Biogenic Amines Increase the Odds of Bacterial Vaginosis and Affect the Growth of and Lactic Acid Production by Vaginal Lactobacillus spp.

ABSTRACT Bacterial vaginosis (BV) is the most common vaginal disorder of reproductive-aged women, yet its etiology remains enigmatic. One clinical symptom of BV, malodor, is linked to the microbial production of biogenic amines (BA). Using targeted liquid chromatography mass spectrometry, we analyzed 149 longitudinally collected vaginal samples to determine the in vivo concentrations of the most common BAs and then assessed their relationship to BV and effect upon the growth kinetics of axenically cultured vaginal Lactobacillus species. Increases in cadaverine, putrescine, and tyramine were associated with greater odds of women transitioning from L. crispatus-dominated vaginal microbiota to microbiota that have a paucity of Lactobacillus spp. and from Nugent scores of 0 to 3 to Nugent scores of 7 to 10, consistent with BV. Exposure to putrescine lengthened the lag time and/or slowed the growth of all vaginal Lactobacillus spp. except L. jensenii 62G. L. iners AB107’s lag time was lengthened by cadaverine but reduced in the presence of spermidine and spermine. The growth rate of L. crispatus VPI 3199 was slowed by cadaverine and tyramine, and strain-specific responses to spermine and spermidine were observed. BAs were associated with reduced production of d- and l-lactic acid by vaginal Lactobacillus spp., and this effect was independent of their effect upon Lactobacillus species growth. The exceptions were higher levels of d- and l-lactic acid by two strains of L. crispatus when grown in the presence of spermine. Results of this study provide evidence of a direct impact of common biogenic amines on vaginal Lactobacillus spp. IMPORTANCELactobacillus spp. are credited with providing the primary defense against gynecological conditions, including BV, most notably through the acidification of the vaginal microenvironment, which results from their production of lactic acid. The microbial production of BAs has been hypothesized to play a mechanistic role in diminishing Lactobacillus species-mediated protection, enabling the colonization and outgrowth of diverse anaerobic bacterial species associated with BV. Here, we demonstrate that in vivo increases in the most commonly observed BAs are associated with a loss of Lactobacillus spp. and the development of BV, measured by Nugent score. Further, we show that BAs formed by amino acid decarboxylase enzymes negatively affect the growth of type strains of the most common vaginal Lactobacillus spp. and separately alter their production of lactic acid. These results suggest that BAs destabilize vaginal Lactobacillus spp. and play an important and direct role in diminishing their protection of the vaginal microenvironment.