The pathogenesis of endometriosis is not yet fully understood, but it is known to involve complex interactions between genetic and environmental factors. In recent years, several studies have suggested that alterations in the microbiota may play a relevant role in the establishment and progression of the disease [1,2].
Altered endometrial and gut microbiota profiles have been identified in women with endometriosis, showing a higher abundance of certain pathogenic bacteria compared to women without the condition [1,3]. Moreover, differences have been observed in the microbial profiles of the eutopic endometrium (inside the uterus) and ectopic lesions (outside the uterus) in women with endometriosis [3], suggesting that microbial involvement may contribute both to lesion development and to the systemic inflammation associated with more severe symptoms.
A New Perspective on Endometrial Health
For decades, the uterus was thought to be a sterile organ. We now know that it hosts a community of microorganisms known as the endometrial microbiome—a specific microbial ecosystem that can influence female reproductive health and may be involved in conditions such as endometriosis.
The presence of microorganisms in the endometrium has been confirmed in both healthy women and those experiencing fertility issues. When the balance between beneficial bacteria (such as lactobacilli) and potentially pathogenic species is disrupted, it results in endometrial dysbiosis. This imbalance has been associated with implantation failure and miscarriage.
For over a decade, at the Carlos Simon Foundation we have been investigating how the composition of the endometrial microbiome affects reproductive outcomes. The research line led by Dr. Inmaculada Moreno has been pioneering in demonstrating this association [2,4]. Our aim is to understand how these microbial communities interact with endometrial cells and to develop diagnostic and therapeutic tools for patients with altered microbiomes.
What Is the Connection with Endometriosis?
Ovarian endometriosis is a chronic inflammatory disease that affects between 10% and 15% of women of reproductive age. It is characterized by the presence of endometrial-like tissue outside the uterus, particularly in the ovaries, and can cause pain, heavy bleeding, and infertility. Although its exact origin remains unclear, growing evidence points to a potential link with the microbiome—both endometrial and intestinal.
Within this research framework, our PhD candidate Mari Carmen Graciano studies how specific microbial profiles within the endometrial microbiome may influence inflammatory processes, immune modulation, and the formation of endometriotic lesions. Our goal is to determine whether an altered endometrial microbiome could be involved in the onset or progression of the disease and, in doing so, to open new avenues for earlier diagnosis or preventive strategies.
A Growing Field with Clinical Implications
Understanding how microorganisms interact with human cells—and in this case, with endometrial cells—offers a new perspective on reproductive health. In conditions such as endometriosis, where diagnosis can take 7 to 10 years from the onset of symptoms, identifying reliable microbial biomarkers could enable earlier detection and more targeted clinical management.
Research into the endometrial microbiome not only sheds light on its role in fertility, but also helps explore novel ways to address complex gynecological diseases. Much remains to be discovered, but each new insight brings us closer to a more personalized and evidence-based reproductive medicine.
References:
1. 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. Sci Rep. 2019;9(1):2204. doi:10.1038/s41598-019-39700-6
2. Moreno I, Codoñer FM, Vilella F, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684-703. doi:10.1016/j.ajog.2016.09.075
3. Wei W, Zhang X, Tang H, Zeng L, Wu R. Microbiota composition and distribution along the female reproductive tract of women with endometriosis. Ann Clin Microbiol Antimicrob. 2020;19(1):15. doi:10.1186/s12941-020-00356-0
4. Moreno I, Garcia-Grau I, Perez-Villaroya D, et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome. 2022;10(1):1. doi:10.1186/s40168-021-01184-w