Wilson Ian D, Nicholson Jeremy K
Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK.
Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK.
Transl Res. 2017 Jan;179:204-222. doi: 10.1016/j.trsl.2016.08.002. Epub 2016 Aug 13.
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.
肠道微生物群对药物和外源性物质的代谢具有直接和间接影响，这可能对疗效和毒性都产生影响。事实上，微生物群驱动的药物代谢对于某些前药的活化至关重要，例如，百浪多息和新百浪多息等偶氮药物会导致磺胺的释放。除了提供还原代谢能力的主要来源外，肠道微生物群还提供一系列其他反应，包括乙酰化、脱酰基、脱羧、脱羟基、去甲基化、脱卤，重要的是，在某些类型的药物相关毒性情况下，还有共轭物水解反应。除了直接影响外，肠道微生物群还可通过例如调节宿主药物代谢和处置以及细菌衍生代谢物对外源性物质代谢途径的竞争来间接影响药物代谢和毒性。当然，治疗药物本身也会产生预期和非预期的效果，这可能会影响肠道微生物群的健康和组成，产生不可预见的后果。
