Bile Acid Metabolism in Children with Cystic Fibrosis

Abstract

. Recycling of bile acids through the enterohepatic cycle is very efficacious. Bile acids contribute to bile formation and, by forming micelles, participate in lipid solubilization and absorption. The small fraction which escapes in the feces, is synthesized daily by the liver to compensate for losses. In CF, bile acid malabsorption has been documented; these large losses are accompanied by an interruption in the enterohepatic circulation with concomitant reduction in bile acid pool and disturbances in biliary composition. The various intraluminal factors implicated in bile acid malabsorption include: unhydrolysed triglycerides and phospholipids, precipitation of bile acids in acidic duodenal content, adsorption to residues and modification of colonic microflora. A defect in bile acid ileal uptake has also been advocated. These disturbances in bile acid metabolism associated with CF might lead to aggravation of diarrhea and steatorrhea, cholelithiasis and perhaps liver disease.

Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis

“…However, children with CF frequently exhibit bile acid malabsorption by the intestine, which leads to altered enterohepatic circulation and hepatobiliary composition of bile acids (22)(23)(24). Excessive fecal bile acid loss has been proposed to influence fat and cholesterol absorption by the gut, bacterial flora in the gut, and the progression of liver disease through alterations in bile acid pool composition (24).…”

In Vivo Bile Acid Uptake from Terminal Ileum in Cystic Fibrosis

“…The study did not examine the effect on bile acid absorption of intraluminal factors such as unhydrolyzed triglycerides and unhydrolyzed phospholipids, precipitation of bile acids in the more acidic CF duodenum, and adsorption of bile acids to food residues. These factors remain possible explanations for excessive fecal bile acid loss in CF (2).…”

Glutathione and the Sulfur‐Containing Amino Acids: An Overview

“…It has long been known to be essential for conjugation of bile acids to give taurocholic acid and taurochenodeoxycholic acid for excretion of cholesterol degradation products into the bile. Most of the bile salts are reabsorbed so this pathway does not normally represent much loss of taurine, but cystic fibrosis patients do have a marked decrease in recycling of bile salts [47] and thus may need a taurine supplement [48]. The cholesterol-lowering anion-exchange resin cholestyramine lowers reabsorption of bile salts and thus patients on this drug may also need supplementary taurine [2].…”