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. Similar content being viewed by others Data Availability No datasets were generated or analysed during the current study. Abbreviations - PCOS: - Polycystic ovary syndrome - Ems: - Endometriosis - GROI: - Gut-Reproduction-Oral-Immune - HPA/O: - hypothalamic-pituitary-adrenal/ovarian - SCFAs: - short-chain fatty acids - IR: - insulin resistance - HA: - hyperandrogenism - GLP-1: - glucagon-like peptide-1 - IL-22: - interleukin-22 - LPS: - Lipopolysaccharide - PGE2 : - prostaglandin E2 - E2 : - 17β-estradiol - FSH: - follicle-stimulating hormone - EEO: - endometrial organoids - PID: - pelvic inflammatory disease - TLRs: - Toll-like receptors - Tregs: - regulatory T cells - IL-1: - interleukin-1 - IL-6: - interleukin-6 - TNF-α: - tumor necrosis factor-alpha - MMP-8: - metalloproteinase-8 - CRP: - C-reactive protein - EECs: - intestinal endocrine cells - GABA: - γ-aminobutyric acid - HPG: - hypothalamic-pituitary-gonadal - GnRH: - gonadotropin-releasing hormone - CRH: - corticotropin-releasing hormone - ACTH: - adrenocorticotropic hormone - LH: - luteinizing hormone - 5-HT: - serotonin - 5-HT2C: - hypothalamic serotonin receptor 2C - VN: - vagus nerve - PAMPs: - pathogen-associated molecular patterns - IL-1β: - interleukin-1 beta - IL-10: - interleukin-10 - GPR41/43: - G protein-coupled receptors - HDAC : - histone deacetylase - CAP: - cholinergic anti-inflammatory pathway - NGF: - nerve growth factor - TRPV1: - transient receptor potential vanillic acid subtype 1 - TrkA: - tropomyosin receptor kinase A - NF-κB: - nuclear factor kappa B - GCs: - Granulosa Cells - CORT: - Cortisol - HYP: - hypothalamus - ENS: - enteric nervous system - CNS: - central nervous system - CD14: - cluster of differentiation 14 - Th17: - T helper 17 cell - EP1: - prostaglandin E receptor 1 - EP4: - prostaglandin E receptor 4 - DC: - dendritic cell

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Author information Authors and Affiliations Contributions **Writing – Original Draft: ** Tiantian Li; **Writing – Review & Editing: ** Hongying Kuang; **Visualization: ** Jianing Zhang, Zimeng Pan; **Investigation/Literature Search: ** Yushan Meng, Xin Mao; **Conceptualization: ** Tiantian Li, HongYing Kuang, Xiaoling Feng; **Supervision: ** Miao Sun. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Li, T., Kuang, H., Zhang, J. et al. The Gut-Reproduction-Oral-Immune Axis: Microbial Dysbiosis as a Shared Driver in Polycystic Ovary Syndrome and Endometriosis. Curr Microbiol 83, 316 (2026). https://doi.org/10.1007/s00284-026-04918-x Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s00284-026-04918-x