Lewy body diseases and the gut

Area of Science:

• Neuroscience
• Gastroenterology
• Microbiology

Background:

• Gastrointestinal (GI) dysfunction is a long-recognized feature of Lewy body diseases (LBDs).
• Emerging evidence suggests pathogenic alpha-synuclein (⍺-syn) may originate in the GI tract and spread to the brain.
• The gut microbiome, immune system, and environmental factors are implicated in LBD pathogenesis.

Purpose of the Study:

• To review clinical observations linking GI dysfunction to LBDs.
• To explore the cellular and mechanistic origins of ⍺-syn propagation in the GI tract.
• To identify critical knowledge gaps in understanding the gut-brain axis in LBDs.

Main Methods:

• Review of clinical observations and experimental LBD models.
• Focus on GI anatomy and relevant cellular components, particularly enteroendocrine cells.
• Analysis of interactions between the gut microbiome, toxicants, and ⍺-syn pathology.

Main Results:

• Enteroendocrine cells expressing ⍺-syn are strategically positioned for gut-brain communication.
• Gut microbes and environmental toxicants can trigger and modify ⍺-syn pathology.
• Metabolic and immunological responses within the GI tract contribute to LBDs.

Conclusions:

• Further research into GI pathophysiology is crucial for understanding LBD risk and progression.
• Targeting the gut-brain axis offers potential therapeutic strategies for LBDs.
• Addressing knowledge gaps will accelerate discoveries in LBD mechanisms and treatments.