The curious link between endometriosis and an infectious bacterium

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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Data Point | The gender disparity in healthcare

The Data Point is a bi-weekly newsletter in which The Hindu’s Data team decodes the numbers behind today’s biggest stories.  

(This article forms a part of the Data Point newsletter curated by The Hindu’s Data team. To get the newsletter in your inbox, subscribe here.)

The difference in the anatomy between various genders implies that diseases and their symptoms may affect them differently. Moreover, some diseases affect certain genders more than others, while a few are gender-specific conditions. Thus, it is imperative to look through a gendered lens for a better understanding of diseases.

Equal representation of genders in clinical trials, and impartiality and unbiasedness in testing and diagnosis help in creating a healthcare system that addresses the needs of all genders.

Yet, various studies conducted in the U.S. reveal that in some fields of medicine such as oncology, psychiatry, neurology and cardiology, the disease burden was higher among women while their share in clinical trials was not proportionate. 

In a study where 1,433 trials were conducted from 0.3 million people in the U.S. between 2016 and 2019, the average share of women was  41.2%. In psychiatry, where women comprised 60% of patients, the share of women participating in clinical trials was 42%. Similarly, the difference was significantly high in the case of cardiovascular diseases (41.9% female participants vs. 49% female patients) and cancer trials (41% female participants vs. 51% female patients)

Gender disparity is also observed in research funding. For instance, according to the National Institutes of Health (NIH) data, the 2023 research funding estimate for substance misuse (a condition more prevalent among men) was $2,583 million while that for depression (a condition more prevalent among women) was $664 million. Similarly, research funding in 2022 for HIV/AIDS, a disease more prominent among men (DALY of 0.361 million in 2015) was $3,294 million, while that for inflammatory bowel disease (IBD), a disease dominant among women (DALY of 0.475 million) was $203 million. (expand DALY somewhere)

To know more about the gender gap in clinical trials and research funding, click here

Women faced the challenge of a gender gap in testing, diagnosis and treatment, which arose from a lack of comprehensive research about conditions dominant among women and biases toward women in healthcare.

In a multicentre observational study published in 2023, it was revealed that the median time taken to diagnose IBD from the onset of a symptom was more prolonged in women than in men. For instance, it took about 12.6 months to diagnose Crohn’s disease (a type of IBD) for women, while it only took 4.5 months for men. Similarly, it took 6.1 months for women and 2.7 months for men, in the case of ulcerative colitis.

NIH data also revealed that funding given for women’s reproductive disorders was significantly lower than that for conditions with a similar disease burden. 

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic abnormality among women with a worldwide prevalence of up to 21%, depending on diagnostic criteria. Yet, while diseases with equal or lesser disease burden like rheumatoid arthritis, tuberculosis, and systemic lupus erythematosus, were awarded funds worth $454.39 million, $773.77 million, and $609.52 million respectively, the funding for PCOS research between 2006 and 2015 was limited to $215.12 million. 

Thus, a limited understanding of disease further delays diagnosis, especially for diseases affecting women’s reproductive system. 

In the Indian context, the taboo towards menstrual health in society, which extends to the health sector adds to this problem. Endometriosis, a disease that affects roughly 10% (190 million) of women and girls of reproductive age worldwide according to the WHO, is highly underreported in the country. 

Despite persistent visits to multiple gynaecologists over a decade, my journey to obtain a proper diagnosis for endometriosis was marked by significant delays. My experiences of enduring intense menstrual cramps, accompanied by nausea and bowel disorders, were consistently dismissed by doctors who attributed them to natural menstrual processes. Prescription of painkillers became routine without a genuine effort to comprehend the severity of my discomfort or suggest diagnostic scans for underlying issues. Only after my insistence, despite initial reluctance from doctors, did I finally receive a diagnosis. Regrettably, by that time, the lesions within my ovaries had grown larger than the organs themselves.

Even with a diagnosis, treatment options remain limited due to the narrow understanding of this condition. While invasive surgeries like laparoscopic procedures and hormonal medications seem to be the only options, these treatments come with significant side effects and cannot guarantee the complete eradication of recurring lesions.

In an article titled, “Male-centric medicine is affecting women’s health” in The Hindu, the author explains that women are less likely to receive appropriate medications, diagnostic tests and clinical procedures even in developed countries such as Canada and Sweden as the stereotype of the “hysterical woman” continues to haunt women even when they need urgent clinical interventions. 

Therefore, it is crucial to implement appropriate interventions, create awareness within the medical community to mitigate bias and push for gender-sensitive clinical trials and equitable allocation of research funding. These measures are imperative to ensure equal and unbiased healthcare for all individuals, regardless of their gender among other identities.

Fortnightly figures

  • 10.3% was the decrease in India’s merchandise exports in May 2023 at $34.98 billion from $39 billion in May 2022. Imports contracted at a slower 6.6% rate to $57.1 billion, lifting the trade deficit to a five-month high of $22.1 billion. This is the sixth time in the last eight months that goods exports have declined year-on-year, although May’s decline was lower than the 12.6% fall recorded in April.
  • 110 million people have had to flee their homes because of conflict, persecution, or human rights violations, the UN High Commissioner for Refugees (UNHCR) said. The war in Sudan, which has displaced nearly 2 million people since April, is but the latest in a long list of crises that have led to the record-breaking figure. Last year alone, an additional 19 million people were displaced, including more than 11 million who fled Russia’s invasion of Ukraine in the fastest and largest displacement of people since World War II.
  • 1 lakh people were shifted to approximately 1,500 temporary shelters set up as part of the disaster management efforts by the Gujarat State against Cyclone Biparjoy before the cyclone made landfall. Cyclone Biparjoy caused widespread damage in Gujarat’s Kutch-Saurashtra region as it made landfall late on June 15, Thursday. The Gujarat government also shut schools and other educational institutions for the next day as the State received heavy downpours in the aftermath of the cyclonic storm.
  • 4.25% was India’s retail inflation in May from 4.7% in April this year, a 20-month low. The price rise in food items faced by consumers moderated to 2.91%. This is the third successive month that inflation has remained below the Reserve Bank of India’s (RBI’s) upper tolerance limit of 6% after a prolonged streak above it. Base effects from May 2022 when retail inflation was over 7% also played a role in lowering the inflation rate this May.
  • ₹1.13 lakh crore was the third instalment of tax devolution released by the Centre to States, according to the Finance Ministry. This surpasses the normal monthly devolution of  ₹59,140 crore. The additional advance aims to enable expedited capital spending, financing of development/welfare-related expenditure and increased resource availability for projects and schemes of the States.

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