When I first heard of the “bacterial contamination hypothesis” in endometriosis, my heart beat a little faster. Being a scientist with a speciality in microbiology and having dove deep into endometriosis literature after getting my official diagnosis of endometriosis in 2016, the connection between both sparked immediately my interest.
It is widely accepted that endometriosis origins from many different factors involving disorders of the immune system, hormonal imbalances, genetic susceptibility and traumatic experiences to name a few. I always like to think of my endo as a puzzle, where the different piecesof the various factors put together lead to the pain every endo sister can tell you about. Researchers have now identified a possible new piece of the puzzle by showing that a bacterial dysbiosis in the genital tract (vagina, cervix, uterus) and gut microbiome can be associated with endometriosis.2 “What the heck are bacteria doing in my uterus?” you may be asking. Most people have heard of the gut flora or gut microbiome describing all the microorganisms that live in a peaceful coexistence in the digestive tract of humans, benefiting the host by breaking down food, synthesizing vitamins and modulating the immune system. However, we are now aware that the human microbiome comprises more than just the gut: commensal bacteria have been found for example in the mouth, on the skin, the bladder, the vagina and also in the uterus. It’s the balance of the different bacterial species in each body location that helps to keep us healthy, while a dysbalance of the human microbiome has been correlated with a host of inflammatory and autoimmune conditions. For endometriosis, it was recently found that the menstrual blood, endometrial samples and peritoneal fluid were highly contaminated with Gram-negative bacteria, especially Escherichia coli, while lacking Gram-positive Lactobacilli.1, 3 “Gram-“ what? Gram staining is a basic staining method used in microbiology named after its inventor Hans Christian Gram. It is used to classify bacteria into two large groups, namely Gram-positive and Gram-negative, based on their cell wall properties. A distinct feature of all Gram-negative bacteria is the presence of the molecule lipopolysaccharide (LPS), also called endotoxin, in the outer membrane of the bacterial cell wall. Whenever you hear of LPS, you should think of inflammation. LPS is the major molecule binding to a wide array of different immune cells, leading to the secretion of pro-inflammatory cytokines. In the case of endometriosis, the presence of too many Gram-negative bacteria and therefore high levels of LPS in the pelvic area could be a major driver in the inflammatory process happening in endometriosis.1 In fact, it has been shown that LPS combined with estrogen leads to the perfect storm of inflammatory cytokines promoting the growth and flare of endometriosis lesions.4 But how do bacteria get in the pelvic area? And why do women with endometriosis have a dysbalance in their microbiota in the first place? There are two possible scenarios how bacteria escape into the peritoneal fluid. Firstly, it is likely that Gram-negative bacteria and/or their endotoxins translocate from the gut into the pelvic cavity, showing once more how a leaky gut is the root of all evil. Secondly, it is thought that the bacterial contamination takes place via retrograde menstruation, so the LPS-rich bacteria are introduced with endometrial tissue flowing backwards through the Fallopian tubes into the peritoneal cavity.1 Interestingly, not only higher levels of Gram-negative bacteria, but also higher levels of prostaglandin – those nasty guys leading to cramping and pain during menstruation – were found in the menstrual and peritoneal fluids of women with endometriosis compared to control women.5 In a bacterial culture system, it could be shown that these prostaglandins were directly promoting the growth of LPS-rich bacteria, suggesting that prostaglandins are influencing the microbiota dysbalance seen in women with endometriosis.5 Now the question arises which has been first: endometriosis leading to dysbiosis or dysbiosis leading to endometriosis? Or in other words: Is the bacterial contamination the effect or the cause of endometriosis? Researchers are still debating about these questions and as is always the case for endometriosis, much more research needs to be done. Nevertheless, the female microbiota dysbalance could be a missing piece of the puzzle holding potential for future treatment of endometriosis.
3. Ata B, Yildiz S, Turkgeldi E et al. The Endobiota Study: Comparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 Endometriosis and Healthy Controls. Scientific reports 2019; 9: 2204.
4. Khan KN, Kitajima M, Inoue T et al. 17beta-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis. Reproductive sciences (Thousand Oaks, Calif) 2015; 22: 585-94.
Lara is a scientist by training and heart currently doing her PhD in the field of antibiotic resistant bacteria and biofilms at the Institute of Infectious Diseases and Infection Control in Germany. Managing and healing her endometriosis holistically for three years, she has experienced first-hand the importance of a healthy gut and balanced microbiome to control pain and inflammation of this debilitating disease. To contribute to the much-needed research of endometriosis, Lara is planning a research project analysing the connection between endometriosis and the estrobolome.
Contact via Email: Lara.Thieme@med.uni-jena.de