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Paediatric and Perinatal Epidemiology Jul 2024Studies evaluating the association between the vaginal microbiota and miscarriage have produced variable results.
BACKGROUND
Studies evaluating the association between the vaginal microbiota and miscarriage have produced variable results.
OBJECTIVE
This study evaluated the association between periconceptual and first-trimester vaginal microbiota and women's risk for miscarriage.
METHODS
At monthly preconception visits and at 9-12 weeks gestation, women collected vaginal swabs for molecular characterisation of the vaginal microbiota. Participants who became pregnant were followed to identify miscarriage versus pregnancy continuing to at least 20 weeks gestation.
RESULTS
Forty-five women experienced miscarriage and 144 had pregnancies continuing to ≥20 weeks. A principal component analysis of periconceptual and first-trimester vaginal bacteria identified by 16S rRNA gene PCR with next-generation sequencing did not identify distinct bacterial communities with miscarriage versus continuing pregnancy. Using taxon-directed quantitative PCR assays, increasing concentrations of Megasphaera hutchinsoni, Mageeibacillus indolicus, Mobiluncus mulieris and Sneathia sanguinegens/vaginalis were not associated with miscarriage. In exploratory analyses, these data were examined as a binary exposure to allow for multivariable modelling. Detection of Mobiluncus mulieris in first-trimester samples was associated with miscarriage (adjusted relative risk [aRR] 2.14, 95% confidence interval [CI] 1.08, 4.22). Additional analyses compared women with early first-trimester miscarriage (range 4.7-7.3 weeks) to women with continuing pregnancies. Mobiluncus mulieris was detected in all eight (100%) first-trimester samples from women with early first-trimester miscarriage compared to 101/192 (52.6%) samples from women with continuing pregnancy (model did not converge). Detection of Mageeibacillus indolicus in first-trimester samples was also associated with early first-trimester miscarriage (aRR 4.10, 95% CI 1.17, 14.31).
CONCLUSIONS
The primary analyses in this study demonstrated no association between periconceptual or first-trimester vaginal microbiota and miscarriage. Exploratory analyses showing strong associations between first-trimester detection of Mobiluncus mulieris and Mageeibacillus indolicus and early first-trimester miscarriage suggest the need for future studies to determine if these findings are reproducible.
PubMed: 38949435
DOI: 10.1111/ppe.13099 -
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 -
Current Microbiology Feb 2024The strains Marseille-Q7072 (= CSUR Q7072 = CECT 30604) and Marseille-Q7826 (= CSUR Q7826 = CECT 30727) were isolated from vaginal samples. As MALDI-TOF mass...
The strains Marseille-Q7072 (= CSUR Q7072 = CECT 30604) and Marseille-Q7826 (= CSUR Q7826 = CECT 30727) were isolated from vaginal samples. As MALDI-TOF mass spectrometry failed to identify them, their genomes were directly sequenced to determine their taxogenomic identities. Both strains are anaerobic without any oxidase and catalase activity. C is the most abundant fatty acid for both strains. Strain Marseille-Q7072 is non-spore-forming, non-motile, Gram-stain-positive, and coccus-shaped, while strain Marseille-Q7826 is non-spore-forming, motile, Gram-stain-variable, and curved rod-shaped. The genomic comparison of the Marseille-Q7072 and Marseille-Q7826 strains showed that all digital DNA-DNA hybridisation (dDDH) and mean orthologous nucleotide identity (OrthoANI) values were below published species thresholds (70% and 95-96%, respectively) with other closely related species with standing in nomenclature. Thus, we conclude that both strains are new bacterial species. Strain Marseille-Q7072 is a new member of the Bacillota phylum, for which the name Peptoniphilus genitalis sp. nov. is proposed, while the Marseille-Q7826 strain is a new member of the Actinomycetota phylum, for which the name Mobiluncus massiliensis sp. nov. is proposed.
Topics: Female; Humans; Mobiluncus; Bacteria; Clostridiales; Microbiota; DNA
PubMed: 38372813
DOI: 10.1007/s00284-023-03584-7 -
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 -
The Journal of Sexual Medicine Nov 2023Culture-based studies have shown that penile prostheses harbor biofilms in the presence and absence of infection, but these findings have not been adequately validated...
BACKGROUND
Culture-based studies have shown that penile prostheses harbor biofilms in the presence and absence of infection, but these findings have not been adequately validated using contemporary microbiome analytic techniques.
AIM
The study sought to characterize microbial biofilms of indwelling penile prosthesis devices according to patient factors, device components, manufacturer, and infection status.
METHODS
Upon penile prostheses surgical explantation, device biofilms were extracted, sonicated, and characterized using shotgun metagenomics and culture-based approaches. Device components were also analyzed using scanning electron microscopy.
OUTCOMES
Outcomes included the presence or absence of biofilms, alpha and beta diversity, specific microbes identified and the presence of biofilm, and antibiotic resistance genes on each prosthesis component.
RESULTS
The average age of participants from whom devices were explanted was 61 ± 11 years, and 9 (45%) of 20 had a diagnosis of diabetes mellitus. Seventeen devices were noninfected, and 3 were associated with clinical infection. Mean device indwelling time prior to explant was 5.1 ± 5.1 years. All analyzed components from 20 devices had detectable microbial biofilms, both in the presence and absence of infection. Scanning electron microscopy corroborated the presence of biofilms across device components. Significant differences between viruses, prokaryotes, and metabolic pathways were identified between individual patients, device manufacturers, and infection status. Mobiluncus curtisii was enriched in manufacturer A device biofilms relative to manufacturer B device biofilms. Bordetella bronchialis, Methylomicrobium alcaliphilum, Pseudoxanthomonas suwonensis, and Porphyrobacter sp. were enriched in manufacturer B devices relative to manufacturer A devices. The most abundant bacterial phyla were the Proteobacteria, Actinobacteria, and Firmicutes. Glycogenesis, the process of glycogen synthesis, was among the predominant metabolic pathways detected across device components. Beta diversity of bacteria, viruses, protozoa, and pathways did not differ among device components.
CLINICAL IMPLICATIONS
All components of all penile prostheses removed from infected and noninfected patients have biofilms. The significance of biofilms on noninfected devices remains unknown and merits further investigation.
STRENGTHS AND LIMITATIONS
Strengths include the multipronged approach to characterize biofilms and being the first study to include all components of penile prostheses in tandem. Limitations include the relatively few number of infected devices in the series, a relatively small subset of devices included in shotgun metagenomics analysis, and the lack of anaerobic and other expanded conditions for culture.
CONCLUSION
Penile prosthesis biofilms are apparent in the presence and absence of infection, and the composition of biofilms was driven primarily by device manufacturer, individual variability, and infection, while being less impacted by device component.
Topics: Humans; Middle Aged; Aged; Penile Prosthesis; Biofilms; Anti-Bacterial Agents; Prosthesis Implantation; Diabetes Mellitus
PubMed: 37837552
DOI: 10.1093/jsxmed/qdad124 -
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 -
Microbes and Environments 2023The umbilicus accumulates more dirt than other body surfaces and is difficult to clean. Hygiene in this area is vital, particularly for surgery, because of its proximity...
The umbilicus accumulates more dirt than other body surfaces and is difficult to clean. Hygiene in this area is vital, particularly for surgery, because of its proximity to the laparotomy site. Although microorganisms in the umbilicus have been extensively examined, those in umbilical dirt have not due to the lack of an efficient method of collection. We previously established a technique to extract umbilical dirt using the anchor effect of polymers, which are injected into the umbilicus. In the present study, we applied this technique for the first time to investigate umbilical dirt. The results obtained revealed an abundance of Corynebacterium among various bacteria, whereas Cutibacterium and Staphylococcus, which are abundant at other skin sites, were rare. The relationships between the microbiota and issues related to the umbilicus were investigated and some covariates, including the odor score and several bacteria, were identified. A detailed ana-lysis of the genera associated with odor revealed no correlation with Corynebacterium; however, some minor anaerobic bacteria, such as Mobiluncus, Arcanobacterium, and Peptoniphilus, were more abundant in the high odor score group. Therefore, this technique to collect umbilical dirt provided insights into the microbiota in umbilical dirt and suggested functions for minor anaerobes. Furthermore, since various pathogenic microorganisms were detected, their control may contribute to the prevention of both odor production and infectious diseases caused by these microorganisms.
Topics: Umbilicus; Odorants; Microbiota; Bacteria; Bacteria, Anaerobic; RNA, Ribosomal, 16S
PubMed: 37407492
DOI: 10.1264/jsme2.ME23007 -
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 -
Microbiology Insights 2023The eradication of neonatal Group B (GBS) infections, considered as a major public health priority, necessarily requires a mastery of the data on vaginal carriage in...
The eradication of neonatal Group B (GBS) infections, considered as a major public health priority, necessarily requires a mastery of the data on vaginal carriage in pregnant women. The aims of this study were to determine the prevalence of vaginal carriage of GBS in pregnant women, antibiotic susceptibility, and associated risk factors. This was a cross-sectional, descriptive study conducted over a period of 9 months (July 2020 to March 2021) in pregnant women between 34 and 38 weeks of gestation (WG) followed at the Nabil Choucair health center in Dakar. Identification and antibiotic susceptibility of GBS isolates were performed on the Vitek 2 from vaginal swabs cultured on Granada medium. Demographic and obstetric interview data were collected and analyzed on SPSS (version 25). The level of significance for all statistical tests was set at < .05. The search of GBS vaginal carriage had involved 279 women aged 16 to 46 years, with a median pregnancy age of 34 (34-37) weeks' gestation. GBS was found in 43 women, for a vaginal carriage rate of 15.4%. In 27.9% (12/43) of volunteers screened, this carriage was monomicrobial, while in 72.1% (31/43) of women, GBS was associated with other pathogens such as spp. (60.5%), (2.3%), (34.9%) and/or spp. (11.6%). The level of resistance was 27.9% (12/43) for penicillin G, 53.5% (23/43) for erythromycin, 25.6% (11/43) for clindamycin and 100% for tetracycline. However, the strains had retained fully susceptible to vancomycin and teicoplanin. The main risk factor associated with maternal GBS carriage were ectocervical inflammation associated with contact bleeding (OR = 3.55; = .005). The high rate of maternal vaginal GBS carriage and the levels of resistance to the various antibiotics tested confirm the importance of continuous GBS surveillance in our resource-limited countries.
PubMed: 37275206
DOI: 10.1177/11786361231174419 -
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