Ursodeoxycholic acid accelerates bile acid enterohepatic circulation

Area of Science:

• Hepatology and Gastroenterology
• Bile Acid Metabolism
• Pharmacology

Background:

• Ursodeoxycholic acid (UDCA) is a primary treatment for primary biliary cholangitis.
• Its impact on bile acid (BA) enterohepatic circulation remains incompletely understood.

Purpose of the Study:

• To investigate the influence of UDCA on BA enterohepatic circulation in vivo.
• To elucidate the mechanisms by which UDCA affects BA kinetics.

Main Methods:

• Mice were administered UDCA and other BAs to assess changes in BA pool and transporters.
• Isotope dilution techniques and biochemical analyses were employed to study BA kinetics.
• Mechanistic investigations focused on the role of FXR and FGF15/19 signaling.

Main Results:

• UDCA administration reduced the overall BA pool and increased conjugated UDCA species (TUDCA, GUDCA).
• Expression of key BA transporters in the ileum and liver was upregulated.
• UDCA shortened BA cycling time, accelerating enterohepatic circulation via FXR and FGF15/19 inhibition.

Conclusions:

• UDCA accelerates BA enterohepatic circulation by inhibiting intestinal FXR signaling and reducing FGF15/19.
• This leads to enhanced BA transporter expression in the liver, promoting BA homeostasis.
• UDCA plays a crucial role in maintaining in vivo BA enterohepatic circulation balance.