Bile acids and gpbar-1: Dynamic interaction involving genes, environment and gut microbiome

Piero Portincasa, Agostino Di Ciaula, Gabriella Garruti, Mirco Vacca, Maria De Angelis, David Q.H. Wang

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects.

Original languageEnglish (US)
Article number3709
Pages (from-to)1-30
Number of pages30
JournalNutrients
Volume12
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Bile
  • Cholestasis
  • FXR
  • Metabolic syndrome
  • Nuclear receptors
  • TGR5
  • Thermogenesis

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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