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      Butyrylated starch intake can prevent red meat-induced O 6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial

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          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 6MeG) 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 6MeG 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 6MeG 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.

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          Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides.

          Resistant starch (RS) is starch and products of its small intestinal digestion that enter the large bowel. It occurs for various reasons including chemical structure, cooking of food, chemical modification, and food mastication. Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFA stimulate colonic blood flow and fluid and electrolyte uptake. Butyrate is a preferred substrate for colonocytes and appears to promote a normal phenotype in these cells. Fermentation of some RS types favors butyrate production. Measurement of colonic fermentation in humans is difficult, and indirect measures (e.g., fecal samples) or animal models have been used. Of the latter, rodents appear to be of limited value, and pigs or dogs are preferable. RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate. RS is a prebiotic, but knowledge of its other interactions with the microflora is limited. The contribution of RS to fermentation and colonic physiology seems to be greater than that of NSP. However, the lack of a generally accepted analytical procedure that accommodates the major influences on RS means this is yet to be established.
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            Bile salt biotransformations by human intestinal bacteria.

            Secondary bile acids, produced solely by intestinal bacteria, can accumulate to high levels in the enterohepatic circulation of some individuals and may contribute to the pathogenesis of colon cancer, gallstones, and other gastrointestinal (GI) diseases. Bile salt hydrolysis and hydroxy group dehydrogenation reactions are carried out by a broad spectrum of intestinal anaerobic bacteria, whereas bile acid 7-dehydroxylation appears restricted to a limited number of intestinal anaerobes representing a small fraction of the total colonic flora. Microbial enzymes modifying bile salts differ between species with respect to pH optima, enzyme kinetics, substrate specificity, cellular location, and possibly physiological function. Crystallization, site-directed mutagenesis, and comparisons of protein secondary structure have provided insight into the mechanisms of several bile acid-biotransforming enzymatic reactions. Molecular cloning of genes encoding bile salt-modifying enzymes has facilitated the understanding of the genetic organization of these pathways and is a means of developing probes for the detection of bile salt-modifying bacteria. The potential exists for altering the bile acid pool by targeting key enzymes in the 7alpha/beta-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.
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              Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria.

              Mucosa-associated bacteria are increased in inflammatory bowel disease (IBD), which suggests the possibility of an increased source of digestible endogenous mucus substrate. We hypothesized that mucolytic bacteria are increased in IBD, providing increased substrate to sustain nonmucolytic mucosa-associated bacteria. Mucolytic bacteria were characterized by the ability to degrade human secretory mucin (MUC2) in pure and mixed anaerobic cultures. Real-time PCR was used to enumerate mucosa-associated mucolytic bacteria in 46 IBD and 20 control patients. Bacterial mucolytic activity was tested in vitro using purified human MUC2. We confirm increased total mucosa-associated bacteria 16S rRNA gene in macroscopically and histologically normal intestinal epithelium of both Crohn's disease (CD) (mean 1.9-fold) and ulcerative colitis (UC) (mean 1.3-fold). We found a disproportionate increase in some mucolytic bacteria. Mean Ruminococcus gnavus were increased >4-fold and Ruminococcus torques ∼100-fold in macroscopically and histologically normal intestinal epithelium of both CD and UC. The most abundantly detected mucolytic bacterium in controls, Akkermansia muciniphila, was reduced many fold in CD and in UC. Coculture of A. muciniphila with MUC2 as the sole carbon source led to reduction in its abundance while it augmented growth of other bacteria. Mucolytic bacteria are present in healthy humans, where they are an integral part of the mucosa-associated bacterial consortium. The disproportionate increase in R. gnavus and R. torques could explain increased total mucosa-associated bacteria in IBD.
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                Author and article information

                Journal
                Br J Nutr
                Br. J. Nutr
                BJN
                The British Journal of Nutrition
                Cambridge University Press (Cambridge, UK )
                0007-1145
                1475-2662
                28 July 2015
                17 June 2015
                : 114
                : 2
                : 220-230
                Affiliations
                [ 1 ]Commonwealth Scientific and Industrial Research Organisation (CSIRO), Food and Nutrition Flagship , PO Box 10041, Adelaide BC, SA5000, Australia
                [ 2 ]Flinders Centre for Innovation in Cancer, Flinders University of South Australia , Bedford Park, SA5042, Australia
                [ 3 ]Rowett Institute of Nutrition and Health, University of Aberdeen , AberdeenAB21 9SB, UK
                [ 4 ]Commonwealth Scientific and Industrial Research Organisation Mathematics, Informatics and Statistics , Glen Osmond, SA5064, Australia
                Author notes
                [* ] Corresponding author: Dr R. K. L. Leu, fax +61 8 8303 8899, email richard.leleu@ 123456csiro.au
                Article
                S0007114515001750 00175
                10.1017/S0007114515001750
                4531472
                26084032
                5de7cdc4-8868-421a-b24b-534cac1086d6
                © 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.

                History
                : 26 November 2014
                : 02 April 2015
                : 23 April 2015
                Categories
                Full Papers
                Human and Clinical Nutrition

                Nutrition & Dietetics
                scfa,butyrate,dna adducts,resistant starch,red meat,fermentation,microbiota
                Nutrition & Dietetics
                scfa, butyrate, dna adducts, resistant starch, red meat, fermentation, microbiota

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