Gut Microbiome Implicated In Endometriosis
By Deborah Borfitz
February 22, 2023 | The gut microbiome has for the first time been linked to a causal role in endometriosis, a complex disease afflicting about 196 million women worldwide that typically causes pelvic pain and infertility. Up to now, efforts to investigate the contributing factors have been focused primarily on genetic changes or epigenetic disorders and yet understanding of the underlying pathology remains largely a mystery, according to Rama Kommagani, Ph.D., associate professor in the departments of pathology and immunology, and molecular virology and microbiology, at Baylor College of Medicine.
Kommagani is on a research team with colleagues at Baylor and Washington University School of Medicine that made the discovery, as reported recently in Cell Death & Discovery (DOI: 10.1038/s41420-023-01309-0). Conducting in vivo studies of the endometriosis and microbiome together has proven “extremely difficult,” he says, noting that mouse models do not fully recapitulate the human condition and managing the disease in rodents can be tricky.
The most surprising study finding was that gut microbes are required for endometriotic lesion growth in mice, he reports. Among microbiota-depleted rodents with surgically induced endometriosis, fecal material administered from mice with endometriosis developed lesions as large as mice retaining their microbiome while those administered feces from healthy mice did not.
“It is the changed [community of] bacteria in the gut that appears to be critical,” Kommagani says. “The abundance of commensal bacteria in the intestines doesn’t seem to be playing much of a role.”
The uterine microbiome also does not seem to affect disease progression, Kommagani says. He, as well as researchers elsewhere, have previously reported “many changes” in the bacterial composition of the uterine, vaginal, and cervical microbiomes of women with endometriosis.
Kommagani and his colleagues additionally discovered a novel signature of microbiome-derived metabolites in the feces of mice with endometriosis. Using quinic acid as a “candidate metabolite,” they treated endometriotic cells and mice to significantly enhance cellular proliferation and lesion growth. This demonstrated the supporting role of microbiome metabolites in disease progression, Kommagani explains.
Among the most-changed metabolites, quinic acid—a sugar acid found in coffee beans and kiwifruit—was chosen because it showed the most potency when tested in cells, he adds. The goal now is to recapitulate this work in women with endometriosis and identify metabolites that could potentially be used for a diagnostic assay as well as targets for treatment by downregulating their expression.
Kommagani says he began his career aiming to address important questions in normal physiological processes and disease states and hadn’t planned to become an endometriosis researcher. “It was where my science took me.”
He was especially interested in the etiology of endometriosis, Kommagani says, since it can involve the peritoneum—the tissue that lines the abdominal wall and covers most of the organs in the abdomen. Perhaps, he thought, something happening in the peritoneum could be putting some women at a disadvantage. After all, it is in the peritoneal cavity where much of the disease “drama” plays out.
As evidenced by the first-hand experience of his friends with the disease, endometriosis is one of the largest under-researched areas in women’s reproductive health. Although bacteria appear to be playing a major role in the gut, Kommagani says, it was until recently challenging to get anyone to consider that intestinal microbes are involved in the development of endometriosis.
That the gut microbiome is implicated in endometriosis implies a healthy diet may help women suffering from the disease, says Kommagani, noting that patients are at high risk of inflammatory bowel disease. But endometriosis is a complex condition with many potential causal factors—related to genetics, lifestyle, and the environment—meaning dietary remedies alone are unlikely to alleviate its multiple and sometimes severe symptoms.