Colonic transit influences deoxycholic acid kinetics

Background & Aims: Prolonged large bowel transit, and an increase in the proportion of deoxycholic acid (DCA), have been implicated in the pathogenesis of cholesterol gallstones - including those developing in acromegalics treated with octreotide. However, there are few data on the effects of intestinal transit on bile acid kinetics. Methods: We therefore measured the kinetics of DCA and cholic acid (CA) using stable isotopes, serum sampling, and mass spectrometry. The results were related to mouth-to-caecum (MCTT) and large bowel transit times (LBTTs) in 4 groups of 8 individuals: (1) non-acromegalic controls, (2) acromegalics untreated with octreotide, (3) acromegalics on long-term octreotide, and (4) patients with constipation. Paired, before and during octreotide, studies were performed in 5 acromegalics. Results: In the unpaired and paired studies, octreotide significantly prolonged MCTT 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 μmol · kg · d, P<0.05) and pool size (18±12 to 40±13 μmol/kg, P<0.05), and a decrease in CA pool size (45±15 to 25±11 μmol/kg, P<0.05). Furthermore, during octreotide treatment, the mean conversion of ¹³C-CA to ¹³C-DCA (micromoles) was greater (P<0.05) on study days 3, 4, and 5. There were also positive linear relationships between LBTT and DCA 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 formation and absorption, prolongation of large bowel transit is a pathogenic factor in the formation of octreotide-induced gallstones.