RESUMEN

Gut microbial ß-glucuronidase (gmGUS) is involved in the disposition of many endogenous and exogenous compounds. Preclinical studies have shown that inhibiting gmGUS activity affects drug disposition, resulting in reduced toxicity in the gastrointestinal tract (GIT) and enhanced systemic efficacy. Additionally, manipulating gmGUS activity is expected to be effective in preventing/treating local or systemic diseases. Although results from animal studies are promising, challenges remain in developing drugs by targeting gmGUS. Here, we review the role of gmGUS in host health under physiological and pathological conditions, the impact of gmGUS on the disposition of phenolic compounds, models used to study gmGUS activity, and the perspectives and challenges in developing drugs by targeting gmGUS.

Asunto(s)

Microbioma Gastrointestinal , Glucuronidasa , Animales , Tracto Gastrointestinal , Glucuronidasa/farmacología

RESUMEN

Over the past decade, the gut microbiota has received considerable attention for its interactions with the host. Microbial ß-glucuronidase generated by this community has hence aroused concern for its biotransformation activity to a wide range of exogenous (foreign) and endogenous compounds. Lately, the role of gut microbial ß-glucuronidase in the pathogenesis of breast cancer has been proposed for its estrogen reactivation activity. This is plausible considering that estrogen glucuronides are the primary products of estrogens' hepatic phase II metabolism and are subject to ß-glucuronidase-catalyzed hydrolysis in the gut via bile excretion. However, research in this field is still at its very preliminary stage. This review outlines the biology of microbial ß-glucuronidase in the gastrointestinal tract and elaborates on the clues to the existence of microbial ß-glucuronidase-estrogen metabolism-breast cancer axis. The research gaps in this field will be discussed and possible strategies to address these challenges are suggested.