Intestinal bile acid malabsorption in cystic fibrosis.

This study aimed at examining the mechanisms participating in excessive faecal bile acid loss in cystic fibrosis. The study was designed to define the relation between faecal fat and faecal bile acid loss in patients with and without cystic fibrosis related liver disease; to assess terminal ileal bile acid absorption by a seven day whole body retention of selenium labelled homotaurocholic acid (SeHCAT); and to determine if small intestinal bacterial overgrowth contributes to faecal bile acid loss. The study population comprised 40 patients (27 men; median age 18 years) with cystic fibrosis (n=8) and without (n=32) liver disease and eight control subjects. Faecal bile acid excretion was significantly higher in cystic fibrosis patients without liver disease compared with control subjects (mean (SEM) 21-5 (2.4) and 7.3 (1.2) umol/kg/24 hours respectively; p<001) and patients with liver disease (7.9 (1.3) umol/kg/24 hours; p<001). No correlation was found between faecal fat (g fat/ 24 hours) and faecal bile acid (umol/24 hours) excretion. Eight (33%) of cystic fibrosis patients had seven day SeHCAT retention <10% (normal retention >20%). SeHCAT retention in cystic fibrosis patients with liver disease was comparable with control subjects (30.0 (SEM) 8-3% v 36-8 (5.9)%; p=NS) while SeHCAT retention in cystic fibrosis patients who did not have liver disease was significantly reduced (19-9 (3.8); p<005). Although evidence of small bowel bacterial overgrowth was present in 40% of patients no relation was found between breath hydrogen excretion, faecal fat, and faecal bile acid loss. The results are consistent with the presence of an abnormality in terminal ileal function in patients with cystic fibrosis who do not have liver disease and that a defect in the ileal absorption of bile acids may be a contributory factor to excessive faecal bile acid loss. Faecal bile acid loss in cystic fibrosis is unrelated to the presence of intraluminal fat or intestinal bacterial overgrowth. (Gut 1993; 34: 1137-1141) Excessive faecal bile acid loss is well recognised in patients with cystic fibrosis'" and has been attributed to an inhibitory effect of intraluminal unhydrolysed triglycerides on the intestinal absorption of bile acids. Some studies, however, have shown no correlation between faecal fat excretion and faecal bile acid loss suggesting that additional factors are responsible for bile acid malabsorption in cystic fibrosis.3 Thus in vitro studies have shown a defect in the terminal ileal bile acid active transport mechanisms in patients with cystic fibrosis, which if present in vivo, would also contribute to excessive faecal bile acid loss.9 '° In addition, intestinal bacterial overgrowth, resulting from prolonged intestinal transit and stasis," may result in deconjugation and dehydroxylation of bile salts and contribute to impaired bile acid absorption and faecal bile acid loss. Excessive faecal bile acid losses have not been found in all studies in adult patients with cystic fibrosis.32 This finding has been attributed to the increased prevalence of hepatic dysfunction, with associated impairment of bile acid synthesis and contraction of the total bile acid pool, in adults with cystic fibrosis.3 The objectives of this study in an adult population of patients with cystic fibrosis were to: (1) define the relation between faecal fat and faecal bile acid excretion in patients with and without liver disease; (2) to discover if a defect in the ileal bile acid active transport mechanism contributes to faecal bile acid loss; and (3) to assess the contribution of small bowel bacterial overgrowth to faecal fat and faecal bile acid losses.