The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism
Key Points The gut microbiome is a neglected component of the first-pass metabolism of xenobiotics before reaching the general circulation. Direct microbial metabolism of xenobiotics and their metabolites often involves reduction or hydrolysis, but most of the enzymes responsible for these reactions...
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| Published in | Nature reviews. Microbiology Vol. 14; no. 5; pp. 273 - 287 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.05.2016
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Key Points
The gut microbiome is a neglected component of the first-pass metabolism of xenobiotics before reaching the general circulation.
Direct microbial metabolism of xenobiotics and their metabolites often involves reduction or hydrolysis, but most of the enzymes responsible for these reactions remain unknown.
Microbial metabolism influences both efficacy and toxicity, producing bioactive compounds, inactive metabolites and toxins.
Relevant host–microbial interactions include the expression of host genes that are involved in drug transport and metabolism, the interference with host enzymatic activity and the modulation of immune responses.
The translational implications of these studies include the development of novel co-therapies and the identification of new biomarkers and drugs.
In this Review, Turnbaugh and colleagues discuss several mechanisms by which the human gut microbiome affects the metabolism of xenobiotics, including drugs and dietary compounds, and explore how this knowledge can be applied to improve the treatment of human disease.
Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that have shed light on the mechanisms that link the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and for the development of a new generation of therapeutics based on, or targeted at, the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within. |
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| AbstractList | Although the significance of human genetic polymorphisms in therapeutic outcomes is well established, the importance of our “second genome” (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that shed light on the mechanisms linking the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and the development of a next generation of therapeutics based on or targeted at the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within. Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that have shed light on the mechanisms that link the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and for the development of a new generation of therapeutics based on, or targeted at, the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within. Key Points The gut microbiome is a neglected component of the first-pass metabolism of xenobiotics before reaching the general circulation. Direct microbial metabolism of xenobiotics and their metabolites often involves reduction or hydrolysis, but most of the enzymes responsible for these reactions remain unknown. Microbial metabolism influences both efficacy and toxicity, producing bioactive compounds, inactive metabolites and toxins. Relevant host–microbial interactions include the expression of host genes that are involved in drug transport and metabolism, the interference with host enzymatic activity and the modulation of immune responses. The translational implications of these studies include the development of novel co-therapies and the identification of new biomarkers and drugs. In this Review, Turnbaugh and colleagues discuss several mechanisms by which the human gut microbiome affects the metabolism of xenobiotics, including drugs and dietary compounds, and explore how this knowledge can be applied to improve the treatment of human disease. Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that have shed light on the mechanisms that link the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and for the development of a new generation of therapeutics based on, or targeted at, the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within. Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that have shed light on the mechanisms that link the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and for the development of a new generation of therapeutics based on, or targeted at, the gut microbiome. Indeed, the admirable goal of precision medicine may reguire us to first understand the microbial pharmacists within. Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that have shed light on the mechanisms that link the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and for the development of a new generation of therapeutics based on, or targeted at, the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within.Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that have shed light on the mechanisms that link the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and for the development of a new generation of therapeutics based on, or targeted at, the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within. |
| Audience | Academic |
| Author | Bess, Elizabeth N. Spanogiannopoulos, Peter Carmody, Rachel N. Turnbaugh, Peter J. |
| AuthorAffiliation | 1 Department of Microbiology & Immunology, G.W. Hooper Foundation, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143, USA |
| AuthorAffiliation_xml | – name: 1 Department of Microbiology & Immunology, G.W. Hooper Foundation, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143, USA |
| Author_xml | – sequence: 1 givenname: Peter surname: Spanogiannopoulos fullname: Spanogiannopoulos, Peter organization: Department of Microbiology & Immunology, George Williams Hooper Foundation, University of California San Francisco – sequence: 2 givenname: Elizabeth N. surname: Bess fullname: Bess, Elizabeth N. organization: Department of Microbiology & Immunology, George Williams Hooper Foundation, University of California San Francisco – sequence: 3 givenname: Rachel N. surname: Carmody fullname: Carmody, Rachel N. organization: Department of Microbiology & Immunology, George Williams Hooper Foundation, University of California San Francisco – sequence: 4 givenname: Peter J. surname: Turnbaugh fullname: Turnbaugh, Peter J. email: peter.turnbaugh@ucsf.edu organization: Department of Microbiology & Immunology, George Williams Hooper Foundation, University of California San Francisco |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26972811$$D View this record in MEDLINE/PubMed |
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| PublicationTitle | Nature reviews. Microbiology |
| PublicationTitleAbbrev | Nat Rev Microbiol |
| PublicationTitleAlternate | Nat Rev Microbiol |
| PublicationYear | 2016 |
| Publisher | Nature Publishing Group UK Nature Publishing Group |
| Publisher_xml | – name: Nature Publishing Group UK – name: Nature Publishing Group |
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The gut microbiome is a neglected component of the first-pass metabolism of xenobiotics before reaching the general circulation.
Direct microbial... Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of our 'second genome' (the microbiome) has been... Although the significance of human genetic polymorphisms in therapeutic outcomes is well established, the importance of our “second genome” (the microbiome)... |
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| SubjectTerms | 631/326/22 631/326/2565/2134 631/326/41/2142 Animals Diet Drug Therapy Gastrointestinal Microbiome - physiology Genetic polymorphisms Health aspects Humans Immune System - physiology Infectious Diseases Innovations Life Sciences Medical Microbiology Metabolome Metagenome Microbiology Microbiota (Symbiotic organisms) Molecular targeted therapy Parasitology Pharmaceutical Preparations - metabolism Pharmacogenetics review-article Toxins Virology Xenobiotics Xenobiotics - metabolism |
| Title | The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism |
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