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Gut microbiota modulation of chemotherapy efficacy and toxicity

Alexander, James L., Wilson, Ian D., Teare, Julian, Marchesi, Julian Roberto, Nicholson, Jeremy K. and Kinross, James M. 2017. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nature Reviews Gastroenterology & Hepatology 14 (6) , pp. 356-365. 10.1038/nrgastro.2017.20

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Abstract

Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Uncontrolled Keywords: Cancer Chemotherapy Microbiome Microbiota
Additional Information: PDF uploaded in accordance with Publisher's polices at http://www.sherpa.ac.uk/romeo/issn/1759-5045/ (accessed 5.5.17).
Publisher: Nature
ISSN: 1759-5045
Date of First Compliant Deposit: 5 May 2017
Date of Acceptance: 8 March 2017
Last Modified: 12 Oct 2017 05:31
URI: http://orca.cf.ac.uk/id/eprint/100186

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