Structure and regulation of the cervicovaginal microbiome in a cohort of Afro-Caribbean women

Abstract

Background The cervicovaginal microbiome, with its well documented dynamic community state types (CSTs I-V) is known to interact with the host immune system in a complex regulatory ecosystem that guards against dysbiosis and invading pathogens. However, the regulatory mechanism of the cervicovaginal microbiome in vaginal eubiosis is not well understood. Therefore, we characterized the cervicovaginal microbiome in a cohort of Afro-Caribbean women to the species-strain taxonomic level using high-throughput targeted sequencing and shotgun metagenomics and conceptualized a hypothetical model that aids in understanding vaginal ecosystem regulation. Results Compared to targeted 16S rRNA V4 sequencing, whole genome shotgun (WGS) metagenomics offered greater species resolution of the cervicovaginal microbiome in the Afro-Caribbean women cohort. Community state type IV predominated in the microbiome of these women, with Prevotella (13.91%), Gardnerella (12.14%) and Lactobacillus (9.37%) being the three most abundant genera. For Prevotella and Lactobacillus the most abundant species-strains were P. timonensis DSM 22865 (5.0%) and L. iners DSM 13335 (7.0%), respectively. The less virulent strain of Gardnerella, G. vaginalis 409-05 (8.0%) was more abundant than G. vaginalis ATCC 14019 (4.0%). In the resistome, 2,753 antimicrobial resistance (AMR) genes consisting of 28 types (mostly tet and Emr; abundances 51% and 15%, respectively) which confer resistance to tetracyclines and the macrolide-lincosamide streptogramin B (MLSb phenotype) group were observed. Functional profiling showed a high abundance of biological processes (bacterial-type flagellum-dependent cell motility, cell adhesion, response to biotic stimulus and quorum sensing) associated with biofilm activity. Conclusions Characterized for the first time, the cervicovaginal microbiome in Afro-Caribbean women is predominantly CST IV with the three most abundant taxa consisting of bacterial strains P. timonensis DSM 22865, G. vaginalis 409-05 and L. iners DSM 13335. Its resistome had multiple AMR genes that confer resistance to antibiotics commonly used in the treatment of sexually transmitted infections (STIs) and bacterial vaginosis (BV). In this study, the occurrence of biofilm activity within the cervicovaginal microbiome suggested a possible regulatory role. We present a conceptual immuno-munibiome model that advances a mechanistic approach for the structure and regulation of the vaginal ecosystem in the Afro-Caribbean women cohort.