Plasma Metabolic Analysis Reveals the Dysregulation of Short-Chain Fatty Acid Metabolism in Parkinson's Disease

Mol Neurobiol. 2023 May;60(5):2619-2631. doi: 10.1007/s12035-022-03157-y. Epub 2023 Jan 24.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by high morbidity, high disability rate, and slow course of disease. The clinical diagnostic method of PD is complex and time-consuming, and there is no clear biomarker for clinical use. We aimed to investigate the plasma metabolites in PD and find out potential biomarkers with diagnostic ability. In the analysis of more than 40 metabolites including short-chain fatty acids, long-chain fatty acids, amino acids, and carbohydrates, the difference of short-chain fatty acids was observed. Acetic acid concentration was higher in PD than in healthy controls, and propanoic acid and 2,3,4-trihydroxybutyric acid were lower in PD. Compared with the early stage of PD, acetic acid increased significantly in the advanced stage of PD. Propanoic acid increased significantly in medicated PD compared with drug naïve PD. ROC analysis revealed acetic acid discriminated PD from healthy controls with 100% sensitivity, 88.9% specificity, and an area under the curve (AUC) of 0.981, and propanoic acid discriminated PD from healthy controls with an AUC of 0.981, 100% sensitivity, and 94.4% specificity. Acetic acid and propanoic acid may be a potential biomarker for differentiating PD from health, and the propanoic acid was evaluated as the most potential diagnostic marker because of its extremely high sensitivity and specificity.

Keywords: Biomarker; Metabolomics; Parkinson’s disease; Short-chain fatty acid.

MeSH terms

  • Biomarkers / metabolism
  • Humans
  • Metabolomics / methods
  • Parkinson Disease* / metabolism
  • Propionates

Substances

  • propionic acid
  • Propionates
  • Biomarkers