Therapeutic targeting of bile acids

Am J Physiol Gastrointest Liver Physiol. 2015 Aug 15;309(4):G209-15. doi: 10.1152/ajpgi.00121.2015. Epub 2015 Jul 2.

Abstract

The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control.

Keywords: bile acids; pharmacotherapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Bile Acids and Salts / pharmacology
  • Bile Acids and Salts / therapeutic use
  • Gastrointestinal Diseases / drug therapy
  • Gastrointestinal Diseases / metabolism*
  • Humans
  • Liver Diseases / drug therapy
  • Liver Diseases / metabolism*
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Bile Acids and Salts
  • GPBAR1 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor