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Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease

Despite the growing number of new drugs approved for the treatment of inflammatory bowel disease (IBD), the long-term clinical use of thiopurine therapy and the well-known properties of conventional drugs including azathioprine have made their place in IBD therapy extremely valuable. Despite the fac...

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Autores principales: Lazarević, Slavica, Đanic, Maja, Al-Salami, Hani, Mooranian, Armin, Mikov, Momir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016117/
https://www.ncbi.nlm.nih.gov/pubmed/35450035
http://dx.doi.org/10.3389/fphar.2022.879170
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author Lazarević, Slavica
Đanic, Maja
Al-Salami, Hani
Mooranian, Armin
Mikov, Momir
author_facet Lazarević, Slavica
Đanic, Maja
Al-Salami, Hani
Mooranian, Armin
Mikov, Momir
author_sort Lazarević, Slavica
collection PubMed
description Despite the growing number of new drugs approved for the treatment of inflammatory bowel disease (IBD), the long-term clinical use of thiopurine therapy and the well-known properties of conventional drugs including azathioprine have made their place in IBD therapy extremely valuable. Despite the fact that thiopurine S-methyltransferase (TPMT) polymorphism has been recognized as a major cause of the interindividual variability in the azathioprine response, recent evidence suggests that there might be some yet unknown causes which complicate dosing strategies causing either failure of therapy or toxicity. Increasing evidence suggests that gut microbiota, with its ability to release microbial enzymes, affects the pharmacokinetics of numerous drugs and subsequently drastically alters clinical effectiveness. Azathioprine, as an orally administered drug which has a complex metabolic pathway, is the prime illustrative candidate for such microbial metabolism of drugs. Comprehensive databases on microbial drug-metabolizing enzymes have not yet been generated. This study provides insights into the current evidence on microbiota-mediated metabolism of azathioprine and systematically accumulates findings of bacteria that possess enzymes required for the azathioprine biotransformation. Additionally, it proposes concepts for the identification of gut bacteria species responsible for the metabolism of azathioprine that could aid in the prediction of dose-response effects, complementing pharmacogenetic approaches already applied in the optimization of thiopurine therapy of IBD. It would be of great importance to elucidate to what extent microbiota-mediated metabolism of azathioprine contributes to the drug outcomes in IBD patients which could facilitate the clinical implementation of novel tools for personalized thiopurine treatment of IBD.
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spelling pubmed-90161172022-04-20 Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease Lazarević, Slavica Đanic, Maja Al-Salami, Hani Mooranian, Armin Mikov, Momir Front Pharmacol Pharmacology Despite the growing number of new drugs approved for the treatment of inflammatory bowel disease (IBD), the long-term clinical use of thiopurine therapy and the well-known properties of conventional drugs including azathioprine have made their place in IBD therapy extremely valuable. Despite the fact that thiopurine S-methyltransferase (TPMT) polymorphism has been recognized as a major cause of the interindividual variability in the azathioprine response, recent evidence suggests that there might be some yet unknown causes which complicate dosing strategies causing either failure of therapy or toxicity. Increasing evidence suggests that gut microbiota, with its ability to release microbial enzymes, affects the pharmacokinetics of numerous drugs and subsequently drastically alters clinical effectiveness. Azathioprine, as an orally administered drug which has a complex metabolic pathway, is the prime illustrative candidate for such microbial metabolism of drugs. Comprehensive databases on microbial drug-metabolizing enzymes have not yet been generated. This study provides insights into the current evidence on microbiota-mediated metabolism of azathioprine and systematically accumulates findings of bacteria that possess enzymes required for the azathioprine biotransformation. Additionally, it proposes concepts for the identification of gut bacteria species responsible for the metabolism of azathioprine that could aid in the prediction of dose-response effects, complementing pharmacogenetic approaches already applied in the optimization of thiopurine therapy of IBD. It would be of great importance to elucidate to what extent microbiota-mediated metabolism of azathioprine contributes to the drug outcomes in IBD patients which could facilitate the clinical implementation of novel tools for personalized thiopurine treatment of IBD. Frontiers Media S.A. 2022-04-05 /pmc/articles/PMC9016117/ /pubmed/35450035 http://dx.doi.org/10.3389/fphar.2022.879170 Text en Copyright © 2022 Lazarević, Đanic, Al-Salami, Mooranian and Mikov. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lazarević, Slavica
Đanic, Maja
Al-Salami, Hani
Mooranian, Armin
Mikov, Momir
Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease
title Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease
title_full Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease
title_fullStr Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease
title_full_unstemmed Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease
title_short Gut Microbiota Metabolism of Azathioprine: A New Hallmark for Personalized Drug-Targeted Therapy of Chronic Inflammatory Bowel Disease
title_sort gut microbiota metabolism of azathioprine: a new hallmark for personalized drug-targeted therapy of chronic inflammatory bowel disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016117/
https://www.ncbi.nlm.nih.gov/pubmed/35450035
http://dx.doi.org/10.3389/fphar.2022.879170
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