Serum Metabolomic Profiling and Clinical Phenotypes in Parkinson's Disease: A Case–Control Study

ABSTRACT Parkinson's disease (PD) is characterized by heterogeneous motor and non‐motor symptoms, but serum metabolic features related to this variability remain unclear. To address this, this small‐scale study investigated serum metabolic alterations in patients with PD and explored their relationships with clinical features. Serum samples from 9 patients with PD and 9 age‐ and sex‐matched normal controls were analyzed using untargeted UPLC–MS/MS metabolomics. OPLS‐DA was used for exploratory group discrimination. Candidate metabolites were selected according to OPLS‐DA‐derived variable importance in projection (VIP) values, nominal p values, and fold‐change criteria (VIP > 1.0, nominal p < 0.05, and |log2FC| > 0.585). In addition, pathway enrichment analysis and exploratory correlation and regression analyses were performed to evaluate the relationships between metabolite changes and clinical characteristics. Using these nominal screening criteria, 169 candidate metabolites were identified, including 84 upregulated and 85 downregulated metabolites. Pathway analysis suggested potential involvement of steroid hormone biosynthesis, bile secretion, biosynthesis of unsaturated fatty acids, and neuroactive ligand‐receptor interaction. Within these pathways, candidate metabolites, including docosahexaenoic acid, 8Z,11Z,14Z‐eicosatrienoic acid, 5α‐dihydrotestosterone, 2‐methoxyestradiol, cortisol, chenodeoxycholic acid, deoxycholate, and adrenic acid, showed exploratory associations with clinical features related to gastrointestinal symptoms, non‐motor manifestations, and motor‐related clinical features. Overall, this study suggests that alterations in serum steroid hormones, bile acids, and unsaturated fatty acids may be related to clinical manifestations of PD, although these findings require validation in larger cohorts.