Navigating complexities of polymorphic microbiomes in endometrial cancer

The microbiome is key to understanding endometrial cancer (EC) etiology and prevention strategies, implicated in the regulation of estrogen in estrogen-driven cancers. Utilizing robust methodologies in the QIIME 2 platform, we examined 16S rRNA vaginal and rectal microbiome data from an EC cohort: 192 women with benign gynecologic conditions, endometrial hyperplasia, or endometrial cancer. Distinct microbial compositions and community networks specific to EC were identified and related to histological grade with adjustments for EC risk factors. Vaginal health-associated Lactobacillus and Limosilactobacillus, and rectal Prevotella and Peptoniphilus, were depleted in EC, while detrimental vaginal Anaerococcus, Porphyromonas, Prevotella, Peptoniphilus, and rectal Buttiaxella were enriched. Significant bacterial features were shared between rectal and vaginal sites in EC, such as Prevotella timonensis and Peptoniphilus A. Vaginal Lactobacillus abundance contributed to less feature sharing from the rectum. Putative microbial metabolic analysis identified dysregulation of amino acid, complex carbohydrate, and hormone metabolism amongst patients with EC.