Intestinal beta-D-glucuronidase

Intestinal beta-D-glucuronidase is a microbiome-derived enzyme prominently expressed by a range of gut bacteria belonging primarily to the phyla Firmicutes and Bacteroidetes. It hydrolyzes β-D-glucuronide conjugates, a process that reverses hepatic phase II metabolism by cleaving glucuronic acid from endobiotics (e.g., bilirubin, hormones) and xenobiotics (notably drugs undergoing glucuronidation such as irinotecan). This hydrolytic activity releases bioactive aglycones that can be reabsorbed and recirculated, altering drug pharmacokinetics and sometimes leading to local gastrointestinal toxicity. The enzyme is encoded by various bacterial genes (e.g., uidA in E. coli), is part of glycoside hydrolase family 2, and shows structural diversity that influences substrate specificity and inhibitor sensitivity. Selective inhibition of intestinal bacterial β-glucuronidase is a promising strategy to prevent gut-related toxicities of some drugs, but care must be taken to preserve beneficial metabolic functions and gut microbial ecology.

Other names

Bacterial β-glucuronidaseMicrobial β-glucuronidaseβ-D-glucuronidase (intestinal form)Intestinal GUSGut microbial beta-glucuronidaseβ-glucuronidase of the gut microbiome

Enzymatic hydrolysis of glucuronide conjugates to yield aglycones (parent drug or toxin) and glucuronic acid; Drug reactivation by deconjugation, causing local toxicity or altering systemic exposure