{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:47:06Z","timestamp":1790128026590,"version":"4.0.1"},"reference-count":348,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Endometriosis (EMS) is a highly heterogeneous chronic gynecological disease characterized by pain, infertility, and relapse, with its etiology and pathogenesis not yet fully elucidated. Traditional theories, including \u201cretrograde menstruation,\u201d \u201cimplantation theory,\u201d and \u201cabnormalities in immune tolerance,\u201d struggle to adequately explain the complex lesion behavior, diverse phenotypic characteristics, and accompanying immune-metabolic disorders. In recent years, the key roles of imbalances in the gut and reproductive microbiomes, abnormal iron metabolism, and the newly proposed ferroptosis in the occurrence and development of EMS have gradually gained attention, suggesting that this disease may be a systemic condition involving the interplay of microbial ecology, iron metabolism, and cell death. Existing studies indicate that the gut-reproductive microbiome profoundly influences the body\u2019s iron homeostasis and iron load by regulating mucosal immunity, systemic inflammatory responses, and metabolic environments. This, in turn, activates the ferroptosis pathway through iron-dependent lipid peroxidation and cell membrane damage, participating in the formation, maintenance, and inflammatory microenvironment shaping of ectopic lesions. Based on these findings, this article systematically reviews the interactions between gut-reproductive microbiome imbalance and iron metabolism disorders, integrating multi-omics evidence such as microbiome analysis, metabolomics, and iron metabolism\/ferroptosis-related molecular markers. It proposes a new pathological mechanism framework of \u201cdysbiosis\u2013iron overload\u2013ferroptosis\u201d incorporating microecological imbalance and ferroptosis into a unified picture of the pathogenesis of EMS. Furthermore, this article discusses potential therapeutic strategies and application prospects surrounding microbiome remodeling (such as probiotics, fecal microbiota transplantation, dietary and lifestyle interventions) and pharmacological targeting of key ferroptosis-related molecules. Through a comprehensive and critical analysis of existing evidence, this review aims to provide a more systematic theoretical framework for the mechanistic research of EMS and offer ideas and directions for future clinical translation of precise classification, individualized intervention, and novel treatment plans.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1762013","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:09:25Z","timestamp":1779430165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["From gut-reproductive microbiota to ferroptosis: a comprehensive insight into the molecular-pathogenicity of endometriosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xianhua","family":"Han","sequence":"first","affiliation":[{"name":"Department of Gynecology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People\u2019s Hospital)","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin lei","family":"Guo","sequence":"additional","affiliation":[{"name":"Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, The First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.3361","article-title":"The clinical anatomy of endometriosis: a review","volume":"10","author":"Alimi","year":"2018","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1020827","article-title":"Endometriosis-associated infertility: from pathophysiology to tailored 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