- Researchers found that nearly two-thirds of patients with endometriosis have elevated levels of certain bacterium around their uterus, compared to less than 10 percent of people without the condition.
- After giving antibiotics to mice with endometriosis, the researchers saw that both the levels of the bacteria and the formation of endometriosis-related lesions were reduced.
- However, further studies are needed to see whether the findings translate to humans.
Endometriosis is a condition in which cells similar to those found in uterine lining grow outside the uterus. This can lead to the formation of scar tissue and inflammation in the pelvic region as well as various organs, alongside symptoms including pain and nausea.
Further research into endometriosis could improve the health and quality of life for millions of people worldwide.
Recently, researchers found that targeting a specific bacterium may reduce lesions linked to endometriosis in mice.
The study was published in Science Translational Medicine.
Dr. Marc Winter, medical director of Minimally Invasive Surgical Gynecology at Hoag, who was not involved in the study, told Medical News Today:
“This study from Japan is extremely interesting as it implicates Fusobacterium — a type of bacteria — as a possible agent stimulating the formation of inflammatory cells that lead to inflammation, scar tissue, and pain associated with endometriosis. This discovery could lead to adding specific antibiotics as a critical part of endometriosis treatment.”
Dr. Joseph Stringfellow, an obstetrician-gynecologist at Novant Health City Lake OB/GYN in Thomasville, NC, not involved in the research, told MNT he was “highly optimistic about the findings.”
”The bacterial pathogenic hypothesis may lead to novel treatments that expand our armamentarium and improve accessibility to efficacious care. A noninvasive, nonhormonal therapy would prove invaluable in the treatment of patients afflicted by endometriosis,” he suggested.
To begin, the researchers conducted a genetic analysis of fibroblasts from four patients with endometriosis and four patients without. Fibroblasts are cells that form connective tissues and are involved in wound healing.
They found that a gene called transgelin (TAGLN) was substantially upregulated in people with endometriosis. The protein it codes for, also called transgelin, is involved in processes such as cell replication, which play a key role in the condition’s development.
Inflammation can upregulate TAGLN expression which may arise from a bacterial infection. Previous
To see how the presence of these bacteria in the uterine influences endometriosis, the researchers next assessed the frequency of a bacterium known as Fusobacterium inside and outside of the uteruses of 79 individuals with and 76 without endometriosis.
Among patients with endometriosis, 64.3% had significantly higher levels of Fusobacterium in their uterine endometrial tissue, and 52.4% had higher levels in endometrial tissue that had formed outside the uterus. Higher levels of the bacterium were found in the uterus of just 7.1% of those without the condition.
Next, the researchers investigated whether Fusobacterium promoted endometriosis in nine mouse models of the condition. They found that mice with Fusobacterim developed more lesions in the uterus than controls.
Comparatively, mice without Fusobacterium did not develop as many lesions in their uteri. This difference remained even after they were stimulated by estrogen, which doctors think could cause uterine-lining-like tissue to form outside the uterus.
Lastly, the researchers sought to see whether antibiotics could eradicate Fusobacterium in mice, thus reducing symptoms of endometriosis.
To do so, they administered two different antibiotics — metronidazole and chloramphenicol — to mouse models of endometriosis for 5 days. After a week, they found that Fusobacterium was no longer present in the mice and that transgelin expression decreased around the uterus.
They further noted that antibiotic-treated mice developed fewer and smaller endometriosis lesions than untreated mice.
The researchers wrote that their findings suggest that both antibiotics may be able to treat endometriosis. They noted, however, that the reason why Fusobacterium infects some individuals is unknown.
MNT spoke with Dr. Karnika Kapoor, a family physician with Medical Offices of Manhattan, who was not involved in the study, about its limitations.
“The mouse model used in this research has some limitations in itself as mice lack a menstrual cycle and do not develop spontaneous endometriosis,” she said.
She added that the study lacks evidence to support the hypothesis that Fusobacterium around the uterus promotes endometriosis following retrograde menstruation — when the period flows upward through the fallopian tubes — which some researchers consider to be a
Dr. Stringfellow did note that “[t]he authors were careful to clarify that their analysis could not prove causality. This is an essential point.“
“Further study is needed to demonstrate a causative role of Fusobacterium. Additional research is also necessary to determine if other microbial species may play a pathogenic role,” he also emphasized.
Dr. Stringfellow did express some optimism about the findings, while still noting that larger sample sizes could offer a more accurate picture:
“The authors’ human tissue analyses focused on ovarian endometriosis lesions. It’s reasonable to expect the findings would be applicable to other types of endometriotic lesions — peritoneal, vaginal, or cervical — but this was beyond the scope of the study. [Additionally,] the sample size for the human tissue data set was small.”
MNT also spoke with Dr. Steven Vasilev, a board certified integrative gynecologic oncologist and medical director of Integrative Gynecologic Oncology at Providence Saint John’s Health Center and Professor at Saint John’s Cancer Institute in Santa Monica, CA, who was also not involved in the study.
“While not a limitation per se, this is relatively early laboratory and mouse model data. This means, as usual, [that] the extrapolation of these findings and proposed molecular mechanisms to humans can’t readily be made yet,” he noted.
“However, this helps form a solid base of understanding toward unraveling how the microbiome and dysbiosis might lead to the formation and growth of endometriotic lesions,” he added.
Dr. Kapoor described current treatment options for endometriosis and their limitations.
“Treatment options for endometriosis are currently based on hormonal therapy but this means women cannot get pregnant during the treatment. Surgical treatment is an option for patients with recurrent pelvic pain but there is a high recurrence rate which is why removal of endometrial lesions is a concern,” she explained.
“[This] research seems to show a potential mechanism of endometriosis involving Fusobacterium, and [that] eradication with antibiotics is a [treatment] option. We may be able to implement antibiotic treatments for endometriosis in our clinical practice if proven effective in future studies.”
— Dr. Karnika Kapoor
Dr. Winter agreed that the findings may lead to new treatment options.
“The role of Fusobacterium in stimulating endometriosis may lead to an entirely different approach in its treatment. Further studies are needed to study the role of Fusobacterium with retrograde menstruation in the formation of endometriosis,” he said.
“The use of a commonly used antibiotic metronidazole may be a key in improving the effectiveness of endometriosis treatment,” he concluded.