scholarly journals molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Mykhaylo Usyk ◽  
Nicolas F. Schlecht ◽  
Sarah Pickering ◽  
LaShanda Williams ◽  
Christopher C. Sollecito ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Hpv Infection ◽  
Rrna Gene ◽  
Clinical Trial Registration ◽  
Gold Standard Method ◽  
Adverse Health Outcomes ◽  
Papillomavirus Infection ◽  
Registration Number ◽  
Hpv Clearance ◽  
16 S Rrna

AbstractBacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV, a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.

scholarly journals Depiction of Vaginal Microbiota in Women With High-Risk Human Papillomavirus Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhen-Tong Wei ◽  
Hong-Liang Chen ◽  
Chun-Feng Wang ◽  
Gui-Lian Yang ◽  
Shu-Mei Han ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Hpv Infection ◽  
Vaginal Microbiota ◽  
Rrna Gene ◽  
Cervical Lesions ◽  
Microbial Composition ◽  
Infection Period ◽  
Papillomavirus Infection ◽  
Rrna Gene Sequencing

Persistent infection with the carcinogenic human papillomavirus (HPV) is a prerequisite for the progression of cervical lesions and cancer. A growing body of research has focused on the functional role of the vaginal microbiota in the persistence of HPV infection. Understanding the microbial composition and structure in women with high-risk (hr)-HPV infection may help reveal associations between the vaginal microbiota and HPV infection, and identify potential biomarkers. Our study investigated the vaginal microbial community in women with and without hr-HPV infection, by using 16s rRNA gene sequencing. We found that microbial perturbations occurred in the early phase of hr-HPV infection. Lactobacillus and Sporolactobacillus were decreased, while bacteria related to bacterial vaginosis (BV), such as Gardnerella, Prevotella, Dialister, Slackia, Actinomyces, Porphyromonas, Peptoniphilus, Anaerococcus, Peptostreptococcus, Streptococcus, Ureaplasma, Megasphaera, and Mycoplasma were increased. Our results could offer insights into the correlations between hr-HPV and the vaginal microbiota in the early infection period, and provide indications that the predominance of some BV-associated bacteria during hr-HPV infection may increase the risk for cervical neoplasia.

scholarly journals The Correlation Between Bacterial Vaginosis, High-Risk Human Papillomavirus Infection, and Cervical Intraepithelial Neoplasia Progression

2021 ◽  
Author(s):  
Xiaolin Xu ◽  
Yichan Zhang ◽  
Liqun Yu ◽  
Xingxian Shi ◽  
Min Min ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Papillomavirus ◽  
High Risk ◽  
Bacterial Vaginosis ◽  
Cervical Intraepithelial Neoplasia ◽  
Protective Factor ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Vaginal Microbiota ◽  
Papillomavirus Infection

Abstract Persistent infection with high-risk human papillomavirus (HR-HPV) is an important reason for the progression of cervical intraepithelial neoplasia (CIN). Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with HPV, but the correlation between BV and HPV during CIN development is still elusive. In this study, we enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with or without BV and HPV co-infection and then calculated risk factors for CIN progression by logistic regression. We found that condom use (OR=3.480; 95% CI=1.069-11.325; P < .05) was a protective factor against CIN, whereas BV (OR=0.358; 95% CI=0.195-0.656; P < .05) and HR-HPV infection (OR= 0.016; 95% CI=0.004-0.072; P < .001) were risk factors for CIN. BV and HPV infection could trigger an increase in the diversity of vaginal microbiota and decrease Lactobacillus domination, which is conducive to CIN regression. The depletion of the carbohydrate metabolism pathway may induce Lactobacillus reduction. Treating BV in the clinical setting could block CIN development and L. iners may be a crucial species during this process.

scholarly journals Cervicovaginal Microbiome Factors in Clearance of Human Papillomavirus Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenkui Dai ◽  
Hui Du ◽  
Shuaicheng Li ◽  
Ruifang Wu
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Hpv Infection ◽  
Cervical Cancer Prevention ◽  
Targeted Interventions ◽  
Papillomavirus Infection ◽  
Hpv Clearance ◽  
Host Microbe Interactions ◽  
Cervical Diseases

Persistent high-risk human papillomavirus (hrHPV) infection is the highest risk to cervical cancer which is the fourth most common cancer in women worldwide. A growing body of literatures demonstrate the role of cervicovaginal microbiome (CVM) in hrHPV susceptibility and clearance, suggesting the promise of CVM-targeted interventions in protecting against or eliminating HPV infection. Nevertheless, the CVM-HPV-host interactions are largely unknown. In this review, we summarize imbalanced CVM in HPV-positive women, with or without cervical diseases, and the progress of exploring CVM resources in HPV clearance. In addition, microbe- and host-microbe interactions in HPV infection and elimination are reviewed to understand the role of CVM in remission of HPV infection. Lastly, the feasibility of CVM-modulated and -derived products in promoting HPV clearance is discussed. Information in this article will provide valuable reference for researchers interested in cervical cancer prevention and therapy.

scholarly journals Diversity of Human Vaginal Bacterial Communities and Associations with Clinically Defined Bacterial Vaginosis

2008 ◽  
Vol 74 (15) ◽  
pp. 4898-4909 ◽  
Author(s):  
Brian B. Oakley ◽  
Tina L. Fiedler ◽  
Jeanne M. Marrazzo ◽  
David N. Fredricks
Keyword(s):  
Bacterial Vaginosis ◽  
Bacterial Communities ◽  
Sequence Data ◽  
Sequence Similarity ◽  
Rrna Gene ◽  
Operational Taxonomic Units ◽  
Adverse Health Outcomes ◽  
Microbial Ecosystems ◽  
Human Vagina ◽  
Medical Importance

ABSTRACT Bacterial vaginosis (BV) is a common syndrome associated with numerous adverse health outcomes in women. Despite its medical importance, the etiology and microbial ecology of BV remain poorly understood. We used broad-range PCR to census the community structure of the healthy and BV-affected vaginal microbial ecosystems and synthesized current publicly available bacterial 16S rRNA gene sequence data from this environment. The community of vaginal bacteria detected in subjects with BV was much more taxon rich and diverse than in subjects without BV. At a 97% sequence similarity cutoff, the number of operational taxonomic units (OTUs) per patient in 28 subjects with BV was nearly three times greater than in 13 subjects without BV: 14.8 ± 0.7 versus 5.2 ± 0.75 (mean ± standard error). OTU-based analyses revealed previously hidden diversity for many vaginal bacteria that are currently poorly represented in GenBank. Our sequencing efforts yielded many novel phylotypes (123 of our sequences represented 38 OTUs not previously found in the vaginal ecosystem), including several novel BV-associated OTUs, such as those belonging to the Prevotella species complex, which remain severely underrepresented in the current NCBI database. Community composition was highly variable among subjects at a fine taxonomic scale, but at the phylum level, Actinobacteria and Bacteroidetes were strongly associated with BV. Our data describe a previously unrecognized extent of bacterial diversity in the vaginal ecosystem. The human vagina hosts many bacteria that are only distantly related to known species, and subjects with BV harbor particularly taxon-rich and diverse bacterial communities.

scholarly journals Data analysis workflow for the detection of canine vector-borne pathogens using 16 S rRNA Next-Generation Sequencing

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Elton J. R. Vasconcelos ◽  
Chayan Roy ◽  
Joseph A. Geiger ◽  
Kristina M. Oney ◽  
Melody Koo ◽  
...  
Keyword(s):  
Veterinary Medicine ◽  
Next Generation Sequencing ◽  
Complete Analysis ◽  
Molecular Diagnostic ◽  
Rrna Gene ◽  
Spotted Fever Group ◽  
Next Generation ◽  
Vector Borne ◽  
16 S Rrna ◽  
Generation Sequencing

Abstract Background Vector-borne diseases (VBDs) impact both human and veterinary medicine and pose special public health challenges. The main bacterial vector-borne pathogens (VBPs) of importance in veterinary medicine include Anaplasma spp., Bartonella spp., Ehrlichia spp., and Spotted Fever Group Rickettsia. Taxon-targeted PCR assays are the current gold standard for VBP diagnostics but limitations on the detection of genetically diverse organisms support a novel approach for broader detection of VBPs. We present a methodology for genetic characterization of VBPs using Next-Generation Sequencing (NGS) and computational approaches. A major advantage of NGS is the ability to detect multiple organisms present in the same clinical sample in an unsupervised (i.e. non-targeted) and semi-quantitative way. The Standard Operating Procedure (SOP) presented here combines industry-standard microbiome analysis tools with our ad-hoc bioinformatic scripts to form a complete analysis pipeline accessible to veterinary scientists and freely available for download and use at https://github.com/eltonjrv/microbiome.westernu/tree/SOP. Results We tested and validated our SOP by mimicking single, double, and triple infections in genomic canine DNA using serial dilutions of plasmids containing the entire 16 S rRNA gene sequence of (A) phagocytophilum, (B) v. berkhoffii, and E. canis. NGS with broad-range 16 S rRNA primers followed by our bioinformatics SOP was capable of detecting these pathogens in biological replicates of different dilutions. These results illustrate the ability of NGS to detect and genetically characterize multi-infections with different amounts of pathogens in a single sample. Conclusions Bloodborne microbiomics & metagenomics approaches may help expand the molecular diagnostic toolbox in veterinary and human medicine. In this paper, we present both in vitro and in silico detailed protocols that can be combined into a single workflow that may provide a significant improvement in VBP diagnostics and also facilitate future applications of microbiome research in veterinary medicine.

scholarly journals Temporal association between human upper respiratory and gut bacterial microbiomes during the course of COVID-19 in adults

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Rong Xu ◽  
Renfei Lu ◽  
Tao Zhang ◽  
Qunfu Wu ◽  
Weihua Cai ◽  
...  
Keyword(s):  
Dynamic Change ◽  
Temporal Association ◽  
Rrna Gene ◽  
Type I ◽  
Dynamic Changes ◽  
Multiple Organs ◽  
Community Types ◽  
Upper Respiratory ◽  
Rrna Gene Sequencing ◽  
16 S Rrna

AbstractSARS-CoV-2 is the cause of COVID-19. It infects multiple organs including the respiratory tract and gut. Dynamic changes of regional microbiomes in infected adults are largely unknown. Here, we performed longitudinal analyses of throat and anal swabs from 35 COVID-19 and 19 healthy adult controls, as well as 10 non-COVID-19 patients with other diseases, by 16 S rRNA gene sequencing. The results showed a partitioning of the patients into 3-4 categories based on microbial community types (I-IV) in both sites. The bacterial diversity was lower in COVID-19 patients than healthy controls and decreased gradually from community type I to III/IV. Although the dynamic change of microbiome was complex during COVID-19, a synchronous restoration of both the upper respiratory and gut microbiomes from early dysbiosis towards late more diverse status was observed in 6/8 mild COVID-19 adult patients. These findings reveal previously unknown interactions between upper respiratory and gut microbiomes during COVID-19.

scholarly journals Genome Sequences of 15 Gardnerella vaginalis Strains Isolated from the Vaginas of Women with and without Bacterial Vaginosis: TABLE 1 

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Lloyd S. Robinson ◽  
Justin Perry ◽  
Sai Lek ◽  
Aye Wollam ◽  
Erica Sodergren ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Health Outcomes ◽  
Bacterial Vaginosis ◽  
Draft Genome ◽  
Gardnerella Vaginalis ◽  
Genome Sequences ◽  
Predominant Species ◽  
Adverse Health ◽  
Adverse Health Outcomes

Gardnerella vaginalis is a predominant species in bacterial vaginosis, a dysbiosis of the vagina that is associated with adverse health outcomes, including preterm birth. Here, we present the draft genome sequences of 15 Gardnerella vaginalis strains (now available through BEI Resources) isolated from women with and without bacterial vaginosis.

scholarly journals Furin Cleavage of L2 during Papillomavirus Infection: Minimal Dependence on Cyclophilins

2016 ◽  
Vol 90 (14) ◽  
pp. 6224-6234 ◽  
Author(s):  
Matthew P. Bronnimann ◽  
Christine M. Calton ◽  
Samantha F. Chiquette ◽  
Shuaizhi Li ◽  
Mingfeng Lu ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Current Model ◽  
Hpv Infection ◽  
Cleavage Product ◽  
Protein Domain ◽  
Furin Cleavage ◽  
Minor Capsid Protein ◽  
Papillomavirus Infection ◽  
Successful Infection ◽  
N Terminus

ABSTRACTDespite an abundance of evidence supporting an important role for the cleavage of minor capsid protein L2 by cellular furin, direct cleavage of capsid-associated L2 during human papillomavirus 16 (HPV16) infection remains poorly characterized. The conserved cleavage site, close to the L2 N terminus, confounds observation and quantification of the small cleavage product by SDS-PAGE. To overcome this difficulty, we increased the size shift by fusing a compact protein domain, thePropionibacterium shermaniitranscarboxylase domain (PSTCD), to the N terminus of L2. The infectious PSTCD-L2 virus displayed an appreciable L2 size shift during infection of HaCaT keratinocytes. Cleavage under standard cell culture conditions rarely exceeded 35% of total L2. Cleavage levels were enhanced by the addition of exogenous furin, and the absolute levels of infection correlated to the level of L2 cleavage. Cleavage occurred on both the HaCaT cell surface and extracellular matrix (ECM). Contrary to current models, experiments on the involvement of cyclophilins revealed little, if any, role for these cellular enzymes in the modulation of furin cleavage. HPV16 L2 contains two consensus cleavage sites, Arg5 (2RHKR5) and Arg12 (9RTKR12). Mutant PSTCD-L2 viruses demonstrated that although furin can cleave either site, cleavage must occur at Arg12, as cleavage at Arg5 alone is insufficient for successful infection. Mutation of the conserved cysteine residues revealed that the Cys22-Cys28 disulfide bridge is not required for cleavage. The PSTCD-L2 virus or similar N-terminal fusions will be valuable tools to study additional cellular and viral determinants of furin cleavage.IMPORTANCEFurin cleavage of minor capsid protein L2 during papillomavirus infection has been difficult to directly visualize and quantify, confounding efforts to study this important step of HPV infection. Fusion of a small protein domain to the N terminus greatly facilitates direct visualization of the cleavage product, revealing important characteristics of this critical process. Contrary to the current model, we found that cleavage is largely independent of cyclophilins, suggesting that cyclophilins act either in parallel to or downstream of furin to trigger exposure of a conserved N-terminal L2 epitope (RG-1) during infection. Based on this finding, we strongly caution against using L2 RG-1 epitope exposure as a convenient but indirect proxy of furin cleavage.

Impact of depression and stress on placental DNA methylation in ethnically diverse pregnant women

Epigenomics ◽  
2021 ◽  
Author(s):  
Markos Tesfaye ◽  
Suvo Chatterjee ◽  
Xuehuo Zeng ◽  
Paule Joseph ◽  
Fasil Tekola-Ayele
Keyword(s):  
Dna Methylation ◽  
Fetal Brain ◽  
Ethnically Diverse ◽  
Antenatal Depression ◽  
Epigenetic Changes ◽  
Clinical Trial Registration ◽  
False Discovery ◽  
Genome Wide ◽  
Neuropsychiatric Diseases ◽  
Registration Number

Aim: To investigate the association between placental genome-wide methylation at birth and antenatal depression and stress during pregnancy. Methods: We examined the association between placental genome-wide DNA methylation (n = 301) and maternal depression and stress assessed at six gestation periods during pregnancy. Correlation between DNA methylation at the significantly associated CpGs and expression of nearby genes in the placenta was tested. Results: Depression and stress were associated with methylation of 16 CpGs and two CpGs, respectively, at a 5% false discovery rate. Methylation levels at two of the CpGs associated with depression were significantly associated with expression of ADAM23 and CTDP1, genes implicated in neurodevelopment and neuropsychiatric diseases. Conclusion: Placental epigenetic changes linked to antenatal depression suggest potential fetal brain programming. Clinical trial registration number: NCT00912132 (ClinicalTrials.gov)

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