@article{fb050efd68154352905392a5cab6b219,
title = "Personalized Mapping of Drug Metabolism by the Human Gut Microbiome",
abstract = "The human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities. Dozens of drugs have been shown to be metabolized by single isolates from the gut microbiome, but the extent of this phenomenon is rarely explored in the context of microbial communities. Here, we develop a quantitative experimental framework for mapping the ability of the human gut microbiome to metabolize small molecule drugs: Microbiome-Derived Metabolism (MDM)-Screen. Included are a batch culturing system for sustained growth of subject-specific gut microbial communities, an ex vivo drug metabolism screen, and targeted and untargeted functional metagenomic screens to identify microbiome-encoded genes responsible for specific metabolic events. Our framework identifies novel drug-microbiome interactions that vary between individuals and demonstrates how the gut microbiome might be used in drug development and personalized medicine.",
keywords = "drug metabolism, drug-microbiome interactions, functional metagenomics, gut microbiome, microbial community, personalized medicine",
author = "Bahar Javdan and Lopez, {Jaime G.} and Pranatchareeya Chankhamjon and Lee, {Ying Chiang J.} and Raphaella Hull and Qihao Wu and Xiaojuan Wang and Seema Chatterjee and Donia, {Mohamed S.}",
note = "Funding Information: We would like to thank Wei Wang and the Lewis Sigler Institute sequencing core facility for assistance with HT sequencing; Matthew Cahn and Abhishek Biswas for assistance with sequencing data analysis; Shuo Wang for assistance with the functional group analysis; Joseph Koos, A. James Link, and Yuki Sugimoto for assistance with Mass Spectrometry; Riley Skeen-Gaar for assistance with statistical analysis; Joseph Sheehan and Zemer Gitai for assistance with obtaining the Keio library mutants; the Laboratory Animal Resources at Princeton University for assistance with mouse studies; Janie Kim for illustrating the graphical abstract; and members of the Donia lab for useful discussions. We are grateful to the 21 anonymous donors who provided the fecal samples that made this project possible. Figure S6 and a part of Figure 7 were created with BioRender.com. Funding for this project has been provided by an Innovation Award from the Department of Molecular Biology, Princeton University and an NIH Director{\textquoteright}s New Innovator Award ( 1DP2AI124441 ), both to M.S.D. B.J. is funded by a New Jersey Commission on Cancer Research Pre-doctoral award ( DFHS18PPC056 ), Y.-C.J.L. is funded by a training grant from the National Institute of General Medicine Sciences ( T32GM007388 ), and J.G.L. is funded by a National Science Foundation Graduate Research Fellowship ( 2017249408 ). Funding Information: We would like to thank Wei Wang and the Lewis Sigler Institute sequencing core facility for assistance with HT sequencing; Matthew Cahn and Abhishek Biswas for assistance with sequencing data analysis; Shuo Wang for assistance with the functional group analysis; Joseph Koos, A. James Link, and Yuki Sugimoto for assistance with Mass Spectrometry; Riley Skeen-Gaar for assistance with statistical analysis; Joseph Sheehan and Zemer Gitai for assistance with obtaining the Keio library mutants; the Laboratory Animal Resources at Princeton University for assistance with mouse studies; Janie Kim for illustrating the graphical abstract; and members of the Donia lab for useful discussions. We are grateful to the 21 anonymous donors who provided the fecal samples that made this project possible. Figure S6 and a part of Figure 7 were created with BioRender.com. Funding for this project has been provided by an Innovation Award from the Department of Molecular Biology, Princeton University and an NIH Director's New Innovator Award (1DP2AI124441), both to M.S.D. B.J. is funded by a New Jersey Commission on Cancer Research Pre-doctoral award (DFHS18PPC056), Y.-C.J.L. is funded by a training grant from the National Institute of General Medicine Sciences (T32GM007388), and J.G.L. is funded by a National Science Foundation Graduate Research Fellowship (2017249408). M.S.D. conceived and directed the research, designed the study, and obtained funding. P.C. and B.J. performed the PD culturing and screening experiments. B.J. performed the D1-D20 culturing and screening experiments. P.C. B.J. Q.W. X.W. and M.S.D. analyzed the PD screening data and characterized the new metabolites. J.G.L. performed the statistical, computational, metabolomic, and quantitative analyses. R.H. and Y.-C.J.L. performed the functional metagenomic screening experiments. S.C. isolated metagenomic DNA and RNA and prepared them for sequencing. M.S.D, B.J. and J.G.L. wrote the manuscript, with input from all authors. M.S.D. is a member of the scientific advisory board of DeepBiome Therapeutics. A patent is being filed by Princeton University for the use of quantitative MDM-Screen to measure inter-individual variability in drug metabolism. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = jun,
day = "25",
doi = "10.1016/j.cell.2020.05.001",
language = "English (US)",
volume = "181",
pages = "1661--1679.e22",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}