Search Results (92)

Background: Chronic endometritis (CE) is a subtle, often asymptomatic endometrial inflammation marked by CD138⁺ plasma cell infiltration and linked to recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and unexplained infertility. Emerging evidence implicates endometrial microbiome dysbiosis in CE. Objective: To systematically review and conduct meta-analysis on the association between CE and endometrial microbiome alterations and their reproductive implications. Methods: We searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar for studies diagnosing CE via CD138 immunostaining, assessing microbiota with molecular techniques. Data extraction, quality assessment, and meta-analysis were performed. Results: Twenty-two studies including 4022 women were analyzed. CE was associated with reduced prevalence of Lactobacillus-dominated microbiota and increased detection of non-Lactobacillus species, particularly Streptococcus spp., Enterococcus spp., Escherichia coli, Staphylococcus spp., Ureaplasma spp., and Gardnerella vaginalis. In the meta-analysis (2947 women), Enterococcus spp. and Ureaplasma spp. were significantly more prevalent in women with CE, whereas Streptococcus spp., E. coli, Staphylococcus spp. and G. vaginalis showed non-significant trends. Only E. coli and Streptococcus spp. showed significant heterogeneity between-studies. Conclusions: CE is linked to microbial dysbiosis with reduced Lactobacillus dominance and enrichment of potentially pathogenic taxa, notably Enterococcus and Ureaplasma spp. These findings suggest that the endometrial microbiome contributes to chronic inflammation and adverse reproductive outcomes, yet heterogeneity and limited evidence call for standardized diagnostics and robust trials before clinical implementation. Full article

Recurrent vulvovaginal candidiasis (RVVC) affects 5–8% of women of reproductive age. Host genetic factors, particularly single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs), may influence RVVC susceptibility by impairing vaginal mucosal antifungal immunity. The aim of this study was to assess the effect of SNPs in genes encoding TLRs on RVVC susceptibility. Τhe distribution of TLR2 Arg753Gln and TLR4 Asp299Gly/Thr399Ile polymorphisms in Greek women, including RVVC (n = 63), first-episode VVC (n = 37), Gardnerella vaginalis vaginitis (GV, n = 36) patients, and healthy controls (n = 61), was investigated using TaqMan SNP genotyping. Genotype and allele frequencies were analyzed under allelic and dominant models, with odds ratios (ORs), 95% confidence intervals (CIs), and linkage disequilibrium assessed. TLR4 Asp299Gly and Thr399Ile heterozygotes were significantly more frequent in RVVC patients compared with controls and affected RVVC susceptibility (OR: 5.57, 95% CI: 1.17–26.56, p: 0.0172; OR: 4.92, 95% CI: 1.02–23.78, p: 0.0306, respectively). No associations were observed for TLR2 Arg753Gln or for any SNP with GV or first-episode VVC. TLR4 variants co-segregated, indicating a haplotype effect. TLR4 haplotypes, rather than TLR2 polymorphism, confer increased RVVC susceptibility, supporting a genetically distinct, mucosal immunity-driven pathogenesis. Larger, ethnically diverse studies with functional assays are warranted to validate these findings and guide personalized prevention and treatment strategies. Full article

Background: Antimicrobial resistance (AMR) is a global healthcare threat. Traditional largely non-selective antibiotics produce side effects due to the natural host microbiome being modified creating a loss in homeostasis. In women, AMR is a cause of acute generational impact. For example, bacterial vaginosis (BV), the most common gynecological infection in reproductive-age women, is a serious public health concern due to its high rates of recurrence, secondary infections, and reproductive issues; and two currently prescribed antibiotics for BV do not fully resolve the symptoms. Objective: The strong need for innovative, potent, safe, and selective therapeutics has prompted a search for such bioactive molecules in milk. Resulting from 200 million years of evolutionary pressure, mammalian lactation not only nourishes infants, but it has also been under relentless Darwinian selective pressure to provide protection from a variety of infections. Methods: Computationally designed human-milk-inspired peptides (AMPs) were tested in standard microbicidal assays for activity against BV pathogens, and evaluated for stability and safety. Results: Several AMPs are bactericidal towards Gardnerella vaginalis, a major BV-associated pathogen, and other BV-associated pathogens. Some novel AMPs do not impact the viability of key lactobacilli linked to a healthy vaginal microbiome. These stable, membrane-acting cationic AMPs reduce inflammation during an infection assay and are safe in EpiVag organoid tissues. Conclusions: AMPs can address concerns like non-selectivity and antibiotic resistance—thereby addressing AMR. Lead AMPs from this study offer a promising solution for the development of novel therapeutics for the treatment of BV, which may reduce the burden of AMR. Full article

Urinary tract infections (UTIs) impose a substantial burden on women’s health, and probiotics have emerged as an alternative strategy to support urogenital wellbeing. This study evaluated the antimicrobial properties of Limosilactobacillus reuteri 3613-1 and its ability to improve UTI outcomes in women with a history of recurrent uncomplicated UTIs. In vitro assays demonstrated that L. reuteri 3613-1 inhibited the growth of Escherichia coli isolates and proved superior inhibition of Gardnerella vaginalis and Candida albicans compared with a comparator L. reuteri strain, supported by confirmed reuterin production and genomic profiling. A randomized, double-blind, placebo-controlled clinical trial (n = 130) assessed daily supplementation with L. reuteri 3613-1 for 24 weeks. While the proportion, frequency, and intensity of confirmed UTIs did not differ significantly between groups, L. reuteri 3613-1 delayed the onset of the first UTI, reaching significance in participants with suspected while unconfirmed UTIs. Vaginal pH and vaginal microbiome composition remained stable and comparable between groups across the intervention. The product was safe and well tolerated. Overall, L. reuteri 3613-1 shows promise as a probiotic candidate with antimicrobial activity and potential to delay symptom onset in women susceptible to recurrent UTIs, warranting further investigation in larger studies. Full article

Background: Vaginal infections often present with overlapping symptoms and involve single or multiple pathogens. However, the relationship between clinical symptoms and molecularly defined vaginal pathogen profiles, especially in multi-pathogen infections, remains poorly characterized in a routine care setting. This study exams the connection between vaginal symptoms and pathogen profiles among women with vaginitis in Northern Vietnam. Methods: We conducted a multicenter cross-sectional study of women with vaginitis at Bac Ninh CDC and Hanoi Obstetrics and Gynecology Hospital between December 2023 and December 2024. Baseline demographics and clinical symptoms were assessed by physicians. Vaginal swabs were collected for pH measurement and pathogen detection using multiplex real-time PCR. The correlation was analyzed using logistic regression in GraphPad Prism v10.1.1. Results: Among 289 symptomatic women, abnormal vaginal discharge and itching were the most common symptoms. Gardnerella vaginalis was the most commonly detected pathogen, occurring alone or in combination with Candida albicans, Mycoplasma hominis, and other genital pathogens. Multi-pathogen infection was associated with abnormal vaginal discharge (OR = 5.44), itching (OR = 2.13), and elevated vaginal pH (OR = 4.70). Women at the tertiary hospital showed greater symptom burden (OR = 1.75) and higher prevalence of multi-pathogen infections (OR = 9.75) than those attending the provincial CDC. Conclusions: Multiplex real-time PCR combined with simple clinical indicators (symptom clustering and vaginal pH) provides practical diagnostic value for identifying multi-pathogen infections in symptomatic women. This integrated approach may support more accurate etiologic diagnosis and guide rational testing strategies, particularly in resource-limited settings. Full article

Objective: To evaluate the clinical and microbiological effects of antimicrobial underwear as an adjunct to standard treatment in women with acute vaginitis. Methods: Sixty reproductive-age women with acute vaginitis received a 7-day intravaginal regimen of metronidazole and miconazole. Participants were assigned either to a group wearing antimicrobial underwear or to a control group wearing non-antimicrobial underwear. Vaginal symptoms and culture results were assessed before and after treatment. Results: The antimicrobial-underwear group showed significant improvement in vaginal symptoms, including discharge (96.7%→6.9% vs. 72.5%→27.5%; p < 0.001), pruritus (37.5% vs. 68.4%; p = 0.044), odor (19.6% vs. 53.8%; p = 0.016), and irritation (36.4% vs. 75%; p = 0.013). Dyspareunia was similar between groups. While no microbiological change was observed in controls (p = 0.950), negative cultures increased from 40% to 80% in the antimicrobial-underwear group (p = 0.018), with marked reductions in Candida spp., Gardnerella vaginalis, E. coli, and Klebsiella spp. Conclusions: Antimicrobial underwear, when used in conjunction with standard treatment, can enhance symptom relief and maintain genital hygiene. By improving the vulvovaginal microenvironment, antimicrobial textiles can reduce moisture and the persistence of pathogens. Full article

Background and Objectives: Vulvo-vaginal atrophy (VVA), a prevalent condition among postmenopausal women, significantly impairs quality of life through symptoms like vaginal dryness, dyspareunia, and burning. Non-hormonal treatments, such as CO₂ laser therapy, have shown promise in managing VVA symptoms with minimal side effects. The addition of adjunctive treatments may enhance efficacy and mitigate possible adverse effects. To evaluate the combined efficacy and safety of CO₂ laser therapy and a collagen-based cream in treating VVA and to explore their potential impact on the vaginal microbiome. Materials and Methods: This was a single-center, randomized, interventional. Sixty postmenopausal women diagnosed with VVA were randomized into two groups: a control group receiving laser-only treatment and a treatment group receiving laser therapy with daily collagen-based cream application. Primary outcome measures included symptom improvement on the Visual Analog Scale (VAS) for VVA-associated symptoms. Secondary outcomes involved microbiome composition analysis. Results: Both groups showed significant symptom improvement, with the combination therapy group demonstrating superior reductions in burning, dyspareunia, and vaginal dryness (p < 0.05). Microbiome analysis revealed increased levels of beneficial species (Lactobacillus iners and Lactobacillus crispatus) and decreased pathogenic bacteria (Gardnerella vaginalis and Atopobium vaginae) in the treatment group, though these changes were not statistically significant. Mild side effects, such as burning and swelling in the first days following the treatment, were less frequent in the combination therapy group, likely due to the anti-inflammatory effects of the collagen-based cream. Conclusions: This study provides evidence supporting the use of CO₂ laser therapy with collagen-based cream as an effective and well-tolerated treatment for VVA in postmenopausal women, achieving significant symptom relief. The combined therapy approach holds potential for enhanced efficacy and reduced side effects compared to laser-only treatment, offering a promising alternative for women ineligible for hormone-based therapies. Full article

This study examined the role of vaginolysin (VLY), a virulence factor of the bacterium Gardnerella vaginalis (GV), in bacterial vaginosis (BV). In a group of 112 women with BV (diagnosis on the Nugent scale ≥7 points) and 122 control cases with normal microbiota, VLY levels, the state of the vaginal microecology (colposcopy, laboratory markers, pH), GV genotypes (clades 1–4), and clinical symptoms were assessed. It was found that GV also occurs in healthy women, but VLY levels are significantly higher in BV and correlate with inflammatory markers (e.g., leukocyte esterase) and symptom severity. However, the relationship is nonlinear: low and moderate VLY levels have little effect on symptoms, while high levels cause a sharp increase in symptoms. Thus, VLY is potentially important for the pathophysiology and clinical assessment of BV. Full article

Background/Objectives: This scoping review aimed to map evidence on metabolic alterations in the vaginal environment associated with dysbiosis, transient and persistent human papillomavirus (HPV) infection, and cervical dysplasia, highlighting potential metabolic and protein biomarkers for early detection of cervical cancer. Methods: Systematic searches were conducted in PubMed, Scopus, and Web of Science, following the JBI methodology and PRISMA-ScR guidelines. Studies jointly evaluating vaginal metabolites and proteins in women with HPV and cervical intraepithelial neoplasia (CIN) in the context of dysbiosis were included. Results: After duplicate removal, 196 records were screened, and 41 studies were selected—mostly cross-sectional observational designs—published between 2006 and 2025, predominantly by Chinese research groups. Lactobacillus spp. predominated in HPV-negative women, while HPV infection was associated with a dysbiotic environment enriched with anaerobes such as Gardnerella vaginalis, Atopobium vaginae, Prevotella, and Sneathia. Of 389 metabolic and protein markers associated with HPV infection and CIN, 44 underwent ROC analysis, with prolineaminopeptidase, 5′-O-methylmelledonal, and calonectin showing high diagnostic performance (AUC > 0.90). Conclusions: These results suggest vaginal microbiome and metabolic profiles may represent promising biomarkers for persistent HPV infection. Further, longitudinal studies with larger samples are needed for clinical validation. Full article

This study describes the development of β-cyclodextrin (β-CD) inclusion complexes of curcumin (CUR) and a synthetic curcuminoid analogue (CN56), which were incorporated into poly(vinyl alcohol)/κ-carrageenan hydrogel films to create a multifunctional system capable of sustained drug release and effective antimicrobial action. Carrageenan was extracted from Gigartina skottsbergii, and hydrogels were prepared using a freeze–thaw crosslinking method. The inclusion complexes were formed at a 1:6 molar ratio, achieving loading efficiencies of 75.62% for CUR and 79.00% for CN56. FTIR confirmed molecular interactions between the complexes and the polymeric matrix, accompanied by reduced crystallinity and increased amorphous character. Thermogravimetric analysis revealed enhanced thermal stability, with degradation onset temperatures above 239 °C, while DSC analysis indicated irreversible amorphization after the first heating cycle. SEM analysis showed improved surface uniformity in complex-loaded films compared with those containing free compounds. Swelling experiments demonstrated significantly greater fluid uptake in complex-loaded hydrogels, particularly for CN56 (1080% after 45 min). Controlled release studies revealed sustained drug release profiles, with 76.49% of CUR and 56.02% of CN56 released over 36 h, following Fickian diffusion mechanisms. In vitro antimicrobial assays confirmed marked activity of CUR and CN56 against Gardnerella vaginalis, a key pathogen associated with bacterial vaginosis. Biocompatibility tests, including hemolysis and MTT reduction assays, indicated low cytotoxicity and satisfactory hemocompatibility. Rheological analysis further demonstrated increased viscosity and potential mucoadhesive behavior. Collectively, these findings highlight the potential of carrageenan-based PVA hydrogels as innovative pharmaceutical platforms for the prevention and treatment of recurrent bacterial vaginosis, offering a promising alternative to conventional therapies. Full article

Background: This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated bacteria, these approaches lack visual tools to explore causal relationships and determine which are the most relevant. In contrast, the CGM generated in this study allows visualization of associated bacteria and their causal links, thereby identifying those most influential. Methods: Path Analysis (PA), a statistical structural equation modeling method, was used to construct the CGM, with emphasis on observable variables and to assess direct and indirect effects through correlations and covariances. PA was applied to an already-collected third-party dataset related to BV diagnosis, consisting of data from 132 pregnant women between 4 and 24 weeks of gestation. Results: The CGM, built using a theoretical model based on the Spearman correlation matrix, was validated through statistical metrics and by a clinical-biological expert. The resultant model highlights bacteria influencing BV diagnosis, specifically Mycoplasma hominis (Mh), Atopobium vaginae (Av), Gardnerella vaginalis (Gv), Megasphaera Type 1 (MT1), and Bacteria Associated with Bacterial Vaginosis Type 2 (BVAB2). Among them, MT1 and BVAB2 showed the strongest association with BV. Conclusions: The CGM effectively identifies causal associations among bacteria related to BV. Full article

Chlamydia trachomatis (CT) remains the most commonly reported bacterial sexually transmitted infection (STI) globally, with particularly high incidence among adolescents and young adults. In Europe, CT cases have continued to rise over the past decade, despite ongoing public health efforts in prevention and screening. Screening coverage, however, remains inconsistent across countries. CT infections are often asymptomatic, especially in women, yet can lead to serious CT-related reproductive complications if left untreated, including pelvic inflammatory disease (PID), tubal factor infertility, and ectopic pregnancy. Emerging evidence highlights the cervicovaginal microbiota as a key factor influencing susceptibility to STIs, including CT infection, its progression, and associated outcomes. A Lactobacillus-dominated microbiota, particularly L. crispatus, is well-known to be a protective factor against CT acquisition, whereas vaginal dysbiosis, characterized by a depletion of these species and an overgrowth of anaerobes, such as Gardnerella vaginalis, Atopobium vaginae, and Prevotella spp., has been linked to increased CT acquisition risk, reduced immune control, and impaired infection resolution. Interaction between microbial communities and host immunity may modulate whether CT infections spontaneously clear, persist, or progress into pathological conditions. This review explores the natural history of CT genital infection in women, emphasizing the role of cervicovaginal dysbiosis in disease progression and reproductive sequelae. By integrating current knowledge about resident cervicovaginal microbes, host-microbe interaction, and CT-related reproductive outcomes, we discuss how microbiota-targeted strategies, including probiotic or microbiome-modulating strategies, may complement current CT prevention, diagnosis, and treatment approaches. Full article

Bacterial vaginosis (BV) is a highly prevalent vaginal infection characterized by a dysbiotic shift in the vaginal microbiota, with Gardnerella vaginalis acting as a principal pathogen. Despite its association with adverse reproductive outcomes, BV remains underexplored from both mechanistic and therapeutic standpoints. Standard antibiotic regimens frequently fail due to high recurrence rates driven by multidrug-resistant (MDR) G. vaginalis strains and biofilm formation. In response, natural compounds and nutraceuticals, owing to their intrinsic antibacterial, antibiofilm, and immunomodulatory properties, have emerged as promising candidates for alternative BV therapies. In this paper, we first compile and critically evaluate preclinical and clinical evidence on the efficacy of plant extracts, essential oils (EOs), probiotics, vitamins, proteins, fatty acids, and enzymes against G. vaginalis, emphasizing their mechanistic insights in restoring vaginal microbial balance. Next, we focus on the integration of these bioactive agents into engineered nanosystems, such as lipid-based nanoparticles (LNPs), polymeric carriers, and inorganic nanostructures, to overcome limitations related to solubility, stability, and targeted delivery. Nonetheless, comparative studies, combination therapies, and recent patent developments are discussed to highlight how naturally derived molecules can enhance antimicrobial potency and reduce cytotoxicity. In conclusion, these platforms demonstrate superior in vitro and in vivo efficacy, offering a paradigm shift in the management of BV. Key challenges include scalable manufacturing, regulatory approval, and comprehensive safety assessment. Future research should prioritize standardized nanoparticle (NP) synthesis, detailed pharmacokinetic and toxicity profiling, and well-designed clinical trials to validate nature-inspired, nanoengineered therapies against G. vaginalis-induced BV. Full article

Preterm prelabor rupture of membranes (PPROM) is a leading cause of preterm birth and significant neonatal morbidity. The vaginal microbiome is implicated in its pathogenesis, but its detailed characteristics and functional consequences remain to be fully elucidated. This study aimed to provide a comprehensive, multi-faceted analysis of the vaginal microbiome and its functional potential in pregnant women with PPROM compared to healthy term controls. We collected vaginal fluid samples from eight PPROM and seven healthy control (HC) pregnant women. The vaginal microbiome was analyzed using 16S rRNA gene sequencing. We assessed community composition and state types (CSTs), alpha and beta diversity, co-occurrence networks, and predicted functional pathways using PICRUSt2. A molecular bacterial vaginosis (molBV) score was also calculated to determine the clinical relevance of the dysbiosis. The PPROM microbiome was characterized by a significant depletion of Lactobacillus crispatus–dominated communities (CST I) and a shift towards L. iners–dominated (CST III) or polymicrobial (CST IV) communities, which was consistent with a BV-positive molBV score. Alpha diversity was significantly higher in the PPROM group, and beta diversity analysis confirmed a distinct microbial structure between the two groups. Co-occurrence network analysis revealed a collapse of the protective, Lactobacillus-centered network in the PPROM group, which was replaced by a densely interconnected network of anaerobic bacteria with Gardnerella vaginalis as a key hub. Functionally, the PPROM microbiome was enriched for amino acid biosynthesis pathways, in contrast to the HC group, which was enriched for nucleotide and peptidoglycan biosynthesis. PPROM appears to be linked with a complex vaginal dysbiosis that encompasses significant alterations in microbial composition, diversity, interactions, and functional potential. These findings highlight the vaginal microbiome as a critical factor in the pathogenesis of PPROM and suggest its potential for risk stratification and as a therapeutic target to improve pregnancy outcomes. Full article

Introduction: The study aimed to provide a systematic review and analysis of previously reported studies investigating the association between the bacterial microbiome and the incidence of preterm premature rupture of membranes (PPROM). Material and Methods: A comprehensive literature search across many databases via 01 March 2023, including PubMed, Web of Science, Embase, and the Cochrane Library. Results: A total of 20 studies were reviewed, all of which provided a comprehensive analysis of the microbial makeup in pregnant women. The findings suggest that disturbances in the bacterial microflora correlate with a heightened risk of PPROM. Conclusions: There was a significant reduction of naturally prevalent vaginal species (in the vaginal flora of women with PPROM such as Lactobacillus spp., Weissella spp., and Rickettsiales spp. This was accompanied by the dominance of other bacterial species such as Sneathia spp., Prevotella spp., Prevotella bivia, Prevotella timonensis, Peptniphilus, Streptococcus spp., Dialister spp., Lactobacillus iners, Gardnerella vaginalis, Ochrobactrum spp. Megasphaera spp., Faecalibacterium spp., Bifidobacterium spp., Xanthomonadales spp., Gammaproteobacteria spp., Alphaproteobacteria spp., Bacteroides spp., Sphingomonas spp., Streptococcus agalactiae, Escherichia coli, Staphylococcus aureus, Chlamydia trachomatis, Ureaplasma urealyticum, Ureaplasma parvum or Group B Streptococcus begin to dominate, leading to PPROM. Recognising the microbial patterns could lead to the development of risk-based microbiological interventions and probiotic treatment, potentially improving the management and outcomes of patients with PPROM. Full article