Gut microbiota–derived short-chain fatty acids protect against the progression of endometriosis

0301 basic medicine 572 Cell Survival Nude Telomere-Binding Proteins Endometriosis Mice, Nude Inbred C57BL Transfection Protective Agents Shelterin Complex Cell Line Feces Mice 03 medical and health sciences Medicine and Health Sciences Animals Humans Research Articles Cell Line, Transformed Cell Proliferation 2. Zero hunger 0303 health sciences Bacteria Animal ICTS (Institute of Clinical and Translational Sciences) Epithelial Cells Gastrointestinal Microbiome 3. Good health Mice, Inbred C57BL Butyrates Disease Models, Animal Transformed Disease Models Heterografts Female Stromal Cells Signal Transduction
DOI: 10.26508/lsa.202101224 Publication Date: 2021-09-30T17:14:03Z
ABSTRACT
Worldwide, ∼196 million are afflicted with endometriosis, a painful disease in which endometrial tissue implants and proliferates on abdominal peritoneal surfaces. Theories on the origin of endometriosis remained inconclusive. Whereas up to 90% of women experience retrograde menstruation, only 10% develop endometriosis, suggesting that factors that alter peritoneal environment might contribute to endometriosis. Herein, we report that whereas some gut bacteria promote endometriosis, others protect against endometriosis by fermenting fiber to produce short-chain fatty acids. Specifically, we found that altered gut microbiota drives endometriotic lesion growth and feces from mice with endometriosis contained less of short-chain fatty acid and n-butyrate than feces from mice without endometriosis. Treatment with n-butyrate reduced growth of both mouse endometriotic lesions and human endometriotic lesions in a pre-clinical mouse model. Mechanistic studies revealed that n-butyrate inhibited human endometriotic cell survival and lesion growth through G-protein–coupled receptors, histone deacetylases, and a GTPase activating protein, RAP1GAP. Our findings will enable future studies aimed at developing diagnostic tests, gut bacteria metabolites and treatment strategies, dietary supplements, n-butyrate analogs, or probiotics for endometriosis.
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