This study investigates the impact of normal gut microbiota on brain development and behavior in mammals. The authors found that germ-free (GF) mice, which lack a normal gut microbiota, exhibit increased motor activity and reduced anxiety compared to specific pathogen-free (SPF) mice with a normal gut microbiota. These behavioral differences are associated with altered expression of genes involved in second messenger pathways and synaptic long-term potentiation in brain regions crucial for motor control and anxiety-like behavior. Early colonization of GF mice with gut microbiota can normalize these behavioral and molecular changes, suggesting a critical period for the effects of gut microbiota on brain development. The study also highlights the involvement of specific proteins, such as synaptophysin and PSD-95, in the striatum, which may contribute to the observed behavioral alterations. Overall, the findings support the hypothesis that normal gut microbiota plays a significant role in modulating brain development and behavioral functions.This study investigates the impact of normal gut microbiota on brain development and behavior in mammals. The authors found that germ-free (GF) mice, which lack a normal gut microbiota, exhibit increased motor activity and reduced anxiety compared to specific pathogen-free (SPF) mice with a normal gut microbiota. These behavioral differences are associated with altered expression of genes involved in second messenger pathways and synaptic long-term potentiation in brain regions crucial for motor control and anxiety-like behavior. Early colonization of GF mice with gut microbiota can normalize these behavioral and molecular changes, suggesting a critical period for the effects of gut microbiota on brain development. The study also highlights the involvement of specific proteins, such as synaptophysin and PSD-95, in the striatum, which may contribute to the observed behavioral alterations. Overall, the findings support the hypothesis that normal gut microbiota plays a significant role in modulating brain development and behavioral functions.