Metabolites

A wide range of metabolites with potential genotoxic, tumor-promoting and anti-carcinogenic activities have been identified in feces.

N-Nitroso Compounds

Nitrate, ingested via diet and drinking water, is reduced by gut bacterial nitrate reductase to its more reactive and toxic reduction product, nitrite. Nitrite reacts with nitrogenous compounds in the body to produce NOC. The reaction can occur chemically in the acidic conditions prevalent in the human stomach and can also be catalyzed at neutral pH by gut bacteria in the colon.

The term NOC covers a wide range of compounds including N-nitrosamines, N-nitrosamides, N-nitrosoguanidines, and N-nitrosoureas, the majority of which are highly carcinogenic, DNA alkylating agents. However, the genotoxic or carcinogenic activity of the NOC produced by the bacterial N-nitrosation process in the large intestine has not yet been established.

Fecal apparent total NOC (ATNC) excretion is increased by red meat consumption. In conjunction with high meat intakes, wheat bran, resistant starch and vegetable consumption had no effect on fecal ATNC excretion or concentration.

Secondary Bile Acids

The primary bile acids, chenodeoxycholic acid and cholic acid, are subject to extensive metabolism, predominantly 7-a-dehydroxylation, by the intestinal microbiota, which converts cholic to DCA and chenodeoxycholic to LCA. These are termed secondary bile acids.

Epidemiological studies indicate that concentrations of secondary bile acids are higher in populations at high risk of CRC and in case control studies 7-a-dehydroxylase activity is higher in cases than controls. In human studies, high fat intake, which correlates with CRC risk, increases FBA concentrations, whereas increased consumption of wheat bran (negatively correlated with CRC risk) reduces FBA concentration.

Short Chain Fatty Acids

The SCFAs acetate, propionate, and butyrate are the principal end-products of carbohydrate fermentation. These are absorbed from the colonic lumen and metabolized by various body tissues. Butyrate is preferentially metabolized by colonocytes.

There is evidence from in vitro studies and animal models (where cecal SCFA concentrations can be measured) that the type of carbohydrate has an important influence on the amount and proportions of SCFA produced, with starch and wheat bran being particularly associated with elevated butyrate production. In human studies, inulin has been shown to enhance excretion of total SCFA in human feces, whereas wheat bran increased absolute or relative proportions of butyrate in feces. Where the butyrate is produced relative to proximal and distal regions of the colon is important and should be a methodological consideration.

Gut bacterial enzymes and fecal metabolites are relatively simple to measure routinely and in general may be of use in assessing effects of diet on modulating exposure of the colon to potential carcinogens, rather than reflecting cancer risk.

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