Endometriosis: Could an altered gut microbiome have a role?
- A new study has found gut microbiota may play a pivotal role in the progression of endometriosis in an animal model.
- Uterine microbiota, on the other hand, did not seem to affect the progression of endometriosis in mice.
- Researchers found microbiota-derived metabolites—or products made by microbes—were significantly altered in the feces of mice with endometriosis.
- The research suggests studying microbiota metabolites in human stool samples may serve as a diagnostic tool for endometriosis.
A poorly understood disease, endometriosis causes tissue similar to the lining of the uterus to grow outside the uterus, which can result in terrible pain, infertility, and a range of other symptoms.
About 10% of people who menstruate have endometriosis, according to the World Health Organization.
The gut microbiota, a collection of microbes present in the gastrointestinal tract, is considered a promising topic for scientific research.
Recently, researchers at Baylor College of Medicine looked at how altered gut microbiota may play a role in how endometriosis progresses.
Their study is published in Cell Death & Discovery.
Endometriosis and the gut
One widely accepted theory is that endometriosis may be caused by retrograde menstruation, where shed endometrial tissue moves through the fallopian tubes and enters the pelvic cavity, where it implants on surrounding tissue such as the intestine. However, up to 90% of women experience retrograde menstruation.
“So we thought there is in those women with endometriosis probably their peritoneal cavity, which is where the gut is [t]hat there’s something wrong,” Ramakrishna Kommagani, principal investigator and associate professor of immunology at Baylor College of Medicine in Houston, Texas, told Medical News Today.
The researchers also considered, according to Kommagani, how many people with endometriosis experience GI problems, such as irritable bowel syndrome.
Several other studies, including this one from 2021, have suggested a link between microbiota and the progression of endometriosis.
The researchers at Baylor College of Medicine set out to show whether gut microbiota directly influences the formation and growth of endometriosis lesions.
Gut microbiota’s causal role in endometriosis
In a 2019 study, Kommagani and other researchers found antibiotic therapy reduces endometriosis progression in mice. The researchers hypothesized that antibiotic therapy possibly reduced specific gut bacteria. However, they weren’t able to determine a causal role of gut microbiota in the progression of endometriosis.
For this study, researchers elected to study microbiota-depleted mice who have been raised normally and then given broad-spectrum antibiotics.
“So, this way we can study what happens in the mice which have normal microbiome and what happens in the mice where we removed the microbiome,” Kommagani explained.
Researchers then surgically induced endometriosis in both control and microbiota-depleted mice. Since surgery can also trigger an inflammatory response in mice, researchers also induced endometriosis using injections in both control and microbiota-depleted mice.
Researchers then gave control mice and microbiota-depleted mice feces from mice without endometriosis and feces from mice with endometriosis. They did this with both mice who had surgically-induced endometriosis and mice who had injection-induced endometriosis.
Additionally, researchers analyzed peritoneal fluid looking for immune cell populations in control and microbiota-depleted mice to determine if altered immune cell composition was associated with reduced lesion growth in microbiota-depleted mice.
Researchers also measured the relative metabolites, products made by microbes, in feces from mice with and without endometriosis. They then treated mice with endometriosis with quinic acid, a metabolite that was present at higher levels in mice with endometriosis.
The mice were given 5 mg/kg of quinic acid every 24 hours for 14 days.
Microbiota and endometriosis lesion growth
When researchers surgically induced endometriosis in both control and microbiota-depleted mice, they found lesions in control mice to be significantly larger and “more obviously fluid—filled and vascularized” than lesions in microbiota-depleted mice.
With control and microbiota-depleted mice who were given injection-based endometriosis, lesions in control mice were significantly larger and greater in number than in microbiota-depleted mice.
Researchers administered fecal matter from mice with and without endometriosis to control mice and microbiota-depleted mice who had surgically induced endometriosis. Transplanting fecal matter from mice with endometriosis into microbiota-depleted mice resulted in typical endometriosis lesions.
Transplanting fecal matter from healthy mice into microbiota-depleted mice failed to restore lesions. Researchers performed similar studies in mice that had injection-induced endometriosis and experienced similar results.
The findings, the researchers write in their paper, suggest gut microbiota and microbiota-derived metabolites play a role in the progression of endometriosis.
Researchers also found that the mice with endometriosis who were given quinic acid for 14 days had enhanced cellular proliferation and developed larger endometriotic lesions than control mice. However, they did not observe changes in the lesion numbers.
The researchers also write in their paper that the results from the peritoneal fluid analysis suggest that “gut microbiota impacts endometriotic lesion growth, possibly through the modulation of peritoneal immune cell populations.”
Additionally, researchers performed several tests to illustrate that uterine microbiota is not responsible for the differences in lesion growth.
“Microbiota from the uterus has no impact on the cells when they grow outside of the uterus,” Kommagani told MNT.
The idea that depletion of gut microbiota would reduce endometriosis-associated inflammation makes sense to Dr. José D. Eugenio-Colón, who practices at The Center for Endometriosis Care in Atlanta, Georgia.
“[W]hen patients have endometriosis, any type of microbiome that would promote inflammation would actually make everything significantly worse because it would allow the endometriosis [t]o proliferate, so they can actually have deeper disease,” he told MNT.
Research in humans needed
A disadvantage of using mice for medical research is that there are anatomical and physiological differences between rats and humans.
“[O]bviously, animal studies have their limitations. Right?” asked Dr. Eugenio-Colón.
However, Kommagani and his team of researchers are already in the lab measuring metabolites in human stool to see if they see similar changes in the metabolites of women with endometriosis.
“[T]his all has to be transferred to human subjects,” Kommagani said.
More timely endometriosis diagnosis
Currently, it takes between four and eleven years for women to receive a diagnosis of endometriosis.
Being able to use human stool samples as a diagnostic tool could mean patients with endometriosis get diagnosed earlier.
“The goal of everything it’s basically to identify patients early, because when we identify them early, the teens, then we have significantly [fewer] possibilities of having them go through [i]infertility [o]r chronic pain, anxiety, and depression,” Dr. Eugenio-Colón told MNT.
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