Role of the Gut Microbiome and Bacterial Amyloids in the Development of Synucleinopathies

Biochemistry (Mosc). 2024 Mar;89(3):523-542. doi: 10.1134/S0006297924030118.

Abstract

Less than ten years ago, evidence began to accumulate about association between the changes in the composition of gut microbiota and development of human synucleinopathies, in particular sporadic form of Parkinson's disease. We collected data from more than one hundred and thirty experimental studies that reported similar results and summarized the frequencies of detection of different groups of bacteria in these studies. It is important to note that it is extremely rare that a unidirectional change in the population of one or another group of microorganisms (only an elevation or only a reduction) was detected in the patients with Parkinson's disease. However, we were able to identify several groups of bacteria that were overrepresented in the patients with Parkinson's disease in the analyzed studies. There are various hypotheses about the molecular mechanisms that explain such relationships. Usually, α-synuclein aggregation is associated with the development of inflammatory processes that occur in response to the changes in the microbiome. However, experimental evidence is accumulating on the influence of bacterial proteins, including amyloids (curli), as well as various metabolites, on the α-synuclein aggregation. In the review, we provided up-to-date information about such examples.

Keywords: Parkinson’s disease; alpha-synuclein; amyloids; bacterial amyloids; curli; dysbiosis; microbiome; neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Amyloid* / metabolism
  • Animals
  • Bacteria / metabolism
  • Bacterial Proteins / metabolism
  • Gastrointestinal Microbiome*
  • Humans
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / microbiology
  • Synucleinopathies* / metabolism
  • Synucleinopathies* / microbiology
  • Synucleinopathies* / pathology
  • alpha-Synuclein* / metabolism

Substances

  • Amyloid
  • alpha-Synuclein
  • Bacterial Proteins