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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 -
Pathogens and Disease Jan 2023Bacterial vaginosis, a type of vaginal inflammation, can be considered the main reason for abnormal discharges of the vagina and vaginal dysbiosis during reproductive...
Bacterial vaginosis, a type of vaginal inflammation, can be considered the main reason for abnormal discharges of the vagina and vaginal dysbiosis during reproductive years. Epidemiological investigations of females suffering from vaginitis demonstrated that at least 30% to 50% of all women had Bacterial vaginosis (BV). One of the fields of treatment is the use of probiotics, probiotics are commonly defined as viable microorganisms (yeasts or bacteria) that can positively affect the health of their hosts. They are used in foods, notably fermented milk products, and medicine-related products. The development of new probiotic strains is aimed at more active advantageous organisms. Lactobacillus species are the dominant bacteria in a normal vagina that can decrease the pH of the vagina by the production of lactic acid. A number of lactobacilli types can produce hydrogen peroxide as well. The presence of hydrogen peroxide-induced low pH can prevent the growth of several other microorganisms. The vaginal flora of BV cases can modify by replacing the Lactobacillus species with a high density of anaerobic bacteria (i.e. Mobiluncus sp. Bacteroides sp.), Mycoplasma hominis, and Gardnerella vaginalis. More vaginal infections are treated with medications, while there is a possibility of recurrence and chronic infection because of the adverse effects on the indigenous lactobacilli. Probiotics and prebiotics have shown capacities for optimizing, maintaining, and restoring the vaginal microflora. Therefore, biotherapeutics can offer alternative approaches to reduce infections of the vagina and thus promote consumers' health.
Topics: Female; Humans; Vaginosis, Bacterial; Hydrogen Peroxide; Vagina; Gardnerella vaginalis; Lactobacillus; Probiotics
PubMed: 37286796
DOI: 10.1093/femspd/ftad012 -
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 -
American Journal of Reproductive... Aug 2023Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with...
PROBLEM
Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with Lactobacillus-deficient vaginal microbial communities. One proposed mechanism is that vaginal microbes ascend through the cervix, colonize the uterus, and activate inflammatory pathways leading to sPTB. This study assessed whether intrauterine colonization with either Gardnerella vaginalis and Mobiluncus mulieris alone is sufficient to induce maternal-fetal inflammation and induce sPTB.
METHOD OF STUDY
C56/B6J mice, on embryonic day 15, received intrauterine inoculation of saline or 10 colony-forming units of G. vaginalis (n = 30), M. mulieris (n = 17), or Lactobacillus crispatus (n = 16). Dams were either monitored for maternal morbidity and sPTB or sacrificed 6 h post-infusion for analysis of bacterial growth and cytokine/chemokine expression in maternal and fetal tissues.
RESULTS
Six hours following intrauterine inoculation with G. vaginalis, M. mulieris, or L. crispatus, live bacteria were observed in both blood and amniotic fluid, and a potent immune response was identified in the uterus and maternal serum. In contrast, only a limited immune response was identified in the amniotic fluid and the fetus after intrauterine inoculation. High bacterial load (10 CFU/animal) of G. vaginalis was associated with maternal morbidity and mortality but not sPTB. Intrauterine infusion with L. crispatus or M. mulieris at 10 CFU/animal did not induce sPTB, alter pup viability, litter size, or maternal mortality.
CONCLUSIONS
Despite inducing an immune response, intrauterine infusion of live G. vaginalis or M. mulieris is not sufficient to induce sPTB in our mouse model. These results suggest that ascension of common vaginal microbes into the uterine cavity alone is not causative for sPTB.
Topics: Actinomycetales Infections; Disease Models, Animal; Gardnerella vaginalis; Mice, Inbred C57BL; Mobiluncus; Mothers; Pregnancy Complications, Infectious; Premature Birth; Vaginosis, Bacterial; Female; Animals; Mice
PubMed: 37491927
DOI: 10.1111/aji.13749 -
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 -
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 -
Anaerobe Feb 2020Recent human clinical studies have identified Mobiluncus mulieris, a fastidious strict anaerobic bacterium present in the cervicovaginal (CV) space, as being strongly...
Microbial supernatants from Mobiluncus mulieris, a bacteria strongly associated with spontaneous preterm birth, disrupts the cervical epithelial barrier through inflammatory and miRNA mediated mechanisms.
Recent human clinical studies have identified Mobiluncus mulieris, a fastidious strict anaerobic bacterium present in the cervicovaginal (CV) space, as being strongly associated with spontaneous preterm birth (sPTB). However, the molecular mechanisms that underlie this association remain unknown. As disruption of the cervical epithelial barrier has been shown to contribute to the premature cervical remodeling that precedes sPTB, we hypothesize that M. mulieris, a microbe strongly associated with sPTB in humans, has the ability to alter cervical epithelial function. We investigated if bacteria-free supernatants of M. mulieris were able to disrupt the cervical epithelial barrier through immunological and epigenetic based mechanisms in an in vitro model system. Ectocervical cells were treated with supernatant from cultured M. mulieris and epithelial cell permeability, immune cytokines and microRNAs (miRNAs) were investigated. M. mulieris supernatant significantly increased cell permeability and the expression of two inflammatory mediators associated with cervical epithelial breakdown, IL-6 and IL-8. Moreover, treatment of the ectocervical cells with the M. mulieris supernatant also increased the expression of miRNAs that have been associated with either sPTB or a shorter gestational length in humans. Collectively, these results suggest that M. mulieris induces molecular and functional changes in the cervical epithelial barrier thought to contribute to the pathogenesis of sPTB, which allows us to hypothesize that targeting CV bacteria such as M. mulieris could provide a therapeutic opportunity to reduce sPTB rates.
Topics: Actinomycetales Infections; Biomarkers; Cell Membrane Permeability; Culture Media, Conditioned; Cytokines; Epithelial Cells; Female; Gene Expression Regulation; Humans; Inflammation Mediators; MicroRNAs; Mobiluncus; Mucous Membrane; Premature Birth
PubMed: 31760081
DOI: 10.1016/j.anaerobe.2019.102127 -
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 -
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