Protein degradation in the large intestine: relevance to colorectal cancer.

Colorectal cancer is the second most common form of cancer death in Western countries. Diet has been implicated in the aetiology of this disease. Epidemiological evidence suggests that diets high in meat and fat and low in fermentable carbohydrate increase colorectal cancer risk. One mechanism that could explain the association with meat is increased colonic protein metabolism due to increased protein intake from high meat diets. Products of colonic protein degradation and metabolism include ammonia, phenols, indoles and amines which have been shown to exert toxic effects in vitro and in animal models. These compounds are present in faecal samples suggesting that they may exert gut mucosal effects. Human studies have shown that colonic protein metabolism via the gut microflora is responsive to dietary protein as faecal ammonia and urinary phenolic compound concentrations increase in response to increased intake of protein rich foods. Other toxic metabolites from dietary protein precursors such as N-nitroso compounds and sulphides are also formed. Recent work has shown that diets high in meat, fat and low in fibre increase human faecal water genotoxicity. It is likely that metabolites from colonic protein metabolism contribute to this increase in genotoxicity during high meat intakes.