Microbes on the Mind: Multi-modal Neuroimaging Reveals Gut-Brain Axes in Infants

Abstract

The gut microbiome develops from birth and is associated with cognition and mental health, but its relationship with early brain maturation remains unclear. We studied 223 typically developing infants aged 0-3 years using multimodal MRI and paired fecal shotgun metagenomics. Microbiome-wide association analysis linked microbial features to cortical morphology, white-matter microstructure, and functional networks. Regularized canonical correlation analysis identified structural-metabolic and functional-taxonomic covariance patterns. Sparse partial least-squares analysis recapitulated both full-sample CCA patterns and their defining structural and functional phenotypes, providing cross-method corroboration. Longitudinal canonical-score slopes did not significantly covary, whereas earlier neuroimaging CCA1 scores predicted microbiome CCA1 scores 1-6 months later in bidirectional autoregressive cross-lag models. These observational results identify coordinated developmental patterns and temporal ordering without establishing causality.