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Clinical Microbiology Reviews Apr 2016Bacterial vaginosis (BV) is the most commonly reported microbiological syndrome among women of childbearing age. BV is characterized by a shift in the vaginal flora from... (Review)
Review
Bacterial vaginosis (BV) is the most commonly reported microbiological syndrome among women of childbearing age. BV is characterized by a shift in the vaginal flora from the dominant Lactobacillus to a polymicrobial flora. BV has been associated with a wide array of health issues, including preterm births, pelvic inflammatory disease, increased susceptibility to HIV infection, and other chronic health problems. A number of potential microbial pathogens, singly and in combinations, have been implicated in the disease process. The list of possible agents continues to expand and includes members of a number of genera, including Gardnerella, Atopobium, Prevotella, Peptostreptococcus, Mobiluncus, Sneathia, Leptotrichia, Mycoplasma, and BV-associated bacterium 1 (BVAB1) to BVAB3. Efforts to characterize BV using epidemiological, microscopic, microbiological culture, and sequenced-based methods have all failed to reveal an etiology that can be consistently documented in all women with BV. A careful analysis of the available data suggests that what we term BV is, in fact, a set of common clinical signs and symptoms that can be provoked by a plethora of bacterial species with proinflammatory characteristics, coupled to an immune response driven by variability in host immune function.
Topics: Bacteria; DNA, Bacterial; Female; Humans; Microbiota; Vaginosis, Bacterial
PubMed: 26864580
DOI: 10.1128/CMR.00075-15 -
International Journal of Molecular... May 2023According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant...
According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to characterize the cervicovaginal microbiota of women undergoing hysterectomy due to benign disease, atypical hyperplasia, and endometrial cancer; The study included 96 patients, who undergone surgical treatment due to benign uterine disease, precancerous endometrial lesion, and endometrial cancer. Quantitative and qualitative real-time PCR analysis of DNA isolated from vaginal fornix and endocervical canal samples was performed to detect the 19 most commonly identified microorganisms, including different spp., , , , and ; At least one of the tested microorganisms was identified in 88.5% of vaginal and 83.3% of cervical samples. was significantly more frequent in patients with benign condition, whereas and was more frequent in cancer patients; and which were identified as significantly more common in endometrial cancer vaginal samples, may be considered as potential endometrial cancer co-factors which promote/stimulate carcinogenesis. However, the exact mechanism of such activity remains unexplained and requires further investigations.
Topics: Humans; Female; Cervix Uteri; Vagina; Endometrial Neoplasms; Uterine Diseases; Microbiota; RNA, Ribosomal, 16S
PubMed: 37175971
DOI: 10.3390/ijms24098266 -
Frontiers in Cellular and Infection... 2021The cervicovaginal microbiome plays an important role in protecting women from dysbiosis and infection caused by pathogenic microorganisms. In healthy reproductive-age...
The cervicovaginal microbiome plays an important role in protecting women from dysbiosis and infection caused by pathogenic microorganisms. In healthy reproductive-age women the cervicovaginal microbiome is predominantly colonized by protective spp. The loss of these protective bacteria leads to colonization of the cervicovaginal microenvironment by pathogenic microorganisms resulting in dysbiosis and bacterial vaginosis (BV). and sp. are two of the many anaerobes that can contribute to BV, a condition associated with multiple adverse obstetric and gynecological outcomes. has been linked to high Nugent scores (relating to BV morphotypes) and preterm birth (PTB), whilst some bacterial members of the family are highly prevalent in BV, and identified in ~85-95% of cases. The functional impact of and sp. in BV is still poorly understood. To determine the individual immunometabolic contributions of sp. and within the cervicovaginal microenvironment, we utilized our well-characterized human three-dimensional (3-D) cervical epithelial cell model in combination with multiplex immunoassays and global untargeted metabolomics approaches to identify key immune mediators and metabolites related to and sp. infections. We found that infection with significantly elevated multiple proinflammatory markers (IL-6, IL-8, TNF-α and MCP-1) and altered metabolites related to energy metabolism (nicotinamide and succinate) and oxidative stress (cysteinylglycine, cysteinylglycine disulfide and 2-hydroxygluatrate). sp. infection significantly elevated multiple sphingolipids and glycerolipids related to epithelial barrier function, and biogenic amines (putrescine and cadaverine) associated with elevated vaginal pH, vaginal amine odor and vaginal discharge. Our study elucidated that elevated multiple proinflammatory markers relating to PTB and STI acquisition, as well as altered energy metabolism and oxidative stress, whilst sp. upregulated multiple biogenic amines associated with the clinical diagnostic criteria of BV. Future studies are needed to evaluate how these bacteria interact with other BV-associated bacteria within the cervicovaginal microenvironment.
Topics: Female; Humans; Infant, Newborn; Microbiota; Mobiluncus; Pregnancy; Premature Birth; Vagina; Vaginosis, Bacterial
PubMed: 35004344
DOI: 10.3389/fcimb.2021.759697 -
Infection and Immunity Feb 2021Bacterial vaginosis (BV) is a vaginal dysbiotic condition linked to negative gynecological and reproductive sequelae. Flagellated bacteria have been identified in women... (Comparative Study)
Comparative Study
Bacterial vaginosis (BV) is a vaginal dysbiotic condition linked to negative gynecological and reproductive sequelae. Flagellated bacteria have been identified in women with BV, including spp. and BV-associated bacterium-1 (BVAB1), an uncultivated, putatively flagellated species. The host response to flagellin mediated through Toll-like receptor 5 (TLR5) has not been explored in BV. Using independent discovery and validation cohorts, we examined the hypothesis that TLR5 deficiency-defined by a dominant negative stop codon polymorphism, rs5744168-is associated with an increased risk for BV and increased colonization with flagellated bacteria associated with BV (BVAB1, , and ). TLR5 deficiency was not associated with BV status, and TLR5-deficient women had decreased colonization with BVAB1 in both cohorts. We stimulated HEK-hTLR5-overexpressing NF-κB reporter cells with whole, heat-killed or and with partially purified flagellin from these species; as BVAB1 is uncultivated, we used cervicovaginal lavage (CVL) fluid supernatant from women colonized with BVAB1 for stimulation. While heat-killed and CVL fluid from women colonized with BVAB1 stimulate a TLR5-mediated response, heat-killed did not. In contrast, partially purified flagellin from both species stimulated a TLR5-mediated response We observed no correlation between vaginal interleukin 8 (IL-8) and flagellated BVAB concentrations among TLR5-sufficient women. Interspecies variation in accessibility of flagellin recognition domains may be responsible for these observations, as reflected in the potentially novel flagellin products encoded by species versus those encoded by BVAB1.
Topics: Adolescent; Adult; Cohort Studies; Female; Flagellin; Genes, Bacterial; Genetic Variation; Genotype; Humans; Middle Aged; Mobiluncus; Toll-Like Receptor 5; Vagina; Vaginosis, Bacterial; Washington; Young Adult
PubMed: 33199356
DOI: 10.1128/IAI.00060-20 -
Acta Crystallographica. Section D,... Nov 2023Cell-surface proteins known as adhesins enable bacteria to colonize particular environments, and in Gram-positive bacteria often contain autocatalytically formed...
Cell-surface proteins known as adhesins enable bacteria to colonize particular environments, and in Gram-positive bacteria often contain autocatalytically formed covalent intramolecular cross-links. While investigating the prevalence of such cross-links, a remarkable example was discovered in Mobiluncus mulieris, a pathogen associated with bacterial vaginosis. This organism encodes a putative adhesin of 7651 residues. Crystallography and mass spectrometry of two selected domains, and AlphaFold structure prediction of the remainder of the protein, were used to show that this adhesin belongs to the family of thioester, isopeptide and ester-bond-containing proteins (TIE proteins). It has an N-terminal domain homologous to thioester adhesion domains, followed by 51 immunoglobulin (Ig)-like domains containing ester- or isopeptide-bond cross-links. The energetic cost to the M. mulieris bacterium in retaining such a large adhesin as a single gene or protein construct suggests a critical role in pathogenicity and/or persistence.
Topics: Female; Humans; Mobiluncus; Adhesins, Bacterial; Esters
PubMed: 37860959
DOI: 10.1107/S2059798323007507 -
NPJ Biofilms and Microbiomes Mar 2024Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis,...
Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis, and preterm birth, while Lactobacillus crispatus is associated with optimal reproductive health. Although host-microbe interactions are hypothesized to contribute to reproductive health and disease, the bacterial mediators that are critical to this response remain unclear. Bacterial extracellular vesicles (bEVs) are proposed to participate in host-microbe communication by providing protection of bacterial cargo, delivery to intracellular targets, and ultimately induction of immune responses from the host. We evaluated the proteome of bEVs produced in vitro from G. vaginalis, M. mulieris, and L. crispatus, identifying specific proteins of immunologic interest. We found that bEVs from each bacterial species internalize within cervical and vaginal epithelial cells, and that epithelial and immune cells express a multi-cytokine response when exposed to bEVs from G. vaginalis and M. mulieris but not L. crispatus. Further, we demonstrate that the inflammatory response induced by G. vaginalis and M. mulieris bEVs is TLR2-specific. Our results provide evidence that vaginal bacteria communicate with host cells through secreted bEVs, revealing a mechanism by which bacteria lead to adverse reproductive outcomes associated with inflammation. Elucidating host-microbe interactions in the cervicovaginal space will provide further insight into the mechanisms contributing to microbiome-mediated adverse outcomes and may reveal new therapeutic targets.
Topics: Infant, Newborn; Humans; Female; Gardnerella vaginalis; Mobiluncus; Proteomics; Premature Birth; Extracellular Vesicles
PubMed: 38514622
DOI: 10.1038/s41522-024-00502-y -
Scientific Reports Oct 2020Vaginal infection is a gynecological problem in women of reproductive age with multiple health outcomes. The most common forms of infection include bacterial vaginosis...
Vaginal infection is a gynecological problem in women of reproductive age with multiple health outcomes. The most common forms of infection include bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and aerobic vaginitis (AV). Our main goals were to evaluate different types of vaginal infections in Ecuadorian women in a large urban area (Quito) and to characterize the vaginal microbiota colonization by opportunistic species. We collected vaginal swabs and epidemiological surveys from 414 women from June 2016 to July of 2017. We analyzed vaginal samples for the presence of any vaginal infection. The microbiological examination was done through Gram-stain, wet mount smears, and polymerase chain reaction (PCR) assays using primers for target genes, such as 16S rRNA (Atopobium vaginae, Mobiluncus mulieris, and Gardnerella species), ddl (Enterococcus faecalis), adk (Escherichia coli) and KER1 (Candida albicans) genes. Most women showed a healthy vaginal microbiota (66.7%). Nearly one-tenth (10.4%) of the participants had intermediate microbiota, and the remaining women (22.9%) had a single vaginal infection (BV, AV, or VC) or coinfections. From the 95 participants that had an infection, AV was the main diagnosed vaginal infection (51.6%), followed by BV (24.2%) and finally VC (7.4%). The remaining women (16.8%) showed coinfections, being BV and AV the most common coinfection. Using univariable logistic regression analyses we found an increased odds of healthy microbiota in women with a sexual partner (P = 0.02, OR = 1.64). Also, women in a free union relationship (P = 0.000, OR = 16.65) had an increased odds of having coinfections. On the other hand, the use of birth control (condom OR = 0.388 or other contraceptive method OR = 0.363) was associated with significantly lower odds of intermediate microbiota (P ≤ 0.05). We found no statistically significant differences between women with infection and a particular group age. Using multivariate logistic regression analyses we initially found an increased odds of having BV in women with M. mulieris (P = 0.020, OR = 4.98) and Gardnerella species (P = 0.010, OR = 4.16). Women with E. coli showed an increased odds of having AV (P = 0.009, OR = 2.81). The presence of C. albicans in women showed an increased odds of having VC (P = 0.007, OR = 17.94). Finally, women with M. mulieris showed a reverse odds of having healthy microbiota (P = 0.008, OR = 0.06). We found no statistically significant differences between women with symptomatic and asymptomatic infections or the presence of Enterococcus faecalis. We found using logistic regression analyses that M. mulieris was the most prevalent opportunistic pathogen among women with vaginal infection. Further studies should evaluate the possibility to use M. mulieris as a potential key predictor for vaginal infections.
Topics: Adult; Age Factors; Candidiasis, Vulvovaginal; Ecuador; Female; Humans; Microbiota; Middle Aged; Prevalence; Risk Factors; Vagina; Vaginal Diseases; Vaginosis, Bacterial; Young Adult
PubMed: 33110095
DOI: 10.1038/s41598-020-74655-z -
Infectious Disease Reports Jan 2022There are few reports of bacteremia caused by in the literature. We present a review of the literature in addition to a case study.
BACKGROUND
There are few reports of bacteremia caused by in the literature. We present a review of the literature in addition to a case study.
METHOD
We describe the case of an 82-year-old patient who underwent gastrointestinal surgery and subsequently presented with dehydration, nausea, and hyperkalemia secondary to diarrhea. Further clinical work included blood cultures, and the patient was started empirically on piperacillin/tazobactam.
RESULTS
After five days, the blood culture bottle showed growth of a gram-variable, curved rod-shaped organism. After culture under anaerobic conditions on sheep blood agar, the organism was identified as by MALDI-TOF mass spectrometry and enzymatic technology. A review of the literature reveals five additional cases of bacteremia.
CONCLUSIONS
This is the sixth case in the literature describing species bacteremia. This organism is rarely identified in blood culture and is most often thought of in the context of bacterial vaginosis. However, the reported cases of bacteremia show gastrointestinal symptoms and presumed gastrointestinal source of infection. The pathogenesis of infection of this organism requires further investigation.
PubMed: 35076503
DOI: 10.3390/idr14010009 -
Nutrients Jan 2023Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption... (Randomized Controlled Trial)
Randomized Controlled Trial
Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4-6 took MED-01 (5.0 × 10 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that was significantly increased in the vagina, whereas harmful bacteria such as spp., and were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.
Topics: Female; Humans; Adult; Vagina; Vaginosis, Bacterial; Probiotics; Gardnerella vaginalis; Dietary Supplements
PubMed: 36678202
DOI: 10.3390/nu15020331 -
MSphere Jun 2022Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome, characterized by low levels of lactobacilli and overgrowth of a diverse group of bacteria, associated...
Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome, characterized by low levels of lactobacilli and overgrowth of a diverse group of bacteria, associated with higher risk of a variety of infections, surgical complications, cancer, and preterm birth (PTB). Despite the lack of a consistently applicable etiology, spp. are often associated with both BV and PTB, and has known symbiotic relationships with both Peptostreptococcus anaerobius and Gardnerella vaginalis. Higher risk of PTB can also be predicted by a composite of metabolites linked to bacterial metabolism, but their specific bacterial source remains poorly understood. Here, we characterize diversity of metabolic strategies among BV-associated bacteria and lactobacilli and the symbiotic metabolic relationships between and its partners and show how these influence the availability of metabolites associated with BV/PTB and/or pro- or anti-inflammatory immune responses. We confirm a commensal relationship between and , refining its mechanism, which sustains a substantial increase in acetate production. In contrast, the relationship between and strains, with sequence variant G2, is mutualistic, with outcome dependent on the metabolic strategy of the strain. Taken together, our data show how knowledge of inter- and intraspecies metabolic diversity and the effects of symbiosis may refine our understanding of the mechanism and approach to risk prediction in BV and/or PTB. Bacterial vaginosis (BV) is the most common vaginal infection for women of childbearing age. Although 50% of women with BV do not have any symptoms, it approximately doubles the risk of catching a sexually transmitted infection and also increases the risk of preterm delivery in pregnant women. Recent studies of the vaginal microbiota have suggested that variation between species in the same genus or between strains of the same species explain better or poorer outcomes or at least some coexistence patterns for bacteria of concern. We tested whether such variation is manifested in how vaginal bacteria grow in the laboratory and whether and how they may share nutrients. We then showed that this affected the overall cocktail of chemicals they produce, including bacterially derived chemicals that we have previously shown are linked to a higher risk of preterm delivery.
Topics: Bacteria; Female; Humans; Infant, Newborn; Lactobacillus; Magnetic Resonance Spectroscopy; Pregnancy; Premature Birth; Symbiosis; Vaginosis, Bacterial
PubMed: 35491843
DOI: 10.1128/msphere.00166-22