Microbiota-gut-brain axis and bile acids-driven neuromodulation

Area of Science:

• Neuroscience
• Metabolic Signaling
• Microbiome Research

Background:

• Bile acids, traditionally viewed as metabolic byproducts, are now recognized as critical signaling molecules.
• Dysregulation of bile acids is linked to various neurodegenerative diseases.
• The microbiota-gut-brain axis plays a significant role in bile acid-mediated neuromodulation.

Purpose of the Study:

• To explore the multifaceted roles of bile acids in neuroinflammation and metabolism.
• To elucidate the connection between the gut microbiota, bile acids, and brain pathology.
• To highlight the impact of sexual dimorphism on bile acid signaling and disease susceptibility.

Main Methods:

• Review of current literature on bile acid signaling pathways.
• Analysis of the interplay between microbiota, bile acids, and the central nervous system.
• Investigation of sex-specific differences in bile acid metabolism and function.

Main Results:

• Bile acids exhibit context-dependent neuroprotective or neurotoxic effects, acting as a "double-edged sword".
• The "microbiota-bile acids-brain axis" links peripheral metabolic changes to CNS pathology.
• Sexual dimorphism is a critical factor in bile acid heterogeneity and disease risk.

Conclusions:

• A novel "microbiota-bile acids-sex" framework is proposed to understand bile acid complexity.
• Bile acids represent a promising target for precision therapeutic interventions in neurodegenerative diseases.
• A systemic, metabolic perspective is advocated over a purely brain-centric view.