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 cervicovaginal anaerobe, alters cervicovaginal epithelial cell function, resulting in immune activation and barrier breakdown. Host-microbial mechanisms inducing this epithelial dysfunction remain unknown. 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 enzyme transcripts responsible for polyamine synthesis and catabolism provide evidence that G. vaginalis modifies polyamine biosynthesis. 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. In vitro transcriptional signatures positively correlated to existing human datasets. 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.