Determinants and consequences of colonic luminal pH: Implications for colon cancer

Newmark, Harold L.; Lupton, Joannè R.

doi:10.1080/01635589009514091

Cited by 94 publications

(43 citation statements)

References 53 publications

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“…These changes may have certain benefits in relation to CRC risk. A low pH is considered to be associated with a reduced risk from CRC (39), whereas butyrate changes the metabolic environment in the lumen to promote a normal cellular phenotype (28). The addition of resistant starch to a high protein diet has been previously shown to reduce the formation of certain metabolites of protein fermentation (7).…”

Section: Discussionmentioning

confidence: 99%

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

Winter

Nyskohus

Young

et al. 2011

Cancer Prevention Research

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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.

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Section: Discussionmentioning

confidence: 99%

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

Winter

Nyskohus

Young

et al. 2011

Cancer Prevention Research

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show abstract

“…It is now apparent that SCFAs are rapidly absorbed in vivo [1,2,18,30,38] and may enhance colonic Na and fluid absorption. SCFAs may be a significant factor in normal colonic function; changes in colonic SCFAs may have both pathophysiological and therapeutic implications [5,14,20,25,29,33,39].…”

Section: Introductionmentioning

confidence: 99%

Segmental differences in short-chain fatty acid transport in rabbit colon: Effect of pH and Na

Sellin¹,

Desoignie²,

Burlingame³

1993

J. Membrain Biol.

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Short-chain fatty acids (SCFAs) are the predominant luminal anion in the mammalian colon. Although they are rapidly absorbed in vivo, little is known about the mechanisms of transepithelial transport in vitro. Previous studies have suggested that SCFA transport may be linked to Na absorption or an anion exchange mechanism. We compared the transport of propionate under short-circuit conditions in rabbit proximal and distal colon to determine whether there were segmental differences, how SCFAs may be linked to either Na absorption or anion transport, and whether SCFAs, as weak electrolytes, may be affected by transepithelial pH gradients. In distal colon, propionate transport was not significantly altered by stimulation of electrogenic Na absorption, epinephrine or Cl removal. However, a modest transepithelial pH gradient (luminal 6.8/serosal 7.4) stimulated propionate absorption. In proximal colon, propionate transport was significantly altered by maneuvers that either stimulated (lowered [Na] in the bathing media) or inhibited (theophylline) apical Na-H exchange. Neither Cl removal, nor the anion exchange inhibitor DIDS, nor a transepithelial bicarbonate gradient, altered propionate transport. A transepithelial pH gradient inhibited propionate secretion, but not in a manner entirely consistent with the effect of pH on the distribution of a weak electrolyte. These results suggest that there is significant segmental heterogeneity in colonic SCFA transport; that transepithelial propionate fluxes are altered by changes in pH or electroneutral Na absorption (Na-H exchange), but not by chloride removal, bicarbonate gradients or electrogenic Na absorption. Regulation of SCFA transport may be an important factor in the physiology of colonic fluid balance.

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“…A historic study of tumour genesis in the colon shed light on the alkaline environment in the lumen of the colon which, combined with secondary bile acids, is a promoter of tumour formation [59] . N-nitroso compounds and ammonia, produced from bacterial action upon undigested protein products, and secondary bile acids alter the luminal environment, which affect colonocyte function and deplete oxygen levels in the colonic mucosa, thus favouring tumourigenesis.…”

Section: Risk Factorsmentioning

confidence: 99%

Colorectal cancer in the young, many questions, few answers

Deen¹,

Silva²,

Deen³

et al. 2016

WJGO

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Determinants and consequences of colonic luminal pH: Implications for colon cancer

Cited by 94 publications

References 53 publications

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

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

Segmental differences in short-chain fatty acid transport in rabbit colon: Effect of pH and Na

Colorectal cancer in the young, many questions, few answers

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