Tauroursodeoxycholic acid

About 90% of gallstones are formed by cholesterol, which may be caused by altered gut microbiota from a high-fat diet and other factors. The gut microbiota regulates bile acid metabolism; thus, altered composition in gut microbiota may significantly change the bile acid pool and alter cholesterol secretion.

While the exact mechanism of action of tauroursodeoxycholic acid in reducing and preventing gallstone formation is unclear, tauroursodeoxycholic acid may achieve this effect in a number of ways. A recent mouse study suggests that tauroursodeoxycholic acid inhibits intestinal cholesterol absorption and lowers liver cholesterol levels by upregulating the bile acid excretion from the liver to the gallbladder. Tauroursodeoxycholic acid lowers the bile cholesterol saturation in the gallbladder, thereby increasing the solubility of cholesterol in bile. It can also maintain a specific gut microbiota composition to promote the synthesis of bile acids and reduce liver inflammation caused by the lipopolysaccharide in the blood. Ultimately, tauroursodeoxycholic acid enhances the synthesis of bile acids in the liver and reduces cholesterol in the serum and liver.

Tauroursodeoxycholic acid inhibits cell apoptosis by disrupting the mitochondrial pathway of cell death. It works by inhibiting oxygen-radical production, ameliorating endoplasmic reticulum (ER) stress, and stabilizing the unfolded protein response. Other anti-apoptotic processes mediated by tauroursodeoxycholic acid include cytochrome c release, caspase activation, DNA and nuclear fragmentation, and inhibition of p53 transactivation. It is believed that tauroursodeoxycholic acid works on multiple cellular targets to inhibit apoptosis and upregulate survival pathways.