From Gut Microbiota to Synaptic Plasticity: Mechanisms Shaping Cognitive Function and Brain Disorders.

Abstract

The gut microbiota has emerged as a key regulator of central nervous system development and function. Accumulating experimental and clinical evidence demonstrates that microbial signals influence brain activity through integrated neural, immune, neuroendocrine, and metabolic pathways. These pathways converge on core mechanisms of synaptic plasticity, including neurotrophic signaling, glutamatergic transmission, dendritic remodeling, and adult neurogenesis, thereby shaping learning, memory, executive function, and emotional regulation. Disruption of microbiota-brain communication is implicated in a range of neurodevelopmental and neurodegenerative disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer's disease (AD), and Parkinson's disease (PD), suggesting shared systems-level vulnerabilities across conditions and highlighting the translational potential of microbiota-targeted interventions such as probiotics, dietary modulation, postbiotics, and precision microbiome-based strategies. Overall, the gut microbiota functions as a dynamic regulator of brain plasticity and cognitive resilience across the lifespan. Future progress will require identification of causal mechanisms at the level of specific microbial metabolites, neural circuits, and developmental windows using integrated multi-omics and spatially resolved approaches, alongside translation into targeted therapeutic strategies.