Is the microbiome implicated in causing endometriosis?

Researchers from Nagoya University Hospital in Japan have identified a possible link between bacterial carriage in the uterus and the development of endometriosis, potentially offering a novel pathway for treatment or even cure of the disease with the use of antibiotics.
 
To date, the cause of endometriosis remains poorly understood, which in turn limits what therapeutic interventions are available. Current options include pain relief, hormonal therapies and surgical interventions.
 
However, the findings, published this month in Science Translational Medicine, have significant potential to impact how endometriosis is managed for the estimated one in 10 women and girls globally who suffer from debilitating pain and infertility as a result of the disease.
 
The team of researchers, led by Professor Yutaka Kondo and Assistant Professor Ayako Muraoka, looked at whether the bacterial genus Fusobacterium, which is usually present in the oral cavity, was present in the uteruses of a cohort of 155 women with and without endometriosis.
 
Of those found to be carriers of Fusobacterium, 64% had endometriosis compared to 7% who did not.
 
AMA President Professor Steve Robson, an endometriosis surgeon and researcher, told the Australian Financial Review the results represent a ‘unique finding’.
 
‘At the risk of appearing over-enthusiastic, if it holds true, I believe it could revolutionise the way we diagnose and manage endometriosis,’ he said.
 
‘In general terms, the lining of the uterus is relatively resistant to infection, so most of us never even thought that infection might be a possibility. That’s why this may have been missed for so long.
 
‘What adds to the excitement is that this is relatively easy for other researchers to test.’
 
According to the research team, Fusobacterium can be spread to the uterus from the oral cavities via two pathways. The first is haematogenous transmission from the gums during pregnancy when blood flows to the placenta, the second is through direct vaginal transmission.
 
The hypothesis for how Fusobacterium leads to the propagation of endometrial lesions is complex, involving activation of a transforming growth factor that then signals endometrial cells to proliferate, adhere and migrate – a pathway the researchers were able to mimic in the laboratory setting to further strengthen their hypothesis.
 
By using an animal model, the researchers transplanted endometrial tissue from mice into the abdominal cavities of a test group, with or without being inoculated with Fusobacterium. They found that while all mice with transplanted endometrial tissue grew lesions, they were seen in greater numbers and larger sizes in the mice with Fusobacterium present.
 
When these mice were treated with intravaginal antibiotics – either metronidazole or chloramphenicol – to eradicate Fusobacterium, this resulted in a reduction in the size and number of endometrial tissue lesions.
 
‘Eradication of this bacterium by antibiotic treatment could be an approach to treat endometriosis for women who are positive for fusobacteria infection, and such women could be easily identified by vaginal swab or uterus swab,’ Professor Kondo said.
 
‘Our data provide a strong and novel rationale for targeting Fusobacterium as a non-hormonal antibiotic-based treatment for endometriosis.’
 
However, while the evidence is of significant interest, the research also had multiple limitations. It remains unclear whether the results are generalisable to a more diverse range of patients such as women based in other geographic locations, different age groups and gender diverse groups.
 
The findings from the animal studies are also yet to be supported by clinical research, and the potential harms of antibiotic use in this setting remain unknown. The research likewise does not explain why some women who carried the bacteria did not develop endometriosis, and why not all women with endometriosis were carriers.
 
Although endometriosis has historically been an under-recognised and under-treated condition, research and funding into the disease has seen substantial attention in recent years. In Australia, the Federal Government recently committed nearly $30 million in research funding in an effort to ‘pave the way for prevention and the development of a cure’.
 
Clinical trials are already underway to further assess if antibiotic treatment may play a role in treating endometriosis.
 
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