Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats

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.

RAS ID

20761

Document Type

Journal Article

Date of Publication

2016

School

School of Medical and Health Sciences

Copyright

free_to_read

Publisher

Oxford

Comments

Hu, Y., Le Leu, R. K., Christophersen, C. T., Somashekar, R., Conlon, M. A., Meng, X. Q., ... & Young, G. P. (2016). Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats. Carcinogenesis, 37(4), 366-375. Available here.

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Link to publisher version (DOI)

10.1093/carcin/bgw019