Oral chenodeoxycholic acid increases small intestinal permeability to lactulose in humans

In animals, chenodeoxyholic acid (chenodiol) causes significant small intestinal mucosal injury which is paralleled by increased intestinal permeability. The objective of this study was to determine whether chenodiol increases small intestinal mucosal permeability in humans. This was assessed in a before-after trial by collecting urine from nine fasted healthy male volunteers for 3 h after oral intake of an isotonic solution containing 1 g mannitol, 5 g L-rhamnose and 10 g lactulose, all nondigestible sugars. After at least 72 h, this was repeated 1 h after taking 750 mg of chenodiol orally. The amount of each sugar excreted in the urine was quantified by high performance liquid chromatography. Chenodiol doubled the percent urinary excretion of lactulose from 0.21 +/- 0.12 (SD) to 0.42% +/- 0.25 (p less than 0.02) and the ratio of lactulose to mannitol or to rhamnose [0.012 +/- 0.005 to 0.027 +/- 0.013 (p less than 0.01) and 0.045 +/- 0.022 to 0.087 +/- 0.039 (p less than 0.05), respectively]. Oral administration of 750 mg chenodiol is associated with increased small intestinal permeability to lactulose in humans, supporting the possibility that this drug may also cause acute small intestinal mucosal injury.