The study titled “Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota,” was published in Human Reproduction.
Endometriosis is a chronic inflammatory disease caused by the abnormal growth of womb cells outside the uterus. It is estimated to affect up to 10% of all women of reproductive age (25-40 years old), which corresponds to approximately 5 million women in the U.S. alone, and 176 million worldwide.
“The current treatments for endometriosis, principally hormone therapy and surgery, have negative side effects and do not prevent recurrences. Therefore, a new approach is needed to combat this disease,” the investigators said.
Although the causes of endometriosis are still unknown, it is thought that bacteria living in the gut (microbiome) may play an important role in the disease.
“Distinct microbial communities have been identified in the reproductive tracts of reproductive-age women, and some microbial compositions appear to correlate with reproductive pathologies [disorders] such as preterm birth and infertility. Additionally, [a recent study] identified differences in the cervical and uterine microbiome communities between women with and without endometriosis,” the researchers said.
To learn more, a team from the Washington University School of Medicine in St. Louis set out to assess the impact of gut bacteria in a mouse model of endometriosis.
The researchers treated mice that had been surgically-induced to develop endometriosis with a combination of four broad-spectrum antibiotics — vancomycin, neomycin, metronidazole, and ampicillin (VNMA) — known to target gut bacteria, for a period of 21 days.
Results showed that mice treated with VNMA developed lesions that were approximately five times smaller compared with control animals treated with a placebo solution. Animals treated with VNMA also had less tissue inflammation and cell proliferation, an hallmark of endometriosis, compared with controls.
“Our initial goal was to understand how these gut bacteria, or microbiota, might be connected to endometriosis, but in the process, we may have found a cost-effective treatment,” Ramakrishna Kommagani, PhD, an assistant professor of obstetrics and gynecology at Washington University’s Center for Reproductive Health Sciences, and the study’s principal investigator, said in a press release.
As expected, bacteria DNA sequencing analyses revealed that mice treated with VNMA had less bacteria diversity in their feces compared with animals treated with the vehicle solution. More specifically, feces from the animals treated with broad-spectrum antibiotics contained much less bacteria from the Bacteroides genus — the most common genus of bacteria found in the gut of humans and other mammals — than controls.
Researchers then sought to test whether decreasing the numbers of bacteria from the Bacteroides genus might reduce the size of endometriosis lesions. The team treated animals with metronidazole, an antibiotic to which these bacteria are highly susceptible. Mice also were treated with neomycin, an antibiotic to which the bacteria are resistant.
Remarkably, in animals treated with metronidazole, the size of endometriosis lesions decreased significantly compared to vehicle-treated animals, regardless of whether the treatment had been performed before or after the lesions had already started forming. Tissue inflammation also was reduced in mice treated with metronidazole.
In animals treated with neomycin, the size of endometriosis lesions was identical to those of control mice.
“In summary, our findings suggest that gut bacteria promote endometriosis disease progression in mice. If our findings are translated to humans, they may lead to new diagnostic strategies and microbiota-based therapies to treat this debilitating disease,” the scientists said.
“This study is exciting as it opens new frontiers in identifying bacterial candidates that can promote endometriosis in reproductive-age women, and it enables us to conduct future studies aimed at developing simpler ways to diagnose endometriosis,” said Indira Mysorekar, PhD, James P. Crane professor of obstetrics and gynecology, and professor of pathology and immunology at Washington University. Mysorekar also is the director of the Center for Reproductive Health Sciences.