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Editorial The enterohepatic circulation (EHC) is an in vivo ecological system for the conservation of bile salts allowing them to be used over and over for the absorption of fat (1–4). Conjugated bile salts are secreted from the liver and concentrated in the gallbladder where they are stored during fasting. When partly digested food products, especially fatty acids and amino acids, are released into the intestine cholecystokinin is released, the gallbladder contracts and empties bile salts into the duodenum where they aid in the digestion and absorption of fat. Bile salts are efficiently reabsorbed in the terminal ileum and return to the liver through the portal vein. A 70-kg human secretes ‫ف‬ 30 g (range 15–45 g) of bile salt per 24 h (‫ف‬ 1 mmol/kg per 24 h). Of that 30 g, ‫ف‬ 0.3–0.5 g (‫ف‬ 1 mmol) is lost in the feces and this loss is compensated by the hepatic synthesis from cholesterol (3). Thus, 98% of the bile acid is reabsorbed, passes into the portal vein, and returns to the liver. However, the total bile acid pool (mainly residing in the gallbladder and the gut) is only ‫ف‬ 3 g (‫ف‬ 100 ␮ mol/kg). This means that on average the pool must circulate ‫ف‬ 10 times every 24 h to give a secretion rate of 30 g. Thus, a small synthetic rate (0.3–0.5 g/d) is adequate to maintain a 3-g pool and the EHC assures the pool to circulate repeatedly allowing us to absorb copious fat. The discovery of the EHC of bile is ascribed to M. Schiff in 1870 (1) but it was later realized that not all bile constituents recirculated, only the bile salts do. The EHC confines the bile salt pool to the liver, bile ducts, gallbladder, small intestine, and the portal vein. This led investigators to postulate that there was an active transport system in the intestines to remove bile salts from the intestinal lumen and a second active transport system in the liver to extract bile salts from portal blood. A number of investigators in the early 1960s located the active transport system in the ileum and noted its dependence on sodium. The active removal of bile salts from portal blood was recognized even earlier (4) because of the virtual absence of bile acids in the systemic circulation. Recently, some of the key molecules of the bile salt EHC have been discovered …

Point mutations in the ileal bile salt transporter cause leaks in the enterohepatic circulation leading to severe chronic diarrhea and malabsorption.