Journal article
Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice
Scientific Reports, Vol.12(1), Art. 17435
2022
Abstract
The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system.
Details
- Title
- Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice
- Authors/Creators
- M.P.M. Letertre (Author/Creator) - Imperial College LondonA.P. Bhatt (Author/Creator)M. Harvey (Author/Creator)J.K. Nicholson (Author/Creator)I.D. Wilson (Author/Creator)M.R. Redinbo (Author/Creator)J.R. Swann (Author/Creator)
- Publication Details
- Scientific Reports, Vol.12(1), Art. 17435
- Publisher
- Springer Nature
- Identifiers
- 991005542332507891
- Copyright
- © 2022 The Authors.
- Murdoch Affiliation
- Australian National Phenome Centre
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.120 Inflammatory Bowel Diseases & Infections
- 1.120.384 Gut Microbiota
- Web Of Science research areas
- Biochemistry & Molecular Biology
- ESI research areas
- Biology & Biochemistry