Predicting and manipulating drug inactivation by the human gut microbiome

ABSTRACT: 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 re

ORGANISM(S): Eggerthella lenta DSM 2243

SUBMITTER: Peter Turnbaugh 

PROVIDER: E-GEOD-43919 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress