Estrobolome and the endocrine-microbiome axis in breast and endometrial carcinogenesis

The estrobolome, the community of gut microbial genes involved in estrogen metabolism, may influence hormone bioavailability and cancer risk, although human evidence remains largely associative. This review summarizes evidence that bacterial β-glucuronidases, sulfatases, and hydroxysteroid dehydrogenases regulate enterohepatic estrogen recycling, while microbial metabolism also shapes receptor signaling, genotoxic estrogen metabolites, inflammation, and immune responses. Observational studies link gut microbial composition and function with breast and endometrial cancer, but causality remains unproven. Early dietary, probiotic, antibiotic, and fecal microbiota transplantation studies show biological effects, yet they are not sufficient for clinical application. We propose a functional framework that prioritizes microbial enzymatic activity over taxonomy and highlight multiparametric biomarkers and selective β-glucuronidase inhibition as promising research directions for prevention and adjunct therapy in hormone-driven cancers.