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bioRxiv · 10.1101/2025.11.20.689523

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

Anton, L.·Kholod, O.·Phatate, R.·Ferguson, B.·Klohonatz, K.·Goods, B. A.·Gerson, K. D.
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Abstract

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.

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Anton, L., Kholod, O., Phatate, R., Ferguson, B., Klohonatz, K., Goods, B. A., Gerson, K. D.. 2025-11-20. Multiomic analysis reveals that polyamines alter G. vaginalis-induced cervicovaginal epithelial cell dysfunction. https://doi.org/10.1101/2025.11.20.689523

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