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Bile Acids – Function, Formation and Clinical Significance

Bile acids are natural compounds produced by the liver from cholesterol. They are essential for fat digestion and the absorption of fat-soluble vitamins in the intestine.

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Things worth knowing about "Bile Acids"

Bile acids are natural compounds produced by the liver from cholesterol. They are essential for fat digestion and the absorption of fat-soluble vitamins in the intestine.

What Are Bile Acids?

Bile acids are biologically active molecules synthesized in the liver from cholesterol. They are a key component of bile and are essential for the digestion and absorption of dietary fats and fat-soluble vitamins (A, D, E, K). In the intestine, they are mostly found as bile salts – conjugates of bile acids with amino acids such as glycine or taurine – which increases their solubility and effectiveness.

Formation and Function

The liver produces approximately 0.2 to 0.6 grams of primary bile acids per day, mainly cholic acid and chenodeoxycholic acid. These are stored in the gallbladder and released into the small intestine after a meal.

Fat digestion: Bile acids surround fat molecules and form structures called micelles – tiny droplets that allow fats to be efficiently absorbed through the intestinal wall.
Cholesterol elimination: Converting excess cholesterol into bile acids and excreting them in stool is one of the main pathways for removing cholesterol from the body.
Signaling molecules: Recent research has revealed that bile acids also act as signaling molecules, influencing metabolic processes such as glucose regulation and immune function.

The Enterohepatic Circulation

Approximately 95% of bile acids are reabsorbed in the final section of the small intestine (the terminal ileum) and transported back to the liver via the bloodstream. This recycling process is known as the enterohepatic circulation. Bile acids cycle through this loop several times per day. A small fraction reaches the large intestine, where gut bacteria convert them into secondary bile acids (e.g., deoxycholic acid, lithocholic acid).

Primary and Secondary Bile Acids

Primary Bile Acids

Synthesized directly in the liver, the main primary bile acids are cholic acid and chenodeoxycholic acid.

Secondary Bile Acids

Formed by bacterial transformation of primary bile acids in the colon, secondary bile acids include deoxycholic acid and lithocholic acid. At elevated concentrations, these compounds may have potentially damaging effects on the intestinal mucosa.

Bile Acids and Disease

Disruptions in bile acid metabolism can cause or contribute to various medical conditions:

Gallstones: An imbalance between bile acids, cholesterol, and phospholipids in bile can lead to the formation of gallstones.
Bile acid malabsorption: When bile acids are not sufficiently reabsorbed in the ileum (e.g., after bowel surgery or in Crohn's disease), excess bile acids enter the colon and cause diarrhea.
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC): Inflammatory conditions of the bile ducts that impair bile flow, leading to a buildup of bile acids in the liver (cholestasis).
Non-alcoholic fatty liver disease (NAFLD): Alterations in bile acid metabolism are linked to the development and progression of this condition.

Therapeutic Use

Bile acids and their synthetic derivatives are also used medically:

Ursodeoxycholic acid (UDCA): A naturally occurring bile acid produced only in small amounts in humans. It is used therapeutically to treat primary biliary cholangitis and to dissolve cholesterol gallstones.
Bile acid sequestrants (e.g., cholestyramine): These agents bind bile acids in the intestine and prevent their reabsorption, stimulating the liver to produce new bile acids from cholesterol, which lowers blood cholesterol levels.
Obeticholic acid: A synthetic bile acid derivative that acts as an agonist at the farnesoid X receptor (FXR) and is used in certain liver diseases.

References

Hofmann, A. F. & Hagey, L. R. (2008): Bile acids: Chemistry, pathochemistry, biology, pathobiology, and therapeutics. In: Cellular and Molecular Life Sciences, 65(16), 2461–2483.
Chiang, J. Y. L. (2013): Bile acids: regulation of synthesis. In: Journal of Lipid Research, 50(10), 1955–1966.
World Gastroenterology Organisation (WGO) Global Guidelines: Disorders of the Bile Ducts. Available at: https://www.worldgastroenterology.org

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