Is bile recycled through the enterohepatic circulation?

From the Guidelines

Bile is indeed recycled through the enterohepatic circulation, with up to 95% of bile acids being reabsorbed in the small intestine and returned to the liver for reprocessing and reuse 1.

Key Points

• The enterohepatic circulation is a highly efficient process that recycles bile salts, allowing them to be reused 4-12 times during a single digestive period.
• The liver plays a crucial role in this process, reprocessing reabsorbed bile salts and secreting them back into bile.
• The small amount of bile salts not reabsorbed (about 5%) is excreted in feces, and the body produces about 0.2-0.6 grams of new bile acids daily to replace what is lost.
• The enterohepatic circulation helps maintain a constant pool of about 2-4 grams of bile acids in the body, which is essential for efficient fat digestion and absorption, as well as for eliminating certain waste products and maintaining cholesterol homeostasis.

Clinical Implications

• Understanding the enterohepatic circulation of bile is important for diagnosing and managing conditions such as bile acid diarrhea, which can be caused by impaired bile acid reabsorption or excessive bile acid production.
• Tests such as SeHCAT scanning and measurement of serum bile acid precursors can help diagnose bile acid diarrhea and monitor response to treatment 1.
• Treatment options for bile acid diarrhea may include bile acid sequestrants, which can help bind excess bile acids in the gut and reduce symptoms.

From the FDA Drug Label

After absorption, ursodiol enters the portal vein and undergoes efficient extraction from portal blood by the liver (i.e., there is a large “first-pass” effect) where it is conjugated with either glycine or taurine and is then secreted into the hepatic bile ducts. Ursodiol in bile is concentrated in the gallbladder and expelled into the duodenum in gallbladder bile via the cystic and common ducts by gallbladder contractions provoked by physiologic responses to eating A small proportion of orally administered drug undergoes bacterial degradation with each cycle of enterohepatic circulation. Reabsorbed free ursodiol is reconjugated by the liver

Bile recycling occurs through the process of enterohepatic circulation, where bile is secreted into the hepatic bile ducts, stored in the gallbladder, and then expelled into the duodenum. The bile is then reabsorbed in the small bowel and returned to the liver via the portal vein, where it can be reconjugated and re-secreted into bile. This process allows for the recycling of bile. 2

From the Research

Bile Recycling Mechanism

• Bile is recycled in the body through a process called enterohepatic circulation, which preserves bile in the body through its efficient synthesis, transport, absorption, and reuptake 3.
• This circulation is mediated by four main bile salt transport pathways, including the apical sodium-dependent bile acid transporter, the basolateral heteromeric organic solute transporter, the Na+ -taurocholate cotransporting polypeptide, and the apical bile salt export pump 4.
• The enterohepatic circulation of bile salts is essential for the efficient elimination of cholesterol, bilirubin, and potentially harmful exogenous lipophilic substances from the body 3.

Factors Affecting Bile Recycling

• Ursodeoxycholic acid (UDCA) has been shown to accelerate bile acid enterohepatic circulation by inhibiting farnesoid X receptor (FXR) signalling in the ileum and FGF15/19 in the liver, leading to increased expression of bile acid transporters in the liver 5.
• Conjugated ursodeoxycholate and cholate have been found to have different effects on bile acid synthesis in chronic bile fistula rats, with taurocholic acid inhibiting synthesis of chenodeoxycholate and its metabolites, while tauroursodeoxycholic acid had no suppressive effect 6.
• The bile acid pool is modulated in the enterohepatic circulation by the liver, the motility of the gallbladder and intestinal tract, and bacterial enzymes in the intestine, with the nuclear receptor FXR and Gpbar1 (TGR5) playing important roles in this process 7.

Importance of Bile Recycling

• Bile acids have a multitude of critical physiologic functions in the body, including emulsification of dietary fat, absorption of fat and fat-soluble vitamins, and maintenance of glucose, lipid, and energy homeostasis 3.
• Dysregulation of bile acid enterohepatic circulation has been implicated in various disorders, including cholestatic and metabolic disorders, and liver cirrhosis 4, 7.