Microbial signatures and continuum in endometrial cancer and benign patients

Abstract

Abstract Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) of 61 patients and showed that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. A microbial continuum, defined by detection of common bacterial species along the genital tract, was noted in most women without cancer while the continuum was less cohesive in endometrial cancer patients. Vaginal microbiota were poorly correlated with rectal microbiota in the studied cohorts. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus, increased bacterial diversity and enrichment of Porphyromonas, Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media had minimal impact on cytokine and chemokine profiles. Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology remains to be elucidated.