The estrobolome: Estrogen-metabolizing pathways of the gut microbiome and their relation to breast cancer

Increasing evidence links the gut microbiome to carcinogenesis. Disruptions in estrogen regulation by the estrobolome-gut microbiota with estrogen-related functions-may promote breast cancer. However, precise information on estrobolome targets and their underlying mechanisms is limited. This review identifies relevant targets for measuring the estrobolome, focusing on enzymes and microbial taxa involved in processing estrogens, precursors, metabolites, and phytoestrogens, to facilitate the exploration of potential links to breast cancer. Evidence from breast cancer case-control studies is synthesized to assess alignment with these targets, highlight gaps in the evidence, and suggest new paths forward. Findings from case-control studies were heterogeneous and showed limited alignment with estrobolome targets, with only Escherichia coli and Roseburia inulinivorans identified as differentially abundant and functionally relevant between cases and controls. The lack of compelling evidence for estrobolome-specific mechanisms may reflect measurement challenges or may suggest that broader ecological changes in the microbiome, which influence a network of interacting mechanisms, are more influential for carcinogenesis. To clarify the estrobolome's role in breast cancer, future research should use advanced sequencing techniques and methods such as metabolomics and transcriptomics, while considering clinical and behavioral factors that may modify estrobolome mechanisms.