Inhibition of secondary bile acid formation in the large intestine by lactulose in healthy subjects of two different age groups

Abstract

Secondary bile acids have been implicated in colonic carcinogenesis. Transformation of primary into secondary bile acids (7.alpha.-dehydroxylation) in the large bowel is a pH-dependent process. Inhibition of this reaction could be achieved by lowering colonic pH. We, therefore, studied the effects of lactulose (a non-absorbable disaccharide), which is capable of acidifying colonic contents, on secondary bile metabolism. Because this metabolism is age dependent, lactulose was given (0.3 g kg-1 twice daily for 12 weeks) to nine middle-aged (age 31-54 years; mean 45.7) and ten elderly subjects (age 56-81 years; mean 66.4). Twice before, and after 6 and 12 weeks'' lactulose administration, biliary and faecal bile acids, while gut transit time, faecal weight and dry weight, and faecal pH were recorded. The concentration of (iso)litocholic and deoxycholic acid in faeces was higher in elderly subjects (P < 0.05) but the excretion was comparable. After lactulose the concentration and excretion of the major secondary bile acids decreased. The primary bile acid fraction rose from 5% before, to more than 20% after, lactulose (P < 0.05). Faecal weight increased and faecal dry weight decreased, resulting in a higher faecal water output during lactulose. Whole gut transit time did not change. The faecal pH dropped after 6 (P < 0.05) and further after 12 weeks'' lactulose (P < 0.05). The percentage deoxycholic acid in bile was higher, and cholic acid lower, in elderly subjects (P < 0.05). After lactulose the deoxycholic acid content decreased (P < 0.05) and chenodeoxycholic acid content increased (P < 0.01) in the whole group (n = 19). The cholic acid content did not change. The results show that lactulose can reduce secondary bile acid formation in the large bowel and that the effect is not mediated through acceleration of intestinal transit. Acidification of colonic contents seems to the the major factor in this reduction.