# The Microbiota Shapes Central Nervous System Myelination in Early Life

## TL;DR

The gut microbiota influences early brain development by affecting myelination and glial cell maturation, with effects that vary by sex and age.

## Contribution

This study reveals conserved microbiota-driven mechanisms affecting myelination and glial maturation during early neurodevelopment across species.

## Key findings

- The microbiota influences myelin growth and integrity in a sex- and time-dependent manner in mice.
- Microbiota affects glial maturation and myelination across species, including zebrafish.
- Microbiota-microglia interactions alter gene expression related to synaptic pruning and maturation.

## Abstract

Maturation of the gut microbiota coincides with neurodevelopmental processes such as myelination, essential for efficient neural signal transmission. While a role for the microbiome in regulating adult prefrontal cortex (PFC) myelination is known, its effects on early‐life myelin formation, growth, and integrity remain unclear. Using a cross‐species approach in germ‐free (GF) mice and zebrafish, we examined how the microbiota influences early myelination and neural development. Multi‐system, multi‐level analyses showed that the microbiota impacts glial maturation and myelination across species. 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.

Gut microbiota shapes brain development by regulating myelination and glial cell maturation in early life. Using germ‐free (GF) mice and zebrafish, this study reveals sex‐ and age‐dependent effects on myelin growth, integrity, and related gene expression. Findings highlight conserved microbiota‐driven mechanisms linking metabolism, neuronal activity, and immune function during critical windows of neurodevelopment.