Colonic transit influences deoxycholic acid kinetics

Background & Aims: Prolonged large bowel transit, and an increase in the pr oportion of deoxycholic acid (DCA), have been implicated in the pathogenesi s of cholesterol gallstones-including those developing in acromegalics trea ted with octreotide. However, there are few data on the effects of intestin al transit on bile acid kinetics. Methods: We therefore measured the kineti cs of DCA and cholic acid (CA) using stable isotopes, serum sampling, and m ass spectrometry. The results were related to mouth-to-caecum (MCTT) and la rge bowel transit times (LBTTs) in 4 groups of 8 individuals: (1) non-acrom egalic controls, (2) acromegalics untreated with octreotide, (3) acromegali cs on long-term octreotide, and (4) patients with constipation. Paired, bef ore and during octreotide, studies were performed in 5 acromegalics. Result s: In the unpaired and paired studies, octreotide significantly prolonged M CTT and LBTT. In the paired studies, the octreotide-induced prolongation of LBTT caused an increase in the DCA input rate (6.4 +/- 2.8 to 12 +/- 2.6 m u mol . kg . d, P < 0.05) and pool size (18 +/- 12 to 40 +/- 13 mu mol/kg, P < 0.05), and a decrease in CA pool size (45 +/- 15 to 25 +/- 11 mu mol/kg , P < 0.05). Furthermore, during octreotide treatment, the mean conversion of C-13-CA to C-13-DCA (micromoles) was greater (P < 0.05) on study days 3, 4, and 5. There were also positive linear relationships between LBTT and D CA input rate (r = 0.78), pool size (r = 0.82, P < 0.001), and a weak (r = -0.49) negative linear relationship between LBTT and CA pool size (P < 0.01 ). Conclusions: These data support the hypothesis that, by increasing DCA f ormation and absorption, prolongation of large bowel transit is a pathogeni c factor in the formation of octreotide-induced gallstones.