Background and Objectives: Short-chain fatty acids (SCFAs) are gut microbial metabolites
that promote the disease process in a rodent model of Parkinson’s disease (PD), but fecal
levels of SCFAs in PD patients are reduced. Simultaneous assessments of fecal and plasma
SCFA levels, and their inter-relationships with the PD disease process are scarce. We aimed
to compare fecal and plasma levels of different SCFAs subtypes in PD patients and healthy
controls to delineate their interrelations and link to gut microbiota changes and clinical
severity of PD.
Methods: A cohort of 96 PD patients and 85 controls were recruited from National Taiwan
University Hospital. Fecal and plasma concentrations of SCFAs were measured using
chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic
shotgun sequencing. Body mass index and medical co-morbidities were evaluated, and
dietary information was obtained using a food frequency questionnaire. To assess motor and
cognitive impairment, we used the Movement Disorder Society-Unified Parkinson’s Disease
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE).
Results: Compared with controls, PD patients had lower fecal but higher plasma
concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease
duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with
reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and
butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ =
0.26, p = 0.042) in PD patients. MMSE scores negatively correlated with plasma levels of
butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for
confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs
in healthy controls but revealed no association in patients with PD. In the PD patient group,
the abundance of pro-inflammatory microbes, such as Clostridiales bacterium NK3B98 and
Ruminococcus sp. AM07-15, significantly correlated with decreased fecal levels and
increased plasma levels of SCFAs, especially propionic acid.
Discussion: Reductions in fecal SCFAs but increased plasma SCFAs were observed in PD
patients and corelated to specific gut microbiota changes and the clinical severity of PD.
Classification of evidence: This study provides Class III evidence that gut metabolite SCFAs distinguish between PD
patients and controls, and are associated with disease severity in patients with PD. CLICK TO REVIEW