Enrichment of gut-derived metabolites in a Parkinson's disease subtype with REM sleep behavior disorder

Area of Science:

• Neuroscience
• Microbiology
• Metabolomics

Background:

• Idiopathic REM sleep behavior disorder (iRBD) is a prodrome of α-synucleinopathies, often showing gut microbial changes.
• Parkinson's disease (PD) is heterogeneous, with less than 50% of cases exhibiting RBD at onset.
• Understanding metabolic differences in PD subtypes is crucial for diagnosis and treatment.

Purpose of the Study:

• To characterize metabolic differences in PD patients with and without RBD using untargeted metabolomics.
• To identify specific gut microbial metabolites associated with PD subtypes.
• To explore potential mechanistic links between gut dysbiosis, iRBD, and PD with RBD.

Main Methods:

• Plasma samples analyzed using untargeted metabolomics.
• Comparison of metabolic profiles between PD patients with RBD, PD patients without RBD, iRBD subjects, and healthy controls.
• Identification and quantification of gut microbial-origin metabolites.

Main Results:

• PD patients with RBD showed enrichment of gut microbial metabolites, including secondary bile acids and p-cresol sulfate.
• PD patients without RBD had elevated levels of metabolites linked to neuropsychiatric diseases.
• P-cresol sulfate, a gut microbial metabolite, was predicted to cross the blood-brain barrier.

Conclusions:

• Distinct metabolic signatures differentiate PD subtypes based on RBD status.
• Gut microbial dysbiosis and specific metabolites like p-cresol sulfate may play a role in PD with RBD.
• The findings highlight the heterogeneity of PD and suggest potential gut-brain axis mechanisms.