Metabolic Signatures of Bacterial Vaginosis

ABSTRACT Bacterial vaginosis (BV) is characterized by shifts in the vaginal microbiota from Lactobacillus dominant to a micro-biota with diverse anaerobic bacteria. Few studies have linked specific metabolites with bacteria found in the human vagina. Here, we report dramatic differences in metabolite compositions and concentrations associated with BV using a global metabo-lomics approach.We further validated important metabolites using samples from a second cohort of women and a different platform tomeasure metabolites. In the primary study, we comparedmetabolite profiles in cervicovaginal lavage fluid from 40 women with BV and 20 women without BV. Vaginal bacterial representation was determined using broad-range PCR with pyro-sequencing and concentrations of bacteria by quantitative PCR.We detected 279 named biochemicals; levels of 62 % of metabo-lites were significantly different in women with BV. Unsupervised clustering of metabolites separated women with and without BV.Women with BV have metabolite profiles marked by lower concentrations of amino acids and dipeptides, concomitant with higher levels of amino acid catabolites and polyamines. Higher levels of the signaling eicosanoid 12-hydroxyeicosatetraenoic acid (12-HETE), a biomarker for inflammation, were noted in BV. Lactobacillus crispatus and Lactobacillus jensenii exhibited similar metabolite correlation patterns, which were distinct from correlation patterns exhibited by BV-associated bacteria. Sev-eral metabolites were significantly associated with clinical signs and symptoms (Amsel criteria) used to diagnose BV, and nome