Bile Acids: A Communication Channel in the Gut-Brain Axis

Neuromolecular Med. 2021 Mar;23(1):99-117. doi: 10.1007/s12017-020-08625-z. Epub 2020 Oct 21.

Abstract

Bile acids are signalling hormones involved in the regulation of several metabolic pathways. The ability of bile acids to bind and signal through their receptors is modulated by the gut microbiome, since the microbiome contributes to the regulation and synthesis of bile acids as well to their physiochemical properties. From the gut, bacteria have been shown to send signals to the central nervous system via their metabolites, thus affecting the behaviour and brain function of the host organism. In the last years it has become increasingly evident that bile acids affect brain function, during normal physiological and pathological conditions. Although bile acids may be synthesized locally in the brain, the majority of brain bile acids are taken up from the systemic circulation. Since the composition of the brain bile acid pool may be regulated by the action of intestinal bacteria, it is possible that bile acids function as a communication bridge between the gut microbiome and the brain. However, little is known about the molecular mechanisms and the physiological roles of bile acids in the central nervous system. The possibility that bile acids may be a direct link between the intestinal microbiome and the brain is also an understudied subject. Here we review the influence of gut bacteria on the bile acid pool composition and properties, as well as striking evidence showing the role of bile acids as neuroactive molecules.

Keywords: Bile acids; Gut microbiome; Gut-brain axis; Neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Brain / metabolism*
  • Cholesterol / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Eating
  • Enterochromaffin Cells / metabolism
  • Fermentation
  • Gallbladder / metabolism
  • Gastrointestinal Microbiome*
  • Germ-Free Life
  • Humans
  • Liver / metabolism
  • Mice
  • Neurodegenerative Diseases / metabolism
  • Neurotransmitter Agents / metabolism
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • Stroke / metabolism
  • Xanthomatosis, Cerebrotendinous / metabolism

Substances

  • Bile Acids and Salts
  • Neurotransmitter Agents
  • Receptors, Cell Surface
  • Cytochrome P-450 Enzyme System
  • Cholesterol