Characterizing the Endometriosis Microbiome and Metabolomic Pain Phenotype

PROJECT SUMMARY Endometriosis affects 200 million individuals globally and is responsible for 87% of chronic pelvic pain. Substantial risks of non-treatment include chronic pain, kidney failure, and bowel obstruction. Disappointingly, more than one-third of individuals fail medical treatments, and fertility-sparing surgical management results in persistent pain in over 37% of cases with long-term recurrence rates close to 50%. The U.S. spends over $69 billion annually as a result of limited effective treatment options for individuals with endometriosis. Growing evidence suggests that alterations in microbial composition and nicotinamide adenine dinucleotide (NAD+)- dependent mechanisms exist in endometriosis and contribute to pain. Determining the contribution of microbiome and NAD+ metabolomic networks, and possible synergies between them is critical to understanding the biology of endometriosis pain. Our proposal aims to stratify individuals with endometriosis into groups that may benefit from different treatment modalities by identifying differences in microbial and NAD+ metabolomic patterns that associate with differing pain characteristics, quality of life, psychological symptoms, and postoperative outcomes. This will be completed via two specific aims: 1) To determine the bacterial composition in stool, ovarian, and endometrial tissue that associates with differing endometriosis chronic pain phenotypes 2) To identify the dominant NAD+ biosynthetic pathway and alterations in NAD+ metabolites associated with chronic pain phenotypes in endometriosis and endometrial tissue. The proposed research represents a necessary new direction in endometriosis by shifting focus from limited hormonal treatments and reliance on repetitive invasive surgical procedures to the novel role of the microbiome and NAD+ metabolome on differing phenotypic pain presentations. This career development award will collect important preliminary data for an R01-funded clinical trial focused on innovative translational approaches to treat endometriosis- related pain while developing the principal investigator into an independent clinician-scientist in multi-omics informed pain research.