Abstract / Summary
Abstract Background Polycystic ovary syndrome (PCOS) is a systemic disorder characterized by metabolic dysfunction and chronic inflammation. Although gut microbiota dysbiosis has been implicated in PCOS, the mechanisms linking gut microbiota-derived metabolites to host immune dysregulation through taurine metabolism-related genes (TMRGs) remain unclear. Methods Public multiomic data were integrated to construct a gut–ovary network. Differentially expressed genes (DEGs) from GSE262735 were intersected with TMRGs to identify candidate genes. Three machine learning algorithms were used to screen biomarkers, which were validated in GSE54248, followed by nomogram construction. Gut microbiota–metabolite interactions, molecular docking, single-cell RNA sequencing of the GSE240688 dataset, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were further performed. Results In total, 28 TMRGs associated with PCOS were identified. These genes were mainly enriched in immune–inflammatory pathways. IL1B and ALPL were recognized as core biomarkers by machine learning and cross-validation. The nomogram based on these two genes displayed acceptable diagnostic performance (area under the curve = 0.728). Network analysis highlighted potential regulatory relationships between the gut metabolite 3-indolepropionic acid (IPA) and host biomarkers, and molecular docking suggested potential binding between IPA and IL-1β (binding energy = − 5.6 kcal/mol). Single-cell analysis identified granulosa lutein cells as the major carriers of IL1B and ALPL , and these cells exhibited metabolic dysregulation and enhanced communication with proliferating granulosa cells in PCOS. RT-qPCR further confirmed significantly increased IL1B and ALPL expression in PCOS samples (both p < 0.05). Conclusion This study revealed a novel TMRG-centered gut microbiota–metabolite–immune axis in PCOS. IPA might be associated with ovarian function through IL-1β, whereas ALPL might serve as a metabolic–immune interface in granulosa lutein cell dysfunction. These findings provide new insights into PCOS pathogenesis and suggest potential targets for precision therapy.