The microRNA Cargo of Human Vaginal Extracellular Vesicles Differentiates Parasitic and Pathobiont Infections from Colonization by Homeostatic Bacteria

Abstract

The disturbed vaginal microbiome defined as bacterial vaginosis (BV) and the parasitic infection by Trichomonas vaginalis (TV), the most common non-viral sexually transmitted pathogen, have well-established adverse effects on reproductive outcomes and susceptibility to infection and cancer. Molecular mechanisms underlying these associations and the failure of antibiotic therapy to mitigate adverse consequences are not fully elucidated. In an in vitro human vaginal colonization model, we tested the hypothesis that responses to TV and/or BV-bacteria will disrupt the micro(mi)RNA cargo of extracellular vesicles (EV) with the potential to modify pathways associated with reproductive function, cancer, and infection. miRNAs were quantified by HTG EdgeSeq. MiRNA differential expression (DE) was established in response to TV, the BV signature pathobiont Prevotella bivia and a homeostatic Lactobacillus crispatus with adjusted p < 0.05 using R. Validated gene targets, pathways, protein-protein interaction networks, and hub genes were identified by miRWalk, STRING, Cytoscape, and CytoHubba. In contrast to L. crispatus, TV and the BV pathobiont dysregulated a massive number of EV-miRNAs, over 50% shared by both pathogens. Corresponding target pathways, protein interaction clusters and top hub genes were related to cancer, infectious disease, circadian rhythm, steroid hormone signaling, pregnancy, and reproductive tissue terms. These data support the emerging concept that bacteria and parasitic eukaryotes disturbing the human vaginal microbiome may impact reproductive health through EV-miRNA dysregulation.

Exosomal miRNAs from maternal vaginal discharge as biomarkers for preterm labor: non-invasive liquid biopsy

“…Exosomes have become a focal point in biomedical research due to their crucial influence on various biological functions and their ability to modulate microenvironments 21,22 . Exosomes, classified as membrane-bound nanovesicles with sizes ranging from 30 to 200 nm 23 , are released from diverse cell types and bodily fluids, including blood 24 , saliva 25 , breast milk 26 , urine 27 , tears 28 , and vaginal discharge 29 .…”