The Utility of Voided Urine Samples as a Proxy for the Vaginal Microbiome and for the Prediction of Bacterial Vaginosis

Recent work has shown that the vaginal microbiome exerts a strong impact on women's gynecological health.However,collection of vaginal specimens is invasive and requires previous clinical training or the involvement of a trained clinician.In contrast,urine sample collection is routine and noninvasive and does not require involvement of a clinician.We sought to compare the vaginal and urogenital microbiomes to assess the utility of voided urine samples as a proxy for the vaginal microbiome.Paired urogenital and vaginal samples were collected from pregnant women and characterized by 16S rRNA taxonomic profiling.We examined diversities and compositions of paired urogenital and vaginal microbiomes using five discrete strategies to explore the similarity between the vaginal and urogenital microbiomes.A strategy comparing the paired urogenital and vaginal microbiomes in which taxa were assigned using the STIRRUPS database and urine-specific taxa were removed showed no significant difference in diversity and composition between the paired urogenital and vaginal microbiomes.Moreover,the relative abundances of common vaginal taxa were linearly correlated with those in the paired urogenitalmicrobiomes.These similarities suggest that voided urine samples could represent a noninvasive protocol for accurate profiling of the vaginalmicrobiome with likely clinical applications.Finally,a machine learning model was established in which the voided urine microbiome was compared favorably to the vaginal microbiome in predicting bacterial vaginosis.

Multi-omic Microbiome Profiles in the Female Reproductive Tract in Early Pregnancy

The vaginal microbiome likely influences host signaling compounds within the reproductive tract,including pro-inflammatory signals,which may play an important role during pregnancy.Vaginal lactobacilli are associated with positive pregnancy outcome,whereas bacterial vaginosis,a dysbiosis of the vaginal microbiome,is associated with an increased risk of adverse pregnancy outcomes including preterm birth.If the host response could be predicted based on the taxonomic composition of the vaginal microbiome,particularly early in pregnancy,then those predictions could potentially be used to personalize intervention methods to reduce preterm birth and other adverse events.In this proof of principle study,we apply multivariate strategies to analyze 16S rRNA-based taxonomic surveys in conjunction with targeted immuno-proteomic and lipidomic data from vaginal samples from 58 women enrolled in the Multi-Omic Microbiome Study-Pregnancy Initiative during early pregnancy.Relationships between the vaginal microbiome and the vaginal lipidome have not been previously reported.Results from this study reveal significant multiple pairwise associations between microbial taxa,specific eicosanoids and sphingomyelins,and cytokines.While the biologic significance of these associations is not yet known,these results support the utility of such multi-omic approaches as a means to predict the impact of the microbiome on the host.