Around 196 million women worldwide suffer from endometriosis, a condition that typically causes pelvic pain and infertility. Endometriosis develops when the lining inside the uterus becomes attached to surrounding tissue, such as the intestine or the membrane that lines the abdominal cavity, causing bleeding, pain and other symptoms. Despite decades of research, little is known about the factors that contribute to the development of endometriosis.
Evidence suggests that the microbiome, a community of microorganisms that live inside the body, is altered in women with endometriosis. In this study published in the journal Cell death and discoveryresearchers at Baylor College of Medicine discovered that an altered gut microbiome plays a central role in endometriosis disease progression in an animal model.
“To investigate the role of the microbiome in endometriosis, we first implemented a new mouse model of the condition in which we eliminated the microbiome using antibiotics,” said lead author Dr. Rama Kommagani, Associate Professor in the Departments of Pathology and Immunology and of Molecular Science. Virology and Microbiology at Baylor.
The researchers found that mice lacking the gut microbiome had smaller endometriotic lesions than mice with the microbiome. Furthermore, when gut microbiome-null mice received gut microbiota from mice with endometriosis, the lesions grew as large as those in mice that retained their microbiome. These findings suggest that altered gut bacteria drive disease progression. On the other hand, the uterine microbiome did not appear to influence disease progression.
The team also discovered a new signature of microbiome-derived metabolites, products produced by the microbes, that were significantly altered in the feces of mice with endometriosis. Supporting the role of microbiota metabolites in disease progression, Kommagani and his colleagues found that treating endometriotic cells and mice with the metabolite called quinic acid significantly improved cellular proliferation and endometriotic lesion growth.
The findings suggest that certain microbiome communities and/or their metabolites may contribute to endometriosis progression, and that altering the composition of these communities may help control the condition in human patients. “We are currently investigating this possibility,” Kommagani said.
The results also suggested that examining microbiome metabolites in human stool samples could be used as a diagnostic tool. “Endometriosis is typically diagnosed with ultrasound, and an invasive procedure is needed to characterize the lesion well,” Kommagani said. “We are investigating whether microbiome metabolites in human stool samples can be a useful diagnostic tool and also whether some of these metabolites can be used as a treatment strategy.”
Women with endometriosis also tend to have bowel problems, such as colitis or inflammatory bowel syndrome.
We are interested in determining whether changes in the gut microbiome can affect gut conditions and the possibility of controlling them by modifying the microbiome or with their metabolites.”
Dr. Rama Kommagani, lead author
Baylor College of Medicine
Chadchan, SB, et al. (2023) Gut microbiota and microbiota-derived metabolites promote endometriosis. Discovery of cell death. doi.org/10.1038/s41420-023-01309-0.