Review article: effect of bile salt pool composition on hepatic and biliary functions

Abstract

Summary The enterohepatic recirculation of bile salts exerts important regulatory effects on many hepatic, biliary and intestinal functions; such regulation is likely to depend, to a large extent, on the physical–chemical property of hydrophobicity of the recirculating pool. The present review summarizes the main experimental evidence carried out by our research group over the past two decades, in the attempt to investigate systematically the relationships between structural properties and biological effects of bile acids in humans. Hydrophobic bile acids (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids (ursodeoxycholic acid), significantly suppressed hepatic activity of HMG‐CoA reductase, the limiting step of cholesterol synthesis, and in vivo cholesterol 7α‐hydroxylation, the limiting step of bile acid synthesis. The output of biliary cholesterol and phospholipid was also directly related to the hydrophobicity of the bile acid pool. Finally, treatment with chenodeoxycholic acid, but not with ursodeoxycholic acid, significantly decreased gall‐bladder emptying rates. When turning to the in vitro model of HepG2 cells, hydrophobic bile acids were found to induce greater cytotoxic and pro‐apoptotic effects. From this series of studies, we conclude that the regulatory effects of bile acids on the liver and biliary tract are largely dependent on the hydrophobic–hydrophilic balance of the recirculating bile acid pool.

Characterization of fasted-state human intestinal fluids collected from duodenum and jejunum

“…However, TC levels appeared to be lower in the previously mentioned studies (6.6-13% vs 13-66% in this study), while the percentage of C was higher (8.8-52% vs 0.14-1.46% in this study). CDC and DOC contents were also lower in this study, as compared with previous reports (Rossi et al 1987;Janowitz et al 1990) of gallstone patients who are well known to display a more lipophilic bile acid pool (Carulli et al 2000). In contrast to a previously reported study in which GC was found to be the most abundant bile salt in fasted state HIF (Persson et al 2005), TC was observed to be the major bile salt present in fasted state HIF in this study.…”

“…The hydrophilic-hydrophobic balance of the bile acid pool influences biliary lipid secretion, cholesterol synthesis, gallbladder emptying rate, cytotoxicity and apoptosis effect, and also affects the capacity to solubilize lipids and lipophilic drugs (Carey 1984;Carulli et al 2000). Taking into account the hydrophobic index (HI) values for the eleven different bile acid species studied, the HI for the different volunteers ranged from 0.14 to 1.08 (Table 4).…”

An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis

“…In addition, a separate study concluded that bile acid levels increased as early as 24 h postirradiation and remained persistently high three days after exposure (7). Under physiological conditions, 90% of bile acids are reabsorbed by the gut by the highly efficient enterohepatic recirculation system (38), which may indicate that the radiation-induced bile acid increases in the colonic contents is due to the reduction of intestinal absorption caused by radiation. The decrease in the secondary bile acid, ketodeoxycholic acid, is further evidence for the shift in the microbial metabolism and lower rate of deconjugation of bile salts (Fig.…”

Bile Formation and the Enterohepatic Circulation

“…97 A fraction of the 7-deoxy bile acids are absorbed from the colon and returned to the liver where they are efficiently reconjugated with glycine or taurine. 98,99 This variation in bile acid 7α-rehydroxylation activity is reflected in biliary DCA concentration that varies from 0-10% of bile acids in rats, mice, guinea pigs, prairie dogs, and hamsters; 100-103 15-30% in dogs and humans; 104,105 and greater than 90% in rabbits. Hepatic bile acid 7α-rehydroxylation varies considerably between species, but is essentially absent in humans.…”