A growing amount of evidence has supported that gut microbiota plays a vital role in the reproductive endocrine system throughout a woman's whole life, and gut microbial β-glucuronidase (gmGUS) is a key factor in regulating host estrogen metabolism. Moreover, estrogen levels also influence the composition as well as the diversity of gut microbiota. In normal condition, the gmGUS-estrogen crosstalk maintains body homeostasis of physiological estrogen level. Once this homeostasis is broken, the estrogen metabolism will be disturbed, resulting in estrogen-related diseases, such as gynecological cancers, menopausal syndrome, etc. together with gut microbial dysbiosis, which may accelerate these pathological processes. In this review, we highlight the regulatory role of gmGUS on the physical estrogen metabolism and estrogen-related diseases, summarize the present evidence of the interaction between gmGUS and estrogen metabolism, and unwrap the potential mechanisms behind them. Finally, gmGUS may become a potential biomarker for early diagnosis of estrogen-induced diseases. Regulating gmGUS activity or transplanting gmGUS-producing microbes shows promise for treating estrogen-related diseases.
Keywords: GUS gene; Gut microbiota; breast cancer; estrobolome; estrogen; gmGUS; hormone replacement therapy; interaction; menopausal syndrome; β-glucuronidase.