{"paper_id":"c71e2e71-c544-4de0-a81d-d4bf2b737942","body_text":"Abstract\nPolycystic 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.\nSimilar content being viewed by others\nData Availability\nNo datasets were generated or analysed during the current study.\nAbbreviations\n- PCOS:\n-\nPolycystic ovary syndrome\n- Ems:\n-\nEndometriosis\n- GROI:\n-\nGut-Reproduction-Oral-Immune\n- HPA/O:\n-\nhypothalamic-pituitary-adrenal/ovarian\n- SCFAs:\n-\nshort-chain fatty acids\n- IR:\n-\ninsulin resistance\n- HA:\n-\nhyperandrogenism\n- GLP-1:\n-\nglucagon-like peptide-1\n- IL-22:\n-\ninterleukin-22\n- LPS:\n-\nLipopolysaccharide\n- PGE2 :\n-\nprostaglandin E2\n- E2 :\n-\n17β-estradiol\n- FSH:\n-\nfollicle-stimulating hormone\n- EEO:\n-\nendometrial organoids\n- PID:\n-\npelvic inflammatory disease\n- TLRs:\n-\nToll-like receptors\n- Tregs:\n-\nregulatory T cells\n- IL-1:\n-\ninterleukin-1\n- IL-6:\n-\ninterleukin-6\n- TNF-α:\n-\ntumor necrosis factor-alpha\n- MMP-8:\n-\nmetalloproteinase-8\n- CRP:\n-\nC-reactive protein\n- EECs:\n-\nintestinal endocrine cells\n- GABA:\n-\nγ-aminobutyric acid\n- HPG:\n-\nhypothalamic-pituitary-gonadal\n- GnRH:\n-\ngonadotropin-releasing hormone\n- CRH:\n-\ncorticotropin-releasing hormone\n- ACTH:\n-\nadrenocorticotropic hormone\n- LH:\n-\nluteinizing hormone\n- 5-HT:\n-\nserotonin\n- 5-HT2C:\n-\nhypothalamic serotonin receptor 2C\n- VN:\n-\nvagus nerve\n- PAMPs:\n-\npathogen-associated molecular patterns\n- IL-1β:\n-\ninterleukin-1 beta\n- IL-10:\n-\ninterleukin-10\n- GPR41/43:\n-\nG protein-coupled receptors\n- HDAC :\n-\nhistone deacetylase\n- CAP:\n-\ncholinergic anti-inflammatory pathway\n- NGF:\n-\nnerve growth factor\n- TRPV1:\n-\ntransient receptor potential vanillic acid subtype 1\n- TrkA:\n-\ntropomyosin receptor kinase A\n- NF-κB:\n-\nnuclear factor kappa B\n- GCs:\n-\nGranulosa Cells\n- CORT:\n-\nCortisol\n- HYP:\n-\nhypothalamus\n- ENS:\n-\nenteric nervous system\n- CNS:\n-\ncentral nervous system\n- CD14:\n-\ncluster of differentiation 14\n- Th17:\n-\nT helper 17 cell\n- EP1:\n-\nprostaglandin E receptor 1\n- EP4:\n-\nprostaglandin E receptor 4\n- DC:\n-\ndendritic cell\nReferences\nThursby E, Juge N (2017) Introduction to the human gut microbiota. 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Am J Physiol Gastrointest Liver Physiol 280:G7–G13. https://doi.org/10.1152/ajpgi.2001.280.1.G7\nFunding\nThis research was funded by the National Natural Science Foundation of China (No.82174195; No.81804138; No. 82505659), the Longjiang Science and Technology Talent Spring Swallow Support Program (No. 2022CYCX0026) and the Natural Science Foundation of Heilongjiang Province (No.PL2025H276).\nAuthor information\nAuthors and Affiliations\nContributions\n**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.\nCorresponding author\nEthics declarations\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer 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.\nAbout this article\nCite this article\nLi, 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\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s00284-026-04918-x","source_license":"public-domain-us","license_restricted":false}