Endometriosis, the microbiome and innate immunity

Project summary Endometriosis is a chronic gynecological condition that is associated with pelvic pain and infertility, impacting 10-15% of reproductive aged women. Endometriosis is typically classified as an inflammatory disease process, and it is thought that an insufficient immunosurveillance system makes some women more susceptible to developing endometriosis. Neutrophils comprise 50-70% of circulating leukocytes, and are a heterogenous population, with multiple phenotypic and functional variants identified. Neutrophils are elevated in peritoneal fluid from women with endometriosis, but data on the mechanisms contributing to this elevation as well as the functional capabilities of neutrophils in endometriosis are currently lacking. We and others have demonstrated that the reproductive microbiome can modulate the phenotypic and functional variants of neutrophils, suggesting a potential role for microbiome-neutrophil interactions in endometriosis. The global hypothesis is that an altered neutrophil response induced by the presence of bacteria or microbial dysbiosis could create a chronic inflammatory environment that underlies the development or pathogenesis of endometriosis. In this project we will enroll a cohort of women undergoing diagnostic laparoscopy with pelvic pain or infertility and indications for endometriosis. We expect approximately half of the women undergoing laparoscopy will receive a diagnosis of endometriosis and the remaining will have no indications of endometriosis and serve as a control population. We will perform a multi-‘omics analysis of peritoneal fluid and cervicovaginal specimens to identify differences in microbial taxa and neutrophil function and phenotype between endometriosis patients and the control population, and investigate potential links between the microbiome and neutrophils in endometriosis. The results of this study could provide rationale for including antibiotics or pharmacologic agents that modulate neutrophils in endometriosis treatments.