scholarly journals Longitudinal profiling of the macaque vaginal microbiome reveals similarities to diverse human vaginal communities: implications for use as a pre-clinical model for bacterial vaginosis

2020 ◽  
Author(s):  
Nicholas S Rhoades ◽  
Sara M Hendrickson ◽  
Danielle R Gerken ◽  
Kassandra Martinez ◽  
Ov D Slayden ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Adverse Outcomes ◽  
Reproductive Age ◽  
Lactobacillus Species ◽  
Vaginal Microbiome ◽  
Clinical Model ◽  
Sexually Transmitted ◽  
Increased Susceptibility

The vaginal microbiota plays an important role in women's reproductive and urogenital health. Disturbances in this microbial community can lead to several adverse outcomes including pelvic inflammatory disease, bacterial vaginosis (BV) as well as increased susceptibility to sexually transmitted infections, miscarriage, and pre-term births. It is now well accepted that while the microbiome of healthy women in the developed world is dominated by Lactobacillus species, vaginal communities in asymptomatic women, especially those in the developing world, can be comprised of a diverse set of micro-organisms. The presence of a diverse vaginal microbiome has been associated with increased susceptibility to HIV infection but their implications for women's health remain poorly understood. Rhesus macaques are an excellent translational animal model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive age female rhesus macaques. Many animals showed hallmarks of BV, including Nugent scores above 7 and high vaginal pH. At both the taxonomic and functional level, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic gram-negative bacteria, including; Snethia, Prevotella, Porphyromonas, and Mobilluncus. Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella. Our in-depth and comprehensive analysis highlights the importance of the model to test interventions for manipulating the vaginal microbiome.

scholarly journals Longitudinal Profiling of the Macaque Vaginal Microbiome Reveals Similarities to Diverse Human Vaginal Communities

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Nicholas S. Rhoades ◽  
Sara M. Hendrickson ◽  
Danielle R. Gerken ◽  
Kassandra Martinez ◽  
Ov D. Slayden ◽  
...  
Keyword(s):  
Microbial Community ◽  
Bacterial Vaginosis ◽  
Rhesus Macaque ◽  
Longitudinal Analysis ◽  
Rhesus Macaques ◽  
Comprehensive Analysis ◽  
Reproductive Age ◽  
Vaginal Microbiome ◽  
Genetic Homology ◽  
Microbiome Data

ABSTRACT The vaginal microbiota plays an important role in women’s reproductive and urogenital health. It is now well accepted that a “healthy” vaginal microbiome is dominated by Lactobacillus species. Disturbances in this microbial community can lead to several adverse outcomes, including pelvic inflammatory disease and bacterial vaginosis (BV), as well as increased susceptibility to sexually transmitted infections, miscarriage, and preterm births. However, vaginal communities, especially those of women in the developing world, can be comprised of a diverse set of microorganisms in the absence of overt clinical symptoms. The implications of these diverse vaginal microbiomes for women’s health remain poorly understood. Rhesus macaques are an excellent translational animal model to address these questions due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive-age female rhesus macaques. At both the taxonomic and functional levels, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic Gram-negative bacteria, including Sneathia, Prevotella, Porphyromonas, and Mobiluncus. Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella. Our in-depth and comprehensive analysis highlights the importance of the model to understand the health implications of a diverse vaginal microbiome and test interventions for manipulating this community. IMPORTANCE It is widely accepted that the “healthy” vaginal microbiome of women in the developed world is dominated by Lactobacillus species. However, in the developing world, many asymptomatic women harbor diverse vaginal microbial communities that are typically associated with bacterial vaginosis. Many questions remain about the drivers and health implications of a diverse vaginal microbial community. Rhesus macaques provide an excellent translational model to address these questions due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from a large cohort of reproductive-age rhesus macaques. At the taxonomic, genomic, and functional levels, the rhesus macaque vaginal microbiome was most similar to that of humans, who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Our in-depth and comprehensive analysis highlights the utility of macaques as a model to study diverse vaginal community state types and test interventions for manipulating the vaginal microbiome.

scholarly journals The Female Vaginal Microbiome in Health and Bacterial Vaginosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaodi Chen ◽  
Yune Lu ◽  
Tao Chen ◽  
Rongguo Li
Keyword(s):  
Bacterial Vaginosis ◽  
Therapeutic Strategies ◽  
Reproductive Age ◽  
Gardnerella Vaginalis ◽  
Obstetric Outcomes ◽  
Antimicrobial Compounds ◽  
Vaginal Microbiome ◽  
Sharp Decline ◽  
Women Of Reproductive Age ◽  
Sexually Transmitted

The vaginal microbiome is an intricate and dynamic microecosystem that constantly undergoes fluctuations during the female menstrual cycle and the woman’s entire life. A healthy vaginal microbiome is dominated by Lactobacillus which produce various antimicrobial compounds. Bacterial vaginosis (BV) is characterized by the loss or sharp decline in the total number of Lactobacillus and a corresponding marked increase in the concentration of anaerobic microbes. BV is a highly prevalent disorder of the vaginal microbiota among women of reproductive age globally. BV is confirmed to be associated with adverse gynecologic and obstetric outcomes, such as sexually transmitted infections, pelvic inflammatory disease, and preterm birth. Gardnerella vaginalis is the most common microorganism identified from BV. It is the predominant microbe in polymicrobial biofilms that could shelter G. vaginalis and other BV-associated microbes from adverse host environments. Many efforts have been made to increase our understanding of the vaginal microbiome in health and BV. Thus, improved novel and accurate diagnosis and therapeutic strategies for BV have been developed. This review covers the features of vaginal microbiome, BV, BV-associated diseases, and various strategies of diagnosis and treatment of BV, with an emphasis on recent research progresses.

scholarly journals Diagnosing Bacterial Vaginosis with a Novel, Clinically-Actionable Molecular Diagnostic Tool

2018 ◽  
Author(s):  
Joseph P. Jarvis ◽  
Doug Rains ◽  
Steven J. Kradel ◽  
James Elliott ◽  
Evan E. Diamond ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Pathogenic Bacteria ◽  
Reproductive Age ◽  
Medical Decision ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Lactobacillus Species ◽  
Research Subjects ◽  
Asymptomatic Patients ◽  
Increased Risk

Abstract/SummaryBacterial vaginosis is a common condition among women of reproductive age and is associated with potentially serious side-effects, including an increased risk of preterm birth. Recent advancements in microbiome sequencing technologies have produced novel insights into the complicated mechanisms underlying bacterial vaginosis and have given rise to new methods of diagnosis. Here we report on the validation of a quantitative, molecular diagnostic algorithm based on the relative abundances of ten potentially pathogenic bacteria and four commensal Lactobacillus species in research subjects (n = 172) classified as symptomatic (n = 149) or asymptomatic (n = 23). We observe a clear and reinforcing pattern among patients diagnosed by the algorithm that is consistent with the current understanding of biological dynamics and dysregulation of the vaginal microbiome during infection. Using this enhanced assessment of the underlying biology of infection, we demonstrate improved diagnostic sensitivity (93%) and specificity (90%) relative to current diagnostic tools. Our algorithm also appears to provide enhanced diagnostic capabilities in ambiguous classes of patients for whom diagnosis and medical decision-making is complicated, including asymptomatic patients and those deemed “intermediate” by Nugent scoring. Ultimately, we establish CLS2.0q as a quantitative, sensitive, specific, accurate, robust, and flexible algorithm for the clinical diagnosis of bacterial vaginosis – importantly, one that is also ideal for the differential diagnosis of non-BV infections with clinically similar presentations.

scholarly journals 1354. Antibiotic Resistance and Coinfections Among Women with Sexually Transmitted Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S764-S764
Author(s):  
Brittany L Carpenter ◽  
Jacqueline D Peacock ◽  
Kyle Dubiak ◽  
Heather Fecteau ◽  
Robert Carlson
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Vaginosis ◽  
Sexually Transmitted Infections ◽  
Trichomonas Vaginalis ◽  
Resistance Testing ◽  
Lactobacillus Species ◽  
Herpes Simplex Virus 1 ◽  
Aerobic Vaginitis ◽  
Sexually Transmitted ◽  
Panel Testing

Abstract Background Sexually transmitted infections (STIs) represent a growing epidemic, particularly among America’s youth. Traditional single or dual organism STI testing is limited in its utility compared to PCR panel-based vaginitis testing. PCR panel testing can identify up to 99% of vaginitis associated organisms, while simultaneously providing information about antibiotic resistance. Methods We analyzed 10,011 vaginosis panel cases released between April 2020 and May 2021. The PCR-based vaginosis panel consists of organisms associated with bacterial vaginosis, aerobic vaginitis, yeast infections, STIs, and Lactobacillus species. This panel simultaneously detects evidence of antibiotic resistance for nine classes of drugs. Results Of 9405 cases from vaginal swabs, 618 (6.8%) were positive for at least one STI including Chlamydia trachomatis (CT), Haemophilus ducreyi, Herpes Simplex Virus 1 or 2 (HSV2), Neisseria gonorrhoeae (NG), and/or Trichomonas vaginalis. Of 603 urine samples, 7.6% were positive for at least one STI and represented a younger population. Patients younger than age 25 (33% of the cohort) were disproportionately affected by STIs, consistent with CDC findings. About 50% of all positive STI cases were in patients under 25. Evidence of bacterial vaginosis was also present in 89% of CT and NG cases, and 75% of HSV2 cases. Strikingly, we found the presence of an antibiotic resistant marker(s) to first line treatment in 76.2% of CT and 19.3% of NG cases. Conclusion Our data illustrates the advantages of utilizing a PCR-panel approach to STI detection over a targeted approach for individual organisms. Coinfections with bacterial vaginosis were common and if left unidentified, patients may receive incomplete treatment. Additionally, our data suggests that antibiotic resistance testing is imperative for effective treatment planning and antibiotic stewardship in suspected STI cases. Disclosures Brittany L. Carpenter, PhD, NxGen MDx (Employee) Jacqueline D. Peacock, PhD, MB(ASCP)CM, NxGen MDx (Employee) Kyle Dubiak, PhD, NxGen MDx (Employee) Heather Fecteau, MS, LCGC, NxGen MDx (Employee) Robert Carlson, MD, FCAP, NxGen MDx (Employee)

scholarly journals Characterization of an α-glucosidase enzyme conserved in Gardnerella spp. isolated from the human vaginal microbiome

2021 ◽  
Author(s):  
Pashupati Bhandari ◽  
Jeffrey P. Tingley ◽  
David R. J. Palmer ◽  
D. Wade Abbott ◽  
Janet E. Hill
Keyword(s):  
Microbial Community ◽  
Bacterial Vaginosis ◽  
Glycogen Metabolism ◽  
Maximum Activity ◽  
Glycoside Hydrolase Family ◽  
Vaginal Microbiome ◽  
Sexually Transmitted ◽  
Multistep Process ◽  
Mixed Bacteria

Gardnerella spp. in the vaginal microbiome are associated with bacterial vaginosis, in which a lactobacilli dominant community is replaced with mixed bacteria including Gardnerella species. Co-occurrence of multiple Gardnerella species in the vaginal environment is common, but different species are dominant in different women. Competition for nutrients, including glycogen, could play an important role in determining the microbial community structure. Digestion of glycogen into products that can be taken up and further processed by bacteria requires the combined activities of several enzymes collectively known as amylases, which belong to glycoside hydrolase family 13 (GH13) within the CAZy classification system. GH13 is a large and diverse family of proteins, making prediction of their activities challenging. SACCHARIS annotation of the GH13 family in Gardnerella resulted in identification of protein domains belonging to eight subfamilies. Phylogenetic analysis of predicted amylase sequences from 26 genomes demonstrated that a putative α-glucosidase-encoding sequence, CG400_06090, was conserved in all Gardnerella spp. The predicted α-glucosidase enzyme was expressed, purified and functionally characterized. The enzyme was active on a variety of maltooligosaccharides with maximum activity at pH 7. K m , k cat and k cat /K m values for the substrate 4-nitrophenyl α- d -glucopyranoside were 8.3 μM, 0.96 min −1 and 0.11 μM −1 min −1 , respectively. Glucose was released from maltose, maltotriose, maltotetraose and maltopentaose, but no products were detected when the enzyme was incubated with glycogen. Our findings show that Gardnerella spp. produce an α-glucosidase enzyme that may contribute to the multistep process of glycogen metabolism by releasing glucose from maltooligosaccharides. IMPORTANCE Increased abundance of Gardnerella spp. is a diagnostic characteristic of bacterial vaginosis, an imbalance in the human vaginal microbiome associated with troubling symptoms, and negative reproductive health outcomes including increased transmission of sexually transmitted infections and preterm birth. Competition for nutrients is likely an important factor in causing dramatic shifts in the vaginal microbial community but little is known about the contribution of bacterial enzymes to the metabolism of glycogen, a major carbon source available to vaginal bacteria. The significance of our research is characterizing the activity of an enzyme conserved in Gardnerella species that likely contributes to the ability of these bacteria to utilize glycogen.

scholarly journals Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lenka A. Vodstrcil ◽  
Christina A. Muzny ◽  
Erica L. Plummer ◽  
Jack D. Sobel ◽  
Catriona S. Bradshaw
Keyword(s):  
Bacterial Vaginosis ◽  
Vaginal Microbiome ◽  
Epidemiological Evidence ◽  
Associated Bacteria ◽  
Sexually Transmitted ◽  
Single Mechanism ◽  
Challenges And Opportunities ◽  
Key Driver ◽  
Barriers And Challenges ◽  
High Level

AbstractBacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6 months of recommended antibiotic therapy. The low rate of sustained cure highlights our limited understanding of the pathogenesis of BV recurrence, which has been attributed to possible persistence and re-emergence of BV-associated bacteria (BVAB) or a BV-associated biofilm following antimicrobials and/or reinfection occurring from sexual partners.There is a robust body of evidence to support the exchange of bacteria between partners during sexual activity, and while the hypothesis that women treated for BV are subsequently reinfected with BVAB following sex with an untreated sexual partner is not new, failure of past partner treatment trials has eroded confidence in this concept. If reinfection is a key driver of recurrence, current antimicrobial regimens directed to women alone are unlikely to achieve a high level of sustained cure, and the approach of partner treatment to reduce reinfection is justified. In this manuscript, we present the molecular and epidemiological evidence that underlies the hypothesis that BV is sexually transmitted, and summarise why research that continues to consider sexual partnerships is necessary. We also outline the significant barriers and challenges that we have identified while undertaking partner treatment studies, and we discuss the factors that impact on our ability to determine their effectiveness.Ultimately, the pathogenesis of BV recurrence is likely to be multifaceted and not attributable to a single mechanism in all women. If we are to achieve sustained cure for women, it is likely that combined and individualised approaches to eradicate BVAB, support an optimal vaginal microbiome, and prevent reinfection from partners will be required.

scholarly journals Vaginal Dysbiosis and Partial Bacterial Vaginosis: The Interpretation of the “Grey Zones” of Clinical Practice

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 191
Author(s):  
Giuseppina Campisciano ◽  
Nunzia Zanotta ◽  
Vincenzo Petix ◽  
Manuela Giangreco ◽  
Giuseppe Ricci ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Vaginal Discharge ◽  
Reproductive Age ◽  
P Value ◽  
Gram Stain ◽  
Aerobic Vaginitis ◽  
Nugent Score ◽  
Sexually Transmitted ◽  
Gram Staining ◽  
Reproductive Age Women

Bacterial vaginosis (BV) affects one-third of reproductive age women, increasing the risk of acquiring sexually transmitted infections (STIs) and posing a risk for reproductive health. The current diagnosis with Gram stain (Nugent Score) identifies a transitional stage named partial BV or intermediate microbiota, raising the problem of how to clinically handle it. We retrospectively analyzed cervicovaginal swabs from 985 immunocompetent non-pregnant symptomaticspp. women (vaginal discharge, burning, itching) by Nugent score and qPCR for BV, aerobic or fungal vaginitis, and STIs (Mycoplasmas spp., Chlamydia t., Trichomonas v., and Neisseria g.). Nugent scores 0–3 and 7–10 were confirmed in 99.3% and 89.7% cases, respectively, by qPCR. Among Nugent scores 4–6 (partial BV), qPCR identified 46.1% of BV cases, with 37.3% of cases negative for BV, and only 16.7% of partial BV. Gram staining and qPCR were discordant (p value = 0.0001) mainly in the partial BV. Among the qPCR BV cases, the presence of aerobic vaginitis and STIs was identified, with a significant association (p < 0.0001) between the STIs and partial BV/overt BV. qPCR is more informative and accurate, and its use as an alternative or in combination with Gram staining could help clinicians in having an overview of the complex vaginal microbiota and in the interpretation of partial BV that can correspond to vaginitis and/or STIs.

scholarly journals Associations between sexual habits, menstrual hygiene practices, demographics and the vaginal microbiome as revealed by Bayesian network analysis

2017 ◽  
Author(s):  
Noelle Noyes ◽  
Kyu-Chul Cho ◽  
Jacques Ravel ◽  
Larry J. Forney ◽  
Zaid Abdo
Keyword(s):  
Bayesian Network ◽  
Bacterial Vaginosis ◽  
Birth Control ◽  
Reproductive Age ◽  
Future Research ◽  
Rrna Gene ◽  
Vaginal Microbiome ◽  
Nugent Score ◽  
Menstrual Hygiene ◽  
Hygiene Practices

AbstractThe vaginal microbiome plays an influential role in several disease states in reproductive age women, including bacterial vaginosis (BV). While demographic characteristics are associated with differences in vaginal microbiome community structure, little is known about the influence of sexual and hygiene habits. Furthermore, associations between the vaginal microbiome and risk symptoms of bacterial vaginosis have not been fully elucidated. Using Bayesian network (BN) analysis of 16S rRNA gene sequence results, demographic and extensive questionnaire data, we describe both novel and previously documented associations between habits of women and their vaginal microbiome. The BN analysis approach shows promise in uncovering complex associations between disparate data types. Our findings based on this approach support published associations between specific microbiome members (e.g.,Eggerthella,Gardnerella,Dialister,SneathiaandRuminococcaceae), the Nugent score (a BV diagnostic) and vaginal pH (a risk symptom of BV). Additionally, we found that several microbiome members were directly connected to other risk symptoms of BV (such as vaginal discharge, odor, itch, irritation, and yeast infection) includingL. jensenii,Corynebacteria, andProteobacteria. No direct connections were found between the Nugent Score and risk symptoms of BV other than pH, indicating that the Nugent Score may not be the most useful criteria for assessment of clinical BV. We also found that demographics (i.e., age, ethnicity, previous pregnancy) were associated with the presence/absence of specific vaginal microbes. The resulting BN revealed several as-yet undocumented associations between birth control usage, menstrual hygiene practices and specific microbiome members. Many of these complex relationships were not identified using common analytical methods, i.e., ordination and PERMANOVA. While these associations require confirmatory follow-up study, our findings strongly suggest that future studies of the vaginal microbiome and vaginal pathologies should include detailed surveys of participants’ sanitary, sexual and birth control habits, as these can act as confounders in the relationship between the microbiome and disease. Although the BN approach is powerful in revealing complex associations within multidimensional datasets, the need in some cases to discretize the data for use in BN analysis can result in loss of information. Future research is required to alleviate such limitations in constructing BN networks. Large sample sizes are also required in order to allow for the incorporation of a large number of variables (nodes) into the BN, particularly when studying associations between metadata and the microbiome. We believe that this approach is of great value, complementing other methods, to further our understanding of complex associations characteristic of microbiome research.

scholarly journals Molecular Diagnosis of Bacterial Vaginosis: an Update

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Jenell S. Coleman ◽  
Charlotte A. Gaydos
Keyword(s):  
Bacterial Vaginosis ◽  
Point Of Care ◽  
The United States ◽  
Reproductive Age ◽  
Clinical Indicators ◽  
Sexually Transmitted ◽  
Reproductive Age Women ◽  
Vaginal Swabs ◽  
Diverse Community ◽  
Point Of Care Tests

ABSTRACTBacterial vaginosis (BV) is the most common cause of vaginal discharge in reproductive-age women. BV has been associated with poor reproductive outcomes such as preterm delivery, the acquisition of sexually transmitted infections, including HIV, and pelvic inflammatory disease. BV represents the acquisition of a diverse community of anaerobic and facultative bacteria and a reduction in lactobacilli. It can be diagnosed using several tests ranging from clinical indicators, point-of-care tests, and molecular assays. Molecular technologies are objective, are able to detect fastidious bacteria, enable quantitation, and are ideal for self-collected vaginal swabs. This paper reviews the currently available BV diagnostic tests in the United States.

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