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Modulating the gut microbiome to enhance drug efficacy

Objective

Individual response rates to drugs that are widely prescribed to treat common diseases are typically in the range of 50-75%, yet the slow progress and high costs associated with new drug development do not meet the urgent need for new treatment options, particularly given the rapidly increasing burden of chronic diseases. This ERC project tackles this pressing issue by defining the impacts of the gut microbiome and genetics on drug metabolism, ultimately enabling personalized approaches that enhance efficacy and safety of already marketed drugs via microbiome modulation. I will start with 23 common drugs used to treat chronic cardiometabolic and psychiatric disorders that threaten public health. The project will address important technical and clinical challenges in three innovative parts: 1) a population-based cohort study using the unique LifeLines-10K cohort to build sophisticated models that take genetic, microbial and lifestyle/health factors into account to improve prediction of drug metabolism; 2) pharmacokinetics analyses using innovative, personalized organ-on-a-chip to better understand causality and mechanism; and 3) an intervention trial using probiotics to achieve greater drug efficacy through modulation of the gut microbiome. In particular, the project will deliver microbiome-targeting solutions to improve the efficacy and safety of one or two drugs and a next-generation drug-testing model that uses an innovative organ-on-a-chip system to mimic metabolic flow along the gut-liver axis while taking an individual’s genetics and gut microbiome into account. This project will lay the foundation for major advances in personalized medicine through: (i) better prediction of individual drug metabolism, which will aid therapeutic decision-making; (ii) better understanding of genetics-microbiome interactions in drug metabolism; and (iii) greater drug efficacy through modulation of the gut microbiome.

Call for proposal

ERC-2020-COG
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Host institution

ACADEMISCH ZIEKENHUIS GRONINGEN
Address
Hanzeplein 1
9713 GZ Groningen
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 999 676

Beneficiaries (1)

ACADEMISCH ZIEKENHUIS GRONINGEN
Netherlands
EU contribution
€ 1 999 676
Address
Hanzeplein 1
9713 GZ Groningen
Activity type
Higher or Secondary Education Establishments