Project Details
Projekt
Deciphering the impact of gut microbiome drug metabolism on therapy response in colorectal cancer
Applicants
Privatdozent Dr. Tianzuo Zhan; Dr. Maria Zimmermann
Subject Area
Gastroenterology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 537604907
The human gut microbiome is a complex ecosystem that can metabolise hundreds of clinically approved drugs. This bacterial drug metabolism can affect both pharmacodynamics and -kinetics of compounds, by biochemical (in-)activation and modification of their resorption and degradation. The impact of gut bacterial drug metabolism on pharmacotherapy of colorectal cancer (CRC) is poorly understood. In this project, we propose to combine computational and experimental microbiome research with expertise in translational and clinical gastrointestinal oncology to characterise gut microbiome drug metabolism in the context of cancer therapy. We hypothesise that gut microbiota metabolism significantly affects treatment response of fluoropyrimidines and multi-kinase inhibitors. We will perform metabolomic analysis of plasma and faecal samples to determine bacterial drug metabolites, use microbiome-drug culture experiments and bacterial genetics to pinpoint responsible strains and genes, and model the impact of bacterial drug metabolism using gnotobiotic mouse models. Furthermore, we will elucidate the biological effects of novel bacterial (drug) metabolites in CRC models. By integration of clinical data, this comprehensive approach will generate biomarkers for precision oncology, and uncover bacterial targets to ameliorate adverse effects or increase drug activity.
DFG Programme
Research Units
