Gut microbiota-mitochondria axis offers a dual-targeted therapeutic framework for gynecological diseasesGut Health and Mitochondria May Impact Gynecological Diseases

The “gut microbiota–mitochondria axis” has become the core hub connecting the metabolism, immunity, and endocrine regulation of gynecological diseases. In this review, the hierarchical regulation mechanism of this axis is systematically combed: at the upstream level, intestinal short-chain fatty acids (SCFAs), bile acids (BAs), tryptophan derivatives, and other metabolites can activate AMPK/PGC-1α, FXR/TGR5, and AhR-mediated energy sensing and receptor signaling pathways; On the functional level, bacterial lipopolysaccharide-TLR4 signal and cGAS–STING/NLRP3 inflammasome pathway activated by cytoplasmic mitochondrial DNA (mtDNA) can amplify innate immune response; At the effect level, mitochondrial reactive oxygen species (ROS), mitochondrial dynamics, and PINK1/Parkin-mediated mitophagy are the common key nodes to regulate mitochondrial quality and inflammatory response. Combined with the two-way relationship between the estrobolome and steroid production, the above processes together form a self-reinforcing closed loop of “metabolic input-immune amplification-oxidative stress/autophagy-endocrine regulation”. Based on this theoretical framework, this paper analyzes the disease-specific correlations among polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, and gynecological malignancies, and puts forward a dual-targeted treatment idea with research value. The intervention plan with microbiota as the core aims to adjust the metabolite spectrum and endotoxin level; Mitochondria-centered interventions focus on restoring cell energy metabolism and apoptosis sensitivity. In addition, this review constructs a hierarchical research framework of “microbiota-metabolomics-mitochondria” to clarify the targeted phenotypes in the pathway, and provide guidance for subsequent clinical trial design and long-term monitoring. With the deep integration of multi-omics technology and targeted interventions, the gut microbiota–mitochondria axis is expected to become an important breakthrough in precision medical treatment of gynecological diseases and build a brand-new bridge between basic mechanism research and clinical transformation.