Distinct Microbial Signatures along the Female Reproductive Tract in Endometrial Cancer Patients

Emerging evidence suggests that microbiota dysbiosis plays a critical role in the pathogenesis of endometrial cancer (EC), a leading cause of cancer-related deaths in women globally. However, few studies have simultaneously examined both the upper and lower genital tract microbiota in such individuals. In this study, we investigated alterations in microbiota composition across different parts of the female genital tract in a Chinese cohort of EC patients. Samples from 59 individuals (22 endometrial cancer patients; 8 endometrial hyperplasia patients, and 29 benign controls) were collected. In addition, a total of 58 vaginal swabs, 39 fallopian swabs, 16 peritoneal fluid samples, 36 urine swabs, and 34 endometrium samples were finally recruited. The composition of bacterial communities was determined by 16S ribosomal RNA Miseq sequencing. Specific taxa were significantly enriched in the EC group, including Akkermansia muciniphila, Acinetobacter, and Pseudomonas in the vagina, and Pseudomonas, Bacillus, Streptomyces, and Burkholderia-Caballeronia-Paraburkholderia in the endometrium. Meanwhile, Acinetobacter was positively correlated with fasting plasma glucose, while Pseudomonas was correlated with estrogen and progesterone receptor expression. An effective random forest model enabled us to distinguish EC patients from benign controls. Moreover, specific alterations in the composition and diversity of the reproductive tract microbiota in endometrial cancer patients were identified. Our findings suggest a potential link between microbiome alterations and estrogen and glucose metabolism in EC. However, further investigation is needed to elucidate the molecular mechanisms underlying these associations.