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
AUTHORS (9)
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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CITATIONS (59)
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