P1.53 Microrna expression induced by vaginal microbiota controls cell proliferation

Introduction Bacterial Vaginosis (BV) is a condition of the human vagina characterised in part by a paucity of Lactobacillus spp. and the presence of a wide array of strict and facultative anaerobes such as Gardnerella vaginalis and Atopobium vaginae . BV is associated with the acquisition of sexually transmitted infections such as HIV and Chlamydia trachomatis . Host microRNAs (miRNAs) are an uncharacterized factor that may control host cellular responses to Lactobacillus and BV-associated bacterial communities. Understanding the molecular mechanisms that drive or are induced by BV-associated vaginal microbiota may help identify targets and develop strategies to restore a healthy vaginal state, which would concurrently reduce the risk of STI acquisition. We hypothesised that specific miRNAs are associated with Lactobacillus -dominated and BV-associated Community State Types (CST) by affecting specific host functions. Methods Leveraging prospectively collected daily vaginal swab samples, the types and abundance of human miRNAs were used to gain insight into host regulatory mechanisms that potentially associate with vaginal microbial community composition shifts using miRNAseq. Random Forest miRNA feature ranking was used to identify miRNAs correlated with types of vaginal microbiota. Additional in vitro cell culture experiments were performed to demonstrate the relationship between miRNA expression, vaginal bacterial culture supernatants and epithelial cell proliferation using qPCR and Western blots. Results miRNASeq was performed on 100 samples from 16 unique subjects in 3 longitudinal microbiota profile groups. One of the most significant miRNAs associated with BV was miR-193b. In vitro, its expression correlated with decreased cell proliferation in cells exposed to Lactobacillus spp. culture media relative to G. vaginalis culture supernatants. Conclusion miR-193b over expression is associated with reduced cell proliferation in non-BV samples. Control of cell proliferation could contribute to reducing the risk of STI in Lactobacillus dominated vaginal microbiota.