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Gut microbiota modulation of chemotherapy efficacy and toxicity.
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Title: | Gut microbiota modulation of chemotherapy efficacy and toxicity. |
Authors: | Alexander, JL Wilson, ID Teare, J Marchesi, JR Nicholson, JK Kinross, JM |
Item Type: | Journal Article |
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. |
Issue Date: | 8-Mar-2017 |
Date of Acceptance: | 1-Mar-2017 |
URI: | http://hdl.handle.net/10044/1/77636 |
DOI: | 10.1038/nrgastro.2017.20 |
ISSN: | 1759-5045 |
Publisher: | Nature Research (part of Springer Nature) |
Start Page: | 356 |
End Page: | 365 |
Journal / Book Title: | Nature Reviews Gastroenterology and Hepatology |
Volume: | 14 |
Issue: | 6 |
Sponsor/Funder: | Bowel & Cancer Research |
Funder's Grant Number: | N/A |
Keywords: | Science & Technology Life Sciences & Biomedicine Gastroenterology & Hepatology CANCER DRUG TOXICITY INDUCED GASTROINTESTINAL MUCOSITIS ACUTE MYELOID-LEUKEMIA COLON-CANCER COLORECTAL-CANCER INTESTINAL MICROBIOTA CYTOSTATIC ACTIVITY ANTITUMOR IMMUNITY FECAL MICROBIOTA ADVERSE EVENTS Animals Anti-Bacterial Agents Antineoplastic Agents Bacterial Infections Bacterial Translocation Biodiversity Biomarkers CTLA-4 Antigen Diet Disease Models, Animal Forecasting Gastrointestinal Diseases Gastrointestinal Microbiome Humans Immunomodulation Immunotherapy Mice Neoplasms Prebiotics Probiotics Programmed Cell Death 1 Receptor Synbiotics Synthetic Biology Animals Humans Mice Bacterial Infections Neoplasms Gastrointestinal Diseases Disease Models, Animal Antineoplastic Agents Anti-Bacterial Agents Immunotherapy Diet Biodiversity Bacterial Translocation Forecasting Probiotics Prebiotics Immunomodulation Synthetic Biology Synbiotics CTLA-4 Antigen Programmed Cell Death 1 Receptor Biomarkers Gastrointestinal Microbiome Animals Anti-Bacterial Agents Antineoplastic Agents Bacterial Infections Bacterial Translocation Biodiversity Biomarkers CTLA-4 Antigen Diet Disease Models, Animal Forecasting Gastrointestinal Diseases Gastrointestinal Microbiome Humans Immunomodulation Immunotherapy Mice Neoplasms Prebiotics Probiotics Programmed Cell Death 1 Receptor Synbiotics Synthetic Biology Gastroenterology & Hepatology 1101 Medical Biochemistry and Metabolomics 1103 Clinical Sciences |
Publication Status: | Published |
Conference Place: | England |
Online Publication Date: | 2017-03-08 |
Appears in Collections: | Department of Surgery and Cancer |