Relationship between Gut microbiome and brain volumes among Japanese Men

Sabrina Ahmed1,2, Zhang Hexun3, Yuichiro Yano1,4

  • 1NCD Epidemiology Research Center (NERC), Shiga University of Medical Science, Otsu, Shiga, Japan.

Plos One
|October 7, 2025
PubMed

Insights

Gut microbiome diversity is linked to brain volumes in healthy older Japanese men. Specific bacteria, like Lachnospiraceae, were associated with higher white matter volume, and others with gray matter volume.

Area of Science:

  • Neuroscience
  • Microbiology
  • Public Health

Background:

  • Emerging evidence suggests a gut-brain axis, linking gut microbiome composition to brain health.
  • Previous studies focused on animal models or specific patient groups, leaving the association in healthy humans understudied.
  • Gut microbiome's influence on brain volumes in apparently healthy middle-aged to older adults requires further investigation.

Purpose of the Study:

  • To investigate the association between gut microbiome diversity and brain volumes (gray and white matter) in a population-based cohort of apparently healthy Japanese men.
  • To identify specific gut microbial taxa associated with variations in brain volumes.
  • To explore the gut-brain axis in the context of structural brain changes in aging.

Main Methods:

  • Cross-sectional study of 623 Japanese men from the Shiga Epidemiological Study on Subclinical Atherosclerosis (SESSA).
  • 16S ribosomal RNA gene sequencing of stool samples to analyze gut microbiome composition and diversity (alpha and beta diversity).
  • Brain magnetic resonance imaging with automated voxel-based morphometry to quantify gray and white matter volumes; statistical analyses included principal coordinate analysis, linear discriminant analysis, and multivariable linear regression.

Main Results:

  • Gray matter volume showed a positive association with gut microbiome alpha diversity (Shannon index) after adjusting for age and intracranial volume, but this was not significant after further adjustments.
  • Beta diversity analysis (weighted UniFrac distances) revealed distinct clustering of brain volumes, indicating differences in microbiome composition related to gray and white matter volumes.
  • Several bacterial genera were significantly associated with brain volumes; Lachnospiraceae (butyrate producer) was consistently linked to higher white matter volume, while Egarthellaceae, Bifidobacteraceae, and Selenomonadaceae were associated with greater gray matter volume.

Conclusions:

  • The study supports an association between gut microbiome diversity and brain volumes in middle-aged to older Japanese men.
  • Specific gut bacteria, such as Lachnospiraceae, may play a role in maintaining white matter volume.
  • These findings provide insights into the gut microbiome's potential influence on human brain structure and volume.

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