About 196 million women worldwide suffer from endometriosis, a condition that commonly causes pelvic pain and infertility. Endometriosis develops when the lining of the uterus attaches to surrounding tissue, such as the lining of the bowel or 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, the community of microbes living inside the body, is altered in women with endometriosis. In this study published in the journal Dr Cell death and discoveryResearchers at Baylor College of Medicine have found that an altered gut microbiome plays a critical role in the progression of endometriosis disease in an animal model.
“To investigate the role of the microbiome in endometriosis, we first applied a new mouse model of the condition in which the microbiome is eliminated using antibiotics,” lead author Dr. said Rama Kommagani, associate professor in the Department of Pathology and Immunology and Molecular. Virology and Microbiology at Baylor.
The researchers found that the mice without the gut microbiome had smaller endometriotic lesions than the mice with the microbiome. Moreover, when gut microbiome-free mice received gut microbiota from mice with endometriosis, the lesions grew as large as those mice that retained their microbiome. These findings suggest that altered gut bacteria drive disease progression. On the other hand, the uterine microbiome does not appear to influence disease progression.
The team also found a new signature of microbiome-derived metabolites, products produced by microbes, that were significantly altered in the feces of mice with endometriosis. Supporting the role of microbiome metabolites in disease progression, Kommagani and his colleagues found that treatment of endometriotic cells and mice with a metabolite called quinic acid significantly increased cellular proliferation and endometriotic lesion growth, respectively.
The findings suggest that certain microbiome communities and/or their metabolites may contribute to endometriosis progression and that modifying the composition of these communities may help control the condition in human patients. “We are currently investigating this possibility,” Komagani said.
The findings also suggested that studying microbiome metabolites in human stool samples could be used as a diagnostic tool. “Endometriosis is usually diagnosed with ultrasound, and an invasive procedure is needed to better delineate the lesion,” Commagani said. “We are investigating whether microbiome metabolites in human stool samples can be a useful diagnostic tool and whether these metabolites can be used as a treatment strategy.”
Women with endometriosis are also more likely to have bowel problems such as colitis or inflammatory bowel syndrome.
We are interested in determining whether changes in the gut microbiome can affect the state of the gut and the possibility of controlling the microbiome by modulating or regulating it through their metabolites.”
Dr. Rama Komagani, lead author
Baylor College of Medicine
Chadchan, SB, et al. (2023) Gut microbiota and microbiota-derived metabolites promote endometriosis. Cell death discovery. doi.org/10.1038/s41420-023-01309-0.