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Microbial Biotechnology Jul 2023Bacterial vaginosis (BV) is the most common cause of vaginal discharge and is often associated with other health consequences mainly in pregnant women. BV is described... (Review)
Review
Bacterial vaginosis (BV) is the most common cause of vaginal discharge and is often associated with other health consequences mainly in pregnant women. BV is described by an imbalance in the vaginal microbiota where strictly and facultative anaerobic bacteria outgrow the lactic acid- and hydrogen peroxide-producing Lactobacillus species. The species involved in BV are capable to grow and form a polymicrobial biofilm in the vaginal epithelium. The treatment of BV is usually performed using broad-spectrum antibiotics, including metronidazole and clindamycin. However, these conventional treatments are associated with high recurrence rates. The BV polymicrobial biofilm may have an important role on the treatment outcome and is accounted as one of the factors for treatment failure. Other possible reasons for treatment failure include the presence of species resistant to antibiotics or the chance of reinfection after treatment. Therefore, novel strategies to increase the rates of treatment have been studied namely the use of probiotics and prebiotics, acidifying agents, antiseptics, plant-based products, vaginal microbiota transplantation, and phage endolysins. Although some of them are still in an initial phase of development with very preliminary results, they show great perspectives for application. In this review, we aimed to study the role of the polymicrobial nature of BV in treatment failure and explore a few alternatives for treatment.
Topics: Pregnancy; Female; Humans; Vaginosis, Bacterial; Metronidazole; Vagina; Anti-Bacterial Agents; Biofilms
PubMed: 37042412
DOI: 10.1111/1751-7915.14261 -
Frontiers in Immunology 2022The female reproductive tract harbors a unique microbiome, especially the vagina. The human vaginal microbiome exhibits a low diversity and is dominated by species,... (Review)
Review
The female reproductive tract harbors a unique microbiome, especially the vagina. The human vaginal microbiome exhibits a low diversity and is dominated by species, compared to the microbiome of other organs. The host and vaginal microbiome mutually coexist in the vaginal microenvironment. Host cells provide glycogen as an energy source, and produce lactic acid, which lowers vaginal pH thereby preventing growth of other bacteria. Bacterial vaginosis can modulate host immune systems, and is frequently associated with various aspects of disease, including sexually transmitted infection, gynecologic cancer, and poor pregnancy outcomes. Because of this, numerous studies focused on the impact of the vaginal microbiome on women`s health and disease. Furthermore, numerous epidemiologic studies also have demonstrated various host factors regulate the vaginal microbiome. The female reproductive tract undergoes constant fluctuations due to hormonal cycle, pregnancy, and other extrinsic factors. Depending on these fluctuations, the vaginal microbiome composition can shift temporally and dynamically. In this review, we highlight the current knowledge of how host factors modulate vaginal microbiome composition and how the vaginal microbiome contributes to maintaining homeostasis or inducing pathogenesis. A better understanding of relationship between host and vaginal microbiome could identify novel targets for diagnosis, prognosis, or treatment of microbiome-related diseases.
Topics: Female; Humans; Lactobacillus; Microbiota; Pregnancy; Sexually Transmitted Diseases; Vagina; Vaginosis, Bacterial
PubMed: 35837395
DOI: 10.3389/fimmu.2022.919728 -
Frontiers in Cellular and Infection... 2020A healthy female genital tract harbors a microbiome dominated by lactic acid and hydrogen peroxide producing bacteria, which provide protection against infections by... (Review)
Review
A healthy female genital tract harbors a microbiome dominated by lactic acid and hydrogen peroxide producing bacteria, which provide protection against infections by maintaining a low pH. Changes in the bacterial compositions of the vaginal microbiome can lead to bacterial vaginosis (BV), which is often associated with vaginal inflammation. Bacterial vaginosis increases the risk of acquiring sexually transmitted infections (STIs) like human immunodeficiency virus (HIV) and affects women's reproductive health negatively. In pregnant women, BV can lead to chorioamnionitis and adverse pregnancy outcomes, including preterm premature rupture of the membranes and preterm birth. In order to manage BV effectively, good diagnostic procedures are required. Traditionally clinical and microscopic methods have been used to diagnose BV; however, these methods require skilled staff and time and suffer from reduced sensitivity and specificity. New diagnostics, including highly sensitive and specific point-of-care (POC) tests, treatment modalities and vaccines can be developed based on the identification of biomarkers from the growing pool of vaginal microbiome and vaginal metabolome data. In this review the current and future diagnostic avenues will be discussed.
Topics: Female; Humans; Infant, Newborn; Microbiota; Pregnancy; Premature Birth; Sexually Transmitted Diseases; Vagina; Vaginosis, Bacterial
PubMed: 32850469
DOI: 10.3389/fcimb.2020.00354 -
Current Opinion in Infectious Diseases Feb 2020The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. We recently published an updated conceptual model on... (Review)
Review
PURPOSE OF REVIEW
The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. In this article, we extend the description of our model to include a discussion on the role of host-vaginal microbiota interactions in bacterial vaginosis pathogenesis.
RECENT FINDINGS
Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host-immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes.
SUMMARY
Elucidating the cause of bacterial vaginosis has important implications for diagnosis and treatment. Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.
Topics: Bacteria; Biofilms; Female; Host-Pathogen Interactions; Humans; Microbiota; Vagina; Vaginosis, Bacterial
PubMed: 31789672
DOI: 10.1097/QCO.0000000000000620 -
Frontiers in Cellular and Infection... 2022Cervical cancer disproportionately affects women of reproductive age, with 80% of cases occurring in low- and middle-income countries. Persistent infection with... (Review)
Review
Cervical cancer disproportionately affects women of reproductive age, with 80% of cases occurring in low- and middle-income countries. Persistent infection with high-risk human papillomavirus (HPV) genotypes has been described as the most common non-systemic biological risk factor for the development of cervical cancer. The mucosal immune system plays a significant role in controlling HPV infection by acting as the first line of host defense at the mucosal surface. However, the virus can evade host immunity using various mechanisms, including inhibition of the antiviral immune response necessary for HPV clearance. Pro-inflammatory cytokines and the vaginal microbiome coordinate cell-mediated immune responses and play a pivotal role in modulating immunity. Recently, diverse vaginal microbiome (associated with bacterial vaginosis) and genital inflammation have emerged as potential drivers of high-risk HPV positivity and disease severity in women. The potential role of these risk factors on HPV recurrence and persistence remains unclear. This article reviews the role of cellular or cytokine response and vaginal microbiome dysbiosis in the clearance, persistence, and recurrence of HPV infection.
Topics: Cytokines; Female; Humans; Microbiota; Papillomavirus Infections; Uterine Cervical Neoplasms; Vagina; Vaginosis, Bacterial
PubMed: 35873158
DOI: 10.3389/fcimb.2022.927131 -
Journal of Clinical Microbiology Aug 2023Bacterial vaginosis (BV) is the most common cause of vaginal discharge among reproductive-age women. It is associated with multiple adverse health outcomes, including... (Review)
Review
Bacterial vaginosis (BV) is the most common cause of vaginal discharge among reproductive-age women. It is associated with multiple adverse health outcomes, including increased risk of acquisition of HIV and other sexually transmitted infections (STIs), in addition to adverse birth outcomes. While it is known that BV is a vaginal dysbiosis characterized by a shift in the vaginal microbiota from protective species to an increase in facultative and strict anaerobic bacteria, its exact etiology remains unknown. The purpose of this minireview is to provide an updated overview of the range of tests currently used for the diagnosis of BV in both clinical and research settings. This article is divided into two primary sections: traditional BV diagnostics and molecular diagnostics. Molecular diagnostic assays, particularly 16S rRNA gene sequencing, shotgun metagenomic sequencing, and fluorescence hybridization (FISH), are specifically highlighted, in addition to multiplex nucleic acid amplification tests (NAATs), given their increasing use in clinical practice (NAATs) and research studies (16S rRNA gene sequencing, shotgun metagenomic sequencing, and FISH) regarding the vaginal microbiota and BV pathogenesis. We also provide a discussion of the strengths and weaknesses of current BV diagnostic tests and discuss future challenges in this field of research.
Topics: Humans; Female; Vaginosis, Bacterial; RNA, Ribosomal, 16S; In Situ Hybridization, Fluorescence; Vagina; Sexually Transmitted Diseases
PubMed: 37199636
DOI: 10.1128/jcm.00837-22 -
Microbiome Nov 2022A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence...
BACKGROUND
A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions.
RESULTS
Here, we describe an organ-on-a-chip (organ chip) microfluidic culture model of the human vaginal mucosa (vagina chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen. We show that the Vagina Chip can be used to assess colonization by optimal L. crispatus consortia as well as non-optimal Gardnerella vaginalis-containing consortia, and to measure associated host innate immune responses. Co-culture and growth of the L. crispatus consortia on-chip was accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines. In contrast, co-culture of G. vaginalis-containing consortia in the vagina chip resulted in epithelial cell injury, a rise in pH, and upregulation of proinflammatory cytokines.
CONCLUSION
This study demonstrates the potential of applying human organ chip technology to create a preclinical model of the human vaginal mucosa that can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products. Video Abstract.
Topics: Female; Pregnancy; Humans; Lab-On-A-Chip Devices; Vagina; Microbiota; Vaginosis, Bacterial; Cytokines
PubMed: 36434666
DOI: 10.1186/s40168-022-01400-1 -
Frontiers in Cellular and Infection... 2020Koch's postulates dictate the use of experimental models to illustrate features of human disease and provide evidence for a singular organism as the cause. The... (Review)
Review
Koch's postulates dictate the use of experimental models to illustrate features of human disease and provide evidence for a singular organism as the cause. The underlying cause(s) of bacterial vaginosis (BV) has been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now known as may be the cause of a condition (BV) resulting in higher vaginal pH, thin discharge, a fishy odor, and the presence of epithelial cells covered in bacteria. Here we review contemporary and historical studies on BV with a focus on reports of experimental infections in human or animal models using . We evaluate experimental evidence for the hypothesis that is sufficient to trigger clinical features of BV or relevant health complications associated with the condition. Additionally, we evaluate models of co-infection employing together with other bacterial species to investigate evidence for the hypothesis that may encourage colonization or virulence of other potential pathogens. Together, these studies paint a complex picture in which has both direct and indirect roles in the features, health complications, and co-infections associated with BV. We briefly review the current taxonomic landscape and genetic diversity pertinent to and note the limitations of sequence-based studies using different marker genes and priming sites. Although much more study is needed to refine our understanding of how BV develops and persists within the human host, applications of the experimental aspects of Koch's postulates have provided an important glimpse into some of the causal relationships that may govern this condition .
Topics: Animals; Epithelial Cells; Female; Gardnerella; Gardnerella vaginalis; Humans; Vagina; Vaginosis, Bacterial; Virulence
PubMed: 32391287
DOI: 10.3389/fcimb.2020.00168 -
Frontiers in Cellular and Infection... 2021, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically... (Review)
Review
, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of in the vaginal microbiome was carefully explored. has the smallest genome among known and it has many probiotic characteristics, but is partly different from other major vaginal species, such as , in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.
Topics: Dysbiosis; Female; Humans; Lactobacillus; Pregnancy; Vagina; Vaginosis, Bacterial
PubMed: 34881196
DOI: 10.3389/fcimb.2021.792787 -
Science Advances May 2023Molecular therapeutics are limited for vaginitis because they damage normal cells and tissues of vagina, aggravating the imbalance of vaginal microbiota and increasing...
Molecular therapeutics are limited for vaginitis because they damage normal cells and tissues of vagina, aggravating the imbalance of vaginal microbiota and increasing the recurrence. To tackle this limitation, through the combination of peroxidase-like rGO@FeS nanozymes [reduced graphene oxide (rGO)] with -produced lactic acid and HO, a responsive hyaluronic acid (HA) hydrogel rGO@FeS/@HA (FeLab) is developed. FeLab has simultaneous anti- and vaginal microbiota-modulating activities. In particular, the hydroxyl radical produced from rGO@FeS nanozymes and kills isolated from clinical specimens without affecting . In mice with vaginitis, FeLab has obvious anti- activity but hardly damages vaginal mucosa cells, which is beneficial to vaginal mucosa repair. Moreover, a higher proportion of (especially ) and a decrease in reshape a healthy vaginal microbiota to reduce the recurrence. These results provide a combined therapeutic of nanozymes and probiotics with translational promise for vaginitis therapy.
Topics: Female; Humans; Animals; Mice; Hydrogen Peroxide; Hydrogels; Candidiasis, Vulvovaginal; Vagina; Candida albicans; Lactobacillus; Probiotics
PubMed: 37196095
DOI: 10.1126/sciadv.adg0949