R W Owen1. 1. Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
Abstract
BACKGROUND: Colorectal cancer is a major disease of Western civilizations and diet may account for approximately 35% of cases. Epidemiologic studies reveal that the major dietary constituents implicated in the disease process are fat/red meat (causative) and fibre (protective). From this standpoint, toxicologists have evaluated a plethora of dietary and intestinal biochemical characteristics and steroids; the bile acids especially have received a great deal of attention. Formerly, bile acids and their bacterial metabolites were implicated, as either mutagens and/or carcinogens, but this was not proven. In recent times, based mainly on animal model systems, opinion favours that if bile acids and their metabolites have a role to play in colon carcinogenesis, they act at the promotion stages of the adenoma-carcinoma sequence-the secondary bile acids deoxycholic and lithocholic acids being of major importance here. From this standpoint, studies have been designed either to lower total bile acid concentration or at least to reduce dehydroxylation of the primary bile acids via high fibre dietary regimes. METHODS AND RESULTS: The prebiotics lactulose and lactitol (non-digestible dietary fibres) appear to have potential here, and so the effect of lactulose on fermentation by intestinal bacteria in a continuous culture model of the human colon was studied. Lactulose reduced dehydroxylation of chenodeoxycholic acid to the potentially toxic secondary bile acid lithocholic by over 90%. By contrast, lactitol, a reduced equivalent of lactulose, had little effect on 7 alpha-dehydroxylation of primary bile acids in the rectosigmoid colon of the miniature pig and in human faeces, but caused a significant decrease in steroid concentration, especially bile acids in human faeces. CONCLUSIONS: If secondary steroid metabolites have a role to play in colorectal carcinogenesis, then dietary supplementation with prebiotics may be ameliorative in high-risk groups.
BACKGROUND:Colorectal cancer is a major disease of Western civilizations and diet may account for approximately 35% of cases. Epidemiologic studies reveal that the major dietary constituents implicated in the disease process are fat/red meat (causative) and fibre (protective). From this standpoint, toxicologists have evaluated a plethora of dietary and intestinal biochemical characteristics and steroids; the bile acids especially have received a great deal of attention. Formerly, bile acids and their bacterial metabolites were implicated, as either mutagens and/or carcinogens, but this was not proven. In recent times, based mainly on animal model systems, opinion favours that if bile acids and their metabolites have a role to play in colon carcinogenesis, they act at the promotion stages of the adenoma-carcinoma sequence-the secondary bile acidsdeoxycholic and lithocholic acids being of major importance here. From this standpoint, studies have been designed either to lower total bile acid concentration or at least to reduce dehydroxylation of the primary bile acids via high fibre dietary regimes. METHODS AND RESULTS: The prebiotics lactulose and lactitol (non-digestible dietary fibres) appear to have potential here, and so the effect of lactulose on fermentation by intestinal bacteria in a continuous culture model of the human colon was studied. Lactulose reduced dehydroxylation of chenodeoxycholic acid to the potentially toxic secondary bile acid lithocholic by over 90%. By contrast, lactitol, a reduced equivalent of lactulose, had little effect on 7 alpha-dehydroxylation of primary bile acids in the rectosigmoid colon of the miniature pig and in human faeces, but caused a significant decrease in steroid concentration, especially bile acids in human faeces. CONCLUSIONS: If secondary steroid metabolites have a role to play in colorectal carcinogenesis, then dietary supplementation with prebiotics may be ameliorative in high-risk groups.