Elevated circulating bile acids driven erythrocyte osmotic resistance marks hepatobiliary disease

Area of Science:

• Hepatology
• Red Blood Cell Physiology
• Biochemistry

Background:

• Cholemia, characterized by elevated circulating bile acids (BA), is an early indicator of hepatobiliary disorders.
• Current detection methods are limited as BA are not routinely measured.
• Bile acids' membrane-disrupting properties may affect red blood cell (RBC) function.

Purpose of the Study:

• To investigate the hypothesis that bile acids impact RBC osmotic resistance (OR).
• To explore the potential of RBC OR as a diagnostic marker for cholemia.
• To assess the relevance of RBC OR changes in cholestatic liver disease.

Main Methods:

• Examined RBC osmotic resistance in mouse models of cholemia and germ-free animals.
• Analyzed RBC OR in patients with cholestatic liver disease.
• Correlated RBC OR with serum BA levels and assessed effects of BA and gut microbiota.

Main Results:

• RBC from cholemic mice showed significantly elevated OR against hypotonic solutions.
• Elevated OR correlated with serum BA levels across various mouse models.
• RBC from patients with cholestatic liver disease also exhibited increased OR, suggesting human relevance.
• Increased membrane rigidity, indicated by a higher cholesterol-to-phospholipid ratio, was observed in RBC from cholemic subjects.

Conclusions:

• Increased RBC osmotic resistance is a novel finding associated with cholemia.
• RBC OR changes, potentially due to increased membrane rigidity, may serve as a basis for a whole-blood diagnostic test for cholemia.
• This study provides proof-of-concept for a new detection method for early-stage liver disease.