Preliminary associations between brain metabolites and oral microbiome profiles during adolescence

Adolescence is a period of significant transformation, including changes in brain chemistry and the microbiome. While gut microbiome-brain connections are well studied, the relationship between the oral microbiome and brain function remains underexplored, despite growing evidence of its relevance to human health-particularly during this developmental period. This study investigates associations between the oral microbiome and neurometabolites in adolescents aged 17-19 (N = 39; 49% female) using 16S rRNA sequencing and proton magnetic resonance spectroscopy. Glutamate (Glu), Glu + glutamine (Glx), and choline-containing metabolites (tCho) and lower total N-acetylaspartate (tNAA) were associated with higher oral microbiome alpha diversity (within sample diversity). Glu, Glx, and tNAA also differentiated the beta diversity (between sample diversity) at the genus and species levels, with additional associations for myo-inositol (mI) and total creatine (tCr) at the species level. Using centered-log ratio abundances, thirteen genera and one species were significantly associated with neurometabolite concentrations, including Glu, mI, tCr, tCho, and tNAA. There were no significant findings related to gamma-aminobutyric acid or glutathione and the oral microbiome. These findings suggest a potential relationship between the oral microbiome and brain chemistry during adolescence, underscoring the importance of further research to unravel how these interactions may shape mental health and neurodevelopment.