Search Results (196)

The vaginal microbiome is often interpreted through static taxonomic patterns. Yet microbial composition alone does not explain why some communities resist perturbation, recover after disruption, or transition toward dysbiosis. This narrative review synthesizes evidence that vaginal microbiome stability is shaped by endocrine phase, epithelial substrate availability, microbial functional capacity, mucosal tone and candidate host modifiers. High-estrogen states, particularly pregnancy, are associated with epithelial maturation, glycogen accumulation, low vaginal pH, and Lactobacillus-dominant communities, whereas postpartum, lactational, menopausal, and other hypoestrogenic states are associated with reduced epithelial support and increased vulnerability to diverse anaerobe-rich configurations. We review the linking of the estrogen–glycogen–Lactobacillus axis, focusing on microbial functions involved in glycogen degradation, lactate production and biofilm persistence, and host pathways that may modify mucosal responsiveness. Direct human genotype-to-vaginal-microbiome stability evidence remains limited; therefore, host genetic features are treated as candidate modifiers rather than validated clinical predictors. We propose a conceptual multi-omic hierarchy for organizing endocrine, epithelial, microbial, immune, temporal, and candidate host-modifier domains relevant to vaginal microbiome resilience. This framework is hypothesis-generating and requires longitudinal, phase-resolved human validation before quantitative prediction or clinical application. Full article

The rise of antimicrobial resistance and the persistence of difficult-to-treat infections have stimulated interest in new strategies to overcome these problems. Among these strategies, dendrimers, which are highly branched monodisperse macromolecules, have emerged as innovative antimicrobial and anti-infective platforms. Dendrimers can act as intrinsic antimicrobial agents through multivalent interactions or membrane disruption or serve as nanocarriers for antibiotics, antiviral agents, antibiofilm compounds, gas-releasing active molecules, or photosensitizers. This review analyzes dendrimer-based anti-infective systems for which in vivo or clinical evaluation has been reported. The literature covers diverse platforms, including PAMAM, poly(L-lysine), peptide, carbosilane, phosphorhydrazone, polyglycerol, polyester, and other dendritic architectures. The available evidence includes infected animal models, pharmacokinetic and biodistribution studies, local tolerance studies, and clinical trials. PAMAM systems are the most extensively explored preclinically, whereas poly(L-lysine) dendrimer astodrimer/SPL7013 remains the most clinically advanced example. Overall, dendrimers provide a chemically tunable and biologically versatile approach to anti-infective research, but the current evidence remains heterogeneous. Direct comparison across studies is limited by differences in dendrimer scaffold, generation, surface chemistry, formulation, pathogen, infection model, administration route, dosing regimen, and biological endpoint. Future development will require better-defined in vivo models, more systematic safety and biodistribution studies, clearer structure–activity relationships, and stronger links between in vitro activity and clinically relevant efficacy. Full article

Background/Objectives: Abnormal vaginal discharge (AVD) is a common complaint among women of reproductive age, often involving multiple, overlapping etiologies, most commonly bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), aerobic vaginitis (AV), and sexually transmitted infections (STIs). We aimed to evaluate a syndromic diagnostic approach by developing qPCR-derived dysbiosis indices for BV, VVC, and AV, subsequently comparing their performance against established reference methods and clinician-assigned diagnoses. Methods: Vaginal swabs were collected in a case–control design from 74 symptomatic and 64 asymptomatic women at two clinics in Slovenia. Commercial qPCR assays quantified the microbial species associated with AVD. Relative abundances were integrated into novel dysbiosis indices. Diagnostic performance was validated against the Nugent scoring system (for BV), semiquantitative Candida culture with clinical symptoms (for VVC), and Hay–Ison criteria (for AV). Results: In this internally validated study, dysbiosis indices demonstrated high agreement with their respective reference tests and outperformed clinician-assigned diagnoses across all three conditions. The syndromic approach further revealed that mixed etiologies were frequent, leading to a diagnostic resolution for this patient subset. Conclusions: qPCR-based microbial dysbiosis indices offer a robust alternative to microscopy, particularly in settings where microscopy is not routinely performed. This method improves the accuracy of AVD evaluation and supports more targeted clinical management. Full article

Vaginal dysbiosis, particularly bacterial vaginosis (BV), is associated with altered immune responses that may influence the formation of extracellular traps (ETs). This study aimed to characterize neutrophil and macrophage extracellular traps (NETs and METs) in vaginal discharge samples obtained from women with normal microbiota (NM) and BV, with particular emphasis on Gardnerella vaginalis (GV) detection. An ex vivo analysis was performed using vaginal smears from 14 patients previously classified according to the Nugent criteria. Immunofluorescence assays targeting neutrophil elastase (NE), citrullinated histone H3 (Citr-H3), CD15, and CD68 were conducted, and quantitative image analysis was performed using the TissueFAXS and StrataQuest platforms. NETs were classified into three morphotypes: spread (spr), diffuse (diff), and aggregated (agg). BV samples exhibited a substantially higher mean NET count than NM samples (842.43 vs. 91.86). The number of diffNETs was significantly higher in BV samples than in NM samples (p = 0.004), whereas GV-positive samples showed increased sprNET abundance compared with that in negative samples (248 vs. 8; p < 0.05). CD68⁺ cell counts were significantly higher in BV samples (p = 0.026), whereas no significant differences in NE or Citr-H3 fluorescence intensity were observed between groups. MET structures were also identified, suggesting macrophage involvement in the local immune response. Collectively, these findings indicate that vaginal dysbiosis and GV presence are associated with enhanced NET formation and distinct morphotype distributions, supporting a role for ETs in the immunopathology of BV. Full article

Background/Objectives: This study aimed to evaluate the association between the clinical parameters of vaginal infection—specifically the presence, type, number of concurrent symptoms, and recurrence frequency—and cervical cytology findings, including inflammation severity, Candida, bacterial vaginosis, cellular abnormalities, and Human Papillomavirus (HPV) positivity. Methods: This prospective, cross-sectional, observational study included 458 women attending our gynecology outpatient clinic for Pap smear screening. Vaginal symptoms were documented through face-to-face interviews using a structured data collection form. Cervical samples were evaluated via liquid-based cytology by a single, experienced cytopathologist, who was blinded to the clinical data; cellular abnormalities, the degree of inflammation and cytomorphological findings indicative of infection were reported. HPV analysis was performed on the 218 women for whom results were available. Chi-square and trend chi-square tests were used in the statistical analysis. Results: No significant association was found between the clinical parameters of vaginal symptoms—specifically presence, concurrency, and recurrence frequency—and cytological abnormalities, HPV positivity and bacterial vaginosis (p > 0.05). In contrast, the prevalence of moderate-to-severe inflammation was significantly higher in women with vaginal discharge and a greater symptom burden (p < 0.05). Pruritus, dysuria, and vaginal burning were significantly associated with Candida positivity (p < 0.05). However, no significant association was found between the severity of cervical inflammation and abnormal cytology or HPV positivity (p > 0.05). In multivariable logistic regression analyses, neither symptom burden nor cervical inflammation severity was independently associated with abnormal cytology or HPV positivity. Conclusions: Our findings indicate that vaginal symptoms and the severity of cervical inflammation may not serve as definitive or independent discriminatory markers for cellular abnormalities or HPV positivity in this context. Nevertheless, specific symptom patterns may assist clinicians in evaluating localized infectious processes. Consequently, while standard cytological and molecular protocols remain essential for oncogenic screening, evaluating the overall symptom burden provides clinicians with a valuable framework for identifying benign dysbiotic and inflammatory processes. These findings remained consistent after adjustment for major clinical confounders. Full article

It is crucial to consider newer antibiotics with activity against anaerobes and Helicobacter pylori, given their healthcare importance, and the constantly growing antibiotic resistance/multidrug resistance, which complicates the therapy. The aim of this review was to emphasize certain recently approved or still-under-investigation antibiotics with potential benefits for treating Clostridioides difficile infections (CDIs), other anaerobic infections, and those caused by H. pylori, covering recent data from articles published primarily in 2020–2026. Given the limited number of antibiotics for treating CDI and fidaxomicin nonavailability in many countries, it is necessary to conduct more extensive laboratory and clinical studies of promising antibiotics such as ibezapolstat, delafloxacin, lascufloxacin, omadacycline, eravacycline, ridinilazole, and CRS3123. Against Bacteroides fragilis group species, delafloxacin and eravacycline showed good activity. Research on rifasutenizol for bacterial vaginosis, sarecycline and nadifloxacin for acne vulgaris and amixicile for periodontal diseases needs to be expanded. For H. pylori infection, delafloxacin, sitafloxacin, nemonoxacin, zoliflodacin, and rifasutenizol may improve the suboptimal success of most eradication regimens. However, more efforts, in coordination between medical, scientific, manufacturing, and government representatives, should ensure wider access to and research on the newer antibacterials. Establishing more research groups, careful examination of market issues, and additional approaches, such as nanomaterials, efflux pump inhibitors, phage therapy, and CRISPR-Cas systems, should be beneficial. Notwithstanding the difficulties, there are many opportunities to promote research on and potential use of newer antibiotics which show advantages over the older antibacterials, and to make them available to numerous countries and patients worldwide. Full article

Bacterial sexually transmitted and sexually associated infections remain a major global health concern, increasingly complicated by antimicrobial resistance and the limited effectiveness of existing therapies. In this context, bacteriophage-based and phage-derived approaches have re-emerged as potential alternative antibacterial strategies. This narrative review examines their applicability across key bacterial pathogens associated with sexually transmitted infections, including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Treponema pallidum and biofilm-associated bacterial vaginosis, with a particular focus on pathogen-specific biological barriers. Available evidence indicates that the success of phage-based interventions is strongly dependent on factors such as intracellular localisation, structural characteristics of the bacterial envelope and the presence of polymicrobial biofilms. While phage-derived platforms, including endolysins, depolymerases and engineered phages, demonstrate antibacterial activity in experimental settings, their effectiveness is uneven across different pathogens. Biofilm-associated infections appear more accessible to these approaches, whereas intracellular and structurally atypical bacteria are currently considered more challenging targets based on available mechanistic and experimental evidence. These observations highlight the need for pathogen-specific engineering strategies and delivery systems. Overall, phage-based therapeutics in this field should be considered within a framework that integrates biological constraints with targeted antimicrobial design. Full article

This study developed two Causal Graphical Models (CGMs) to analyze the transitions associated with Bacterial Vaginosis (BV) and to identify key bacterial species at each stage. BV results from an imbalance in the vaginal microbiota, whose composition varies among women and across developmental stages. A previous CGM identified influential bacteria but did not address changes between microbiota states. Here, we extend that framework to capture these associations. Path Analysis, a structural equation modeling method based on observed variables that estimates effects through correlations and covariances, was applied to a dataset of 132 pregnant women (4–24 weeks of gestation) from Tabasco, Mexico, previously collected by third parties during healthy pregnancy campaigns and associated with BV diagnosis. Models were validated using statistical metrics and evaluation by a clinical microbiologist. The first model, representing the transition from normal microbiota (BV−) to an indeterminate state (I), identified Megasphaera Type 1 as significant. The second model, from I to bacterial vaginosis-positive (BV+), identified Atopobium vaginae and Bacterial Vaginosis-Associated Bacterium Type 2 as significant contributors. These findings highlight the importance of the intermediate state in dysbiosis progression and support the use of CGMs for studying microbiome dynamics. Full article

Endocrine-disrupting chemicals (EDCs) are a diverse group of environmental pollutants capable of interfering with hormonal and immune system regulation. In recent years, increasing concern has been raised about the effects of chemicals, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), insecticides, and parabens, on maternal and fetal health, primarily due to their widespread exposure in human populations. Pregnancy represents a critical window characterized by tightly regulated hormonal and immunological adaptations. Emerging evidence suggests that EDC exposure during this period may alter maternal microbiota, disrupt immune responses, and interfere with endocrine signaling. These changes may increase susceptibility to bacterial and viral infections, including bacterial vaginosis, urinary tract infections, and intrauterine infections, all of which are associated with adverse pregnancy outcomes. This review summarizes the current evidence on the sources and mechanisms of exposure to endocrine disruptors during pregnancy and examines the potential biological pathways linking endocrine disruption to the development of infections. Particular emphasis is placed on the interactions between immune regulation, hormonal signaling, and changes in the microbiome, which may contribute to increased susceptibility to infections. A deeper understanding of these complex mechanisms is critical to improve risk assessment, develop effective public health strategies, and ultimately protect maternal and fetal health in an environment of increasing chemical exposure. A literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including studies published up to January 2026. Full article

TFF1 is a secretory polypeptide that is typical of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. Originally, TFF1 was discovered as an estrogen-responsive gene in breast cancer cell lines. However, its major physiological expression site is the stomach where it exists mainly in a monomeric form, with minor amounts of homodimeric as well as heterodimeric forms, such as a high-molecular-mass complex with IgG Fc binding protein (FCGBP). For the first time, we characterized different low-molecular-mass forms of TFF1 in human post-menopausal vaginal specimens, i.e., monomeric and dimeric forms. Attempts to identify high-molecular-mass forms of TFF1, such as TFF1-FCGBP, failed. Based on its known anti-inflammatory effects, TFF1 could play an important role in the homeostasis of vaginal microbiota, which is normally predominated by Lactobacillus spp. Due to its lectin activity, TFF1 might also be capable of binding to members of the vaginal microbiota or to vaginal fungal pathogens. This points to a potential role for TFF1 in the vagina’s innate immune defence and could be of clinical relevance particularly after menopause, e.g., for the treatment of bacterial vaginosis or vulvovaginal candidiasis, as here vaginal dysbiosis is often observed as a consequence of estrogen deficiency. 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

Bacterial vaginosis (BV) is a common vaginal dysbiosis characterized by the depletion of Lactobacillus species and the overgrowth of facultative anaerobic bacteria, particularly Gardnerella spp. and Fannyhessea vaginae. The vaginal microbiota plays a key role in local immune modulation, and BV has been associated with a molecular pro-inflammatory profile. This study included 152 women with normal microbiota (n = 68), intermediate microbiota (n = 24), or BV (n = 60). Vaginal lavage samples were used to quantify Gardnerella spp. and F. vaginae and to measure IL-1β, IL-6, CXCL-8, IL-10, and TNF-α levels. Bacterial loads of Gardnerella spp. were significantly higher in the BV group than in normal microbiota (p < 0.001). F. vaginae loads were higher in BV than in both normal and intermediate microbiota (p < 0.001). IL-1β levels were increased in intermediate microbiota (p = 0.011) and BV (p = 0.024) compared with normal microbiota, while CXCL-8 levels were higher in intermediate microbiota (p = 0.021). No differences were observed for IL-6, IL-10, or TNF-α. BV is associated with increased Gardnerella spp. and F. vaginae loads and a selective increase in IL-1β, supporting a distinct inflammatory signature linked to vaginal dysbiosis. Full article

Objective: Bacterial vaginosis is a dysbiosis of the vaginal microbiome, typically characterized by a loss of Lactobacillus. Lactobacillus plays a crucial role in vaginal immunity and protection against sexually transmitted infections. Herpes simplex virus 2, the primary cause of genital herpes, impacts 13% of people worldwide. We undertook this systematic review and meta-analysis to examine the risk of herpes simplex virus 2 acquisition in women with bacterial vaginosis. Secondarily, we examined the impact of bacterial vaginosis on herpes simplex virus 2 shedding, reactivation, and symptoms. Data sources: We searched PubMed, EMBASE, Cochrane, Web of Science, Google Scholar, and ClinicalTrials.gov for articles published before 1 July 2023 for microbiome and herpes simplex virus type 2. Studies were limited to human subjects and the English language. An updated search was performed in January 2026. This study was registered on PROSPERO (CRD42023439139). Methods of study selection: Studies on non-pregnant, reproductive-aged cisgender women that diagnosed bacterial vaginosis by Amsel Criteria, Nugent Scoring or used molecular techniques, and those that detected herpes simplex virus 2 by serological assay or PCR testing were included. Our search identified 863 results with four publications eligible for inclusion. For our secondary outcomes, 40 results were identified regarding herpes simplex virus 2 shedding, with two publications eligible for inclusion, which did not meet our threshold for meta-analysis. There were 21 results identified for herpes simplex virus 2 reaction and 115 results for herpes simplex virus 2 symptoms, with no articles being eligible for inclusion. Tabulation, integration, and results: Quality assessment was performed following data extraction using the quality assessment scales from the Joanna Briggs Institute. Results were extracted, and the pooled hazard ratio was calculated with 95% confidence interval. A total of 1906 women were included in this analysis, and 255 acquired herpes simplex virus 2. The pooled unadjusted hazard ratios produced an effect size of 1.91, (95% confidence interval 1.4649–2.4980), and a p-value of <0.0001, while the pooled adjusted hazard ratios produces an effect size of 1.85, (95% confidence interval of 1.3556–2.5162), and a p-value of 0.0001 indicating that bacterial vaginosis is associated with a increased risk of herpes simplex virus 2 acquisition. Conclusions: This systematic review with meta-analysis indicates that bacterial vaginosis is associated with a significantly increased risk (91% unadjusted, 85% adjusted) of herpes simplex virus 2 acquisition, indicating that bacterial vaginosis treatment may reduce herpes simplex virus 2 acquisition. A notable limitation of these findings is the relatively small number of studies eligible for inclusion in this systematic review and meta-analysis. Full article

Background: Bacterial vaginosis and vaginal dysbiosis represent major causes of morbidity among women in sub-Saharan Africa, yet data from Madagascar remain scarce. This study aimed to assess the prevalence and determinants of vaginal bacterial infections among women in northern Madagascar and to explore how vaginal microflora composition reflects broader aspects of reproductive health. Methods: A cross-sectional study was conducted in April 2024 among 159 women (15–80 years) attending a rural second-referral clinic in Manerinerina, Ambatoboeny District. Sociodemographic and hygiene data were obtained through structured questionnaires. Vaginal pH was measured in situ, and Gram-stained smears were evaluated using the Nugent scoring system. The presence of Trichomonas vaginalis, Neisseria gonorrhoeae, and Candida spp. was assessed microscopically. Associations were analyzed using Chi-square or Fisher’s exact tests, with p < 0.05 considered significant. Results: Abnormal vaginal flora was observed in 68.6% of women, including 43.4% with BV (Nugent 7–10) and 25.2% with intermediate flora. Elevated vaginal pH correlated strongly with higher Nugent scores (p < 0.01). T. vaginalis and N. gonorrhoeae were detected in 10.7% and 9.4% of women, respectively, and both were significantly associated with dysbiosis (p = 0.02 and p = 0.04). Poor hygiene practices, vaginal douching (79.1% vs. 64.5%; p = 0.04), and unsafe water sources (p = 0.04) were major behavioral and environmental determinants. Conclusions: Vaginal dysbiosis is highly prevalent among women in northern Madagascar and closely linked to modifiable hygiene behaviors and environmental conditions. In resource-limited settings, Gram-stained microscopy and Nugent scoring remain cost-effective tools for surveillance and patient care. Culturally adapted education, improved water access, and integration of low-cost diagnostics are essential for reducing the burden of vaginal infections in rural Madagascar. 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