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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



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