The Microbiota-Endometriosis Axis: An Immune-Endocrine Integration Model and Emerging Therapeutic Targets

Endometriosis is a chronic, estrogen-dependent inflammatory disorder characterized by the ectopic implantation and persistence of endometrial-like tissue outside the uterine cavity. Despite its high prevalence and significant impact on quality of life, the pathogenesis of endometriosis remains incompletely understood and involves a complex interplay between hormonal dysregulation, immune dysfunction, and chronic inflammation. In recent years, growing evidence has highlighted the role of the microbiota as a potential modulator of these interconnected pathways. This review proposes an integrative framework in which the microbiota acts as a central modulator of immune-endocrine interactions in endometriosis, while synthesizing current evidence on underlying biological mechanisms. We discuss how alterations in the gut, vaginal, and endometrial microbiota contribute to disease pathophysiology through multiple mechanisms, including disruption of intestinal barrier integrity, activation of pro-inflammatory signaling pathways, immune dysregulation, and modulation of estrogen metabolism via the estrobolome. Microbial β-glucuronidase activity and enterohepatic recirculation of estrogens are explored as key processes linking gut dysbiosis to the hyperestrogenic environment characteristic of endometriosis. Furthermore, we review current pharmacological treatments and highlight their limitations, emphasizing the need for novel therapeutic strategies targeting upstream disease mechanisms. Emerging approaches, including probiotics, postbiotics, short-chain fatty acids, and dietary interventions, are discussed as promising adjunctive therapies capable of modulating inflammation, immune responses, and metabolic pathways. Although current evidence remains heterogeneous and largely derived from preclinical and observational studies, the microbiota emerges not only as a potential therapeutic target but as a key integrative node linking endocrine, immune, and metabolic pathways in endometriosis. Future research should focus on well-designed clinical trials to validate microbiome-based interventions and to define their role in personalized management strategies for endometriosis.