Taxonomic and functional profiling of the vulvar microbiome indicates variations related to ecological signatures, ageing, and health status

Arnout Mieremet¹Michelle Van Der Wurff¹Lisa Pagan²Edgar Ferrer Gonzalez³Jin Seo³Frank Schuren^1*

• ¹Microbiology & Systems Biology, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, Netherlands
• ²Centre for Human Drug Research (CHDR), Leiden, Netherlands
• ³Reckitt (United States), Montvale, New Jersey, United States

The vulvar microbiome is adjacent to that of the skin and the vagina and connects microbiomes present on a stratified epithelial barrier to that of a mucosal barrier. Yet, the characterization of the microbiome in the vulvar region of the body is understudied, although dysbiosis in the microbiome of the skin or vagina have been linked to impairments in women's health. To better understand the role of the vulvar microbiome during healthy ageing or during presentation of vulvar diseases, we analyzed the vulvar microbiome by shotgun metagenomic sequencing on composition at species level and for functional capacity. This was performed in a large population enrolled in the Vulvar Microbiome Leiden Cohort (VMLC), including a total of 58 healthy women in a broad age range (22-82 years). Moreover, we analyzed vulvar microbiome derived from 9 participants presenting a vulvar disease, including vulvar lichen sclerosus (LS; N=6), or high-grade squamous intraepithelial lesion (HSIL; N=3). Compositional analyses showed a skin-, vagina-, or multispecies mixture-dominant bacterial signature, which revealed differences in the alpha diversity and functional capacity of the microbiome. Upon ageing the presence of Lactobacillus iners, L. crispatus, and L. gasseri in the vulvar microbiome shifted towards reduction. In the microbiome of individuals with a vulvar disease, higher abundance of Staphylococcus hominis, Micrococcus luteus, Corynebacterium amycolatum, and Corynebacterium simulans was detected and an altered functional capacity for the L-histidine pathway. In conclusion, we identified variations in microbial taxa and functional capacities in the vulvar microbiome that are associated with age and disease (LS and HSIL), which can be targeted to develop microbiome-based vulvar therapies promoting women's health.