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Vaginal microbiome (VMB) dysbiosis is associated with increased acquisition of HIV. Cervicovaginal inflammation and other changes to the mucosal barrier are thought to have important roles but human data are scarce. We compared the human cervicovaginal proteome by mass spectrometry of 50 Rwandan female sex workers who had previously been clustered into four VMB groups using a 16S phylogenetic microarray; in order of increasing bacterial diversity: Lactobacillus crispatus-dominated VMB (group 1), Lactobacillus iners-dominated VMB (group 2), moderate dysbiosis (group 3), and severe dysbiosis (group 4). We compared relative protein abundances among these VMB groups using targeted (abundance of pre-defined mucosal barrier proteins) and untargeted (differentially abundant proteins among all human proteins identified) approaches. With increasing bacterial diversity, we found: mucus alterations (increasing mucin 5B and 5AC), cytoskeleton alterations (increasing actin-organizing proteins; decreasing keratins and cornified envelope proteins), increasing lactate dehydrogenase A/B as markers of cell death, increasing proteolytic activity (increasing proteasome core complex proteins/proteases; decreasing antiproteases), altered antimicrobial peptide balance (increasing psoriasin, calprotectin, and histones; decreasing lysozyme and ubiquitin), increasing pro-inflammatory cytokines, and decreasing immunoglobulins immunoglobulin G1/2. Although temporal relationships cannot be derived, our findings support the hypothesis that dysbiosis causes cervicovaginal inflammation and other detrimental changes to the mucosal barrier.

Purpose: Next generation sequencing and quantitative polymerase chain reaction technologies are now widely available, and research incorporating these methods is growing exponentially. In the vaginal microbiota (VMB) field, most research to date has been descriptive. The purpose of this article is to provide an overview of different ways in which next generation sequencing and quantitative polymerase chain reaction data can be used to answer clinical epidemiologic research questions using examples from VMB research., Methods: We reviewed relevant methodological literature and VMB articles (published between 2008 and 2015) that incorporated these methodologies., Results: VMB data have been analyzed using ecologic methods, methods that compare the presence or relative abundance of individual taxa or community compositions between different groups of women or sampling time points, and methods that first reduce the complexity of the data into a few variables followed by the incorporation of these variables into traditional biostatistical models., Conclusions: To make future VMB research more clinically relevant (such as studying associations between VMB compositions and clinical outcomes and the effects of interventions on the VMB), it is important that these methods are integrated with rigorous epidemiologic methods (such as appropriate study designs, sampling strategies, and adjustment for confounding)., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Background: Candidate vaginal microbicides could cause genital irritation, which in turn could facilitate HIV transmission instead of preventing it. While genital epithelial findings are documented in a standardized manner in most microbicide trials, little is known about background rates and predictors for many types of genital findings., Study Design: A secondary analysis was conducted using data from a Phase II expanded safety study of the candidate microbicide Carraguard gel (Population Council, NY, USA) in Thailand. Genital findings were identified by visual inspection of the cervix, vaginal walls and external genitalia during pelvic exams prior to gel use (screening and enrollment) and during gel use (at 2 weeks and Months 1-12). Women were interviewed about potential risk factors for genital findings at every visit and tested routinely for sexually transmitted and vaginal infections., Results: A total of 258 genital findings were identified in 152 woman-years of follow-up. Genital findings were positively associated with older age, increased parity, self-report of genital symptoms, positive HSV-2 serology, bacterial vaginosis by Nugent scoring and the presence of a genital finding at baseline. Furthermore, vaginal findings were positively associated with vaginal practices and yeast infections. Genital findings were negatively associated with use of hormonal contraception, inconsistently associated with frequency of sex and applicator use, and not associated with condom use., Conclusions: Several factors that are common in women of reproductive age account for the background rate of genital epithelial findings in this population.