taurochenodeoxycholic-acid and Crohn-Disease

To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon.. One-gram sodium butyrate coated tablets containing 13C-butyrate were orally administered to 12 healthy subjects and 12 Crohn's disease patients and the rate of 13C-butyrate absorption was evaluated by 13CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid (500 mg) was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration.. The coated formulation delayed the 13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn's disease patients than in healthy subjects. The variability of the peak 13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time.. Simultaneous evaluation of breath 13CO2 and tauroursodeoxycholic acid concentration-time curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn's disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.

Topics: Administration, Oral; Adolescent; Adult; Aged; Butyrates; Carbon Dioxide; Carbon Isotopes; Cecum; Chemistry, Pharmaceutical; Colon; Crohn Disease; Female; Humans; Ileum; Male; Middle Aged; Sodium; Tablets, Enteric-Coated; Taurochenodeoxycholic Acid

Bile acids regulate the expression of intestinal bile acid transporters and are natural ligands for nuclear receptors controlling inflammation. Accumulating evidence suggests that signaling through these receptors is impaired in inflammatory bowel disease. We investigated whether tauroursodeoxycholic acid (TUDCA), a secondary bile acid with cytoprotective properties, regulates ileal nuclear receptor and bile acid transporter expression and assessed its therapeutic potential in an experimental model of Crohn's disease (CD). Gene expression of the nuclear receptors farnesoid X receptor, pregnane X receptor and vitamin D receptor and the bile acid transporters apical sodium-dependent bile acid transporter and organic solute transporter α and β was analyzed in Caco-2 cell monolayers exposed to tumor necrosis factor (TNF)α, in ileal tissue of TNF

Topics: Adult; Animals; Bile Acids and Salts; Caco-2 Cells; Carrier Proteins; Crohn Disease; Disease Models, Animal; Down-Regulation; Female; Homeostasis; Humans; Ileitis; Ileum; Male; Membrane Glycoproteins; Mice; Mice, Transgenic; Receptors, Cytoplasmic and Nuclear; Taurochenodeoxycholic Acid; Young Adult

Fasting and postprandial serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a high-pressure liquid chromatographic-enzymatic assay in 17 patients with ileal Crohn's disease and in 17 controls. The postprandial concentrations of the taurine-conjugated bile acids in the patients were significantly lower than in the controls, whereas the concentrations of the glycine conjugates were not significantly different. The total glycine to taurine ratios of serum bile acids were significantly higher in the patients (means, 2.9 fasting and 4.8 postprandial) than in the controls (1.9 and 2.6). Of the patients, 65% had a postprandial total G/T ratio of serum bile acids which was above the control interval.

Topics: Adult; Aged; Bile Acids and Salts; Crohn Disease; Fasting; Female; Glycochenodeoxycholic Acid; Glycocholic Acid; Humans; Male; Middle Aged; Taurochenodeoxycholic Acid; Taurocholic Acid