Bile acids

Bile acids are steroid acids found predominantly in the bile.

Diverse bile acids are synthesized in the liver.

Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.  

Primary bile acids are those synthesized by the liver. 

Secondary bile acids result from bacterial actions in the colon. 

The major bile acids: taurocholic acid and glycocholic acid, derivatives of cholic acid, and taurochenodeoxycholic acid and glycochenodeoxycholic acid, (

derivatives of chenodeoxycholic acid.

These are roughly equal in concentration.

The salts of their 7-alpha-dehydroxylated derivatives, deoxycholic acid and lithocholic acid, are also found, with derivatives of cholic, chenodeoxycholic and deoxycholic acids accounting for over 90% of human biliary bile acids.

Bile acids comprise about 80% of the organic compounds in bile.

Other organic compounds in bile

are phospholipids and cholesterol.

An increased secretion of bile acids produces an increase in bile flow. 

Bile acids help in the  digestion of dietary fats and oils. 

Bile acids are micelle-forming surfactants, which encapsulate nutrients, facilitating their absorption.

Bile acids also have hormonal actions throughout the body, particularly through the farnesoid X receptor.

Bile acid synthesis occurs in liver cells.

Liver cells synthesize the primary bile acids cholic acid and chenodeoxycholic acid via cytochrome P450-mediated oxidation of cholesterol in a multi-step process. 

Approximately 600 mg of bile salts are synthesized daily.

Bile acids are produced to replace bile acids lost in the feces.

Larger amounts of bile acids are secreted, and reabsorbed in the gut and recycled.

Prior to secreting any of the bile acids the liver cells conjugate them with either glycine or taurine, to form a total of 8 possible conjugated bile acids. 

Conjugated bile acids are often referred to as bile salts. 

The pKa of the unconjugated bile acids are between 5 and 6.5.

The pH of the duodenum ranges between 3 and 5, so when unconjugated bile acids are in the duodenum, they are almost always protonated, making  them relatively insoluble in water. 

Conjugating bile acids with amino acids lowers the pKa of the bile-acid/amino-acid conjugate to between 1 and 4. 

Conjugated bile acids are almost always in their deprotonated (A-) form in the duodenum, making them much more water-soluble and much more able to fulfil their physiologic function of emulsifying fats.

Bile salts are modified by gut bacteria by partial dehydroxylation.

Their glycine and taurine groups are removed to give the secondary bile acids, deoxycholic acid and lithocholic acid. 

Cholic acid is converted into deoxycholic acid and chenodeoxycholic acid into lithocholic acid. 

These bile acids are recycled in the enterohepatic circulation.

When the concentration of bile acids/salts in the small intestine is high enough, they form micelles and solubilize lipids. 

Bile acid-containing micelles aid lipases to digest lipids and bring them near the intestinal brush border membrane, which results in fat absorption.

The body produces about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis producing 400–600 mg daily. 

Adults secrete between 12-18 g of bile acids into the intestine each day, mostly after meals. 

The bile acid pool size is between 4–6 g, which means that bile acids are recycled several times each day. 

About 95% of bile acids are reabsorbed by active transport in the ileum and recycled back to the liver for further secretion into the biliary system and gallbladder: referred to as the enteropathic circulation.

This enterohepatic circulation of bile acids allows a low rate of synthesis, only about 0.3g/day, but with large amounts being secreted into the intestine.

Additionally, bile acids functions include: eliminating cholesterol from the body, driving the flow of bile to eliminate certain catabolites, emulsifying fat-soluble vitamins to enable their absorption, and aiding in motility and the reduction of the bacteria flora found in the small intestine and biliary tract.

Bile acids have metabolic act through two specific receptors, the farnesoid X receptor and G protein-coupled bile acid receptor/TGR5.

The principal human bile acids

Cholic acid


Glycocholic acid


Taurocholic acid

Deoxycholic acid


Chenodeoxycholic acid

Glycochenodeoxycholic acid

Taurochenodeoxycholic acid

Lithocholic acid

Chenodeoxycholic acid is the prototypic functional bile acid.

Cholic acid is the most abundant bile acid in humans.

Deoxycholic acid is formed from cholic acid by 7-dehydroxylation, and is water-soluble and rather toxic to cells.

Because they are surfactants or detergents, bile acids are potentially toxic to cells.

Their concentrations are tightly regulated: FXR activation in the liver inhibits synthesis of bile acids, and is one mechanism of feedback control when bile acid levels are too high. 

FXR activation by bile acids during absorption in the intestine increases transcription and synthesis of FGF19, which then inhibits bile acid synthesis in the liver.

Bile acids bind to some other proteins in addition to their hormone receptors (FXR and TGR5) and their transporters, and 

play important roles in stress and pain responses, appetite, and lifespan. 

Bile acids are made from endogenous cholesterol, and disruption of the enterohepatic circulation of bile acids results in lower cholesterol levels.

Bile acid sequestrants bind bile acids in the gut, preventing reabsorption, therefore more endogenous cholesterol is shunted into the production of bile acids, thereby lowering cholesterol levels. 

Sequestered bile acids are then excreted in the feces.

Structural or functional abnormalities of the biliary system result in an increase in bilirubin and in bile acids in the blood. 

Bile acids are related to pruritus.

Pruritus is common in cholestatic conditions such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis or intrahepatic cholestasis of pregnancy.

Ursodeoxycholic  acid is used for cholestatic disorders.

Gallstones may result from increased saturation of cholesterol or bilirubin, or from bile stasis. 

Lower concentrations of bile acids or phospholipids in bile reduce cholesterol solubility and lead to microcrystal formation. 

Oral therapy with chenodeoxycholic acid and/or ursodeoxycholic acid has been used to dissolve cholesterol gallstones.

Bile acid therapy may be of value to prevent stones following bariatric surgery.

Excess concentrations of bile acids in the colon are a cause of chronic diarrhea. 

Bile acid diarrhea is commonly found when the ileum is abnormal or has been surgically removed, as in Crohn’s disease.

Bile acid diarrhea can cause a condition that resembles diarrhea-predominant irritable bowel syndrome (IBS-D). 

Bile acid diarrhea/bile acid malabsorption can be treated with bile acid sequestrants.

Deoxycholic acid (DCA) is increased in the colonic contents of humans in response to a high fat diet.

In populations with a high incidence of colorectal cancer, the fecal concentrations of bile acids are higher, suggesting that aan increased colonic exposure to bile acids could play a role in the development of cancer. 

Fecal DCA concentrations in Native Africans in South Africa who have a low fat diet, compared to African Americans, who eat a higher fat diet, is  7.30 vs. 37.51 nmol/g wet weight stool.

Native Africans in South Africa have a low incidence rate of colon cancer of less than 1:100,000, compared to the high incidence rate for male African Americans of 72:100,000.

Exposure of colonic cells to high DCA concentrations increase formation of reactive oxygen species, causing oxidative stress, and also increase DNA damage.

Bile acids may be used in subcutaneous injections to remove unwanted fat.

Deoxycholic acid as an injectable has received FDA approval to dissolve submental fat.

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