# Bile acids as therapeutic agents

## TL;DR

Bile acids, once known for aiding digestion, are now being explored for their potential in treating various diseases like liver and metabolic disorders.

## Contribution

This review highlights the expanding therapeutic applications of bile acids and their mechanisms of action in multiple disease contexts.

## Key findings

- Ursodeoxycholic acid is FDA-approved for primary biliary cholangitis and used off-label for other disorders.
- Bile acids modulate signaling pathways and reduce liver injury through receptors like FXR, VDR, and TGR5.
- New bile acid therapies are being tested for diseases such as cerebrotendinous xanthomatosis and primary sclerosing cholangitis.

## Abstract

Bile acids (BAs) are amphiphilic molecules traditionally recognized for their role in lipid digestion but have gained increased interest for their therapeutic potential. Among them, ursodeoxycholic acid (UDCA) is the most widely prescribed and has been FDA-approved in the treatment of primary biliary cholangitis (PBC), the most common chronic cholestatic liver disease, while also being used off-label in multiple other disorders. The therapeutic effects of BAs are linked to their capacity to modulate signaling pathways, reduce hepatocellular injury, and regulate inflammation. Their physicochemical properties, particularly hydrophobicity, influence both efficacy and toxicity, of which the mechanisms involving receptors such as farnesoid X receptor (FXR), vitamin D receptor (VDR) and Takeda G protein-coupled receptor 5 (TGR5) help to explain. Recent regulatory milestones include the FDA-approval of chenodeoxycholic acid (CDCA) in the treatment of cerebrotendinous xanthomatosis (CTX) and ongoing clinical trials such as that of norucholic acid (NCA) in the treatment of primary sclerosing cholangitis (PSC). Expanding research is redefining the BA therapeutic landscape, with applications spanning cholestatic, metabolic, and neurodegenerative diseases. This review will explore established and emerging BA-based monotherapies, combination regimens, and novel BA-driven drug delivery systems.