Investigating Plasma Metabolomics and Gut Microbiota Changes Associated With Parkinson Disease

BACKGROUND AND OBJECTIVES: Coffee intake is linked to a reduced risk of Parkinson disease (PD), but whether this effect is mediated by gut microbiota and metabolomic changes remains unclear. This study examines PD-associated metabolomic shifts, caffeine metabolism, and their connection to gut microbiome alterations in a multicenter study. METHODS: We conducted an untargeted serum metabolomic assay using liquid chromatography with high-resolution mass spectrometry on an exploratory cohort recruited from National Taiwan University Hospital (NTUH). A targeted metabolomic assay focusing on caffeine and its 12 downstream metabolites was conducted and validated in an independent cohort from University Malaya Medical Centre (UMMC). In the exploratory cohort, the association of each caffeine metabolite with gut microbiota changes was investigated by metagenomic shotgun sequencing. A clustering-based approach was used to correlate microbiome changes with plasma caffeine metabolite level and clinical severity. Body mass index, antiparkinsonism medication use, and dietary habits (including coffee and tea intake) were recorded. RESULTS: . DISCUSSION: This study identifies PD-related changes in microbial-caffeine metabolism compared with controls. Our findings offer insights for future functional research on caffeine-microbiome interactions in PD.