Bile acids, bioactive signalling molecules in interoceptive gut-to-brain communication

Area of Science:

• Biochemistry
• Physiology
• Neuroscience

Background:

• Bile acids (BAs) are crucial for dietary lipid and vitamin absorption.
• Beyond digestion, BAs function as bioactive signaling molecules with diverse roles.
• Significant species-specific variations exist in BA structures and modifications.

Purpose of the Study:

• To explore the potential of bile acids as cross-barrier signaling molecules.
• To investigate the role of BAs in interoceptive pathways connecting the gut to the central nervous system.
• To elucidate the mechanisms by which BAs signal from the gut lumen to internal tissues.

Main Methods:

• Review of existing literature on bile acid signaling.
• Analysis of BA interactions with nuclear and membrane receptors.
• Consideration of indirect and direct BA signaling pathways.

Main Results:

• Bile acids are excreted into the gut lumen but act on receptors in internal tissues like the liver, intestines, and brain.
• BA diversity and receptor interactions contribute to their varied functions.
• Indirect signaling occurs via activation of enterocytes, enteroendocrine cells, and immune cells.

Conclusions:

• Bile acids act as crucial interoceptive signals, informing the brain about gut lumen conditions.
• Direct BA signaling in the brain is likely significant under pathophysiological conditions with elevated BA levels.
• Understanding BA signaling pathways is key to deciphering their physiological roles.