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Gut Microbiota and White Matter Integrity: A Two-Sample Mendelian Randomization Analysis.

Lan Zhang1,2,3, Xiao-Wei Pang1,2,3, Lu-Yang Zhang1,2,3

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This study reveals a genetically predicted causal link between gut microbiota and white matter integrity. Specific gut bacteria influence white matter hyperintensities, microstructure, connectivity, and neurological diseases.

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gut microbiota; Mendelian randomizationwhite matter connectivitywhite matter hyperintensitieswhite matter microstructure

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Area of Science:

  • Neuroscience
  • Microbiology
  • Genetics

Background:

  • The gut microbiota's role in brain health, particularly white matter integrity and neurological diseases, is not fully understood.
  • Existing research suggests potential links, but causal relationships require robust investigation.

Purpose of the Study:

  • To investigate the causal impact of gut microbiota on white matter hyperintensities, microstructure, connectivity, and neurological diseases using Mendelian randomization.
  • To identify specific bacterial taxa and genetic factors associated with white matter changes and neurological conditions.

Main Methods:

  • Utilized Mendelian randomization study design.
  • Analyzed genome-wide association study (GWAS) data for gut microbiota and neurological traits.
  • Identified statistically significant associations between genetic liability of gut microbiota and white matter characteristics.

Main Results:

  • Identified specific bacterial taxa associated with white matter hyperintensities (e.g., Melainabacteria, Ruminiclostridium 6).
  • Found bacterial taxa influencing white matter microstructure and connectivity.
  • Established associations between gut microbiota and neurological diseases like ischemic stroke, neuromyelitis optica spectrum disorder, and amyotrophic lateral sclerosis.
  • Highlighted specific genes (e.g., CPNE1, PIGU) causally correlated with white matter connectivity.

Conclusions:

  • Demonstrated a genetically predicted causal relationship between gut microbiota and white matter integrity.
  • Highlighted the potential of gut microbiota as a modifiable factor influencing brain structural integrity and neurological disease risk.
  • Findings underscore the gut-brain axis's importance in neurological health.