title: 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.
authors.affiliation: Flinders Centre for Innovation in Cancer , Flinders University of South Australia , Bedford Park , South Australia , Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University of South Australia, Bedford Park, South Australia, Australia.|CSIRO Food and Nutrition, Adelaide, South Australia, Australia.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Le Leu
authors.affiliation: CSIRO Food and Nutrition, Adelaide, South Australia, Australia.|School of Medical and Health Science, Edith Cowan University, Western Australia, Australia, and.
authors.forename: Claus T
authors.initials: CT
authors.lastname: Christophersen
authors.affiliation: Flinders Centre for Innovation in Cancer , Flinders University of South Australia , Bedford Park , South Australia , Australia.
authors.forename: Roshini
authors.initials: R
authors.lastname: Somashekar
authors.affiliation: CSIRO Food and Nutrition , Adelaide , South Australia , Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Conlon
authors.affiliation: Biostatistics, Flinders Prevention, Promotion and Primary Health Care , General Practice , Flinders University of South Australia , Bedford Park , South Australia , Australia.
authors.forename: Xing Q
authors.initials: XQ
authors.lastname: Meng
authors.affiliation: Flinders Centre for Innovation in Cancer , Flinders University of South Australia , Bedford Park , South Australia , Australia.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Winter
authors.affiliation: Biostatistics, Flinders Prevention, Promotion and Primary Health Care , General Practice , Flinders University of South Australia , Bedford Park , South Australia , Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Woodman
authors.affiliation: Flinders Centre for Innovation in Cancer , Flinders University of South Australia , Bedford Park , South Australia , Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: McKinnon
authors.affiliation: Flinders Centre for Innovation in Cancer , Flinders University of South Australia , Bedford Park , South Australia , Australia.
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
mesh_terms: D000818:Animals; D003092:Colitis / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D007422:Intestines / Q000382:microbiology*; D051381:Rats; D013213:Starch / Q000378:metabolism*
chemical_list: D013213:Starch