Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment

Mol Neurobiol. 2021 Aug;58(8):3745-3758. doi: 10.1007/s12035-021-02375-0. Epub 2021 Apr 6.

Abstract

The search for therapeutic targets for Parkinson's disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.

Keywords: Gut microbiota; Microbial metabolites; Microbiota-gut-brain axis; Mitochondrial dysfunction; Parkinson’s disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain-Gut Axis / physiology*
  • Dysbiosis / genetics
  • Dysbiosis / metabolism
  • Dysbiosis / therapy
  • Fecal Microbiota Transplantation / methods
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / therapy*
  • Probiotics / therapeutic use
  • Treatment Outcome
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein