期刊
GUT MICROBES
卷 5, 期 2, 页码 233-238出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/gmic.27915
关键词
digoxin; Eggerthella lenta; RNA-scq; gnotobiotics; metagenomics; pharmacokinetics; human microbiome
资金
- National Institutes of Health [P50 GM068763]
- Harvard Digestive Diseases Center [2P30DK034854-26]
- Canadian Institutes of Health Research [MFE-112991]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK034854] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P50GM068763] Funding Source: NIH RePORTER
The human gut microbiota plays a key role in pharmacology, yet the mechanisms responsible remain unclear, impeding efforts toward personalized medicine. We recently identified a cytochrome-encoding operon in the common gut Actinobacterium Eggerthella lenta that is transcriptionally activated by the cardiac drug digoxin. These genes represent a predictive microbial biomarker for the inactivation of digoxin. Gnotobiotic mouse experiments revealed that increased protein intake can limit microbial drug inactivation. Here, we present a biochemical rationale for how the proteins encoded by this operon might inactivate digoxin through substrate promiscuity. We discuss digoxin signaling in eukaryotic systems, and consider the possibility that endogenous digoxin-like molecules may have selected for microbial digoxin inactivation. Finally, we highlight the diverse contributions of gut microbes to drug metabolism, present a generalized approach to studying microbe-drug interactions, and argue that mechanistic studies will pave the way for the clinical application of this work.
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