Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice
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.
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BibTeX
@article{letertre2026characterizing,
title = {{Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice}},
author = {Marine Letertre and Aadra Bhatt and Michael Harvey and Jeremy Nicholson and Ian Wilson and Matthew Redinbo and Jonathan Swann},
journal = {Scientific Reports},
year = {2026},
month = nov,
doi = {10.1038/s41598-022-21518-4},
url = {https://hal.science/hal-04236485v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice
AU - Marine Letertre
AU - Aadra Bhatt
AU - Michael Harvey
AU - Jeremy Nicholson
AU - Ian Wilson
AU - Matthew Redinbo
AU - Jonathan Swann
PY - 2026
DA - 2026/11/05
JO - Scientific Reports
DO - 10.1038/s41598-022-21518-4
UR - https://hal.science/hal-04236485v1
AB - 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.
SN - 2045-2322
ER -