The microbiome of bacterial vaginosis - clinical studies and model biofilms

Abstract

This work focuses on different aspects of the vaginal disorder bacterial vaginosis (BV). After (i) the identification of a new compound against BV, and (ii) the in vivo application of this compound and vaginal and urinary microbiota analyses, (iii) metatranscriptomics were applied on the vaginal microbiome, (iv) ending with a new in vitro multispecies biofilm model. First, different compounds were tested on a Gardnerella vaginalis biofilm model. Amphoteric tensides were effective either alone or in combination with the antibiotic metronidazole. Second, the amphoteric tenside sodium cocoamphopropionate (SCAP) was formulated into a pessary and its safety, tolerability and effectiveness was evaluated in a randomized controlled clinical trial. Patients with BV were included into the study and received the pessary after they had been treated with the antibiotic metronidazole. WO 3191 was safe and tolerated well but was not able to reduce BV recurrence. Vaginal fluid and urine samples were obtained from BV patients and from healthy women and were analysed using Illumina 16S rRNA gene sequencing. Vaginal microbial profiles of BV patients were more diverse than those of healthy women and the most common species in BV were Lactobacillus iners, Prevotella bivia, Sneathia amnii and P. amnii. The L. crispatus dominated vaginal microbial community observed in health could not be restored after metronidazole treatment and L. iners was the most abundant species after treatment. Most urinary microbial community profiles (urotypes) were similar in health and BV. However, the L. crispatus urotype was only identified in healthy women and was not restored after metronidazole treatment. These findings suggest that supporting L. crispatus in the vaginal and urinary microbiota after incidents of BV may have beneficial health outcomes. Third, metatranscriptomic analyes were performed on vaginal fluid samples. G. vaginalis was the most active species in BV and upregulated functional pathways related to biofilm formation. After metronidazole treatment, either L. crispatus or L. iners dominated the community and covered different functional patterns. Lastly, a multispecies biofilm model containing G. vaginalis, A. vaginae and L. crispatus was developed. Metronidazole promoted L. crispatus growth whereas SCAP promoted the growth of G. vaginalis and A. vaginae thus highlighting the importance of multispecies biofilm models in compound research against polymicrobial diseases.