Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta
| Autor: | Henry J. Haiser, David B. Gootenberg, Gopal Sirasani, Kelly Chatman, Peter J. Turnbaugh, Emily P. Balskus |
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| Rok vydání: | 2013 |
| Předmět: |
Drug
Digoxin General Science & Technology media_common.quotation_subject Inbred Strains Mice Inbred Strains Eggerthella lenta Biology Arginine Cardiovascular Article Microbiology Feces Mice Pharmacokinetics In vivo Operon medicine Genetics Animals Humans Germ-Free Life Microbiome media_common Multidisciplinary digestive oral and skin physiology Gastrointestinal Microbiome Human Genome Bacterial Gene Expression Regulation Bacterial Gastrointestinal Tract Actinobacteria Gene Expression Regulation 5.1 Pharmaceuticals Toxicity Cytochromes Metagenome Dietary Proteins Development of treatments and therapeutic interventions Transcriptome Infection medicine.drug Biotechnology |
| Zdroj: | Science (New York, N.Y.), vol 341, iss 6143 |
| Popis: | Digoxin Dangers A proportion of patients treated with digoxin, a cardiac glycoside used to treat heart function abnormalities, generate the inactive metabolite, dihydrodigoxin, resulting in poor efficacy. Haiser et al. (p. 295 ) examined a potential culprit responsible for this transformation—the actinobacterium, Eggerthella lenta —to probe the microbiota-digoxin interaction. Microbe growth was promoted by arginine, and differential expression analysis revealed a two-gene cardiac glycoside reductase ( cgr ) operon that was induced by digoxin in low arginine conditions. Not all strains of E. lenta could reduce digoxin and, when fecal samples from healthy people were tested, a spectrum of digoxin inactivation was detected. When the digoxin-reducing strain of E. lenta was given to germ-free mice that were fed a high-protein (that is, high-arginine) diet, digoxin levels stayed high in serum, and drug inactivation was suppressed. |
| Databáze: | OpenAIRE |
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