We are proud and happy to present this new review, published by Medicen Microbiome Drug Metabolism Working Group!
Including Sylvie Maubant, head of study & Research at Oncodesign Services, more than thirty international leading experts from pharma, academia, biotech, CROs and regulatory affairs has developed proposals to facilitate integration of the microbiome in drug discovery and development.
Abstract
Human microbiomes, particularly in the gut, could have a major impact on efficacy and toxicity of the drugs. However, gut microbial metabolism is often neglected in the drug discovery and development process. Medicen, a Paris-based human health innovation cluster, has gathered more than thirty international leading experts from pharma, academia, biotech, CROs and regulatory affairs to develop proposals to facilitate integration of the microbiome in drug discovery and development. Seven subteams were implemented to cover the complementary expertise areas of 1) Pharma experience and case studies, 2) in silico microbiome-drug interaction, 3) in vitro microbial stability screening, 4) gut fermentation models, 5) animal models, 6) microbiome integration in clinical and regulatory aspects, and 7) microbiome standards. Each expert team produced a state-of-the-art report of their respective field highlighting existing microbiome-related tools at every stage of drug discovery and development. Most critical limitations are the growing, but still limited, drug-microbiome interaction data to produce predictive models, and the lack of agreed standards despite recent progress. In the paper we will report and share proposals covering: 1) How can microbiome tools help move a compound from drug discovery to clinical proof-of-concept studies, and alert early on potential undesired properties arising from microbiome-induced drug metabolism, 2) How microbiome data can be generated and integrated in pharmacokinetic models that are predictive of the human situation. Examples of drugs metabolized by the microbiome will be detailed to support recommendations from the working group.
Significance Statement Gut microbial metabolism is often neglected in the drug discovery and development process despite growing evidence of drugs’ efficacy and safety impacted by their interaction with the microbiome. This paper will detail existing microbiome-related tools covering every stage of drug discovery and development, current progress and limitations, as well as recommendations to integrate them in the process.
Autors :
Patrick Jimonet, Céline Druart, Stéphanie BLANQUET-DIOT, Lilia Boucinha, Stephanie Kourula, Francoise Le Vacon, Sylvie Maubant, Sylvie Rabot, Tom Van de Wiele, Frank Schüren, Vincent Thomas, Bernard Walther, Michael Zimmermann.
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