily as coatings on catheters to prevent and treat catheter‐associated UTIs. Finally, this review summarizes the limitations of hydrogels in PID prevention and future directions for development with the aim of elucidating avenues for clinical treatment of PID and informing further research.

Formulation Development of Mucoadhesive Vaginal Gel of Secnidazole and Voriconazole.

Purpose: Over the preceding decades, developing conventional drug delivery in to modified form has acquired importance in the pharmaceutical industry. Vaginal drug delivery system offers localized drug administration of drug and also avoids unwanted side effects of oral drug delivery. Vaginal drug delivery system has significant role in medical practice. Even though VDDS has a lot of advantages over the other routes of administration. The goal of developing the Mucoadhesive Vaginal Gel was to achieve the synergistic effect of voriconazole and secnidazole in the treatment of bacterial and fungal vaginal infections. Method: Mucoadhesive antimicrobial vaginal gel was optimised using Design expert software using Carbopol 934, HPMC K4M polymers. Result: Formulation was evaluated for various rheological parameters ,antimicrobial activity, invitro drug release and stability study. The spreadability and pH was found to be 5.5 to 7.4 cm and 4.12. Its compatible with vaginal pH. The selected optimized F8 formulation is the best formulation and the drug ratio is 2:1. and optimum gel viscosity is 1874 cps. antimicrobial study revealed that faster drug release of test formulation was compared to marketed product. It indicates as inhibition zone. Conclusion: The combination of drugs can serves as better option for treating vaginitis, compared to single drug formulation. Mucoadesion increases contact time of drug with affected area which rendered formulation more effective.

Abstract C017: Race-Specific Patterns of Vaginal Microbiome and HPV Infections Predict Risk of Precancerous Cervical Lesions

Abstract Background: Our previous research indicated that high-grade squamous intraepithelial lesions (HSIL), precursors to cervical cancer (CCa), are influenced by the vaginal microbiome (VMB) differentially by self-reported race. VMB enriched for certain anti-inflammatory Lactobacillus species confer protection against the risk of HSIL for white, but not Black women. Black women exhibit greater VMB diversity (associated with HPV tumorigenesis) and a lower prevalence of anti-inflammatory Lactobacillus species. But not all Black women with diverse VMB develop HSIL. Objective: Given HPV's essential role in cervical cancer, we aimed to assess the influence of sociodemographic, clinical, and microecological HPV attributes on HSIL risk within the context of the vaginal microbiome's variation by race. Methods: The VMB and HPV profiles of 1,168 women were analyzed alongside over 100 sociodemographic and clinical variables. Spearman’s correlation, Point-Biserial Correlation, chi-squared tests, and machine learning models, were employed to evaluate associations between sociodemographic, clinical, and microecological variables with HSIL, with a particular focus on the impact of race on these relationships. Results: The cohort was predominantly Black (72%), showing no significant race-based differences in HPV positivity (45%). However, HSIL incidence was nearly twice as high in Black (7%) compared to White women (4%). Women with HSIL had a higher prevalence of non-Lactobacillus-dominant VMB (68% vs. 51%) and were more likely to be HPV+ (73% vs. 44%) than those without HSIL. Co-infection with multiple HPV strains was associated with a higher risk of CIN3. Specifically, HPV16, HPV56, HPV58, HPV33, and HPV42 infections were significantly associated with higher CIN3 risks. The random forest model identified the relative abundance of Lactobacillus crispatus as the most essential factor in predicting CIN3 risk, followed by the number of HPV strains per sample. However, differential abundance analysis specifically indicated lower L. crispatus levels were associated with HSIL in white but not Black women. Conversely, HPV abundance was only associated with HSIL in Black women. Additionally, Black patients with 2 or more HPV co-infections had a higher likelihood of being diagnosed with CIN3+ compared to white counterparts. ML models highlighted different HPV-specific HSIL predictors by race: HPV number, and HPV 56, 16, and 33 in Blacks; sexual partners, HPV 90, 56, and 16 in whites. Conclusions: Our findings reveal race-specific interplays among individual risk factors, HPV infection, and VMB composition in HSIL development. The identification of key microbial and viral predictors highlights the importance of personalized approaches in preventing and managing HSIL, particularly among racially diverse populations. Citation Format: Katherine Y. Tossas, Bin Zhu, Katarzyna Tyc, Myrna Serrano, Jerome Strauss, Gregory Buck. Race-Specific Patterns of Vaginal Microbiome and HPV Infections Predict Risk of Precancerous Cervical Lesions [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C017.

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.

Synthetic bacterial consortia transplantation attenuates vaginal inflammation and modulates the immune response in a mouse model of Gardnerella vaginalis-induced bacterial vaginosis

This study aimed to evaluate the efficacy of synthetic bacterial consortia transplantation (SBCT) and compare it with VMT (vaginal microbiota transplantation) in a mouse model of Gardnerella vaginalis-induced Bacterial vaginosis (BV). A murine model of G. vaginalis-induced BV was established, and mice were treated with SBCT, VMT, or saline. Histopathological changes, inflammatory cytokine levels, pro-inflammatory biomarker expression, helper T cell transcription factor expression, and vaginal microbiota composition were assessed. SBCT and VMT effectively suppressed G. vaginalis growth, reduced inflammation, and restored vaginal microbiota diversity. Both treatments attenuated epithelial damage, downregulated pro-inflammatory cytokines (IL-1β and IL-8), and upregulated the anti-inflammatory cytokine IL-10. SBCT and VMT also inhibited NF-κB activation, suppressed IL-17 expression, and enhanced Foxp3 expression in vaginal tissues. SBCT is a promising therapeutic approach for treating BV, as it effectively modulates the immune response and restores vaginal microbiota diversity in a mouse model of G. vaginalis-induced BV.

Progesterone promotes CXCl2-dependent vaginal neutrophil killing by activating cervical resident macrophage-neutrophil crosstalk.

Vaginal infections in women of reproductive age represent a clinical dilemma with significant socioeconomic implications. The current understanding of mucosal immunity failure during early pathogenic invasions that allows the pathogen to grow and thrive is far from complete. Neutrophils infiltrate most tissues following circadian patterns as part of normal repair, regulation of microbiota, or immune surveillance and become more numerous after infection. Neutrophils are responsible for maintaining vaginal immunity. Specific to the vagina, neutrophils continuously infiltrate at high levels, although during ovulation, they retreat to avoid sperm damage and permit reproduction. Here we show that, after ovulation, progesterone promotes resident vaginal macrophage-neutrophil crosstalk by upregulating Yolk sac early fetal organs (FOLR2+) macrophage CXCl2 expression, in a TNFA-patrolling monocyte-derived macrophage-mediated (CX3CR1hiMHCIIhi-mediated) manner, to activate the neutrophils' capacity to eliminate sex-transmitted and opportunistic microorganisms. Indeed, progesterone plays an essential role in conciliating the balance between the commensal microbiota, sperm, and the threat of pathogens because progesterone not only promotes a flurry of neutrophils but also increases neutrophilic fury to restore immunity after ovulation to thwart pathogenic invasion after intercourse. Therefore, modest progesterone dysregulations could lead to a suboptimal neutrophilic response, resulting in insufficient mucosal defense and recurrent unresolved infections.

Gardnerella vaginalis, Fannyhessea vaginae, and Prevotella bivia Strongly Influence Each Other's Transcriptome in Triple-Species Biofilms

Bacterial vaginosis (BV), the most common vaginal infection worldwide, is characterized by the development of a polymicrobial biofilm on the vaginal epithelium. While Gardnerella spp. have been shown to have a prominent role in BV, little is known regarding how other species can influence BV development. Thus, we aimed to study the transcriptome of Gardnerella vaginalis, Fannyhessea vaginae, and Prevotella bivia, when growing in triple-species biofilms. Single and triple-species biofilms were formed in vitro, and RNA was extracted and sent for sequencing. cDNA libraries were prepared and sequenced. Quantitative PCR analysis (qPCR) was performed on the triple-species biofilms to evaluate the biofilm composition. The qPCR results revealed that the triple-species biofilms were mainly composed by G. vaginalis and P. bivia was the species with the lowest percentage. The RNA-sequencing analysis revealed a total of 432, 126, and 39 differentially expressed genes for G. vaginalis, F. vaginae, and P. bivia, respectively, when growing together. Gene ontology enrichment of G. vaginalis downregulated genes revealed several functions associated with metabolism, indicating a low metabolic activity of G. vaginalis when growing in polymicrobial biofilms. This work highlighted that the presence of 3 different BV-associated bacteria in the biofilm influenced each other’s transcriptome and provided insight into the molecular mechanisms that enhanced the virulence potential of polymicrobial consortia. These findings will contribute to understand the development of incident BV and the interactions occurring within the biofilm.