Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency.

Background & Aims: The final step in bile acid synthesis involves conjugation with glycine and taurine, which promotes a high intraluminal micellar concentration to facilitate lipid absorption. We investigated the clinical, biochemical, molecular, and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat-soluble vitamin deficiency, some with growth failure or transient neonatal cholestatic hepatitis.

Methods: We identified the genetic defect that causes this disorder using mass spectrometry analysis of urine, bile, and serum samples and sequence analysis of the genes encoding bile acid-CoA:amino acid N-acyltransferase (BAAT) and bile acid-CoA ligase (SLC27A5).

A new amino acid derivative of ursodeoxycholate, (N-L-Glutamyl)-UDCA (UDCA-Glu), to selectively release UDCA in the colon.

Background: Ursodeoxycholic acid (UDCA) is chemoprotective in animal models of colon cancer but results from clinical trials have been less impressive probably because UDCA is rapidly absorbed in the small intestine and little reaches the colon. UDCA-glutamate (Glu), a novel bile acid, was synthesized with the objective of utilizing peptide bond cleavage by brush border enzymes to enhance delivery of UDCA to the colon.

Materials And Methods: Qualitative and quantitative intestinal intraluminal and fecal bile acid composition measured by mass spectrometry was determined in Fisher rats after intragastric administration of UDCA, or UDCA-Glu for 5 days.

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17alpha-ethynyl-estradiol-induced cholestasis in rats.

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), the 7alpha-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17alpha-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.

Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosis.

Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD).

Influence of breast feeding, and adapted and hydrolyzed formulas on biliary bile acids in newborn guinea pigs.

Background: The type of feeding can differently influence bile acid ontogeny during the period of physiologic cholestasis that characterizes early human development.

Aim: To investigate the effects of feeding from birth, conventional or partially protein hydrolyzed cow's milk formulas were compared with breast milk regarding bile acid concentration and the composition of gallbladder bile in newborn guinea pigs.

Methods: Forty newborn guinea pigs were allocated to one of three different feeding regimens: breast milk (n = 14), intact protein formula (n = 13) and partially protein hydrolyzed formula (n = 13).

Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy.

Background & Aims: Inborn errors of bile acid metabolism may present as neonatal cholestasis and fat-soluble vitamin malabsorption or as late onset chronic liver disease. Our aim was to fully characterize a defect in bile acid synthesis in a 2-week-old African-American girl presenting with coagulopathy, vitamin D and E deficiencies, and mild cholestasis and in her sibling, whose liver had been used for orthotopic liver transplantation (OLT).

Methods: Bile acids were measured by mass spectrometry in urine, bile, serum, and feces of the patient and in urine from the unrelated recipient.