The Serum Metabolome as a Potential Biochemical Indicator of Parkinson's Disease
Objective:
To profile the serum metabolome in Parkinson’s Disease (PD) for potential biochemical indicators of disease and compare the transcriptional signature of peripheral blood mononuclear cells (PBMCs) in patients with PD with those of healthy controls (HC).
Background:
The gut microbiome is altered in PD. In addition, the innate and adaptive immune responses are activated in both the central nervous system (CNS) and the periphery of PD patients where higher levels of inflammatory cytokines and chemokines are found in the blood and CSF. However, the etiology of said inflammation and PD remains unknown. In order to elucidate mechanistic answers, we leverage metagenomic, fecal and serum metabolomic, and single cell RNA-sequencing (scRNA-seq) data.
Design/Methods:
At the time of writing, 45 individuals have been enrolled. We expect 100 individuals to be enrolled by December, 2022. Shotgun metagenomic sequencing has been conducted on stool, metabolomics on serum, and scRNA-seq on PBMCs.
Results:
When compared to the microbiome of non-PD patients, pathway enrichment analysis reveals that the microbiome of PD patients has unique metabolic potential and produces microbially derived metabolites that are bioactive and confer differing immunogenicity.
Conclusions:
(1) The serum metabolome may be a biochemical indicator of PD. (2) Gene expression patterns in PBMCs are different between patients with PD and HC. These findings strengthen our understanding of the etiology of PD and provide an avenue for future microbiome-based therapeutics.