APPARENT SELECTIVE BILE-ACID MALABSORPTION AS A CONSEQUENCE OF ILEAL EXCLUSION - EFFECTS ON BILE-ACID, CHOLESTEROL, AND LIPOPROTEIN METABOLISM

A new model has been developed to characterise the effect of a standar dised ileal exclusion on bile acid, cholesterol, and Lipoprotein metab olism in humans. Twelve patients treated by colectomy and ileostomy fa r ulcerative colitis were studied on two occasions: firstly with a con ventional ileostomy and then three months afterwards with an heal pouc h operation with an ileoanal anastomosis and a protective loop ileosto my, excluding on average 95 cm of the distal ileum. The ileostomy cont ents were collected during 96 hours and the excretion of bile acids an d cholesterol was determined using gas chromatography-mass spectrometr y. Pasting blood and duodenal bile samples were collected on two conse cutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased fo ur to five times without any change in cholesterol excretion. Serum co ncentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycer ides were also increased whereas the concentrations of total and LDL c holesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The r esults show that the exclusion of about 95 cm of distal ileum causes m alabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids an d cholesterol in the Liver. It is suggested that bile acids can regula te cholesterol synthesis by a mechanism independent of the effect of b ile acids on cholesterol absorption. enhanced demand for cholesterol l eads to a decrease in plasma LDL cholesterol and apolipoprotein B conc entrations. The malabsorption of bile acids did not affect biliary lip id composition or cholesterol saturation, but increased the plasma con centrations of VLDL triglycerides.