Active and Passive Bile Acid Absorption in Man. PERFUSION STUDIES OF THE ILEUM AND JEJUNUM

Intestinal transport and metabolism of bile acids

“…Passive absorption of protonated uncharged bile acid species, unconjugated bile acids, and a small fraction of the glycine conjugates occurs down the length of the intestine ( 35 ). However, as most of the bile acid pool is conjugated to taurine or glycine and ionized, their uptake across the apical brush border membrane requires the presence of a transporter, and active carrier-mediated absorption of bile acids is restricted to the ileum ( 36,37 ). Indeed, in all vertebrates examined to date, including primitive vertebrates such as the little skate ( Leucoraja erinacea ) and sea lamprey ( Petromyzon marinus ) ( 38 ), the ileal epithelium maintains an effi cient transport system for the active reclamation of bile acids ( 39 ).…”

“…Support for this role of OST ␣ -OST ␤ , a heterodimer consisting of a 352-amino acid polytopic membrane protein (OST ␣ ) and a 182-amino acid predicted type I membrane protein (OST ␤ ), includes: 1 ) intestinal expression that overlaps the ASBT, 2 ) plasma membrane localization restricted to the basolateral aspect of the enterocyte, 3 ) transport specifi city that includes the major bile acid species, 4 ) expression that is strongly induced by bile acids acting through FXR, and 5 ) impaired intestinal bile acid absorption and altered bile acid metabolism in OST ␣ -null mice ( 18,19 ). Although expressed at highest levels in the ileum, OST ␣ -OST ␤ is also expressed in the proximal small intestine, cecum, and colon where it may function to export glycine-conjugated or unconjugated bile acids that entered the cell by passive diffusion ( 35,36,89 ). A fraction of these bile acids would be uncharged when the pH of the intestinal lumen or microclimate overlaying the mucosa is suffi ciently low to protonate the bile acid anion ( 45 ).…”

In Vivo Bile Acid Uptake from Terminal Ileum in Cystic Fibrosis

“…Ileal passive absorption of both glycocholate and taurocholate appears to be negligible (12); thus the relatively decreased uptake of taurocholate in CF and control subjects for perfusates of CF G/T ratio most likely represents competetitive inhibition of taurocholate uptake by the higher glycocholate concentration rather than resulting from passive absorption. This conclusion is consistent with the similarity of uptake values for taurocholate (at normal G/T ratio) and for glycocholate; uptake values of both bile acids are similar in normal man (12). Thus the bile acid absorption demonstrated was almost certainly active for both taurocholate and glycocholate.…”

“…Several factors may contribute to the difference. The infusion of both bile acids together will have resulted in competitive inhibition (12) and the ileal uptake mechanisms may not have been fully mature in subjects in the current study. Also, Krag and Phillips (12) used a perfusate infusion rate of 10 ml/min whereas that used herein (1.5 ml/min) is similar to the normal ileal flow rate of about 0.67 ml/min (15); infusion rates above 7 ml/min may cause unphysiologic changes in intraintestinal pressure and volume (27).…”

Inhibition of Ileal Na + /Bile Acid Cotransporter by S-8921 Reduces Serum Cholesterol and Prevents Atherosclerosis in Rabbits

“…Bile acids are known to be reabsorbed from the intestine by both passive and active mechanisms. 42,43 Because S-8921 is an IBAT inhibitor and could not inhibit passive absorption of bile acids, 17 only inhibition of the active absorption of bile acids may be sufficient to change liver cholesterol metabolism and reduce serum cholesterol.…”