Plasma Short-Chain Fatty Acids Differences in Multiple System Atrophy from Parkinson's Disease

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) have overlapping symptoms, making diagnosis challenging. Short-chain fatty acids (SCFAs) are produced exclusively by gut microbiota and were reduced in feces of MSA patients. However, plasma SCFA concentrations in MSA patients have not been investigated. Objective: We aimed to investigate the plasma SCFAs in MSA patients and to identify the potential differential diagnostic ability. Methods: Plasma SCFA were measured in 25 MSA patients, 46 healthy controls, and 46 PD patients using gas chromatography-mass spectrometry. Demographic and clinical characteristics of the participants were evaluated. Results: Acetic acid concentration was lower in MSA patients than in healthy controls. Acetic acid and propionic acid concentrations were lower inMSAandMSAwith predominant parkinsonism (MSA-P) patients than inPDpatients. Areceiver operating characteristic curve (ROC) analysis revealed reduced acetic acid concentration discriminated MSA patients from healthy controls with 76% specificity but only 57% sensitivity and an area under the curve (AUC) of 0.68 (95% confidence interval (CI): 0.55-0.81). Combined acetic acid and propionic acid concentrations discriminated MSA patients from PD patients with an AUC of 0.82 (95% CI: 0.71-0.93), 84% specificity and 76% sensitivity. Especially, with combined acetic acid and propionic acid concentrations, MSA-P patients were separated from PD patients with an AUC of 0.89 (95% CI: 0.80-0.97), 91% specificity and 80% sensitivity. Conclusion: Plasma SCFAs were decreased in MSA patients. The combined acetic acid and propionic acid concentrations may be a potential biomarker for differentiating MSA patients from PD patients.