Abstract MP02: Gut Microbiome Alteration and Structural Brain Features Among Healthy Japanese Men

Introduction: Growing evidence supports the bidirectional brain-gut microbiome interaction that contributes to brain health. However, no prior study has assessed the association between gut microbiomes and structural brain features in a healthy general population. Hypothesis: We assess the hypothesis that the gut microbiome composition is associated with structural brain features in healthy humans. Methods: Healthy Japanese men (n=623) aged 40-79 years participated in the examination of the Shiga Epidemiological Study of Subclinical Atherosclerosis II (SESSA II) between 2010 and 2014. Gut microbiota composition including diversity was assessed using 16S rRNA sequencing with DNA extracted from stool samples, and brain volumes (i.e., total brain volume, white matter, gray matter, and hippocampus) and white matter lesion volume (WMLV, reflecting Cerebral small vessel disease) were quantified using brain magnetic resonance imaging (MRI). We performed principal coordinate analysis (PCoA), multivariable-adjusted linear regression models, and linear discriminant analysis (LDA) by measuring effect size (Lefse). Results: Higher alpha diversity was associated with lower brain volumes of gray matter, white matter, and hippocampus (FDR adjusted Q <0.01). For beta diversity, weighted unifrac Bray-Curtis distances measured by PCoA showed lower and higher groups formed distinct clusters in white and gray matter volumes. Multivariable linear regression and LDA analysis suggested that higher amount of the genera Lachnospiraceae butyrate-producing bacteria were associated with greater gray and white matter volume (see Figure). Conclusions: In conclusion, the gut microbiome was associated with the brain gray and white matter structural alterations in healthy Japanese adult men. Persons with higher amount of Lachnospiraceae butyrate-producing bacteria had higher gray and white matter volumes compared to those with lower amount of the bacteria.