Molecular mechanisms in endometriosis: linking JAK/STAT pathway, ferroptosis, and microbial dysbiosis.

Endometriosis 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.