Search Results (145)

Genital Mycoplasmas are implicated in adverse pregnancy outcomes and the development of infertility. However, the role of Mycoplasma fermentans in these outcomes has not been adequately studied; therefore, its participation in these sufferings requires further investigation. This study aimed to evaluate the prevalence of M. fermentans in pregnant and non-pregnant women. End-point PCR was used to analyze two hundred and twenty-eight endocervical samples for M. hominis, M. genitalium, M. fermentans, M. pirum, Ureaplasma urealyticum, and U. parvum diagnoses. The prevalence of Mycoplasma spp. was as follows: U. parvum was found in 83 samples (36.4%), U. urealyticum in 39 instances (17.1%), M. hominis in 36 (15.7%), M. fermentans in 32 (14%), M. genitalium in 15 (6.6%), and M. pirum in 0 samples. No association was found between the Mycoplasma spp. and some infertility conditions or adverse pregnancy. However, M. fermentans and M. hominis were found to be associated with bacterial vaginosis (RR = 3.4 CI 95% 1.85–6.3, p < 0.005). In conclusion, M. fermentans and M. hominis were isolated more often in women with bacterial vaginosis, which suggests that these bacteria could contribute to the development of this pathology. Full article

Cervical cancer is more common in Sub-Saharan Africa (SSA) compared to developed countries, with persistent genital high-risk HPV (HR-HPV) infection identified as the cause. However, other factors contributing to this gap remain unclear. This review explores the potential role of cervicovaginal microbiota (CVM) in genital HPV infection and cervical cancer development among women in SSA. Many women of African descent, including those from SSA, lack lactobacilli dominance in their CVM, which is considered a biomarker of cervicovaginal health. Published literature has associated Lactobacillus-dominated CVM with a lower risk of HPV infection and cervical cancer. The converse is true for women with high diversity non-Lactobacillus-dominated CVM and bacterial vaginosis, the most common form of vaginal disorder. However, findings on the relationship between specific bacterial abundance and cervical disease severity are inconsistent and inconclusive due to differences in study design, study population, sampling, and potential confounders. Thus, there is a need to form consensus to advance research on CVM and HPV-associated cervical disease. Despite the exact mechanisms by which CVM influence HR-HPV persistence and cervical carcinogenesis being unknown, the backbone of the mechanisms appears to be mediated in part by the following: cervicovaginal dysbiosis, elevated vaginal pH, high ratio of L-to-D-lactic acid, cohesive biofilm formation, chronic inflammation, and immune dysregulation. Consequently, these promote cellular proliferation, genetic instability, and evasion of immune surveillance. This review calls for larger, prospective studies to unravel causal links, identify protective features, and integrate CVM interventions into HPV and cervical cancer prevention strategies in SSA. Full article

Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application. Full article

Background/Objectives: Bacterial vaginosis (BV), an infection caused primarily by Gardnerella vaginalis, is the most prevalent vaginal infection. Although BV is often characterized by an asymptomatic course, it can lead to considerable health complications. Currently, BV therapy choices are limited, and available treatments are complicated by concerns about antibiotic resistance. Ceragenins, which together comprise an innovative class of low molecular-weight, cholic acid-based antibacterial agents, have emerged as potential alternatives to conventional treatments. Methods: This study investigates (i) the antibacterial activity of ceragenins against G. vaginalis in in vitro experimental settings at varied pH, and (ii) the effectiveness and anti-inflammatory properties of CSA-13 in a G. vaginalis-induced bacterial vaginosis animal model. Results and Conclusions: We demonstrate that ceragenins, particularly CSA-13, maintain their antibacterial efficacy throughout pH range of 4.5–7, with the highest activity observed at neutral pH (7.0). Additionally, in an animal model, beneficial effects of ceragenins are attributed to anti-inflammatory properties of these compounds, making these compounds promising agents as potential new treatment options against G. vaginalis-associated vaginal infections. Full article

This prospective cohort study aimed to evaluate the performance of Flora select™ (FS), a newly developed real-time PCR test, for the assessment of the vaginal microbiome during early pregnancy. Five hundred and fifty-six pregnant women underwent examinations of FS, Nugent score—a Gram-staining scoring system for the diagnosis of bacterial vaginosis (BV)—and conventional bacterial culture between 8 weeks and 12 gestational weeks. Nugent scores of 0–3, 4–6, and ≥7 were found in 469 (84.2%), 41 (7.4%), and 47 (8.5%) of the women, respectively. Relative dominance rates of Lactobacillus species of high (≥80% medium (50%≤, <80%), and low (0.1≤, <50%), and no detection (<0.1%) were 63.0%, 8.8%, 17.1%, and 11.2%, respectively. Gardnerella, Prevotella, Atopobium, Streptococcus, Ureaplasma, and Mycoplasma species were detected in 23.9%, 17.6%, 17.1%, 7.0%, 23.0%, and 4.9% of the women, respectively. Gardnerella species were detected in all women with Nugent scores ≥7 and Ureaplasma were detected in 40.4% of them. BV-associated bacterial species were also detected in 70.7% of women with Nugent scores of 4–6. Gardnerella, Prevotella, Atopobium, Streptococcus, Ureaplasma, and Mycoplasma species were highly prevalent in women with Nugent scores ≥4 or Lactobacillus species <50%. FS detected Gardnerella, Prevotella, and Atopobium species more effectively than conventional bacterial culture. FS could determine relative dominance rates of Lactobacillus species in the vaginal microbiome, and simultaneously detect four kinds of BV-associated bacteria, Ureaplasma and Mycoplasma species. Therefore, FS may be clinically useful for the screening of the vaginal microbiome during pregnancy to prevent preterm birth and for the assessment of the vaginal microbiome after BV treatments. Full article

Background/Objectives: the vaginal microbiota is known to confer protection in the genital ecosystem, due to the predominance of different Lactobacillus species, playing a crucial role in women’s health; alterations in the composition of the microbial communities in the vagina can be associated with the development of bacterial vaginosis (BV). Current therapy for BV involves oral or intravaginal administration of metronidazole or clindamycin, albeit the high recurrence rates suggest a need for alternative therapeutic tools, such as probiotics. Herein, the diversity and composition of vaginal microbiota in women with asymptomatic BV was investigated before and after the oral administration of a multi-strain probiotic formulation. Methods: a prospective observational pilot study with pre–post design was carried out from 1 June 2022, to 31 December 2022, on reproductive-age women with asymptomatic BV, as diagnosed via Nugent score, and matched healthy controls. The probiotic was administered to all study participants as acid-resistant oral capsules (twice daily), and a vaginal swab was collected at baseline and after 2 months of treatment, for the metagenomic analysis of 16s rDNA. Results: the diversity and richness of the vaginal microbiota in women with BV were significantly reduced after 2 months of supplementation with the oral probiotic, as evidenced by measures of α-diversity. Interestingly, some bacterial genera typically associated with dysbiosis, such as Megasphaera spp., were significantly decreased; whereas, at the same time, Lactobacillus spp. Doubled. Conclusions: our preliminary results suggest that the multi-strain oral probiotic is a beneficial treatment specifically targeting the dysbiotic vaginal microenvironment. Full article

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. Full article

Vulvovaginal candidosis (VVC) represents a frequent and cumbersome vaginal infection. Recurrent and/or persistent infections remain common among a significant number of patients despite the use of antifungals. Probiotics offer a promising adjunctive or alternative therapeutic strategy to antifungals in the management of VVC. We aimed to explore and thoroughly examine the various roles and potential applications of probiotics in VVC. A comprehensive literature search was conducted to identify relevant clinical trials and systematic reviews that examine the effectiveness of probiotics in the treatment and prevention of VVC and recurrent VVC (rVVC). Following the initial screening of 4563 articles, a total of 25 clinical studies and seven systematic reviews were finally included in this analysis. The studies reviewed provide a generally positive yet inconsistent view of the efficacy of probiotics in managing VVC, including clinical, mycological response, and prevention perspectives. Nonetheless, fluconazole remains more effective than probiotics in treating VVC, while the combination of the two seems to reduce recurrence and improve symptoms significantly. For prevention, probiotics seem to improve vaginal health and reduce symptoms, while safety and tolerability are consistently reported across the studies, affirming that probiotics represent a low-risk intervention. However, clear conclusions are difficult to establish since relative studies explore different clinical endpoints and follow-up times, variable populations are included, different probiotics are used, and diverse schedules and regimens are administered. We propose that future studies should study the benefit of probiotics in well-defined categories such as (1) treatment with acute probiotics instead of antifungals, (2) adjuvant probiotic therapy together or after antifungals, and (3) VVC recurrence prevention using probiotics. Full article

Gardnerella vaginalis is a Gram-variable bacillus capable of causing bacterial vaginosis, a condition prevalent in reproductive-age women, this bacterium is present in almost 100% of cases and is also considered a gateway to various sexually transmitted infections. This organism exhibits high pathogenicity linked to virulence and resistance genes acquired throughout evolution, showcasing elevated resistance to a broad spectrum of drug classes. This study conducted comparative genomic analyses to identify these genes and correlate their presence with positive Darwinian selection. Additionally, new drug targets were selected through docking and molecular modeling, guided by the heightened antimicrobial resistance exhibited by this microbial species. The available genomes of G. vaginalis were analyzed, and the orthologous genes were delineated and positively selected, whereby 29 groups were found. Of these genes, one of great importance was predicted, Mef(A), which is related to resistance to the macrolide group of antibiotics, which are one of the main choices for the treatment of sexually transmitted infections. Additionally, two potential protein candidates were selected as drug targets. These proteins were linked with a natural compound each and are considered good potential drug targets. The analyses in this study contribute to analyzing the evolution of the species and how resistance genes are related to their permanence as a potential pathogen. Full article

Background/Objectives: There are indications that the microbial composition of the maternal mucosal surfaces is associated with adverse events during pregnancy. The aim of this review is to investigate the link between vaginal microbiome alterations and gestational complication risk. Methods: This comprehensive literature review was performed using Medline and Scopus databases. The following search algorithm was used, “Pregnancy Complications” [Mesh] AND (Vagin*), and after the literature screening, 44 studies were included in the final review. Results: The studies that were included investigated the association between vaginal microbial composition and preterm birth, miscarriage, preeclampsia, ectopic pregnancy, gestational diabetes mellitus, chorioamnionitis, and preterm premature rupture of membranes. In most of the studies, it was well established that increased microbial diversity is associated with these conditions. Also, the depletion of Lactobacillus species is linked to most of the gestational complications, while the increased relative abundance and especially Lactobacillus crispatus may exert a protective effect in favor of the pregnant woman. Several pathogenic taxa including Gardnerella, Prevotella, Sneathia, Bacterial Vaginosis-Associated Bacteria-2, Atopobium, and Megasphera seem to be correlated to higher maternal morbidity. Conclusions: Vaginal microbiome aberrations seem to have an association with pregnancy-related adverse events, but more high-quality homogenous studies are necessary to reliably verify this link. Full article

Vaginally administered postbiotics derived from Lactobacillus were recently demonstrated to be effective in alleviating bacterial vaginosis and increasing pregnancy rates. However, their potential effect on sperm quality has not been well investigated. This controlled in vitro study aimed to assess the dose- and time-dependent effects of postbiotics derived from Lactobacillus rhamnosus PB01 (DSM 14870) on sperm quality parameters. The experiment was conducted in vitro to eliminate potential confounding factors from the female reproductive tract and vaginal microbiota. Sperm samples from 18 healthy donors were subjected to analysis using Computer-Aided Sperm Analysis (CASA) in various concentrations of postbiotics and control mediums at baseline, 60 min, and 90 min of incubation. Results indicated that lower postbiotic concentration (PB5) did not adversely affect sperm motility, kinematic parameters, sperm DNA fragmentation, and normal morphology at any time. However, concentrations exceeding 15% demonstrated a reduction in progressively motile sperm and a negative correlation with non-progressively motile sperm at all time points. These findings underscore the importance of balancing postbiotic dosage to preserve sperm motility while realizing the postbiotics’ vaginal health benefits. Further research is warranted to understand the underlying mechanisms and refine practical applications in reproductive health. Full article

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation. Full article

The vaginal microbiota can be classified into five major community state types (CSTs) based on the bacterial content. However, the link between different CST subtypes and vaginal infection remains unclear. Here, we analyzed 2017 vaginal microbiota samples from women of a reproductive age with vaginal infections that were published in the last decade. We found that L. iners was the most dominant in 34.8% of the vaginal samples, followed by L. crispatus (21.2%). CST I was common in healthy individuals, whereas CST III and IV were associated with dysbiosis and infection. CST III-B, IV-A, IV-B, and IV-C0 were prevalent in patients with bacterial vaginosis (BV). Based on the relative abundance of bacteria at the (sub)genus level, a random forest classifier was developed to predict vaginal infections with an area under the curve of 0.83. We further identified four modules of co-occurring bacterial taxa: L. crispatus, Gardnerella, Prevotella, and Bacteroides. The functional prediction revealed that nucleotide biosynthesis pathways were upregulated in patients with human papilloma virus, and carbohydrate degradation pathways were downregulated in patients with BV. Overall, our study identified the bacterial signatures of healthy and infected vaginal microbiota, providing unique insights into the clinical diagnosis and health status prediction of women of a reproductive age. Full article

Objectives: Twin pregnancy implies a higher risk of preterm birth and, consequently, higher neonatal morbidity and mortality. In singleton pregnancies, infections of the lower genital tract (LGTIs) and bacterial vaginosis are associated with preterm labor, and their early detection has been proven effective in reducing complications like the preterm premature rupture of membranes (pPROM) and preterm delivery. The same evidence, however, is lacking for twin pregnancies. This study aimed to evaluate whether the early identification and treatment of LGTIs or bacterial vaginosis in asymptomatic women with twin pregnancy could reduce the rate of miscarriages, pPROM, and preterm birth. Methods: This study performed a retrospective comparison of 285 women with a multiple pregnancy submitted for a cervico-vaginal swab only at 20–22 weeks (Single Test Group, STG), and 199 women who underwent the swab at 12–14 and again at 20–22 weeks (Double Test Group, DTG). All women included in the study had a twin pregnancy and were followed up at Sant’Anna Hospital, Turin (Italy), between September 2012 and February 2021. Results: In STG, 21.7% of patients had a positive swab; in DTG, 19.9% had an early positive swab that was immediately treated by targeted antibiotics; and 16.7% had a mid-pregnancy positive swab. The DTG showed a significantly lower incidence of pPROM in univariate analysis (14.4% vs. 23.1%, p = 0.021), which was confirmed by multivariate analysis (OR 0.55, CI 0.33–0.93, p = 0.025). Conclusions: Our study suggests that, in asymptomatic women with twin pregnancy, the early screening of LGTIs and bacterial vaginosis by a cervico-vaginal swab at 12–14 weeks of gestational age is effective in reducing the risk of pPROM. Full article

Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing Lactobacillus spp. and the overgrowth of facultative and strict anaerobic bacteria. Prevotella species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, P. bivia, P. amnii, and P. timonensis have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of Prevotella spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common Prevotella spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area. Full article