Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial.

Richard K Le Leu,Claus T Christophersen,Ying Hu,Michael A Conlon,Karen J Humphreys,Anthony R Bird,Rosalind B Miller,Jean M Winter,David L Topping,Graeme P Young,Silvia W Gratz

doi:10.1017/s0007114515001750

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.

Highlights

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective
There was a significant increase in the rectal crypt O6MeG adduct load when the participants consumed the HRM diet first compared with all the other intervention stages (P, 0·01; see online Supplementary Fig. S2(A)); when the participants consumed the HRM þ butyrylated high-amylose maize starch (HAMSB) diet as the first intervention, there was no change in the O6MeG adduct load with the subsequent consumption of HRM (see online Supplementary Fig. S2(B))
We reported that feeding a diet rich in red meat to rodents can increase the level of the pro-mutagenic DNA adduct (O6MeG) in the colon, whereas co-consumption of a fermentable carbohydrate can reduce this effect[8]

Summary

Introduction

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. We examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P,0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG 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.

Methods

Results

Conclusion