Gut Microbiota-Mediated SN-38G Metabolism In Vitro: Effects of Murraya koenigii and Ruta graveolens
- 1Microbiology and Systems Biology, TNO The Netherlands Organization for Applied Scientific Research, 2333 BE Leiden, The Netherlands
- 2Independent Researcher
- 3AVS Bio Netherlands B.V., Uppsalalaan 17, 3584 CT Utrecht, The Netherlands
Abstract
The influence of the human microbiome on health and disease has been extensively studied over the past two decades. More recently, the microbiota has also been implicated in modulating the efficacy and toxicity of various drugs, including cancer therapies. This study focuses on irinotecan, a chemotherapeutic prodrug used in colorectal cancer treatment. Irinotecan is converted to the active metabolite SN-38, which is then glucuronidated in the liver to form the inactive metabolite SN-38G. Following biliary secretion into the intestine, microbial enzymes can cleave the glucuronide group and release SN-38, a process that may contribute to gastrointestinal toxicity. Human fecal microbiota converted SN-38G to SN-38 in vitro. Antibiotic treatment markedly reduced conversion, indicating that microbial activity accounted for most of the conversion under these conditions. In an exploratory screen, extracts from Murraya koenigii and Ruta graveolens reduced SN-38G conversion. Differences in community composition and beta-glucuronidase gene abundance were observed after extract exposure. These results show microbiota-dependent SN-38G conversion in vitro and identify compounds and plant extracts that delay or inhibit this conversion. Whether this effect is caused by direct inhibition of microbial beta-glucuronidase or by more generic microbiota effects is open for future research.
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BibTeX
@article{scheithauer2026microbiotamediated,
title = {{Gut Microbiota-Mediated SN-38G Metabolism In Vitro: Effects of Murraya koenigii and Ruta graveolens}},
author = {Torsten P. M. Scheithauer and Emanuele Olgiati and Elwin Verheij and Wieke van Butselaar and Michel Ossendrijver and Michelle van der Wurff and Frank H. J. Schuren},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219582},
url = {https://www.mdpi.com/1422-0067/27/21/9582},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gut Microbiota-Mediated SN-38G Metabolism In Vitro: Effects of Murraya koenigii and Ruta graveolens
AU - Torsten P. M. Scheithauer
AU - Emanuele Olgiati
AU - Elwin Verheij
AU - Wieke van Butselaar
AU - Michel Ossendrijver
AU - Michelle van der Wurff
AU - Frank H. J. Schuren
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219582
UR - https://www.mdpi.com/1422-0067/27/21/9582
AB - The influence of the human microbiome on health and disease has been extensively studied over the past two decades. More recently, the microbiota has also been implicated in modulating the efficacy and toxicity of various drugs, including cancer therapies. This study focuses on irinotecan, a chemotherapeutic prodrug used in colorectal cancer treatment. Irinotecan is converted to the active metabolite SN-38, which is then glucuronidated in the liver to form the inactive metabolite SN-38G. Following biliary secretion into the intestine, microbial enzymes can cleave the glucuronide group and release SN-38, a process that may contribute to gastrointestinal toxicity. Human fecal microbiota converted SN-38G to SN-38 in vitro. Antibiotic treatment markedly reduced conversion, indicating that microbial activity accounted for most of the conversion under these conditions. In an exploratory screen, extracts from Murraya koenigii and Ruta graveolens reduced SN-38G conversion. Differences in community composition and beta-glucuronidase gene abundance were observed after extract exposure. These results show microbiota-dependent SN-38G conversion in vitro and identify compounds and plant extracts that delay or inhibit this conversion. Whether this effect is caused by direct inhibition of microbial beta-glucuronidase or by more generic microbiota effects is open for future research.
SN - 1422-0067
ER -