Inhibition by Resistant Starch of Red Meat–Induced Promutagenic Adducts in Mouse Colon

Abstract

Population studies have shown that high red meat intake may increase colorectal cancer risk. Our aim was to examine the effect of different amounts and sources of dietary protein on induction of the promutagenic adduct O 6 -methyl-2-deoxyguanosine (O 6 MeG) in colonocytes, to relate these to markers of large bowel protein fermentation and ascertain whether increasing colonic carbohydrate fermentation modified these effects. Mice (n ¼ 72) were fed 15% or 30% protein as casein or red meat or 30% protein with 10% high amylose maize starch as the source of resistant starch. Genetic damage in distal colonocytes was detected by immunohistochemical staining for O 6 MeG and apoptosis. Feces were collected for measurement of pH, ammonia, phenols, p-cresol, and short-chain fatty acids (SCFA). O 6 MeG and fecal p-cresol concentrations were significantly higher with red meat than with casein (P < 0.018), with adducts accumulating in cells at the crypt apex. DNA adducts (P < 0.01) and apoptosis (P < 0.001) were lower and protein fermentation products (fecal ammonia, P < 0.05; phenol, P < 0.0001) higher in mice fed resistant starch. Fecal SCFA levels were also higher in mice fed resistant starch (P < 0.0001). This is the first demonstration that high protein diets increase promutagenic adducts (O 6 MeG) in the colon and dietary protein type seems to be the critical factor. The delivery of fermentable carbohydrate to the colon (as resistant starch) seems to switch from fermentation of protein to that of carbohydrate and a reduction in adduct formation, supporting previous observations that dietary resistant starch opposes the mutagenic effects of dietary red meat. Cancer Prev Res; 4(11); 1920-8. Ó2011 AACR.

Dietary Manipulation of Oncogenic MicroRNA Expression in Human Rectal Mucosa: A Randomized Trial

“…Rodent studies have shown that resistant starch can raise colonic butyrate levels, alter gut microbiota abundance, reduce adenocarcinoma formation in response to a carcinogen, and attenuate red meat-induced DNA damage (5,11,22,38). In this human study, supplementation with butyrylated resistant starch significantly raised fecal butyrate levels.…”

“…20 and 21). In rodents, resistant starch supplementation to an HRM diet increased colonic butyrate, altered gut microbiota, decreased inflammation, and attenuated red meat-induced DNA damage (3,5,22). HAMSB was more effective than standard amylose maize starch in lowering genetic damage (23).…”

Dietary Red Meat Aggravates Dextran Sulfate Sodium-Induced Colitis in Mice Whereas Resistant Starch Attenuates Inflammation

“…Increased dietary heme from haemoglobin in 299 red meat can form reactive oxygen species, [37] Sesink 300 et al [38] showed that dietary heme increases luminal 301 cytotoxicity which causes damage to the colonic 302 epithelium. Previous animal studies by us have also shown 303 that red meat consumption results in a thinning of the 304 colonic mucus layer and increases damage to the colono-305 cytes in the form of DNA strand breaks [39] or pro-306 mutagenic adducts [40]. 307 Mice consuming RS along with the red meat diet had 308 reduced clinical signs of colitis when compared to mice fed 309 only the red meat diet.…”

Association between red meat consumption and colon cancer: A systematic review of experimental results

“…68,69 The combination of heme-containing proteins as they occur in red meat was evaluated only in studies that provided meat. 21,22,59 Myoglobin is a ubiquitous and significant form of heme iron in red meat and the use of surrogates, such as hemin or isolated hemoglobin, are not equivalent to meat.…”