Investigating the impact of condomless vaginal intercourse and lubricant use on the vaginal metabolome: a pre-post observational study

The vaginal metabolome is a significant factor in the vaginal microenvironment, and data are emerging on its independent role in urogenital health. Condomless vaginal intercourse and personal lubricant use are common practices that may affect the vaginal metabolome. The aim of the present study is to describe the associations between condomless intercourse and lubricant use on the vaginal metabolome.This study used archived mid-vaginal swabs from a 10-week observational cohort of reproductive age women who self-collected samples and recorded behavioural diaries daily. Cases and controls were defined as participants who self-reported condomless vaginal intercourse with or without lubricant use, respectively. Samples were drawn prior to and following condomless vaginal intercourse. Twenty-two case participants were race/ethnicity matched to 22 control participants. Mid-vaginal swabs were subjected to 16S rRNA gene amplicon sequencing and untargeted ultrahigh performance liquid chromatography tandem mass spectroscopy metabolomics. Bayesian mixed-effects regression (unadjusted and adjusted for the vaginal microbiota) was used to evaluate differences in metabolite concentration associated with vaginal intercourse and lubricant use.Both condomless penile-vaginal intercourse and lubricant use were independently associated with higher (up to 8.3-fold) concentrations of metabolites indicative of epithelial damage (eg, sarcosine) and many host-produced antioxidants. Lubricant use was significantly associated with increases in lipids related to cellular damage, host-produced sphingolipids (antimicrobials), antioxidants and salicylate, a cooling agent common to lubricants, in a study design which controls for the independent effect of intercourse. Metabolites involved in oxidative stress and salicylate were strongly correlated with several molecular bacterial vaginosis-associated bacteria.This study provides important foundational data on how condomless vaginal-penile intercourse and lubricant use affect the vaginal metabolome and may affect the protective mechanisms in the vaginal microenvironment.