Microbiome and Endometriosis: Emerging Insights

Endometriosis and the Microbiome: Insights and Emerging Research

Endometriosis is a multifaceted, heterogeneous, inflammatory condition that affects 10%-15% of women (XX) during their reproductive years and is most commonly associated with chronic pelvic pain and infertility. Although many theories have been proposed to explain its pathogenesis, none has definitively clarified its origins. In recent years, research has increasingly focused on the interplay between endometriosis and the human microbiome, with growing attention to gut health, inflammation, and mechanisms of disease development.

Understanding Endometriosis

Endometriosis is characterized by the presence of endometrial-like tissue outside the uterine cavity. These implants are most often found on visceral and peritoneal surfaces within the abdominopelvic cavity but can also involve connective tissue and organs throughout the body. The condition may cause severe dysmenorrhea, pelvic pain, and subfertility among numerous other symptoms and manifestations, significantly impairing a person’s quality of life.4

The Human Microbiome and Its Role in Health and Disease

The human microbiome consists of microorganisms that colonize the body and play essential roles in nutrient metabolism and diverse physiological processes. Its composition and balance can have a substantial impact on health. The gut microbiota, for example, synthesizes vitamins B12 and K, maintains intestinal mucosal integrity, promotes angiogenesis and epithelial repair, and modulates immune functions.5

Disruption of gut microbial composition, or dysbiosis, can contribute to the onset and progression of a wide range of diseases, including inflammatory bowel diseases, arthritis, psoriasis, neuropsychiatric conditions, and malignancies.4 Given that endometriosis is a chronic inflammatory disease potentially driven by altered immune function and increased angiogenesis, there is growing interest in the contribution of microbiota dysbiosis to the pathogenesis and pathophysiology of endometriosis.1,4

The Microbiome–Endometriosis Connection: An Emerging Field of Research

Early investigations suggest that microbiome composition may differ in individuals with endometriosis. In one study, researchers reported significant alterations in microbial community structure between those with and without the condition.1,5 The abundance of Acinetobacter, Pseudomonas, Streptococcus, and Enhydrobacter increased significantly, while Propionibacterium, Actinomyces, and Rothia decreased significantly in the endometriosis group.5

Another line of research has examined the microbiota associated with extracellular vesicles in peritoneal fluid.4,5 These vesicles, which are small bilayered lipid structures released by cells, carry proteins, nucleic acids, and lipids and are integral to immune function, inflammatory responses, and disease development. Bacteria also release extracellular vesicles that can modulate host immune responses and other health-related processes. Significant differences in the microbial community within these vesicles have been observed between women with and without endometriosis.5

Adding complexity to the picture, multiple studies have found increased bacterial colonization in menstrual blood and endometrial tissue of women with endometriosis compared to controls.5 A study in rhesus monkeys indicated that changes in intestinal microflora composition and intestinal inflammation are associated with endometriosis. While animal findings do not directly translate to humans, the reproductive tract of rhesus monkeys closely resembles humans in both form and function.7

Microbiome and the Inflammatory Response in Endometriosis

Endometriosis is associated with heightened inflammatory activity, including increased production of pro-inflammatory cytokines, autoantibodies, growth factors, oxidative stress, and alterations in T-cell and natural killer cell reactivity.1 This dysregulated immune landscape may foster an immunosuppressive environment that supports lesion growth.1

Emerging evidence points to a potential role for gut microbiome-derived extracellular vesicles in these processes.5 Ranging from 20 to 400 nm in diameter, these vesicles can cross the intestinal barrier, enter systemic circulation, and potentially affect the peritoneal environment. Their cargo of proteins, nucleic acids, and lipids may influence immune function, inflammatory responses, and diseases such as endometriosis. One study showed that extracellular vesicles from women with endometriosis carry unique cargo capable of influencing inflammation, angiogenesis, and cellular proliferation.5 Another investigation identified specific proteins in exosomes from peritoneal fluid of patients with endometriosis, suggesting a diagnostic and therapeutic role for these vesicles.5

The Gut Microbiome and Estrogen Levels

The gut microbiome is a key regulator of estrogen levels and influences estrogen metabolism, thereby potentially impacting estrogen-dependent conditions such as endometriosis.3 In postmenopausal women, both fecal microbiota richness and the abundance of fecal Clostridia taxa have been linked to systemic estrogen levels. Gut dysbiosis that results in abnormal circulating estrogen may therefore contribute to the development of endometriosis or to its associated symptoms.3

The Microbiome as a Diagnostic and Therapeutic Target

Altered microbiota composition in endometriosis may yield clinically useful biomarkers. One study proposed a microbiota-based model capable of distinguishing infertile patients with and without endometriosis.1 Another reported enrichment of specific bacterial species in the endometrium and peritoneal fluid of patients with the disease.2

On the therapeutic front, modulation of the gut microbiota—through dietary strategies, prebiotics, probiotics, or fecal microbiota transplantation—has been proposed as a potential treatment avenue.4 Further research is needed to clarify mechanisms and evaluate the efficacy and safety of such approaches in endometriosis management.

Conclusion

The relationship between the microbiome and endometriosis remains an active and evolving area of study. Current findings suggest that microbiota alterations may be associated with the condition, offering new insights into pathogenesis and pointing toward innovative diagnostic and therapeutic strategies. As research into the microbiome advances, so too does the promise of integrative health approaches that consider the complex ecosystem of microbes within and around us. Continued investigation is essential to confirm observed associations, elucidate underlying mechanisms, and determine whether microbiota changes in those with endometriosis are a cause, a consequence, or both. While there are limitations in the current usefulness of this research, we do know that the immune system is involved with regulating the disease. An important question remains: are the microbiota changes seen in those with endo the chicken or the egg?