Gut microbial metabolites in Parkinson's disease: Association with lifestyle, disease characteristics, and treatment status

Robin M. Voigt*, Zeneng Wang, J. Mark Brown, Phillip A. Engen, Ankur Naqib, Christopher G. Goetz, Deborah A. Hall, Leo Verhagen Metman, Maliha Shaikh, Christopher B. Forsyth, Ali Keshavarzian

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


There is growing appreciation of the importance of the intestinal microbiota in Parkinson's disease (PD), and one potential mechanism by which the intestinal microbiota can communicate with the brain is via bacteria-derived metabolites. In this study, plasma levels of bacterial-derived metabolites including trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA), the branched chain fatty acid isovalerate, succinate, and lactate were evaluated in PD subjects (treatment naïve and treated) which were compared to (1) population controls, (2) spousal / household controls (similar lifestyle to PD subjects), and (3) subjects with multiple system atrophy (MSA). Analyses revealed an increase in the TMAO pathway in PD subjects which was independent of medication status, disease characteristics, and lifestyle. Lactic acid was decreased in treated PD subjects, succinic acid positively correlated with disease severity, and the ratio of pro-inflammatory TMAO to the putative anti-inflammatory metabolite butyric acid was significantly higher in PD subjects compared to controls indicating a pro-inflammatory shift in the metabolite profile in PD subjects. Finally, acetic and butyric acid were different between PD and MSA subjects indicating that metabolites may differentiate these synucleinopathies. In summary, (1) TMAO is elevated in PD subjects, a phenomenon independent of disease characteristics, treatment status, and lifestyle and (2) metabolites may differentiate PD and MSA subjects. Additional studies to understand the potential of TMAO and other bacterial metabolites to serve as a biomarker or therapeutic targets are warranted.

Original languageEnglish (US)
Article number105780
JournalNeurobiology of Disease
StatePublished - Aug 2022


  • MSA
  • Metabolites
  • Microbiota
  • PD
  • Parkinson's disease
  • TMAO

ASJC Scopus subject areas

  • Neurology


Dive into the research topics of 'Gut microbial metabolites in Parkinson's disease: Association with lifestyle, disease characteristics, and treatment status'. Together they form a unique fingerprint.

Cite this