A new approach that directly measures the ability of the collective human gut microbiome to metabolize drugs promises to inform future drug design and guide efforts for personalized medicine.
The system evaluates how the microbial community in the intestines chemically transforms or metabolizes oral medications in ways that impact the drugs' safety and efficacy. The new methodology provides a more complete picture of how gut bacteria affect drug safety and performance, and could aid the development of new drugs that are more effective, have fewer side effects, and are personalized to an individual’s microbiome.
The human gut microbiome is composed of hundreds of individual species of bacteria and varies greatly between individuals. Bacteria isolated from the gut microbiome can directly metabolize clinically used drugs, with important effects on toxicity or effectiveness. However, these contributions to drug pharmacokinetics have not been taken into account in the drug-development pipeline.
The microbiome-derived metabolism quantitative screen (MDM-QScreen) provides a measure of individual variability in the drug metabolism, degradation and metabolite formation. The screen could be used to inform drug design, enabling undesired effects on the drug by the microbiome to be discovered and eliminated early in the process. For drugs already in use, the screen could explain variability in drug response or toxicity.
The approach could also help personalize treatment according to the microbiome of each patient, predicting how a drug will behave and enabling changes to the therapeutic strategy if undesired effects are predicted.
"This approach allows us to gain a more comprehensive and realistic view of the microbiome’s contribution to drug metabolism." – Mohamed Abou Donia
Mohamed Abou Donia, Associate Professor of Molecular Biology
Bahar Javdan, Graduate Student in the Princeton-Rutgers M.D./Ph.D. Program
Jaime Lopez, Graduate Student in the Lewis-Sigler Institute for Integrative Genomics
Pranatchareeya Chankhamjoh, Qihao Wu and Xiaojuan Wang, Postdoctoral Research Associates;
Ying-Chiang J. Lee, Graduate Student in Molecular Biology;
Raphaella Hull, Oxford-Princeton Exchange Student;
Seema Chatterjee, Research Lab Manager
Patent protection is pending. Princeton is seeking outside interest for the development of this technology.
National Institutes of Health, National Science Foundation, New Jersey Commission on Cancer
Office of Technology Licensing