Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease

Area of Science:

• Microbiome research
• Neurodegenerative disease mechanisms
• Parkinson's disease subtypes

Background:

• Parkinson's disease (PD) may have distinct subtypes: body-first and brain-first.
• Identifying subtype-specific biomarkers is crucial for understanding PD pathogenesis.

Purpose of the Study:

• To identify microbial and functional biomarkers differentiating body-first and brain-first PD subtypes.
• To elucidate unique pathogenic mechanisms in PD subtypes.

Main Methods:

• Classified 36 PD patients into body-first, brain-first, or undetermined subtypes using premotor REM sleep behavior disorder (RBD) and cardiac MIBG uptake.
• Performed shotgun metagenomic analysis of gut microbiome in PD subtypes and healthy controls.

Main Results:

• Body-first PD patients exhibited significant gut microbiome differences compared to brain-first PD and controls.
• Distinct profiles included increased Escherichia coli and Akkermansia muciniphila, and decreased short-chain fatty acid producers.
• Microbial gene analysis revealed higher curli protein biosynthesis and lower putrescine/spermidine biosynthesis genes in body-first PD.

Conclusions:

• Dysbiotic gut microbial alterations are significant in body-first PD, supporting the body-first/brain-first hypothesis.
• The gut microbiome represents a potential therapeutic target for PD.
• Findings suggest possibilities for developing subtype-specific PD treatments.