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 acid 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, whole gut transit time, faecal weight and dry weight, and faecal pH were recorded. The concentration of (iso)lithocholic and deoxycholic acid in faeces was higher in elderly subjects (P less than 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 less than 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 less than 0.05) and further after 12 weeks' lactulose (P less than 0.05). The percentage deoxycholic acid in bile was higher, and cholic acid lower, in elderly subjects (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Lactulose ingestion increases faecal bifidobacterial counts: A randomised double-blind study in healthy humans

“…Under our experimental conditions, the partial replacement of other anaerobes with bifidobacteria did not alter the faecal pH, concentrations of bile acids and neutral sterols, which are factors potentially implicated in colon carcinogenesis (Nair, 1988;Owen, 1997). The absence of modification of the microbial transformation of cholesterol and bile by oral lactulose results probably from the low level of the dose, which is the half or the sixth of that used by other authors (Berge Henegouwen et al, 1987;Nagengast et al, 1988). In fact, the effects of the poorly digestible carbohydrates or prebiotics such as lactose, lactulose and amylomaize starch on bile acid transformations depend linearly on the prebiotic dose (Andrieux et al, 1989).…”

Retrograded high-amylose corn starch reduces cholic acid excretion from the small bowel in ileostomy subjects

“…Addition of wheat bran (30 ± 57 g/d) or lactulose to the diet in healthy individuals decreased the content of deoxycholic acid and increased the content of chenodeoxycholic acid in bile, whereas cholic acid remained unchanged (Pomare & Heaton, 1973;Pomare et al, 1976, Wicks et al, 1978Thornton & Heaton, 1981;Nagengast et al, 1988). In subjects with an intact intestine, deoxycholic acid is formed after bacterial dehydroxylation of cholic acid excreted from the small intestine to the large intestine.…”

Calcium, phosphorus, vitamin D, dairy products and colorectal carcinogenesis: a French case - control study

“…In lactose malabsorbers, the non-absorbed lactose is fermented in the colon. Fermentation of the closely related lactulose has been demonstrated to be an asset against colorectal carcinogenesis (Nagengast et al, 1988). It decreases intestinal pH, thus reducing the transformation of primary into secondary bile acids.…”