Abstract: Endometriosis, which causes pain in the pelvis and lower abdomen, afflicts 1 in 10 women between 15 and 49 years of age in the United States. Nearly half of these women experience chronic pelvic pain, and many find that available treatments (hormone therapy and surgery) have negative side effects and do not prevent recurrences. A well-accepted theory is that endometriosis occurs when endometrial tissue enters the peritoneal cavity via retrograde menstruation and implants onto pelvic organs and peritoneal surfaces. However, whereas up to 90% of women experience retrograde menstruation, only 10% of women develop endometriosis, suggesting that unknown factors contribute to development of endometriosis. Thus, identifying such causal factors is essential to develop new tools to diagnose and treat this painful disease. Our recent work found that whereas some gut bacteria promote endometriosis, others protect against endometriosis by fermenting fiber to produce short chain fatty acids (SCFAs). We found that altered gut microbiota promotes lesion growth and that gut-derived butyrate concentration is decreased in feces from mice with endometriosis. Further, we found that butyrate acts through both GPR signaling and HDAC inhibition to inhibit lesion growth. These findings are the first to provide evidence that a gut microbiota-derived metabolite protects against endometriosis. These results will enable future studies aimed at developing diagnostic tests (e.g., fecal n-butyrate concentration) and treatment strategies (e.g., n-butyrate analogs or n-butyrate-producing probiotics) for endometriosis.

Biography: Dr. Rama Kommagani is an Assistant Professor in the Department of Obstetrics & Gynecology and a faculty member in the Center for Reproductive Health Sciences at Washington University School Of medicine. Dr. Kommagani received B.S. and M.S. in Microbiology from Osmania University, India and Ph.D. in Biomedical Sciences from Wright State University, Ohio. Subsequently, Dr. Kommagani conducted postdoctoral training in the laboratory of Dr. Bert O’Malley at Baylor College of Medicine, where he investigated the cellular and molecular mechanisms of Steroid Receptors function in normal endometrial functions. Dr. Kommagani was then a recruited to Washington University where he is focusing on the molecular pathogenesis and translational aspects of gynaecological pathologies. Specifically, on the functional crosstalk between microbiome and inflammation with endometriosis.

In 2015 Dr. Kommagani received the Early Investigators Award from the Endocrine Society. He has published more than 40 peer-reviewed manuscripts in high impact journals including Cell Metabolism, PNAS, eLife and Human reproduction. He is also a recipient of the NIH K99/R00 grant and served on several NIH study sections.