Microbial beta-glucuronidase (GUS)

Microbial beta-glucuronidase is an enzyme produced by diverse commensal bacteria in the human gut microbiome, primarily within the Firmicutes and Bacteroidetes phyla (Dashnyam et al., 2023). Its primary biological role is to catalyze the hydrolysis of beta-glucuronide conjugates, which are formed in the liver during Phase II detoxification and excreted into the intestinal lumen via bile (Parvez et al., 2021). While this process allows bacteria to scavenge glucuronic acid as a carbon source, it frequently results in the reactivation of drugs and toxins, leading to severe local toxicities (Wallace et al., 2010). A classic example is the reactivation of the SN-38 metabolite of the chemotherapy drug irinotecan, which causes dose-limiting late-onset diarrhea (Roberts et al., 2013). Additionally, the enzyme is implicated in the development of NSAID-induced enteropathy and the reactivation of endogenous estrogens, which may contribute to the progression of hormone-dependent cancers like breast cancer (Ervin et al., 2020). Consequently, microbial beta-glucuronidase has emerged as a significant therapeutic target for selective small-molecule inhibitors designed to mitigate drug-induced side effects and modulate systemic metabolite levels without interfering with the human ortholog (Bhatt et al., 2017).

Other names

Bacterial beta-glucuronidaseGut microbial beta-glucuronidaseBeta-D-glucuronoside glucuronosohydrolasemGUSgmGUS

Selective enzyme inhibition to prevent the deconjugation of drug metabolites in the gut, thereby reducing local toxicity and preventing the reactivation of toxic or carcinogenic compounds.