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Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics
Rachel N. Carmody, Peter J. Turnbaugh
Rachel N. Carmody, Peter J. Turnbaugh
Published October 1, 2014; First published August 8, 2014
Citation Information: J Clin Invest. 2014;124(10):4173-4181. https://doi.org/10.1172/JCI72335.
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Category: Review

Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics

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Abstract

Our associated microbial communities play a critical role in human health and predisposition to disease, but the degree to which they also shape therapeutic interventions is not well understood. Here, we integrate results from classic and current studies of the direct and indirect impacts of the gut microbiome on the metabolism of therapeutic drugs and diet-derived bioactive compounds. We pay particular attention to microbial influences on host responses to xenobiotics, adding to the growing consensus that treatment outcomes reflect our intimate partnership with the microbial world, and providing an initial framework from which to consider a more comprehensive view of pharmacology and nutrition.

Authors

Rachel N. Carmody, Peter J. Turnbaugh

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Figure 1

Gut microbial modulation of xenobiotic metabolism.

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Gut microbial modulation of xenobiotic metabolism.
Direct mechanisms inc...
Direct mechanisms include (i) production of active compounds, (ii) detoxification, and (iii) direct binding to bacterial cells. Indirect mechanisms involve microbial manipulation of host physiology. (iv) Microbial participation in enterohepatic cycling: (1) compounds are inactivated by conjugation in the liver; (2) the conjugated compound passes into bile and is excreted into the intestinal lumen; (3) microbial enzymes release the conjugate group, reactivating the compound; and (4) the active compound reenters circulation. (v) Altered expression of host genes involved in xenobiotic metabolism. (vi) Altered kinetics due to microbial metabolites competing with xenobiotics for enzyme binding sites. (vii) Microbial production of metabolic pathway intermediates. (viii) Stimulation of immune responses through translocation or inflammation.
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