Does the path to endometriosis treatment start in the gut?

researcher A much-needed tool for endometriosis research may be on track: An alternative non-invasive stool test The current gold standard for laparoscopy.

Their approach, which focused on the connection between the gut microbiome and endometriosis, also identified bacterial metabolites that could be developed as oral drugs for endometriosis. A condition that affects at least 11% of women.

In previous research, Dr. Rama Kommagani, an associate professor in the Department of Pathology and Immunology at Baylor College of Medicine in Houston, injected donor rodent endometrial tissue into the peritoneal cavity of healthy rodents and A study was conducted using the model. hindrance.

Transfer of fecal microbiota from mice with endometriosis to mice without endometriosis induced trademark lesionssuggesting that the microbiome influences the development of endometriosis. Treat animals with antibiotics Metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated that the microorganisms release metabolites that stimulate the growth of endometrial lesions. “Bad bacteria release metabolites that actually promote disease,” Konmaghani says. “However, there is a possibility that beneficial bacteria may be released.” Some protective metabolites such as short-chain fatty acids. ”

in new researchKommagani et al. sought to identify a unique profile of bacterial metabolites that could reliably diagnose endometriosis. His team performed global metabolic profiling of the gut microbiome using stool samples taken from 18 women with the disease and 31 women without the disease.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings raised further questions. “If metabolites are low in women with endometriosis, is there a functional link?” Kommagani said.

One candidate is 4-hydroxyindole (4HI), which was detected at low levels in patients' stools. This substance is a derivative of it that is poorly understood. Parent compound, indoleoccurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Konmaghani's lab demonstrated that giving 4HI to mice before undergoing endometrial transplantation prevented the development of lesions typical of endometriosis. When mice with endometriosis were treated with 4HI, they observed regression of the lesions and decreased response to painful stimuli.

“In a nutshell, we discovered a specific set of bacterial metabolites in the stool, which could potentially be used for non-invasive diagnostic tests,” Konmaghani said. “But we also discovered this distinct and specific metabolite that can be used as a therapeutic molecule.”

Tatnai Barnett, M.D., assistant professor of obstetrics and gynecology at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said the noninvasive test has several advantages over current methods of diagnosing endometriosis. He said there is. Clinicians will be able to detect and treat women's illnesses earlier. Second, a test with sufficient negative predictive value can help decide whether to start treatment with hormones or other oral medications or proceed directly to surgery. “I would choose not to have surgery if I was very confident that we wouldn't find anything,” Barnett said.

Finally, a test that is quantitative and responsive to treatment could be used as a marker of disease activity to monitor the progress of someone's treatment.

But Barnett said more data on this approach is needed. “This is a fairly small study to develop a screening test,” he says. “We need to see what the positive predictive value, negative predictive value, sensitivity and specificity are in a larger group.”

The road to a cure is even longer than the road to developing a screening test. Konmaghani's lab is currently conducting further studies in mice to understand the pharmacokinetics and toxicology of 4HI before attempting human clinical trials.

And, as Burnett pointed out, while mouse models are great for experimentation and hypothesis generation, “we've seen many times in the past that something is really exciting in a mouse model, or a rat model, or a monkey model. But that's not really the case.'' It doesn't work in humans. ”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a research fellowship from the American Cancer Society. Mr. Barnett reported no financial conflicts of interest.

Anne Thomas, a former pediatrician and disease detective, is a freelance science writer living in Portland, Oregon.