PFC expression data from germ-free vs non-germ-free, male & female mice. Measurements at day 2, 8, 14, 21.

Maturation of the gut microbiota coincides with neurodevelopmental processes such as myelination, essential for efficient neural signal transmission. While its role in adult prefrontal cortex (PFC) myelination is known, effects on early-life myelin formation, growth, and integrity remain unclear. Here, we track gene expression in the PFC of germ-free (GF) and non-germ-free (conventional) mice. Alongside metabolomics (HP/LC) from the same region across early life development, in males and females. Metabolomics data available here In GF mice, we observed sex- and age-dependent alterations in pathways linked to neuronal activity and myelination, with myelin-related transcriptomic changes correlating with functional shifts in neurotransmission- and metabolism-related metabolites over time. Myelin growth and integrity were also affected in a sex- and time-dependent manner. As microglia regulate neuronal activity and engulf myelin, we examined microbiota-microglia interactions and found altered expression of genes involved in microglia maturation and synaptic pruning in both species. In zebrafish larvae, the microbiota influenced the spatial distribution of microglia and oligodendrocytes within the brain and spinal cord. These findings reveal conserved microbiota-mediated modulation of neuronal activity, myelination, and glial maturation in early life, providing a foundation for future studies into these mechanisms. These files contain the RNAseq data underlying this study.