Multiscale crosstalk between oral-gut microbiome and brain structure.

BACKGROUNDBrain macrostructural variations reflect deterioration due to disease and comprehensive profiling of the associated digestive tract microbiome signature advances mechanistic understanding.

METHODSHere, employing genome-wide association study(GWAS) data from MiBioGen consortium, Danish ADDITION-PRO cohort, and United Kingdom Biobank(UKB), through bidirectional Mendelian randomization(MR) analyses, we analyzed the associations between 239 microbiota(196 gut microbiota and 43 salivary microbiota) and 283 imaging-derived phenotypes(IDPs) of brain structure measures, involving gray matter volume (GMV), orientation dispersion index (ODI), volume fraction of intracellular water (ICVF), and volume fraction of the isotropic diffusion compartment (ISOVF). Ultimately, keyword co-occurrence was conducted by bibliometric analysis to summarize the research realm of "microbiome-brain".

RESULTSAfter Bonferroni correction, in forward MR results, we identified 123 associations between 50 microbiota and 92 IDP measures, with Parvula species, unknown-Streptococcus species, and Neisseria genus showing the most associations. The brain regions that showed the most MR relationships with microbiota were posterior division of the right middle temporal gyrus, left cerebral peduncle, left cingulum hippocampus, and splenium of corpus callosum. However, in inverse MR results, merely 8 associations were discovered between IDPs and microbiota. Furthermore, bibliometric outcome indicated that depression was the most studied disease in "microbiome-brain" research.

CONCLUSIONSIn summary, this study generates a comprehensive atlas mapping the patterns of association between microbiota and brain structure, highlighting their potential value for studying brain disorders.