Emerging research shows a strong relationship between endometriosis and the microbiome. Here we explore the link and what it means for women’s health.
When the balance of good and bad microbes in your microbiome is disrupted (dysbiosis) can contribute to endometriosis by causing immune system dysregulation and altered estrogen metabolism [1].
Here we dive into the latest research and explain how this microbiome link could be utilized for better management of endometriosis. If you need to learn more about the basics of endometriosis first, check out the information available from the Office on Women’s Health.
Endometriosis is a condition affecting 1 in 10 women, where tissue similar to the lining of the womb (endometrium) builds in places where it shouldn’t, such as the ovaries and fallopian tubes. It can cause chronic pain, difficulty getting pregnant [2] and an increased risk of developing depression and anxiety disorders [3].
The cause of endometriosis is not completely understood but it is thought to be due to a combination of factors, including genetics, retrograde menstruation, inflammation, and your microbiome.
Retrograde menstruation is when tissue shed from the endometrium during the menstrual period flows upwards out of the uterus into the peritoneal cavity (the space between your abdomen and your internal organs), rather than flowing out of your body via the cervix and vagina [4]. These endometrial fragments can implant in the peritoneal cavity and seed endometrial growths [4].
The idea that retrograde menstruation is involved in endometriosis is almost 100 years old and still stands as the leading theory for disease onset and progression. However, 90% of menstruators experience retrograde menstruation [5] but only 10% will develop endometriosis. So what is different in endometriosis sufferers that causes the endometrial tissue to adhere outside of the uterus and grow into lesions? The answer lies, at least in part, in inflammation.
Inflammation is part of your immune system’s natural response to an injury or infection, there to protect you from harm. In some cases, the inflammatory response can be too much and can make things worse.
The peritoneal cavity of women with endometriosis exists in a constant state of inflammation (chronic). The progression of endometriosis involves a vicious cycle of inflammation and endometrial growth, so it is not clear if the inflammation is a cause or effect of endometriosis [1].
Your microbiome is the community of bacteria and microbes living in and on you, including many good bacteria which play an important role in protecting your health. Studies have shown that there is a bidirectional relationship between your microbiome and the progression of endometriosis [1]. That means that endometriosis can cause disruption to your microbiome, but also that a disruption in your microbiome can contribute to endometriosis. The research into this link is still in its infancy, but these are some of the most interesting findings [1].
So, what are some of the possible explanations for this link? There is a large amount of preliminary research into this relationship but much remains unclear. Some of the most interesting evidence points towards a relationship with the hallmark of endometriosis: inflammation.
The microbiomes of women with endometriosis have elevated levels of Gram-negative bacteria. These Gram-negative bacteria shed a toxin called lipopolysaccharide (LPS). The bacterial contamination hypothesis suggests that retrograde mensuration transports LPS from the uterus into the peritoneal cavity, triggering the immune system and promoting the onset and progression of endometriosis lesions [6].
This is supported by studies in animals that show LPS promotes the development of endometrial lesions and that antibiotic treatment can reduce peritoneal inflammation and the size of lesions [1].
Your microbiome can influence endometriosis by up or down-regulating your immune system, for example by increasing the concentration of circulating inflammatory proteins or reducing immunosurveillance. Over time, this dysregulation can lead to chronic inflammation, creating the perfect environment to drive endometriosis onset and progression [1].
In return, endometriosis can make the environment in your gut less favorable to good bacteria and more favorable to bad bacteria, by releasing inflammatory proteins called cytokines which travel from the peritoneal cavity to the gut and suppress gastric acid secretion and gut motility.
There could be many factors influencing this relationship. Some other possible contributors to this association include [1]:
It takes 8-10 years to get a diagnosis of endometriosis after the onset of symptoms and surgery remains the gold standard for diagnosis and treatment [7]. Unlocking the microbiome could be key to earlier, less invasive and more reliable endometriosis care.
The gut microbiome is already used as a diagnostic for colorectal cancer and has potential for other gastrointestinal disorders. The vaginal microbiome has had less research behind it but could be key to a better diagnostic for endometriosis.
There is promising research that treatment targeting the microbiome could be effective for endometriosis [1]:
It’s clear that the microbiome of the reproductive tract is closely linked to endometriosis onset and progression, but it’s too soon to know how to use this information. More research is needed. That’s why Juno Bio exists, to power up research into women’s health conditions and the vaginal microbiome. We hope that in the future, vaginal microbiome testing can be used to detect disease and guide treatment plans.
Until then, the Juno Vaginal Microbiome Test can give you a picture of the microbiome of your reproductive tract and can be used as a simple, non-invasive screen to rule out vaginal dysbiosis as a factor in disease progression.
1. Jiang I, Yong PJ, Allaire C, Bedaiwy MA. Intricate Connections between the Microbiota and Endometriosis. Int J Mol Sci. 2021;22(11):5644.
2. Office on Women's Health. Endometriosis. 2021. Available from: https://www.womenshealth.gov/a-z-topics/endometriosis [Accessed 9th Jun 2022]
3. Chen LC, Hsu JW, Huang KL, Bai YM, Su TP, Li CT, Yang AC, Chang WH, Chen TJ, Tsai SJ, Chen MH. Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study. J Affect Disord. 2016;190:282-285.
4. Sampson, JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. AJOG. 1927;4(4):422-469
5. Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984;64(2):151-4.
6. Khan KN, Fujishita A, Hiraki K, Kitajima M, Nakashima M, Fushiki S, Kitawaki J. Bacterial contamination hypothesis: a new concept in endometriosis. Reprod Med Biol. 2018;17(2):125-133.
7. Perrotta AR, Borrelli GM, Martins CO, Kallas EG, Sanabani SS, Griffith LG, Alm EJ, Abrao MS. The Vaginal Microbiome as a Tool to Predict rASRM Stage of Disease in Endometriosis: a Pilot Study. Reprod Sci. 2020;27(4):1064-1073.
8. Huang L, Liu B, Liu Z, Feng W, Liu M, Wang Y, Peng D, Fu X, Zhu H, Cui Z, Xie L, Ma Y. Gut Microbiota Exceeds Cervical Microbiota for Early Diagnosis of Endometriosis. Front Cell Infect Microbiol. 2021;11:788836.
9. Chen C, Song X, Wei W, Zhong H, Dai J, Lan Z, Li F, Yu X, Feng Q, Wang Z, Xie H, Chen X, Zeng C, Wen B, Zeng L, Du H, Tang H, Xu C, Xia Y, Xia H, Yang H, Wang J, Wang J, Madsen L, Brix S, Kristiansen K, Xu X, Li J, Wu R, Jia H. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8(1):875.
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