The Gut-Reproduction-Oral-Immune Axis: Microbial Dysbiosis as a Shared Driver in Polycystic Ovary Syndrome and Endometriosis.

Polycystic ovary syndrome (PCOS) and Endometriosis (EMs) are common reproductive endocrine disorders in women of reproductive age, characterized by the co-occurrence of infertility, chronic low-grade inflammation, and chronic pelvic pain. In this review, the “Gut-Reproduction-Oral-Immune Axis” (GROI axis) is introduced as a shared upstream pathophysiological mechanism for PCOS and EMs, with microbial dysbiosis playing a crucial role in its dysregulation. Despite distinct core pathologies, with PCOS characterized by metabolic/endocrine dysfunction and EMs by inflammatory/estrogen-dependent lesion formation, similar microbial dysbiosis patterns may drive disease pathogenesis via host-specific factors. Research indicates that patients with PCOS and EMs have common microbiota dysbiosis characteristics, such as lower alpha diversity (α-diversity), increased levels of Prevotella, decreased levels of Lactobacillus, although the specific patterns may vary by location (e.g., gut, reproductive tract, oral cavity) due to site-specific physiological niches. This type of dysbiosis participates in the disease process through the dysbiosis-brain axis mechanism in three aspects: disrupting the hypothalamic-pituitary-adrenal/ovarian (HPA/O) axis to cause neuroendocrine imbalance; activating the immune inflammatory pathway to lead to chronic low-grade inflammation; and inducing peripheral and central neural sensitization through pro-inflammatory factors and neuroactive substances. These mechanisms are interwoven, forming a self-reinforcing vicious cycle: microbial dysbiosis triggers the neuroendocrine-immune-pain cascade reaction, and the subsequent hormone disorders, inflammatory state and chronic stress further feedback to aggravate the microbial ecological imbalance. This article systematically expounds the common mechanism of the GROI axis in PCOS and EMs, providing a new perspective for understanding their shared pathological basis and developing intervention strategies targeting the microecology.