Plasma Short-Chain Fatty Acids in Patients With Parkinson's Disease

Background: Short-chain fatty acids are exclusively produced by gut microbiota and are reduced in feces of patients with Parkinson's disease (PD). The objective of this study was to conduct a case-control study on peripheral concentration of short-chain fatty acids based on evidence of pathologic changes in the blood-brain barrier in PD and the possible role of short-chain fatty acids in blood-brain barrier permeability.

Methods: The plasma short-chain fatty acid concentration was measured in 38 PD and 33 normal controls using gas chromatography. The clinical characteristics of patients with PD and controls were evaluated, and dietary information was obtained using a food frequency questionnaire. Short-chain fatty acid concentrations were further compared after adjusting for age, sex, and significant food frequency questionnaire items.

Results: The concentrations of acetate, propionate, and butyrate did not differ between patients with PD and controls in unadjusted comparison. Dietary intakes of fibers, carbohydrates, lipids (total and fatty acids), and proteins did not differ between groups. After correction of covariates, acetic acid concentration was higher in patients with PD than in controls (116.47 ± 16.83 vs 108.20 ± 18.37 μmol/L; P = 0.010). In correlation analyses, acetic acid concentration was positively correlated (R = 0.374, P = 0.021) with age, propionic acid concentration was negatively correlated with UPDRS part III score (R = -0.376, P = 0.020) and use of entacapone (R = -0.325, P = 0.047), and butyric acid concentration was correlated with monoamine oxidase inhibitor use (R = 0.382, P = 0.018) and anticholinergic use (R = -0.385, P = 0.024).

Conclusions: Plasma short-chain fatty acids were paradoxically increased in PD and were associated with disease severity and antiparkinsonian medications. Further studies are warranted to elucidate the relationships of gut dysbiosis and inflammation with plasma short-chain fatty acids. © 2020 International Parkinson and Movement Disorder Society.