Ursodiol (Ursodeoxycholic acid, UDCA) is a naturally-occurring bile acid that can be detected in small amounts in normal human bile and greater amounts in the bile of certain bear species. It’s a bitter-tasting white or almost white powder made up of crystalline particles that are easily soluble in alcohol and glacial acetic acid, sparingly soluble in chloroform, marginally soluble in ether, acetone, and methylene chloride, and almost insoluble in water.


Bile acids are acidic steroids produced by the liver’s hepatocytes from cholesterol. UDCA is a dihydroxy (i.e. 3, 7-dihydroxy-5-cholan-24-oic acid) hydrophilic bile acid . Its protonated form has a solubility of 9 mol/l and a melting point of 203°C. UDCA contributes to up to 4% of the bile acid pool in humans, and because it is not generated in the liver, it is thought to originate in the colon through bacterial 7 epimerization of the major bile acid chenodeoxycholic. Following its production, UDCA is passively absorbed by the colonic mucosa, allowing it to enter the portal circulation and, as a result, the bile acid pool.

How does Ursodiol help in liver disease?

Bile acids accumulate in the liver, systemic circulation, and peripheral organs in experimental models of cholestatic liver disorders. The intracellular accumulation of hydrophobic (toxic) bile acids in the liver cause a variety of cell-damaging processes, including increased cell-membrane fluidity and permeability, as well as programmed cell death (apoptosis) and necrosis. The degree of cell damage is related to the level and duration of liver exposure to hepatotoxic bile acids. A brief rise in bile acids inside hepatocytes, for example, can cause reversible transaminase elevation.

Hepatocytes exposed to toxic bile acids during prolonged cholestasis, on the other hand, are likely to cause liver fibrosis and cirrhosis.

One of the main therapeutic mechanisms of UDCA in cholestatic liver illnesses has been proposed to be the displacement of endogenous hepatotoxic bile through the growth of the hydrophilic bile acid pool (i.e. enrichment by UDCA). This protective activity of UDCA could be linked to competitive displacement of endogenous (i.e. harmful) bile acids at the ileal absorption level or the hepatocyte level (i.e. cell-plasma membrane, intracellular organelles, etc.) Indeed, by inhibiting ileal absorption of endogenous bile acids at the terminal ileum level, oral treatment of UDCA may limit the ileal absorption of endogenous bile acids. The composition of the bile acid pool is not considerably altered by UDCA’s competition for the ileal uptake of more hydrophobic bile salts. Furthermore, intravenous infusion of conjugated UDCA reduced the hepatotoxicity caused by toxic bile acids in the bile fistula rat model. As a result, it appears that UDCA has a protective effect at the level of the liver. Because UDCA is hydrophilic, it causes no cell membrane or subcellular damage in people or in vitro models at concentrations up to 500 mol/l. Furthermore, when compared to the effects of bile acid-binding resins, which were previously utilized to alleviate the intrahepatic consequences of cholestasis, treatment with UDCA had no significant effect on de novo bile acid synthesis in the liver.

The precise role of UDCA in avoiding liver injury by ‘displacement’ of endogenous (i.e. hepatotoxic) bile acids is unknown. Beuers et al. found that 1 month of UDCA therapy improved the liver blood tests of individuals with cholestatic liver disorders without a decrease in the pool size or serum levels of the key endogenous hydrophobic bile acids. The pool size of bile acids and serum concentration of chenodeoxycholic acid did not alter before and after treatment in another trial of individuals with primary sclerosing cholangitis (PSC) treated with UDCA for 3 months.

What does new research say?

In the ileum and cecum, dose-dependent ursodiol-mediated changes in gut microbial community structures were found. Members of the Lachnospiraceae Family (Phylum Firmicutes, Class Clostridia) largely contributed to the observed changes in both the ileum and the cecum. Lachnospiraceae are Gram-positive obligate anaerobes found in large numbers in the intestines of numerous mammals, including humans and mice. Because of their involvement with butyric acid synthesis, which is required for microbial and host cell proliferation, members of the Lachnospiraceae have been related to obesity and may protect from colon cancer. Furthermore, moon colonization of germ-free mice with a Lachnospiraceae isolate enhanced clinical outcomes and partially restored colonization resistance to the intestinal pathogen Clostridioides difficile. Overall, stressing the various illness states in which members of the Lachnospiraceae family play a role, as well as demonstrating prospective applications of ursodiol-mediated Lachnospiraceae expansion to precisely modify microbial-mediated disease states.

Recurrent primary biliary cholangitis (PBC) following liver transplantation (LT) is thought to affect 10–35 percent of patients, albeit identifying and diagnosing the condition is difficult. Differences in immunosuppression and the presence of anti-mitochondrial antibody titers post-transplant have been suggested as risk factors for recurrence. Although ursodiol has been demonstrated to enhance patient alkaline phosphatase (ALP) levels, there are no established guidelines for the treatment of recurrent PBC.

Sources and references: Ursodeoxycholic acid ‘Mechanisms of action and clinical use in Hepatobiliary disorders’ by Lazaridis et al. (2001).

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