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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The association of Chlamydia trachomatis and Mycoplasma genitalium infection with the vaginal metabolome.

Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) are two highly prevalent bacterial sexually transmitted infections (STIs) with a significant rate of co-infection in some populations. Vaginal metabolites are influenced by resident vaginal microbiota, affect susceptibility to sexually transmitted infections (STIs), and may impact local inflammation and patient symptoms. Examining the vaginal metabolome in the context of CT mono (CT+) and CT/MG co-infection (CT+/MG+) may identify biomarkers for infection or provide new insights into disease etiology and pathogenesis. Yet, the vaginal metabolome in the setting of CT infection is understudied and the composition of the vaginal metabolome in CT/MG co-infected women is unknown. Therefore, in this analysis, we used an untargeted metabolomic approach combined with 16S rRNA gene amplicon sequencing to characterize the vaginal microbiota and metabolomes of CT+, CT+/MG+, and uninfected women. We found that CT+ and CT+/MG+ women had distinct vaginal metabolomic profiles as compared to uninfected women both before and after adjustment for the vaginal microbiota. This study provides important foundational data documenting differences in the vaginal metabolome between CT+, CT+/MG+ and uninfected women. These data may guide future mechanistic studies that seek to provide insight into the pathogenesis of CT and CT/MG infections.