Gut microbiome interactions with drug metabolism, efficacy, and toxicity
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- 作者：Ian D. Wilson ; ianwilsonprof@gmail.com ; Jeremy K. Nicholson
- 关键词：ADMET ; absorption ; distribution ; metabolism ; excretion ; toxicity ; AHR ; aryl hydrocarbon receptor ; AUC ; area under the curve ; BVU ; (E)-5-(2-bromovinyl) uracil ; CAR ; constitutive androstane receptor ; cMOAT ; Canalicular multispecific organic anion transporter 1 ; cgr ; cardiac glycoside reductase ; CYP450s ; cytochromes P450 ; DPD ; dihydropyrimidine dehydrogenase ; DNA ; deoxyribonucleic acid ; EPHXs ; epoxide hydrolases ; DMI&rsquo ; s ; drug-microbiome interactions ; FDA ; Food and Drug Administration ; GF ; germ
- 刊名：Translational Research
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：179
- 期：Complete
- 页码：204-222
- 全文大小：503 K
- 卷排序：179
文摘
The gut microbiota has both direct and indirect effects on drug and xenobiotic metabolisms, and this can have consequences for both efficacy and toxicity. Indeed, microbiome-driven drug metabolism is essential for the activation of certain prodrugs, for example, azo drugs such as prontosil and neoprontosil resulting in the release of sulfanilamide. In addition to providing a major source of reductive metabolizing capability, the gut microbiota provides a suite of additional reactions including acetylation, deacylation, decarboxylation, dehydroxylation, demethylation, dehalogenation, and importantly, in the context of certain types of drug-related toxicity, conjugates hydrolysis reactions. In addition to direct effects, the gut microbiota can affect drug metabolism and toxicity indirectly via, for example, the modulation of host drug metabolism and disposition and competition of bacterial-derived metabolites for xenobiotic metabolism pathways. Also, of course, the therapeutic drugs themselves can have effects, both intended and unwanted, which can impact the health and composition of the gut microbiota with unforeseen consequences.