Therapeutic targeting of bile acids

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.

Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT‐777: role of submucosal neurons

“…These data raise a point of discussion about the physiological relevance of this unexpected ‘submucosal retrocontrol’ of chloride secretion in the distal colon by the membrane bile acid receptor . Until recently, it has been widely accepted, that bile acids – mainly dihydroxy bile acids − enhance the permeability and the colonic secretion of water or electrolytes.…”

Bile acids and cardiovascular function in cirrhosis

“…This profound cardiovascular dysfunction contributes to multiorgan failure in decompensated cirrhosis but its’ underlying pathogenesis is not fully understood. Exploration of the therapeutic opportunities presented by bile acid (BA) modulation in cholestatic disorders as well as in nonalcoholic fatty liver disease, obesity, diabetes and inflammatory bowel disease has imposed a new paradigm of bile acids as a signalling and metabolic crossroad . Thus, there is an abundance of data on the role of altered BA homeostasis in diseases ranging from metabolic syndrome to tumorigenesis to cirrhosis.…”

Review article: an analysis of safety profiles of treatments for diarrhoea‐predominant irritable bowel syndrome

“…A meta-analysis of six studies estimated that 28.1% of 908 patients with IBS-D were affected by bile acid malabsorption (7-day selenium homocholic acid taurine retention <10%), 64 which can occur when the absorption of bile acids in the ileum is disrupted and results in diarrhoea. 65,66 Similar results were found in a previous meta-analysis that estimated the prevalence of mild (7-day selenium homocholic acid taurine retention <15%) and moderate (7-day selenium homocholic acid taurine retention <10%) bile acid malabsorption as 26% (seven studies, n = 618) and 32% (17 studies, n = 1073), respectively, in patients with symptoms of IBS-D. 67 However, clinical studies examining the efficacy and safety of bile acid sequestrants (eg, colesevelam, cholestyramine)…”