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Frontiers in Cellular and Infection... 2021The vaginal microbiome is a well-defined compartment of the human microbiome. It has unique conditions, characterized by the dominance of one bacterial species, the... (Review)
Review
The vaginal microbiome is a well-defined compartment of the human microbiome. It has unique conditions, characterized by the dominance of one bacterial species, the This microbiota manifests itself by a low degree of diversity and by a strong dynamic of change in its composition under the influence of various exogenous and endogenous factors. The increase in diversity may paradoxically be associated with dysbiosis, such as bacterial vaginosis (BV). BV is the result of a disturbance in the vaginal ecosystem; i.e., a sudden replacement of by anaerobic bacteria such as , and others. It is the most common cause of vaginal discharge in women of childbearing age, approximately 30% of all causes. The etiology of this dysbiosis remains unknown, but its health consequences are significant, including obstetrical complications, increased risk of sexually transmitted infections and urogenital infections. Its diagnosis is based on Amsel's clinical criteria and/or a gram stain based on the Nugent score. While both of these methods have been widely applied worldwide for approximately three decades, Nugent score are still considered the "gold standard" of BV diagnostic tools. Given the limitations of these tools, methods based on molecular biology have been developed as alternative rational strategies for the diagnosis of BV. The treatment of BV aims at restoring the balance of the vaginal flora to stop the proliferation of harmful microorganisms. Prescription of antibiotics such as metronidazole, clindamycin, etc. is recommended. Faced with the considerable uncertainty about the cause of BV, the high rate of recurrence, the unacceptable treatment options, and clinical management which is often insensitive and inconsistent, research on this topic is intensifying. Knowledge of its composition and its associated variations represents the key element in improving the therapeutic management of patients with the most suitable treatments possible.
Topics: Ecosystem; Female; Gardnerella vaginalis; Humans; Lactobacillus; Vagina; Vaginosis, Bacterial
PubMed: 35118003
DOI: 10.3389/fcimb.2021.672429 -
American Journal of Obstetrics and... Mar 2021Bacterial vaginosis, pelvic inflammatory disease, and endometritis are infections of the genital tract that can lead to many adverse health outcomes, including... (Review)
Review
Bacterial vaginosis, pelvic inflammatory disease, and endometritis are infections of the genital tract that can lead to many adverse health outcomes, including infertility. Bacterial vaginosis is characterized by a lower prevalence of lactobacilli and a higher prevalence of anaerobic bacteria, including Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae. Endometritis and pelvic inflammatory disease are caused by the ascension of pathogenic bacteria to the uterus, although the mechanisms by which they do so are unclear. Bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease have been linked to infertility in retrospective and prospective trials. Similarly, the causes of bacterial vaginosis and endometritis-related infertility are likely multifactorial and stem from inflammation, immune targeting of sperm antigens, the presence of bacterial toxins, and increased risk of sexually transmitted infections. Diagnosis and treatment of bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease before attempting conception may be important components of preconceptional care for symptomatic women to improve outcomes of natural and assisted reproduction.
Topics: Endometritis; Female; Humans; Infertility, Female; Pelvic Inflammatory Disease; Vaginosis, Bacterial
PubMed: 33091407
DOI: 10.1016/j.ajog.2020.10.019 -
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 -
F1000Research 2017Bacterial vaginosis is the most prevalent cause of abnormal vaginal discharge in women of childbearing age. It can have a major impact on quality of life and... (Review)
Review
Bacterial vaginosis is the most prevalent cause of abnormal vaginal discharge in women of childbearing age. It can have a major impact on quality of life and psychological wellbeing if frequently recurrent and strongly symptomatic. The use of molecular techniques to study the vaginal microbiome is increasing our understanding of the dynamic changes in flora that occur in health and disease. It might soon be possible to separate into different pathogenic and non-pathogenic species. Many groups are studying compounds that can disrupt the biofilm which is dominated by and . Several studies in the last decade support the concept of bacterial vaginosis as a sexually transmitted infection.
PubMed: 29043070
DOI: 10.12688/f1000research.11417.1 -
Genome Medicine Nov 2016Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators...
BACKGROUND
Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer.
METHODS
We undertook a study of the microbiome in samples taken from different locations along the female reproductive tract in patients with endometrial cancer (n = 17), patients with endometrial hyperplasia (endometrial cancer precursor, n = 4), and patients afflicted with benign uterine conditions (n = 10). Vaginal, cervical, Fallopian, ovarian, peritoneal, and urine samples were collected aseptically both in the operating room and the pathology laboratory. DNA extraction was followed by amplification and high-throughput next generation sequencing (MiSeq) of the 16S rDNA V3-V5 region to identify the microbiota present. Microbiota data were summarized using both α-diversity to reflect species richness and evenness within bacterial populations and β-diversity to reflect the shared diversity between bacterial populations. Statistical significance was determined through the use of multiple testing, including the generalized mixed-effects model.
RESULTS
The microbiome sequencing (16S rDNA V3-V5 region) revealed that the microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries) are significantly correlated (p < 0.001) and that there is a structural microbiome shift in the cancer and hyperplasia cases, distinguishable from the benign cases (p = 0.01). Several taxa were found to be significantly enriched in samples belonging to the endometrial cancer cohort: Firmicutes (Anaerostipes, ph2, Dialister, Peptoniphilus, 1-68, Ruminococcus, and Anaerotruncus), Spirochaetes (Treponema), Actinobacteria (Atopobium), Bacteroidetes (Bacteroides and Porphyromonas), and Proteobacteria (Arthrospira). Of particular relevance, the simultaneous presence of Atopobium vaginae and an uncultured representative of the Porphyromonas sp. (99 % match to P. somerae) were found to be associated with disease status, especially if combined with a high vaginal pH (>4.5).
CONCLUSIONS
Our results suggest that the detection of A. vaginae and the identified Porphyromonas sp. in the gynecologic tract combined with a high vaginal pH is statistically associated with the presence of endometrial cancer. Given the documented association of the identified microorganisms with other pathologies, these findings raise the possibility of a microbiome role in the manifestation, etiology, or progression of endometrial cancer that should be further investigated.
Topics: Adult; Aged; Bacteria; DNA, Bacterial; DNA, Ribosomal; Endometrial Hyperplasia; Endometrial Neoplasms; Fallopian Tubes; Female; Humans; Middle Aged; Ovary; Phylogeny; RNA, Ribosomal, 16S; Risk Factors; Sequence Analysis, DNA; Urine; Uterus; Vagina
PubMed: 27884207
DOI: 10.1186/s13073-016-0368-y -
The Journal of Infectious Diseases Aug 2021Pelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have...
Pelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have been isolated from the genital tract of people with PID: sexually transmitted organisms such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis; bacterial vaginosis (BV)-associated species and genera such as Atopobium vaginae, Sneathia, and Megasphaera; and genera and species usually associated with the gastrointestinal or respiratory tracts such as Bacteroides, Escherichia coli, Streptococcus, or Haemophilus influenza. Although PID is often considered to be synonymous with gonorrhea or chlamydia, these pathogens are found in only one quarter to one third of people with PID, suggesting that broader screening and diagnostic and treatment strategies need to be considered to reduce the burden of PID and its associated sequelae.
Topics: Chlamydia Infections; Chlamydia trachomatis; Female; Gonorrhea; Humans; Mycoplasma Infections; Mycoplasma genitalium; Neisseria gonorrhoeae; Pelvic Inflammatory Disease; Sexually Transmitted Diseases; Vagina
PubMed: 34396407
DOI: 10.1093/infdis/jiab067 -
Current Clinical Pharmacology Feb 2012As bacterial vaginosis (BV) is a potential cause of obstetric complications and gynecological disorders, there is substantial interest in establishing the most effective... (Comparative Study)
Comparative Study Review
As bacterial vaginosis (BV) is a potential cause of obstetric complications and gynecological disorders, there is substantial interest in establishing the most effective treatment. Standard treatment - metronidazole or clindamycin, by either vaginal or oral route � is followed by relapses in about 30% of cases, within a month from treatment completion. This inability to prevent recurrences reflects our lack of knowledge on the origins of BV. Atopobium vaginae has been recently reported to be associated with BV in around 80% of the cases and might be involved in the therapeutic failures. This review looks at the potential benefits of nifuratel against A. vaginae compared to the standard treatments with metronidazole and clindamycin. In vitro, nifuratel is able to inhibit the growth of A. vaginae, with a MIC range of 0.125-1 μg/mL; it is active against G. vaginalis and does not affect lactobacilli. Metronidazole is active against A. vaginae only at very high concentrations (8-256 μg/mL); it is partially active against G. vaginalis and also has no effect on lactobacilli. Clindamycin acts against A. vaginae with an MIC lower than 0.125 μg/mL and is active on G. vaginalis but it also affects lactobacilli, altering the vaginal environment. These observations suggest that nifuratel is probably the most valid therapeutic agent for BV treatment.
Topics: Actinobacteria; Anti-Bacterial Agents; Clindamycin; Dose-Response Relationship, Drug; Female; Gardnerella vaginalis; Humans; Metronidazole; Microbial Sensitivity Tests; Nifuratel; Secondary Prevention; Vaginosis, Bacterial
PubMed: 22082330
DOI: 10.2174/157488412799218824 -
Journal of Infection in Developing... Sep 2021The aim of the study was to investigate prevalence of bacteria most frequently associated with bacterial vaginosis using Amsel's criteria as well as to quantify these...
INTRODUCTION
The aim of the study was to investigate prevalence of bacteria most frequently associated with bacterial vaginosis using Amsel's criteria as well as to quantify these bacteria by real-time PCR and to explore the difference in their quantity between healthy and bacterial vaginosis samples.
METHODOLOGY
For classification of vaginal discharge samples Amsel's criteria have been used. To detect and quantify Gardnerella vaginalis Atopobium vaginae, Lactobacillus spp. and total vaginal microbiome, real-time PCR has been applied.
RESULTS
According to results of our study Amsel's criteria matched well with real-time PCR diversification of healthy women and women with BV. Nevertheless, real-time PCR has been more sensitive in diagnosis of bacterial vaginosis. DNA quantification of bacteria demonstrated that mutual abundance of G.vaginalis and A. vaginae was good bacterial vaginosis marker . On the contrary, Lactobacillus spp. was present in high amount in both healthy and bacterial vaginosis samples, but ratio of investigated bacteria was different between them. In fact, G. vaginalis and A. vaginae comprised only 0.1% of total microbiome in healthy, whereas Lactobacillus spp. took 99.3% of it. Nonetheless, in bacterial vaginosis, G. vaginalis and A. vaginae made up 34.4% of total microbiome, while Lactobacillus spp. was 21.6%.
CONCLUSIONS
According to the results of our study real-time PCR analysis was more sensitive in diagnosis of bacterial vaginosis than Amsel's method, as well as it represented fine tool in making a difference between microbial entities in healthy and bacterial vaginosis samples.
Topics: Actinobacteria; Adult; Case-Control Studies; Female; Gardnerella vaginalis; Gram-Positive Bacterial Infections; Humans; Lactobacillus; Real-Time Polymerase Chain Reaction; Serbia; Vaginosis, Bacterial; Young Adult
PubMed: 34669599
DOI: 10.3855/jidc.13091 -
Pathogens (Basel, Switzerland) Feb 2021Bacterial vaginosis (BV) is associated with a highly structured polymicrobial biofilm on the vaginal epithelium where species presumably play a pivotal role. , , and...
Bacterial vaginosis (BV) is associated with a highly structured polymicrobial biofilm on the vaginal epithelium where species presumably play a pivotal role. , , and are vaginal pathogens detected during the early stages of incident BV. Herein, we aimed to analyze the impact of and on a pre-established biofilm using a novel in vitro triple-species biofilm model. Total biofilm biomass was determined by the crystal violet method. We also discriminated the bacterial populations in the biofilm and in its planktonic fraction by using PNA FISH. We further analyzed the influence of and on the expression of key virulence genes of by quantitative PCR. In our tested conditions, and were able to incorporate into pre-established biofilms but did not induce an increase in total biofilm biomass, when compared with 48-h biofilms. However, they were able to significantly influence the expression of , a gene suggested to be associated with biofilm maintenance in . This study suggests that microbial relationships between co-infecting bacteria can deeply affect the biofilm, a crucial marker of BV.
PubMed: 33672647
DOI: 10.3390/pathogens10020247 -
Nutrients Jan 2020Spontaneous preterm birth is associated with vaginal microbial dysbiosis. As certain strains of lactobacilli help restore homeostasis in non-pregnant women, the goal was... (Randomized Controlled Trial)
Randomized Controlled Trial
Spontaneous preterm birth is associated with vaginal microbial dysbiosis. As certain strains of lactobacilli help restore homeostasis in non-pregnant women, the goal was to determine the effect of GR-1 and RC-14 administered orally, twice daily for 12 weeks on the vaginal microbiota, cytokines and chemokines of low-risk pregnant women. A double-blind, placebo-controlled, randomized trial comparing probiotic lactobacilli to placebo daily was performed in 86 asymptomatic pregnant women who had an Intermediate or Bacterial Vaginosis Nugent score at 13 weeks. After drop outs, 32 women receiving probiotics and 34 receiving placebo completed the study. The Nugent score returned to normal in 30% of the women in both groups at 28 weeks and was maintained until 35 weeks. The majority of subjects had normal pregnancy outcomes. Ninety-three bacterial species were detected at 13 weeks, with and being the most abundant across pregnancy. There was no difference in the Shannon diversity index between the probiotic and placebo groups at 13, 28 or 35 weeks. Almost all subjects consumed fermented foods and many of the organisms in the vagina are also known to be present in fermented foods. Interleukin-4 in the placebo group and Interleukin-10 in both probiotic and placebo groups increased slightly at 28 weeks but were not different at 35 weeks when compared to 13 weeks. In conclusion, this study showed no adverse issues resulting from 12 week use of probiotic strains GR-1 and RC-14 during pregnancy in women at low risk for premature birth. The vaginal microbiota demonstrated flux irrespective of this oral probiotic administration.
Topics: Administration, Oral; Adult; Chemokines; Cytokines; Double-Blind Method; Dysbiosis; Female; Humans; Limosilactobacillus reuteri; Lacticaseibacillus rhamnosus; Microbiota; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Probiotics; Treatment Outcome; Vagina; Vaginosis, Bacterial
PubMed: 32019222
DOI: 10.3390/nu12020368