Role of gallbladder emptying and small bowel transit in regulation of bile acid pool size in man

Eleven normal human subjects were studied after a 2 to 3 week equilibration period on a metabolic ward to determine the relationship of both gallbladder emptying rate and small bowel transit time to bile acid metabolism. ICG was used as a marker of gallbladder contents. Output of ICG in response to a standard test meal was monitored by a constant perfusion technique using ¹⁴C-PEG as a nonabsorbable marker. Small bowel transit time was measured as the delay between ingestion of nonabsorbable carbohydrate and the appearance of H₂ gas on the breath. Pool sizes, synthesis rates, and fractional turnover rates of bile acid were measured by standard isotope dilution techniques after simultaneous administration of ¹⁴C-cholic and ¹⁴C-chenodeoxycholic acid. Gallbladder emptying was well approximated by first-order kinetics for 40 to 120 min following the test meal. The first-order rate constant of emptying (λ) ranged from 0.0127 to 0.0390 min.^-1 Linear regression analysis revealed strong correlations between gallbladder emptying rate and pool sizes of both cholic (r = -0.76, p < 0.01) and chenodeoxycholic (r = -0.70, p < 0.02). The smaller pools associated with more rapid gallbladder emptying were largely a result of changes in fractional turnover rate which correlated significantly with gallbladder emptying for cholic (r = 0.64, p < 0.05) and for chenodeoxycholic (r = 0.71, p < 0.02). Gallbladder emptying was not significantly related to synthesis rate for either bile acid (r = -0.21, cholic; r = -0.39, chenodeoxycholic). Transit time correlated only weakly with pools of cholic (r = 0.50) and chenodeoxycholic (r = 0.37), relationships that were not statistically significant. What relationship there was between primary bile acid pools and transit arose entirely from dependence of synthesis rate on transit time for both cholic (r = 0.56, p < 0.05) and chenodeoxycholic (r = 0.57, p < 0.05). Fractional turnover rates of these two bile acids were completely independent of transit time (r = -0.16 and r = -0.08). Pool size of the secondary bile acid, deoxycholic, was dependent on transit time (r = 0.62, p < 0.05) but was independent of gallbladder emptying rate (r = -0.09). Total bile acid pool was closely related to both transit time (r = 0.69, p < 0.025) and to gallbladder emptying rate (r = -0.61, p < 0.05). Multiple regression analysis of total pool vs. both variables simultaneously yielded a correlation coefficient of 0.84 (p < 0.01). These findings, in conjunction with studies altering transit time in our laboratory and altering gallbladder emptying in other laboratories, provide strong support for roles of both small bowel transit and gallbladder emptying in the regulation of bile acid pool sizes in man.