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Microbiome

Microbial beta-glucuronidase

DEMikrobielle Beta-Glucuronidase

Microbial beta-glucuronidases (GUS) are bacterial enzymes encoded by gus genes in many gut Firmicutes, Bacteroidota and Enterobacteriaceae. They cleave glucuronide groups added by host phase-II conjugation, regenerating the parent compound in the gut lumen. This has two well-described consequences: reactivation of xenobiotics, including SN-38 (the active metabolite of the chemotherapy irinotecan, where GUS-driven deconjugation drives dose-limiting diarrhoea) and NSAIDs; and deconjugation of host steroid hormones such as estrogens, which Plottel and Blaser termed the estrobolome. The 2017 Pollet et al. structural atlas in Structure catalogued 279 unique gut GUS proteins across six structural classes from Human Microbiome Project metagenomes, motivating selective GUS inhibitors as adjuncts to chemotherapy.

Sources

  1. Pollet RM, D'Agostino EH, Walton WG, et al.. (2017). An atlas of beta-glucuronidases in the human intestinal microbiome. *Structure*doi:10.1016/j.str.2017.05.003
  2. Plottel CS, Blaser MJ. (2011). Microbiome and malignancy. *Cell Host & Microbe*doi:10.1016/j.chom.2011.10.003
  3. Hu S, Ding Q, Zhang W, et al.. (2023). Gut microbial beta-glucuronidase: a vital regulator in female estrogen metabolism. *Gut Microbes*doi:10.1080/19490976.2023.2236749