Le Leu, R.Winter, J.Christophersen, C.Young, G.Humphreys, K.Hu, Y.Gratz, S.Miller, R.Topping, D.Bird, A.Conlon, M.2017-10-262017-10-262015British Journal of Nutrition, 2015; 114(2):220-2300007-11451475-2662http://hdl.handle.net/2440/109056Epidemiological 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.en© The Authors 2015. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.SCFA; butyrate; DNA adducts; resistant starch; red meat; fermentation; microbiotaJournal article003004069610.1017/S00071145150017500003590842000072-s2.0-849385563352-s2.0-84931346872192299Le Leu, R. [0000-0003-4704-4943]Winter, J. [0000-0002-2041-8602]