Bile Acid Physiology

Abstract

The primary bile acids (BAs) are synthetized from colesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat, as well as bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolism by activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circulation of BAs and their functions as signaling molecules on lipid and glucose metabolism.

Exercising the hepatobiliary‐gut axis. The impact of physical activity performance

“…16 BAs contribute to digestion and absorption of fat, cholesterol and fat-soluble vitamins, but also act as signalling molecules and display antimicrobial and anti-inflammatory functions. Approximately 50% of secondary BAs are reabsorbed in the terminal ileum and colon and return to the liver via the portal vein across the enterohepatic circulation.…”

“…16 Physical activity might ameliorate BAs circulation and their pleiotropic functions because of improved gastrointestinal motility and peristalsis, but studies show conflicting results. 16 Thus, one might speculate that increased intestinal motility would also increase BA flow and therefore FXR expression, with ultimate inhibition of BA synthesis. [173][174][175] BAs activate intestinal farnesoid X receptor (FXR) which, in turn, increases the expression of the human enterokine fibroblast growth factor 19 (FGF19) leading to activation of the hepatic FGF4 receptor/b-clotho and subsequent small heterodimer-mediated inhibition of BA synthesis.…”

“…16,179 Whether physical exercise will induce additional BA-mediated metabolic or anti-inflammatory effects (see below) is unclear so far, due to the poor translational value of animal studies (see above). Intestinal GPBAR-1 governs metabolically relevant hormonal pathways (ie, release of peptide YY and glucagon-like peptides GLP-1 and GLP-2) with effects on appetite, glucose and insulin metabolism via the tissue GPBAR-1 receptors located in the cells of brown adipose tissue and skeletal muscle.…”

“…15 The role of physical activity should also be considered with respect to intestinal bile acid (BA) metabolism and intestinal microbiota. 16 This review discusses current views on the mechanisms relating physical activity to NAFLD, gallbladder disease, bile acids, gut microbiota and metabolic inflammatory changes ( Figure 1). Of note, BAs are also signalling molecules which modulate epithelial cell proliferation, gene expression and energy, glucose, lipid and lipoprotein metabolism via activation of intestinal farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (GPBAR-1) found in the intestine, liver Kupffer cells, striated muscle and brown adipose tissue.…”

Pathophysiological connections between gallstone disease, insulin resistance, and obesity

“…In patients with obesity, treatment with vancomicyn but not amoxicillin for 7 days decreased microbioma diversity and faecal secondary BAs in association with impaired insulin sensitivity, suggesting a direct impact of the microbioma‐BAs axis on insulin sensitivity. The differential potency of specific BAs to activate nuclear and cell surface receptors is a hypothetic mechanism by which microbiota influences insulin sensitivity status; however, this hypothesis remains to be experimentally tested (Figure B).…”