Favaron, Alessia;
Abdalla, Youssef;
McCoubrey, Laura E;
Nandiraju, Laxmi Prasanna;
Shorthouse, David;
Gaisford, Simon;
Basit, Abdul;
(2024)
Exploring the interactions of JAK inhibitor and S1P receptor modulator drugs with the human gut microbiome: Implications for colonic drug delivery and inflammatory bowel disease.
European Journal of Pharmaceutical Sciences
, 200
, Article 106845. 10.1016/j.ejps.2024.106845.
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Abstract
The gut microbiota is a complex ecosystem, home to hundreds of bacterial species and a vast repository of enzymes capable of metabolising a wide range of pharmaceuticals. Several drugs have been shown to affect negatively the composition and function of the gut microbial ecosystem. Janus Kinase inhibitors and Sphingosine-1-phosphate receptor modulators are drugs recently approved for inflammatory bowel disease through an immediate release formulation and would potentially benefit from targeted colonic targeted delivery to enhance the local drug concentration at the diseased site. However, their impact on the human gut microbiota and susceptibility to bacterial metabolism remain unexplored. With the use of calorimetric, optical density measurements, and metagenomics next-generation sequencing, we show that JAK inhibitors have a minor impact on the composition of the human gut microbiota, while ozanimod exerts a significant antimicrobial effect, leading to a prevalence of the Enterococcus genus and a markedly different metabolic landscape when compared to the untreated microbiota. Moreover, ozanimod is the only drug subject to enzymatic degradation by the human gut microbiota sourced from six healthy donors.. Overall, given the crucial role of the gut microbiome in health, screening assays to investigate the interaction of drugs with the microbiome should be encouraged for the pharmaceutical industry as a standard in the drug discovery and development process.
| Type: | Article |
|---|---|
| Title: | Exploring the interactions of JAK inhibitor and S1P receptor modulator drugs with the human gut microbiome: Implications for colonic drug delivery and inflammatory bowel disease |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejps.2024.106845 |
| Publisher version: | http://dx.doi.org/10.1016/j.ejps.2024.106845 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Biotransformation, bioaccumulation, colonic drug delivery, drug metabolism, JAK inhibitors, drug-microbiome interactions, gut microbiota, ozanimod |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10194893 |
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