The curious link between endometriosis and an infectious bacterium

A new study could help expand the range of treatment options for a condition that affects millions of women with chronic pain and infertility.

July 14, 2023 10:30 am | Updated 10:30 am IST - Chennai

A diagram illustrating endometriosis.

A diagram illustrating endometriosis. | Photo Credit: BruceBlaus (CC BY 3.0)

Endometriosis, a reproductive disease affecting one in 10 women worldwide, involves the growth of lesions on pelvic organs such as the ovaries.

These lesions are composed of endometrium, a layer of tissue lining the uterus. It causes infertility, chronic pain during periods, pelvic pain, bloating, nausea, fatigue, and is also associated with depression and anxiety among women.

A new study points to a link between a bacteria associated with infections in the oral cavity, and endometriosis.

What was the study design?

The experiment was conducted with a cohort of 155 women in Japan, of which 79 were diagnosed with endometriosis while 76 were healthy. Researchers found a species of Fusobacterium bacteria in 64% of endometriosis patients, while it was present in 7% of those who did not have the condition.

To assess the direct effect of the bacteria on the disease, the scientists transplanted endometrial tissue inside the abdominal cavity of two sets of mice, one infected with a bacteria of the genus Fusobacterium and another without the bacteria. They found that the bacteria triggered the growth of larger lesions of endometriosis in the former mice, relative to the latter.

The study concluded that the bacteria had a role in the formation and aggravation of endometrial lesions.

Common condition, different experiences

Experts told The Hindu that the study broadens our understanding of endometriosis, a condition whose underlying origins and mechanisms are still obscure. Part of the problem is that different women experience endometriosis differently.

Ramakrishna Kommagani, an associate professor at Baylor College of Medicine, Houston, said scientists are yet to figure out why the locations of the lesions vary in each woman. He also said that there may not be a directly proportional relationship between the number of lesions and the intensity of chronic abdominal pain, a primary symptom of the condition.

“Women with small lesions have more pain while women with deeply infiltrating large black lesions that could be located close to the bowel region or the rectum may experience less pain,” he said.

Common condition, unknown cause

Scientists worldwide have come up with different ideas of the disease’s cause. One is retrograde menstruation – when some part of the menstrual blood flows backwards, into the abdominal region, instead of flowing out of the vagina. But this is common, occurring in close to 90% of menstruating women, whereas endometriosis affects only 10%.

Another possibility: The inability of the immune system to detect and eliminate blood cells from retrograde menstruation, allowing it to persist in the pelvic region, points to some dysfunction in the immune system.

Researchers have also linked endocrine-disrupting substances to the endometriosis as they interfere with the signalling, production, transport and metabolism of hormones such as oestrogen and progesterone, which are causal factors of endometriosis. The condition has also been linked to genetic and metabolic factors.

But for all their efforts, scientists are yet to identify the root cause of endometriosis. So treatment options are limited to hormone therapies, contraceptive pills, and laparoscopic surgery to remove the lesions. (The last can control the symptoms but can’t prevent the lesions from growing back.)

Gut microbes and Fusobacterium

There’s a link between inflammatory bowel disease – among others – with endometriosis; the latter’s proximity to the gut has had scientists asking whether a bacteria could be the problem.

An October 2022 paper co-authored by Dr. Kommagani reported that people with endometriosis had gut dysbiosis – an imbalance in the various microbe populations in the gut. He said that the altered microbiota (range of microorganisms) could help endometriosis progress, but also that more research will be required on this front.

There were some limitations. “Though this finding is important, metronidazole as an antibiotic has many side effects if used on a long-term basis, since it can adversely affect the patient’s physiology … [Further] study is required before we come up with new treatment options,” Dr. Kommagani said.

Fusobacterium already has known links to infections of the gum, vagina, and rectum – yet it isn’t commonly found in meaningful quantities in the gut. Experts have suggested that it could be moving to the abdomen through the bloodstream or to the vaginal region from the rectum.

While the new study is compelling and shows the bacteria’s role in aggravating the disease, according to Dr. Kommagani, researchers are yet to prove that the bacteria is present in all those who have this condition.

He also said that the results from experiments to understand endometriosis – including in his study – were limited by the fact that they were conducted with mice, a species that doesn’t menstruate itself.

So, to comprehensively understand the disease, it is essential to study a population of diverse women, he added.

What do the findings portend?

Endometriosis currently takes six years on average to be diagnosed. And even after a diagnosis, few treatment options are available.

A common response to bacterial infections is antibiotics; the new study considered it as well – and in doing so, opened up potentially new ways to diagnose and treat endometriosis.

For example, a 2019 study investigating the relationship between gut dysbiosis and endometriosis found that treating mice with metronidazole, an antibiotic that targets certain microbes, instead of broad-spectrum antibiotics slowed the rate at which the condition progressed.

If the presence of Fusobacterium bacteria indicates that a person has endometriosis, experts have said they could develop non-invasive tests for the condition – like vaginal swabs or stool samples – in place of the currently used laparoscopy or an ultrasound scan. The former could also be more sensitive to the presence of lesions in different parts of pelvic organs than the latter.

In elucidating an inherent connection between gut health and endometriosis, the studies also pave the way for a future in which researchers can devise personalised treatment options.

Dr. Kommagani said that fibrous food can help manage the condition because, while metabolites released by certain microbes can aggravate endometrial lesions, other metabolites produced by the fermentation of certain types of food can protect from the condition. This is because the latter can decrease the abundance of Fusobacterium and other infectious bacterial species.

This is why the consumption of food with high amounts of antioxidants, probiotic foods (with Lactobacillus gasseri bacteria), and food rich in omega-3 fatty acids have also been found to help suppress the development of endometriosis.

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