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Microbial Pathogenesis Jul 2022Vaginosis is a condition experienced by most women at least once in their lifetime. This condition arises due to the imbalance in the microbiome of the vaginal... (Review)
Review
Vaginosis is a condition experienced by most women at least once in their lifetime. This condition arises due to the imbalance in the microbiome of the vaginal ecosystem. Most of the pathogens of this disease are organisms which are commonly found in a normal healthy vagina. The vaginal microbiome is important as they act as a primary defence against secondary infections and Sexually transmitted diseases and infections (STDs and STIs). The vagina is mostly dominated by Lactobacillus along with other microbes including Gardnerella vaginalis, Atopobium vaginae., Prevotella spp., Mobiluncus spp., etc. Vaginal microbiome also includes Candida albicans and other species of the genus. The ratio in which these species are present varies from person to person and the dominant species decides the whether a vagina is "normal" or not. Lactobacillus dominated vagina is considered normal and if dominated by Gardnerella and such it is considered to be Bacterial vaginosis (BV) and similarly for Vulvovaginal Candidiasis (VVC). The microbiome also undergoes changes during menstrual cycles and menopausal stages. Due to the dynamic nature of this microbiome, it is tough to perfectly restore the balance. But several treatments are currently available with antibiotics like Clindamycin and derivatives of 5-nitroimidazole drugs like Metronidazole. The extensive use and the non-adherence to the treatment regimen has led to drug resistance through biofilm formation, efflux pumps, single nucleotide polymorphisms and resulting recurrent episode of vaginosis in women. Alternative medicines, preparations from plant sources, anti-microbial peptides and nano formulations are also being explored. Most of these medicines tend to focus on reducing the pathogen load rather than restoring the balance of the ecosystem. Vaginal microbiome transplant, an effort to restore the normalcy in the vaginal environment is becoming a popular treatment. In this review we discuss about the types of vaginosis, available treatments, challenges in treating the condition and the new drugs that are under investigation.
Topics: Candidiasis, Vulvovaginal; Female; Gardnerella vaginalis; Humans; Lactobacillus; Microbiota; Vagina; Vaginosis, Bacterial
PubMed: 35644292
DOI: 10.1016/j.micpath.2022.105606 -
Frontiers in Microbiology 2022Bacterial vaginosis (BV) is a common vaginal infection and has been associated with increased risk for a wide array of health issues. BV is linked with a variety of...
Bacterial vaginosis (BV) is a common vaginal infection and has been associated with increased risk for a wide array of health issues. BV is linked with a variety of heterogeneous pathogenic anaerobic bacteria, among which is strongly associated with BV diagnosis. However, their genetic features, pathogenicity, interspecific diversity, and evolutionary characters have not been illustrated at genomic level. The current study performed phylogenomic and comparative genomic analyses of . Phylogenomic analyses revealed remarkable phylogenetic distinctions among different species. Compared with had a larger genome and pangenome size with more insertion sequences but less CRISPR-Cas systems. In addition, these two species were diverse in profile of virulence factors, but harbored similar antibiotic resistance genes. Statistically different functional genome profiles between strains from the two species were determined, as well as correlations of some functional genes/pathways with putative pathogenicity. We also showed that high levels of horizontal gene transfer might be an important strategy for species diversification and pathogenicity. Collectively, this study provides the first genome sequence level description of , and may shed light on its virulence/pathogenicity, functional diversification, and evolutionary dynamics. Our study could facilitate the further investigations of this important pathogen, and might improve the future treatment of BV.
PubMed: 35865929
DOI: 10.3389/fmicb.2022.939406 -
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 -
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 -
Frontiers in Cellular and Infection... 2022Thyroid disease has been reported to associate with gut microbiota, but the effects of thyroid cancer and thyroid nodules on the oral microbiota are still largely...
OBJECTIVE
Thyroid disease has been reported to associate with gut microbiota, but the effects of thyroid cancer and thyroid nodules on the oral microbiota are still largely unknown. This study aimed to identify the variation in salivary microbiota and their potential association with thyroid cancer and thyroid nodules.
METHODS
We used 16S rRNA high-throughput sequencing to examine the salivary microbiota of thyroid cancer patients (n = 14), thyroid nodules patients (n = 9), and healthy controls (n = 15).
RESULTS
The alpha-diversity indices Chao1 and ACE were found to be relatively higher in patients with thyroid cancer and thyroid nodules compared to healthy controls. The beta diversity in both the thyroid cancer and thyroid nodules groups was divergent from the healthy control group. The genera Alloprevotella, Anaeroglobus, Acinetobacter, unclassified Bacteroidales, and unclassified Cyanobacteriales were significantly enriched in the thyroid cancer group compared with the healthy control group. In contrast, the microbiome of the healthy controls was mainly composed of the genera Haemophilus, Lautropia, Allorhizobium Neorhizobium Pararhizobium Rhizobium, Escherichia Shigella, and unclassified Rhodobacteraceae. The thyroid nodules group was dominated by genre uncultured Candidatus Saccharibacteria bacterium, unclassified Clostridiales bacterium feline oral taxon 148, Treponema, unclassified Prevotellaceae, Mobiluncus, and Acholeplasma. In contrast, the genera unclassified Rhodobacteraceae and Aggregatibacter dominated the healthy control group. The study also found that clinical indicators were correlated with the saliva microbiome.
CONCLUSION
The salivary microbiota variation may be connected with thyroid cancer and thyroid nodules.
Topics: Animals; Cats; Humans; Microbiota; RNA, Ribosomal, 16S; Saliva; Thyroid Neoplasms; Thyroid Nodule
PubMed: 36034695
DOI: 10.3389/fcimb.2022.989188 -
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 -
BJU International Jan 2022To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS)....
OBJECTIVE
To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS). Despite no previous identification of a distinct IC/BPS microbial urotype, HL IC/BPS, an inflammatory subtype of IC/BPS, was hypothesized most likely to be associated with a specific bacterial species or microbial pattern.
PARTICIPANTS AND METHODS
The bacterial microbiota of midstream urine specimens from HL IC/BPS and age- and gender-matched IC/BPS patients without HL (non-HL IC/BPS) were examined using the pan-bacterial domain clinical-level molecular diagnostic Pacific Biosciences full-length 16S gene sequencing protocol, informatics pipeline and database. We characterized the differential presence, abundances, and diversity of species, as well as gender-specific differences between and among HL and non-HL IC/BPS patients.
RESULTS
A total of 59 patients with IC/BPS were enrolled (29 HL, 30 non-HL; 43 women, 16 men) from a single centre and the microbiota in midstream urine specimens was available for comparison. The species abundance differentiation between the HL and non-HL groups (12 species) was not significantly different after Bonferroni adjustments for multiple comparisons. Similarly, the nine differentiating species noted between female HL and non-HL patients were not significantly different after similar statistical correction. However, four species abundances (out of the 10 species differences identified prior to correction) remained significantly different between male HL and non-HL subjects: Negativicoccus succinivorans, Porphyromonas somerae, Mobiluncus curtisii and Corynebacterium renale. Shannon diversity metrics showed significantly higher diversity among HL male patients than HL female patients (P = 0.045), but no significant diversity differences between HL and non-HL patients overall.
CONCLUSIONS
We were not able to identify a unique pathogenic urinary microbiota that differentiates all HL from all non-HL IC/BPS. It is likely that the male-specific differences resulted from colonization/contamination remote from the bladder. We were not able to show that bacteria play an important role in patients with HL IC/BPS.
Topics: Adult; Aged; Aged, 80 and over; Bacteria; Corynebacterium; Cystitis, Interstitial; DNA, Bacterial; Female; Humans; Male; Microbiota; Middle Aged; Mobiluncus; Porphyromonas; Sex Factors; Urine; Veillonellaceae
PubMed: 34143561
DOI: 10.1111/bju.15519 -
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 -
Microbiome May 2020Gender reassignment surgery is a procedure some transgender women (TW) undergo for gender-affirming purposes. This often includes the construction of a neovagina using...
BACKGROUND
Gender reassignment surgery is a procedure some transgender women (TW) undergo for gender-affirming purposes. This often includes the construction of a neovagina using existing penile and scrotal tissue and/or a sigmoid colon graft. There are limited data regarding the composition and function of the neovaginal microbiome representing a major gap in knowledge in neovaginal health.
RESULTS
Metaproteomics was performed on secretions collected from the neovaginas (n = 5) and rectums (n = 7) of TW surgically reassigned via penile inversion/scrotal graft with (n = 1) or without (n = 4) a sigmoid colon graft extension and compared with secretions from cis vaginas (n = 32). We identified 541 unique bacterial proteins from 38 taxa. The most abundant taxa in the neovaginas were Porphyromonas (30.2%), Peptostreptococcus (9.2%), Prevotella (9.0%), Mobiluncus (8.0%), and Jonquetella (7.2%), while cis vaginas were primarily Lactobacillus and Gardnerella. Rectal samples were mainly composed of Prevotella and Roseburia. Neovaginas (median Shannon's H index = 1.33) had higher alpha diversity compared to cis vaginas (Shannon's H = 0.35) (p = 7.2E-3, Mann-Whitney U test) and were more similar to the non-Lactobacillus dominant/polymicrobial cis vaginas based on beta diversity (perMANOVA, p = 0.001, r = 0.342). In comparison to cis vaginas, toll-like receptor response, amino acid, and short-chain fatty acid metabolic pathways were increased (p < 0.01), while keratinization and cornification proteins were decreased (p < 0.001) in the neovaginal proteome.
CONCLUSIONS
Penile skin-lined neovaginas have diverse, polymicrobial communities that show similarities in composition to uncircumcised penises and host responses to cis vaginas with bacterial vaginosis (BV) including increased immune activation pathways and decreased epithelial barrier function. Developing a better understanding of microbiome-associated inflammation in the neovaginal environment will be important for improving our knowledge of neovaginal health. Video Abstract.
Topics: Adult; Bacteria; Female; Humans; Male; Microbiota; Middle Aged; Sex Reassignment Surgery; Transgender Persons; Vagina
PubMed: 32370783
DOI: 10.1186/s40168-020-00804-1