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Exploring the Relationship Between Sporadic Creutzfeldt-Jakob Disease and Gut Microbiota Through a Mendelian

Tengfei Su1, Yue Lang1, Jiaxin Ren1

  • 1Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, China.

Molecular Neurobiology
|July 25, 2024
PubMed

Insights

This study used Mendelian randomization to investigate the gut microbiome

Area of Science:

  • Neuroscience
  • Microbiology
  • Genetics

Background:

  • Observational studies suggest gut microbiota alterations in sporadic Creutzfeldt-Jakob disease (sCJD).
  • The causal link between gut microbiota and sCJD remains unclear.

Purpose of the Study:

  • To investigate the causal relationship between gut microbiota composition and sporadic Creutzfeldt-Jakob disease (sCJD).
  • To explore potential bidirectional effects between gut bacteria and sCJD.

Main Methods:

  • Mendelian randomization analysis utilizing large-scale genetic data for gut microbiota (N=18,340) and sCJD cases (5208).
  • Employed inverse variance weighted, MR-Egger, weighted median, and mode-based methods.
  • Assessed pleiotropy, heterogeneity, and outliers using MR-PRESSO and conducted reverse analysis.

Main Results:

  • Identified negative associations between sCJD and specific gut bacteria (e.g., Defluviitaleaceae, Ruminococcaceae, Butyricicoccus, Desulfovibrio, Eubacterium nodatum).
  • Observed a positive correlation between sCJD and Lachnospiraceae UCG010.
  • Reverse analysis revealed bidirectional genetic links, including decreased Peptococcaceae, Faecalibacterium, Phascolarctobacterium and increased Butyrivibrio.

Conclusions:

  • Established bidirectional causal effects between specific gut microbiota and sporadic Creutzfeldt-Jakob disease.
  • Certain gut microbes may inhibit sCJD pathogenesis, while others are positively associated.
  • Gut microbiota modulation presents a potential therapeutic avenue for prion diseases.
Keywords:
Gut microbiotaGut-microbiota-brain axisPrion proteinShort-chain fatty acidsSporadic Creutzfeldt-Jakob disease

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