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Review
. 2025 Jan;82(1):134-153.
doi: 10.1016/j.jhep.2024.09.032. Epub 2024 Sep 28.

Bile acid metabolism and signalling in liver disease

Claudia D Fuchs  1 , Benedikt Simbrunner  1 , Maximillian Baumgartner  2 , Clarissa Campbell  3 , Thomas Reiberger  1 , Michael Trauner  4
Affiliations
Free article
Review

Bile acid metabolism and signalling in liver disease

Claudia D Fuchs et al. J Hepatol. 2025 Jan.
Free article

Abstract

Bile acids (BAs) serve as signalling molecules, efficiently regulating their own metabolism and transport, as well as key aspects of lipid and glucose homeostasis. BAs shape the gut microbial flora and conversely are metabolised by microbiota. Disruption of BA transport, metabolism and physiological signalling functions contribute to the pathogenesis and progression of a wide range of liver diseases including cholestatic disorders and MASLD (metabolic dysfunction-associated steatotic liver disease), as well as hepatocellular and cholangiocellular carcinoma. Additionally, impaired BA signalling may also affect the intestine and kidney, thereby contributing to failure of gut integrity and driving the progression and complications of portal hypertension, cholemic nephropathy and the development of extrahepatic malignancies such as colorectal cancer. In this review, we will summarise recent advances in the understanding of BA signalling, metabolism and transport, focusing on transcriptional regulation and novel BA-focused therapeutic strategies for cholestatic and metabolic liver diseases.

Keywords: Microbiota; Transport; bile acid homeostasis; cholestatic and metabolic disease.

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Conflict of interest statement

Conflict of interest CDF received travel grants from Gilead, Roche, Falk, Merck, Vifor, AbbVie, and Boehringer-Ingelheim. BeSi has received travel support from AbbVie, Gilead, and Falk. TR received grant support from Abbvie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Abbvie, Boehringer-Ingelheim, Gilead and Roche. MT received grant support from Albireo, Alnylam, Cymabay, Falk, Genentech, Gilead, Intercept, MSD, Takeda and UltraGenyx, honoraria for consulting from AbbVie, Albireo, Agomab, Boehringer Ingelheim, BiomX, Chemomab, Dexoligo Therapeutics, Falk, Genfit, Gilead, GSK, Hightide, Intercept, Ipsen, Jannsen, MSD, Novartis, Phenex, Pliant, Regulus, Siemens and Shire, speaker fees from Albireo, Boehringer Ingelheim, Bristol-Myers Squibb, Falk, Gilead, Ipsen, Intercept, MSD and Madrigal, as well as travel support from AbbVie, Falk, Gilead, Jannsen and Intercept. He is also co-inventor of patents on the medical use of 24-norursodeoxycholic acid filed by the Medical University of Graz. MB and CC report no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details.

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