Bile acids / Bile salts & Farnesoid X receptor (FXR / NR1H4)

Intestinal Farnesoid X receptor (FXR / NR1H4) induces the sinusoidal organic solute transporter alfa/beta (OST alfa/beta) heterodimer to efflux Bile acids / Bile salts into the portal blood for circulation to the liver. In the liver, Bile acids / Bile salts are taken up via sodium taurocholate co-transporting polypeptide (NTCP) for conjugated BAs and organic anion-transporting polypeptide (OATP) 1B1 and 1B3 for unconjugated BAs into hepatocytes
Fuchs & Trauner 2022 Nat Rev Gastroenterol Hepatol 19: 432-450

Bile Acids / Bile Salts are the endogenous ligands for FXR with different potencies in the following order: CDCA > DCA > LCA > CA > UDCA
Li et al. 2021g Inflamm Bowel Dis. 27: 1525-1540
Xie et al. 2021a

The profile of bile acids capable of agonizing or antagonizing FXR correlates with particular bacterial groups
Ding et al. 2019

Bile acid metabolites modulate colonic RORγ +T reg cells via the bile acid receptors vitamin D receptor (VDR) and FXR
Song et al. 2019b Nature 577(7790): 410-415

Oral administration of a combination of UDCA and LCA enhances expression of tight-junction molecules , including ZO-1 and Claudin-1 / CLDN1 via the FGF 15 - FXR pathway and thereby, promotes mucosal wound repair
Wang et al. 2019s Cell Rep. 26: 222–235

Bile acid activation of intestinal farnesoid X receptor (FXR ) leads to the transcription of fibroblast growth factor 19 (FGF19), which in turn modulates gut barrier integrity and downregulates bile acids synthesis in the liver
Baja & Hylemon 2018 Hepatology 67: 2074–2075

The most potent ligand for FXR is chenodeoxycholic acid , with cholic acid , deoxycholic acid and litocholic acid having a lower effect
Wahlström et al. 2016 Cell Metab. 24: 41-50

Bile Acids / Bile Salts are also ligands for the Farnesoid X receptor (FXR / NR1H4) and the G protein-coupled bile acid receptor 1 (GPBAR1)
Fiorucci et al. 2009 Trends Pharm. Sci. 30: 570-580

There is circumstantial evidence to link the activity of FXR to the regulation of bile acid synthesis from cholesterol
Mencarelli et al. 2009 J. Immunol. 183: 6657-6666

Because Bile Acids / Bile Salts might be toxic for the liver, activation of Farnesoid X Receptor (FXR / NR1H4) by natural and synthetic ligands has been shown to prevent bile acid-induced liver toxicity in a variety of rodent models
Goodwin et al. 2000 Mol. Cell 6: 517-526
Lu et al. 2000 Mol. Cell. 6: 507-515
Watanabe et al. 2004 J. Clin. Invest. 113: 1408-1418
Cariou et al. 2006 J. Biol. Chem. 281: 11039-11049
Ma et al. 2006 J. Clin. Invest. 116: 1102-1109
Kalaany et al. 2006 Annu. Rev. Physiol. 68: 159-191
Zhang et al. 2006 Proc. Natl. Acad. Sci. USA 103: 1006-1011

FXR is highly expressed in the liver, intestine, kidney, and Adrenal gland where it function as a bile acid sensor
Parks et al. 1999 Science 284: 1365-1368
Makishima et al. 1999 Science 284: 1362-1365
Wang et al. 1999b Mol. Cell 3: 543-553

see also:
Bile acids / Bile salts & Pregnane-X Receptor (PXR)
Bile acid receptors (BARS)
Biological effects / Functions & Secondary bile salts / Secondary bile acids (SBAs)