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http://hdl.handle.net/2440/109160
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Type: | Journal article |
Title: | Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats |
Author: | Hu, Y. Le Leu, R. Christophersen, C. Somashekar, R. Conlon, M. Meng, X. Winter, J. Woodman, R. McKinnon, R. Young, G. |
Citation: | Carcinogenesis, 2016; 37(4):366-375 |
Publisher: | Oxford University Press |
Issue Date: | 2016 |
ISSN: | 0143-3334 1460-2180 |
Statement of Responsibility: | Ying Hu, Richard K. Le Leu, Claus T. Christophersen, Roshini Somashekar, Michael A. Conlon, Xing Q. Meng, Jean M. Winter, Richard J. Woodman, Ross McKinnon and Graeme P. Young |
Abstract: | This study evaluated whether dietary resistant starch (RS) and green tea extract (GTE), which have anti-inflammatory and anticancer properties, protect against colitis-associated colorectal cancer (CAC) using a rat model, also investigated potential mechanisms of action of these agents including their effects on the gut microbiota. Rats were fed a control diet or diets containing 10% RS, 0.5% GTE or a combination of the two (RS + GTE). CAC was initiated with 2 weekly azoxymethane (AOM) injections (10mg/kg) followed by 2% dextran sodium sulphate in drinking water for 7 days after 2 weeks on diets. Rats were killed 20 weeks after the first AOM. Colon tissues and tumours were examined for histopathology by H&E, gene/protein expression by PCR and immunohistochemistry and digesta for analyses of fermentation products and microbiota populations. RS and RS + GTE (but not GTE) diets significantly (P< 0.05) decreased tumour multiplicity and adenocarcinoma formation, relative to the control diet. Effects of RS + GTE were not different from RS alone. RS diet caused significant shifts in microbial composition/diversity, with increases in Parabacteroides, Barnesiella, Ruminococcus, Marvinbryantia and Bifidobacterium as primary contributors to the shift. RS-containing diets increased short chain fatty acids (SCFA) and expression of the SCFA receptor GPR43 mRNA, and reduced inflammation (COX-2, NF-kB, TNF-α and IL-1β mRNA) and cell proliferation P< 0.05. GTE had no effect. This is the first study that demonstrates chemopreventive effects of RS (but not GTE) in a rodent CAC model, suggesting RS might have benefit to patients with ulcerative colitis who are at an increased risk of developing CRC. |
Keywords: | Resistant starch; colorectal cancer |
Rights: | © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
RMID: | 0030072210 |
DOI: | 10.1093/carcin/bgw019 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1007501 |
Appears in Collections: | Medicine publications |
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