Multiomic analysis reveals that polyamines alter G. vaginalis-induced cervicovaginal epithelial cell dysfunction

An anaerobe-dominant, Lactobacillus-deplete cervicovaginal microbiome is associated with adverse reproductive outcomes. Gardnerella vaginalis, a common cervicovaginal anaerobe, alters cervicovaginal epithelial cell function, resulting in inflammatory immune responses and epithelial barrier breakdown. Specific host-microbial mechanisms inducing this epithelial dysfunction remain unknown. Here we show microbe-specific alterations in cervicovaginal epithelial cell metabolite profiles where G. vaginalis, but not Lactobacillus crispatus, increases polyamine biosynthesis. Pretreatment with polyamines (putrescine, spermidine and spermine) globally shifts G. vaginalis-induced transcriptomic profiles. Alterations in transcripts encoding enzymes responsible for polyamine synthesis and catabolism provides further evidence that G. vaginalis modifies polyamine biosynthesis. Additionally, polyamine-mediated transcriptomic changes include genes related to bacterial defense, inflammation, and epigenetic processes. Polyamines mitigate G. vaginalis-induced inflammatory responses through reduction of cytokines, chemokines, and matrix metalloproteinases. The ability of cervicovaginal metabolites to alter microbe-mediated changes in epithelial cell function suggests that metabolite-microbe interactions are critical mediators of epithelial defense against a Lactobacillus-deplete microbiota.