Beyond estrobolome 1.0: unraveling endocrine-microbiome axis as a driver and therapeutic target in hormone-driven cancers

The endocrine-microbiome axis extends the estrobolome concept, recognizing gut microbes as active endocrine partners. Bacteria modulate estrogen recycling via diverse enzymes and produce SERM-like metabolites, while host hormones shape microbial communities. This bidirectional crosstalk influences hormone-driven carcinogenesis through inflammation, genomic instability, and epigenetic changes. Therapeutic opportunities include precision probiotics and selective enzymatic inhibition. Advancing the field requires causal models, multi-omics integration, and sex as a biological variable.