{"paper_id":"ec18784a-fb38-4729-85bf-c42e6d8658aa","body_text":"Abstract\nEndometriosis is a chronic gynaecological disorder characterized by ectopic endometrial growth, inflammation, pain, and infertility. Current therapies, largely hormonal and surgical, have limited efficacy and compromise fertility, underscoring the need for alternative approaches that directly address the inflammatory drivers. Recent evidence suggests that gut microbiota dysbiosis and iron overload contribute to the pathophysiology of endometriosis, with excess iron potentially inducing ferroptosis, a regulated form of lipid peroxidation-driven cell death that amplifies inflammation. Concurrently, cytokine-mediated JAK/STAT signalling, particularly IL-6/STAT3, integrates signals from immune cells, ferroptotic processes, and microbial metabolites, positioning it as a central regulatory axis in endometriosis. This review synthesizes mechanistic data linking alterations in the gut microbiota, microbial metabolites, ferroptosis, and JAK/STAT signalling in the inflammatory microenvironment of endometriosis. While direct causal evidence remains limited, converging findings from preclinical and translational studies suggest that the microbiota-ferroptosis-JAK/STAT interaction network forms an interconnected system that contributes to sustained inflammation. Our discussion brings these mechanisms into a shared framework, suggesting that their combined influence may give clearer insight into endometriosis. We propose that exploring these molecular pathways may open new avenues for microbiota- and ferroptosis-informed strategies that target inflammation while preserving fertility.\nSimilar content being viewed by others\nData availability\nNo datasets were generated or analysed during the current study.\nChange history\n14 April 2026\nGrant number in the funding section has been corrected as “FRGS/FP011-2023/UM”.\nAbbreviations\n- AGER:\n-\nAdvanced Glycation End-product Receptor\n- Akt:\n-\nProtein kinase B\n- COX-2:\n-\nCyclooxygenase-2\n- GnRH:\n-\nGonadotropin-releasing Hormone\n- GPX4:\n-\nGlutathione peroxidase 4\n- GSH:\n-\nGlutathione\n- IFN-γ:\n-\nInterferon-gamma\n- IL-1:\n-\nInterleukin-1\n- IL-6:\n-\nInterleukin-6\n- IL-8:\n-\nInterleukin-8\n- JAK:\n-\nJanus Kinase\n- KIR:\n-\nKiller cell inhibitory receptor\n- MALAT1:\n-\nMetastasis-associated lung adenocarcinoma transcript 1\n- MAPK/Erk1/2:\n-\nMitogen-activated protein kinase / Extracellular signal–regulated kinase 1/2\n- MCP-1:\n-\nMonocyte chemoattractant protein-1\n- MIF:\n-\nMacrophage migration inhibitory factor\n- MMP:\n-\nMatrix metalloproteinase\n- NF-κB:\n-\nNuclear Factor Kappa-light-chain-enhancer of Activated B cells\n- NRF2:\n-\nNuclear factor erythroid 2–related factor 2 (NFE2L2)\n- SCFAs:\n-\nShort-chain fatty acids\n- SLC7A11:\n-\nSolute carrier family 7 member 11\n- STAT:\n-\nSignal Transducer and Activator of Transcription\n- TFRC:\n-\nTransferrin receptor (protein 1)\n- TGF-β:\n-\nTransforming growth factor\n- TNF-α:\n-\nTumor Necrosis Factor Alpha\n- VEGF:\n-\nVascular endothelial growth factor\nReferences\nWHO, Endometriosis (2023) [Available from: https://www.who.int/news-room/fact-sheets/detail/endometriosis\nSaunders PTK, Horne AW (2021) Endometriosis: etiology, pathobiology, and therapeutic prospects. 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Phytomedicine 136:156227\nFunding\nThis work was financially supported by the Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme (FRGS/FP011-2023/UM).\nAuthor information\nAuthors and Affiliations\nContributions\nAll authors contributed to the conceptualization, analyses, funding acquisition, drafting, and final editing of the manuscript. 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Mol Biol Rep 53, 387 (2026). https://doi.org/10.1007/s11033-025-11401-6\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s11033-025-11401-6","source_license":"public-domain-us","license_restricted":false}