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Gut microbiome interactions with drug metabolism, efficacy, and toxicity

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Title: Gut microbiome interactions with drug metabolism, efficacy, and toxicity
Authors: Wilson, ID
Nicholson, JK
Item Type: Journal Article
Abstract: 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.
Issue Date: 13-Aug-2016
Date of Acceptance: 5-Aug-2016
URI: http://hdl.handle.net/10044/1/41044
DOI: https://dx.doi.org/10.1016/j.trsl.2016.08.002
ISSN: 1931-5244
Publisher: Elsevier
Start Page: 204
End Page: 222
Journal / Book Title: Translational Research
Volume: 179
Copyright Statement: © 2016 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Bacteria
Drug-Related Side Effects and Adverse Reactions
Gastrointestinal Microbiome
Humans
Pharmaceutical Preparations
Treatment Outcome
Xenobiotics
1103 Clinical Sciences
General Clinical Medicine
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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