Choline metabolism disorder induced by Prevotella is a risk factor for endometrial cancer in women with polycystic ovary syndrome.

Abstract

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with an increased risk of endometrial cancer, potentially mediated by vaginal microbiota dysbiosis and hormonal disturbances. This study investigates how hormonal imbalances in PCOS patients affect the vaginal microbiome and choline metabolism, thereby influencing endometrial cancer risk.

Methods: In this observational study, 70 women were enrolled, including 36 with PCOS and 34 controls. We analyzed their vaginal microbiota, lipid metabolism, and endometrial transcriptome using 16S rRNA sequencing, untargeted lipidomics, and transcriptomic sequencing.

Results: The PCOS group showed significant differences in vaginal microbiota composition, notably an increase in LPS-producing Prevotella spp. Functional analyses indicated activation of LPS biosynthesis and inflammatory signaling pathways. Lipidomics revealed disrupted choline metabolism, with alterations in phosphocholine and total choline levels. Transcriptomic data highlighted the up-regulation of inflammatory and metabolic dysregulation pathways.

Conclusions: Hormonal imbalances in PCOS contribute to significant changes in the vaginal microbiome and metabolic pathways, increasing the risk of endometrial cancer. These findings suggest potential therapeutic targets for reducing cancer risk in this population.