Decoding the microbial landscape of endometrial cancer: a case-control study

The human microbiome plays an emerging role in cancer biology, yet its contribution to endometrial cancer (EC) remains poorly defined. This study investigates the microbial composition of the vaginal, rectal, and endometrial sites in women with and without EC, aiming to uncover microbial signatures associated with the disease. We performed shotgun metagenomic sequencing on vaginal, rectal, and endometrial samples from 25 patients with EC and 27 control women undergoing hysterectomy for benign conditions. Vaginal and rectal swabs were collected before surgery, while endometrial swabs were obtained post-hysterectomy using a sterile brushing technique to prevent cross-contamination. Vaginal microbiota in patients with EC showed significantly higher microbial diversity and distinct community composition compared to controls. These differences remained significant after adjusting for age and body mass index. Several bacterial species, including Peptococcus niger, Anaerococcus murdochii, Mobiluncus, Porphyromonas, and Prevotella, were more abundant in the vaginal microbiota of patients with cancer. In contrast, Lactobacillus spp. were more abundant in vaginal and rectal samples of control subjects. This work represents one of the few studies to comprehensively examine the relationship between the vaginal, rectal, and endometrial microbiomes in the context of EC, suggesting a potential role for microbial imbalance in disease development. The findings underscore the importance of site-specific microbial analyses in gynecologic oncology and support further investigation into the microbiome as a possible biomarker for early detection and a target for preventive strategies.