Gut microbiota modulation of chemotherapy efficacy and toxicity.
File(s)
Accepted version
Author(s)
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.
Date Issued
2017-03-08
Date Acceptance
2017-03-01
Citation
Nature Reviews Gastroenterology and Hepatology, 2017, 14 (6), pp.356-365
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
Bowel & Cancer Research
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/28270698
PII: nrgastro.2017.20
Grant Number
N/A
Subjects
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
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2017-03-08