E-GEOD-43919 - Predicting and manipulating drug inactivation by the human gut microbiome

Status
Released on 15 June 2013, last updated on 4 July 2013
Organism
Eggerthella lenta DSM 2243
Samples (22)
Protocols (4)
Description
The trillions of microorganisms in the human gastrointestinal tract are an underexplored aspect of pharmacology. Despite numerous examples of microbial effects on drug efficacy and toxicity, there is often an incomplete understanding of the underlying mechanisms. Here, we dissect the inactivation of the commonly prescribed cardiac glycoside, digoxin, by Eggerthella lenta. Whole genome transcriptional profiling, comparative genomics, and culture-based assays revealed a cytochrome-encoding operon up-regulated by digoxin, absent in non-metabolizing E. lenta strains, and predictive of the efficiency of digoxin inactivation by the human gut microbiome. Digoxin inactivation was further enhanced by microbial interactions and inhibited by arginine. Pharmacokinetic studies using gnotobiotic mice revealed that increasing dietary protein reduces the in vivo metabolism of digoxin by E. lenta, with significant changes to drug concentration in the urine and serum. These results emphasize the importance of viewing pharmacology from the perspective of both our human and microbial genomes. RNA-Seq analysis of Eggerthella lenta cultured with or without digoxin.
Experiment type
RNA-seq of coding RNA 
Contacts
Peter James Turnbaugh <pturnbaugh@fas.harvard.edu>, Henry J Haiser, Peter J Turnbaugh
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-43919.idf.txt
Sample and data relationshipE-GEOD-43919.sdrf.txt
Processed data (1)E-GEOD-43919.processed.1.zip
Links