Bacterial beta-glucuronidase (GUS)

Bacterial beta-glucuronidase (GUS) is a diverse family of enzymes produced by the human intestinal microbiota, particularly by species within the Firmicutes, Bacteroidetes, and Proteobacteria phyla (Pollet et al., 2017, Frontiers in Microbiology). These enzymes play a pivotal role in the enterohepatic circulation by hydrolyzing glucuronide conjugates—metabolites formed in the liver to facilitate the excretion of both endogenous compounds (like bilirubin and estrogens) and exogenous drugs (Wallace et al., 2010, Science). While this activity allows bacteria to utilize the glucuronide sugar moiety as a carbon source, it simultaneously releases aglycones back into the intestinal lumen, often leading to localized toxicity. A classic example is the reactivation of SN-38G, the inactive metabolite of the chemotherapeutic irinotecan, into the potent topoisomerase inhibitor SN-38, which causes severe, dose-limiting diarrhea (Bhatt et al., 2017, Scientific Reports). Consequently, bacterial GUS has become a high-interest therapeutic target; selective small-molecule inhibitors are being developed to prevent drug-induced GI toxicity and improve the safety profile of various medications, including NSAIDs and certain oncology agents, without disrupting the overall viability of the gut microbiome (Roberts et al., 2013, ACS Chemical Biology).

Other names

Microbial beta-glucuronidaseBeta-D-glucuronoside glucuronosohydrolasebGUSGlucuronidase betaIntestinal bacterial beta-glucuronidase

Inhibition of bacterial beta-glucuronidase prevents the reactivation of glucuronidated drug metabolites in the gut, thereby reducing local mucosal toxicity.