Page 14 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 1
Bile acid biology and the enterohepatic cycle
Since the 1928 Nobel Prize was awarded to Adolf Windaus for his research into the chemical structure of bile acids, bile acids have been recognized mainly for their function as enteral detergents, facilitating the uptake of fat and fat-soluble vitamins in the gut. Bile acids are synthesized from a cholesterol backbone in hepatocytes, forming the primary bile acids cholate (CA) and chenodeoxycholate (CDCA) (Lefebvre, Cariou, & Lien, 2009). After synthesis, bile acids are stored in the gallbladder and mixed with bicarbonate-rich bile fluid to be secreted as bile into the lumen of the duodenum after ingestion of a meal containing fats and carbohydrates. There, their amphipathic nature aids digestion and absorption by forming micelles with dietary lipids.
Subsequently, bile acids are absorbed in the distal ileum and transported back to the liver via the portal circulation for reuse, forming a closed loop known as the enterohepatic circulation. Generally, bile acids do not pass the enterocyte membrane by passive diffusion, but, rather, are taken up by dedicated molecular transport in the distal part of the small intestine (Hofmann & Hagey, 2008). A fraction of primary bile acids that escape uptake in the terminal ileum is deconjugated and dehydroxylated by the bacterial microbiome in the colon to form deoxycholate (DCA) and lithocholate (LCA), the so-called secondary bile acids. CA and CDCA are converted into DCA and LCA, respectively. Because human hepatocytes lack the molecular pathway to rehydroxylate DCA (in contrast to rodents) this secondary bile acid accumulates to form a considerable part of the circulating bile acid mix in humans, usually around 35%. These secondary bile acids are predominantly taken up by colonic mucosa, allowing for efficient recycling of sterols. The fraction of the bile acid pool that is not reabsorbed and thus lost in the feces, ~5% per cycle of the enterohepatic circulation, is compensated for by de novo bile acid synthesis. This process refuels the enterohepatic cycle. It is worth mentioning that the enterohepatic cycle is highly dynamic. The flow of bile acids through the different compartments is not only dependent on the chemical structure and conjugation status of the bile acid mix, but also on factors such as intestinal motility (Sips et al., 2018).
Because of their soap-like nature, bile acids are reported to be cytotoxic in high concentrations, although evidence for in vivo toxic effects is sparse. However, conjugation to a glycine or taurine amino-acid group decreases cytotoxicity and
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