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. In recent years, the gut microbiome (the trillions of micro-organisms that reside in the human gut) has been recognized as a vital “organ” that plays an important role in health and disease.
While evidence for the role of the gut microbiome in drug metabolism dates back to the 1930s, the rise of next-generation sequencing and new technologies to culture anaerobic bacteria have put the gut microbiome at the forefront of a new domain of personalized medicine in which genetics and the gut microbiome together can better predict drug response and optimize clinical outcomes. These advances mean that the microbiome can now be approached as a modifiable entity to enhance drug efficacy. However, the role of the gut microbiome in drug metabolism remains poorly understood, as do its interactions with host genetics and exogenous factors, a knowledge gap that greatly limits clinical application of approaches that target the microbiome.
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. The project will address important technical and clinical challenges in three innovative parts:
1) a population-based cohort study to better understand the interindividual difference in the gut microbiome and 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
3) an intervention trial using probiotics to achieve greater drug efficacy through modulation of the gut microbiome.
In summary, this project will lay the foundation for major advances in personalized medicine.
