O13.4 Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier

Abstract

Introduction Vaginal microbiome (VMB) dysbiosis is associated with increased acquisition of HIV and sexually transmitted infections (STIs). Cervicovaginal inflammation and other changes to the mucosal barrier are thought to play important roles but human data are scarce. In this study, we compared the cervicovaginal proteome among women with different VMB compositions. Methods Cervicovaginal lavages of 50 Rwandan female sex workers with known VMB composition were selected for human proteome analysis using mass-spectrometry. These women were previously clustered into four VMB groups in order of increasing bacterial diversity: group 1 had a Lactobacillus crispatus-dominated VMB; group 2 a L. iners -dominated VMB; group 3 moderate dysbiosis; and group 4 severe dysbiosis. 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. Results With increasing bacterial diversity, we found: mucus alterations (increasing mucin 5B and 5AC), cytoskeleton alterations (increasing actin-organising proteins; decreasing keratins and cornified envelope proteins), increasing cell death (using LDHA/B as biomarkers of cell death), altered proteolytic activity (increasing proteasome core complex proteins/proteases; decreasing antiproteases), altered antimicrobial peptide balance (increasing psoriasin, calprotectin, and histones; decreasing lysozyme and ubiquitin), increasing proinflammatory cytokines, and decreasing immunoglobulins IgG1/2. Conclusion The VMB is strongly associated with the cervicovaginal human proteome in this cohort of Rwandan women at high risk of HIV and other STIs. Although temporal relationships cannot be derived, our findings support the hypothesis that dysbiosis causes cervicovaginal inflammation and other detrimental changes to the mucosal barrier that may lead to increased HIV/STI acquisition. Disclosure of interest statement This work was funded by the Institute of Infection and Global Health of the University of Liverpool, the Aids Fonds Netherlands (project number 201102), European and Developing Countries Clinical Trials Partnership (project number CT.2005.33070.001) and the European Commission (CHAARM consortium). The authors declare no conflicts of interest.