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Bile acids are potent detergents and are essential for efficient digestion and absorption of dietary fat. Bile acids are synthesized by the liver from cholesterol, excreted into bile, and stored in the gallbladder. After ingestion of a fat-containing diet, the gallbladder contracts, forcing bile to enter the lumen of the proximal duodenum. Lipids in bile acid emulsions are absorbed in the proximal jejunum, whereas the majority of bile acids are absorbed in distal ileum, whereupon they are transported back to the liver through the portal blood. Each cycle of the bile acid enterohepatic circulation pathway is associated with a small (≈5%) loss, which is replaced through de novo hepatic synthesis (1). The same amphipathic properties that allow bile acids to emulsify lipids also make them membrane-disruptive agents (2). Thus, limiting the accumulation of bile acids within cells making up the enterohepatic circulation helps to prevent cytotoxicity. Because bile acids have vastly different structures and abilities to emulsify lipids (2), the composition of the bile acid pool can markedly influence their ability to facilitate lipid digestion and absorption. The itinerary of bile acids involves transport across apical and basolateral surfaces of cells in the liver (hepatocytes) and intestine (enterocytes) (Fig. 1). Identification of the apical ileal sodium-dependent bile acid transporter (Asbt) explained how bile acids are efficiently reabsorbed by the ileal epithelial cell (3). This …

Deletion of the ileal basolateral bile acid transporter identifies the cellular sentinels that regulate the bile acid pool