Intestinal Bile Acid Malabsorption in Cystic Fibrosis: a Primary Mucosal Cell Defect

Abstract

Summary: Bile acid malabsorption in cystic fibrosis reduces intraluminal bile acid concentration and may impair fat absorption. The cause of this malabsorption is unknown but it is believed due to intraluminal inhibition of uptake by undigested dietary nutrients. The purpose of this study was to determine the bile acid absorptive capability of cystic fibrosis intestine in a physiologic environment. Direct ileal mucosal taurocholic acid uptake was examined in vitro in seven patients with cystic fibrosis, and seven children and adolescents with ileostomies as controls. Jejunal uptake was studied in five normal individuals. A Crosby-Kugler biopsy capsule was used to obtain all tissues. Tissue was incubated in Krebs buffer, 10 mM glucose, and taurocholic acid at 0.1, 1.0 and 10.0 mM with shaking at 37°C. Significant reduction of taurocholic acid uptake was present in every cystic fibrosis patient with mean uptake rates being 24%, 38%, and 29% of control ileum, respectively, at the three concentrations. Values paralleled those for passive jejunal taurocholic acid uptake in controls. These data illustrate a marked reduction in taurocholic acid uptake capability of cystic fibrosis ileal mucosa and may indicate a cellular defect suggestive of a primary lesion in this disease. Speculation: Results of the present study suggest that bile acid malabsorption in cystic fibrosis may be due to a primary functional defect of the ileal mucosal cells in this disease. This is demonstrated in vitro by the reduced uptake rates for taurocholic acid by ileal mucosa taken from cystic fibrosis patients when compared to controls. Furthermore, the taurocholic acid uptake rate in cystic fibrosis ileal mucosa are comparable to that of jejunal mucosa from health volunteers. This suggests that active transport mechanisms for bile acid absorption are absent in cystic fibrosis intestine. Although these studies do not impugn an intral~minaml echanism, they point to a primary functional ileal mucosal cell defect as the pathophysiologic mechanism of bile acid malabsorption in cystic fibrosis.