title: Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial.
abstract: Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O(6)-methyl-2-deoxyguanosine (O(6)MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O(6)MeG adducts relative to its baseline by 21% (P < 0.01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P < 0.001) and HRM + HAMSB (P < 0.05) diets when compared with their respective baseline levels, but was lower following the HRM + HAMSB diet compared with the HRM diet (P < 0.05). Relative to its baseline, the HRM + HAMSB diet increased the excretion of SCFA by over 20% (P < 0.05) and increased the absolute abundances of the Clostridium coccoides group (P < 0.05), the Clostridium leptum group (P < 0.05), Lactobacillus spp. (P < 0.01), Parabacteroides distasonis (P < 0.001) and Ruminococcus bromii (P < 0.05), but lowered Ruminococcus torques (P < 0.05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P < 0.01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O(6)MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation (CSIRO), Food and Nutrition Flagship,PO Box 10041,Adelaide BC,SA5000,Australia.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Le Leu
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University of South Australia,Bedford Park,SA5042,Australia.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Winter
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation (CSIRO), Food and Nutrition Flagship,PO Box 10041,Adelaide BC,SA5000,Australia.
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,SA5042,Australia.
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University of South Australia,Bedford Park,SA5042,Australia.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Humphreys
authors.affiliation: Flinders Centre for Innovation in Cancer, Flinders University of South Australia,Bedford Park,SA5042,Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen,AberdeenAB21 9SB,UK.
authors.forename: Silvia W
authors.initials: SW
authors.lastname: Gratz
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation Mathematics, Informatics and Statistics,Glen Osmond,SA5064,Australia.
authors.forename: Rosalind B
authors.initials: RB
authors.lastname: Miller
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation (CSIRO), Food and Nutrition Flagship,PO Box 10041,Adelaide BC,SA5000,Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Topping
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation (CSIRO), Food and Nutrition Flagship,PO Box 10041,Adelaide BC,SA5000,Australia.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Bird
authors.affiliation: Commonwealth Scientific and Industrial Research Organisation (CSIRO), Food and Nutrition Flagship,PO Box 10041,Adelaide BC,SA5000,Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Conlon
mesh_terms: D000688:Amylose / Q000737:chemistry; D000818:Animals; D001439:Bacteroides / Q000302:isolation & purification; D002417:Cattle; D003013:Clostridium / Q000302:isolation & purification; D003106:Colon / Q000382:microbiology; D003296:Cooking; D018592:Cross-Over Studies; D018736:DNA Adducts; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004032:Diet; D015930:Diet Records; D004311:Double-Blind Method; D002149:Energy Intake; D004926:Escherichia coli / Q000302:isolation & purification; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D006801:Humans; D007778:Lactobacillus / Q000302:isolation & purification; D008297:Male; D008460:Meat / Q000009:adverse effects*; D064307:Microbiota; D008875:Middle Aged; D045857:Ruminococcus / Q000302:isolation & purification; D013213:Starch / Q000737:chemistry*; D003313:Zea mays / Q000737:chemistry
chemical_list: D018736:DNA Adducts; D013213:Starch; D000688:Amylose; C015558:O(6)-methyl-2'-deoxyguanosine; D003849:Deoxyguanosine
keywords: Butyrate; DNA adducts; Fermentation; Microbiota; Red meat; Resistant starch; SCFA