Recent research has revealed the role of bile acids as metabolic regulators and uncovered their potential to treat a variety of diseases

Bile acids are synthesised from cholesterol in the liver. Primary bile acids in humans are cholic acid (CA) and chenodeoxycholic acid (CDCA). These are converted to secondary bile acids in the gut by microbial actions; deoxycholic acid is produced from CA, lithocholic acid from CDCA along with many other bacterial derived bile acid metabolites. Bile salts play an essential nutritional role in the solubilisation and absorption of dietary fat and lipid-soluble vitamins, as they are natural detergents. In addition, due to the detergent nature of bile acids and bile salts, they are part of the mechanism to control bacterial overgrowth in the gut by disrupting and fragmenting the cell walls of the bacteria.

It was discovered in 1999 that the natural ligand for the nuclear hormone receptor FXR was chenodeoxycholic acid and in 2002 lithocholic acid was shown to be the ligand for G-protein coupled receptor TGR5. Thus, bile acids and their salts act as hormones and are essential in the homeostasis of metabolic activities. This makes bile acids an excellent class of molecules to target metabolic conditions such as type 2 diabetes, obesity and NAFLD.

Bile acids are now shown to act on a number of other nuclear receptor’s (NRs) and G-protein coupled receptor’s (GPCRs), including VDR, PXR, CAR, M3R and S1PR2. It is thus becoming clear that bile acid signalling properties are complex and extend beyond that of FXR and TGR5, where most of current bile acid research has been conducted. One growing area of interest for bile acids is with neurodegenerative disease where UDCA is showing promising results in current clinical studies.

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Azer, Samy A; Hasanato, Rana, Medicine: October 15, 2021 – Volume 100 – Issue 41 – p e27464

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Novel Semisynthetic Derivatives of Bile Acids as Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibitors

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Colon cancer checks in when bile acids check out: the bile acid-nuclear receptor axis in colon cancer

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The role of bile acids in cholestatic liver injury

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Role of bile acids in inflammatory liver diseases

Ioannis Evangelakos, Joerg Heeren, Esther Verkade and Folkert Kuipers Semi Immunopathol. 2021 43(4):577-590.

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Molecular Physiology of Bile Acids Signaling in Health, Disease and Aging

Alessia Perino, Hadrien Demagny, Laura Velazquez-Villegas, Kristina Schoonjans, Physiological Review 2021, 101: 683-73.

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Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

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