An Organ‐on‐Chip Platform for Simulating Drug Metabolism Along the Gut–Liver Axis [* Cross-Reference *]

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Mara Lucchetti; Kehinde Aina; Léa Grandmougin; Christian Jäger; Pau Pérez Escriva; Elisabeth Letellier; Alexander S. Mosig; Paul Wilmes, 2026, "An Organ‐on‐Chip Platform for Simulating Drug Metabolism Along the Gut–Liver Axis [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.FE2NGV, LIST Open Repository, V1

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Description	The human microbiome significantly influences drug metabolism through the gut–liver axis, leading to modified drug responses and potential toxicity. Due to the complex nature of the human gut environment, the understanding of microbiome-driven impacts on these processes is limited. To address this, a multiorgan-on-a-chip (MOoC) platform that combines the human microbial-crosstalk (HuMiX) gut-on-chip (GoC) and the Dynamic42 liver-on-chip (LoC), mimicking the bidirectional interconnection between the gut and liver known as the gut–liver axis, is introduced. This platform supports the viability and functionality of intestinal and liver cells. In a proof-of-concept study, the metabolism of irinotecan, a widely used colorectal cancer drug, is imitated within the MOoC. Utilizing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), irinotecan metabolites are tracked, confirming the platform's ability to represent drug metabolism along the gut–liver axis. Further, using the authors’ gut–liver platform, it is shown that the colorectal cancer-associated gut bacterium, Escherichia coli, modifies irinotecan metabolism through the transformation of its inactive metabolite SN-38G into its toxic metabolite SN-38. This platform serves as a robust tool for investigating the intricate interplay between gut microbes and pharmaceuticals, offering a representative alternative to animal models and providing novel drug development strategies. (2024-03-07) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1002/adhm.202303943 for the original and latest version of the publication* (2026-07-01)
Subject	Chemistry; Engineering; Medicine, Health and Life Sciences; Physics
Keyword	Irinotecan, Drug metabolism, Gut microbiome, Metabolite, Drug, Organ-on-a-chip, Colorectal cancer, SN-38, Gut flora, Microbiome, Metabolism, Camptothecin, Pharmacology, Biology, Bioinformatics, Cancer, Medicine, Biochemistry, Internal medicine, Nanotechnology
License/Data Use Agreement	CC BY 4.0


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Citation Metadata

Persistent Identifier	perma:LIST.FE2NGV
Publication Date	2026-07-06
Title	An Organ‐on‐Chip Platform for Simulating Drug Metabolism Along the Gut–Liver Axis [* Cross-Reference *]
Other Identifier	https://doi.org/10.1002/adhm.202303943 OpenAlex ID: https://openalex.org/W4392542378
Author	Mara Lucchetti (University of Luxembourg) - ORCID: https://orcid.org/0000-0002-3057-983X Kehinde Aina (Jena University Hospital) - ORCID: https://orcid.org/0000-0002-5748-8559 Léa Grandmougin (University of Luxembourg) - ORCID: https://orcid.org/0009-0009-3820-3958 Christian Jäger (University of Luxembourg) - ORCID: https://orcid.org/0000-0003-4235-7430 Pau Pérez Escriva (University of Luxembourg, Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0002-2330-4248 Elisabeth Letellier (University of Luxembourg, Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0001-8242-9393 Alexander S. Mosig (Jena University Hospital) - ORCID: https://orcid.org/0000-0002-5687-2444 Paul Wilmes (University of Luxembourg, Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0002-6478-2924
Point of Contact	Use email button above to contact. LIST QDKM (LIST)
Description	The human microbiome significantly influences drug metabolism through the gut–liver axis, leading to modified drug responses and potential toxicity. Due to the complex nature of the human gut environment, the understanding of microbiome-driven impacts on these processes is limited. To address this, a multiorgan-on-a-chip (MOoC) platform that combines the human microbial-crosstalk (HuMiX) gut-on-chip (GoC) and the Dynamic42 liver-on-chip (LoC), mimicking the bidirectional interconnection between the gut and liver known as the gut–liver axis, is introduced. This platform supports the viability and functionality of intestinal and liver cells. In a proof-of-concept study, the metabolism of irinotecan, a widely used colorectal cancer drug, is imitated within the MOoC. Utilizing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), irinotecan metabolites are tracked, confirming the platform's ability to represent drug metabolism along the gut–liver axis. Further, using the authors’ gut–liver platform, it is shown that the colorectal cancer-associated gut bacterium, Escherichia coli, modifies irinotecan metabolism through the transformation of its inactive metabolite SN-38G into its toxic metabolite SN-38. This platform serves as a robust tool for investigating the intricate interplay between gut microbes and pharmaceuticals, offering a representative alternative to animal models and providing novel drug development strategies. (2024-03-07) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1002/adhm.202303943 for the original and latest version of the publication* (2026-07-01)
Subject	Chemistry; Engineering; Medicine, Health and Life Sciences; Physics
Keyword	Irinotecan Drug metabolism Gut microbiome Metabolite Drug Organ-on-a-chip Colorectal cancer SN-38 Gut flora Microbiome Metabolism Camptothecin Pharmacology Biology Bioinformatics Cancer Medicine Biochemistry Internal medicine Nanotechnology
Topic Classification	Gut microbiota and health 3D Printing in Biomedical Research Innovative Microfluidic and Catalytic Techniques Innovation
Deposit Date	2024-03-07
Data Type	Article
Data Source	Advanced Healthcare Materials

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