Intestinal Absorption of Bile Acids in Health and Disease

Abstract

The intestinal reclamation of bile acids is crucial for the maintenance of their enterohepatic circulation. The majority of bile acids are actively absorbed via specific transport proteins that are highly expressed in the distal ileum. The uptake of bile acids by intestinal epithelial cells modulates the activation of cytosolic and membrane receptors such as the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1), which has a profound effect on hepatic synthesis of bile acids as well as glucose and lipid metabolism. Extensive research has focused on delineating the processes of bile acid absorption and determining the contribution of dysregulated ileal signaling in the development of intestinal and hepatic disorders. For example, a decrease in the levels of the bile acid-induced ileal hormone FGF15/19 is implicated in bile acidinduced diarrhea (BAD). Conversely, the increase in bile acid absorption with subsequent overload of bile acids could be involved in the pathophysiology of liver and metabolic disorders such as fatty liver diseases and type 2 diabetes mellitus. This review article will attempt to provide a comprehensive overview of the mechanisms involved in the intestinal handling of bile acids, the pathological implications of disrupted intestinal bile acid homeostasis, and the potential therapeutic targets for the treatment of bile acid-related disorders.

The 1β-Hydroxy-Deoxycholic Acid to Deoxycholic Acid Urinary Metabolic Ratio: Toward a Phenotyping of CYP3A Using an Endogenous Marker?

“…However, as most of the drugs are administered orally, we believe that an ideal endogenous probe should also reflect CYP3A intestinal metabolism. In this context, bile acids are promising CYP3A biomarkers, since they are actively reabsorbed in the distal ileum by the apical sodium-dependent bile acid transporter [ 47 ]. DCA is a secondary bile acid produced through 7-dehydroxylation by gut bacteria of cholic acid (CA), which is a primary bile acid synthesized from cholesterol into the liver [ 22 ].…”

Disturbances in Cholesterol Homeostasis and Non-alcoholic Fatty Liver Diseases

“…Other processes involving cholesterol in the liver include esterification by ACAT2 for storage, excretion into bile by the function of heterodimer of ATP-binding cassette transporters ABCG5/G8 found on the canalicular membrane of hepatocytes, or the conversion to bile acids by a complex process in which the cytochrome P450 7A1 (CYP7A1) enzyme mediates the rate-limiting reaction ( 8 ). The expression of CYP7A1 is mainly regulated by a signal generated from the ileum represented by fibroblast growth factor 19 in human and 15 in rodents (FGF19/15) ( 12 ). The synthesis and secretion of FGF19/15 are induced by the uptake of bile acids by enterocytes in the distal ileum that is mediated by the action of the apical sodium dependent bile acid transporter ASBT.…”

“…Blocking the absorption of bile acids eliminates the negative feedback inhibition on their hepatic synthesis and promotes cholesterol degradation ( 12 ). ASBT mediates the first and rate limiting step in bile acid absorption and its inhibition represents an attractive therapeutic target to reduce hepatic cholesterol toxicity in NAFLD/NASH ( 12 ). Recent studies provided a compelling evidence showing that the lack of ASBT in knockout mice protected against diet-induced liver injury and steatosis ( 54 ).…”

Microbial Metabolites in Colorectal Cancer: Basic and Clinical Implications

“…In the gastrointestinal tract, primary bile acids are mostly re-absorbed via enterohepatic circulation in the ileum. However, ~5% of bile acids are deconjugated and biotransformed to secondary bile acids via the action of gut microbiota in colon [ 75 ]. CA and CDCA are dehydroxylated to generate deoxycholic acid (DCA) and lithocholic acid (LCA) respectively.…”