Project description
Small microbes with big effects on drug metabolism
Why do individuals respond differently to the same dose of a drug? Several factors such as diet, comorbidities, age, sex, weight, and genetics are responsible for this variation, but the gut microbiota is also emerging as a key player. The EU-funded BugDrug project aims to understand how gut bacteria impact drug metabolism along the gut-liver axis. Researchers will combine different novel approaches, including systematic analysis of large human cohorts, personalised in-vitro drug tests using organ-on-a-chip, and clinical probiotics intervention. Results will lay the foundation for microbiota-based personalised strategies that can fine-turn the metabolism, efficacy, and safety of drugs.
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.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
9713 GZ Groningen
Netherlands