Early-Life Microbiota Modulation and Neurodevelopment in Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Changes in microbial composition during early infancy by various factors (mode of delivery, nutritional practices, antibiotic usage, and environmental influences) have been correlated with observable variances in cognitive abilities, temperament, stress response, and the predisposition to neurodevelopmental disorders. Consequently, microbiota-targeted interventions such as probiotics, prebiotics, and synbiotics are being explored as avenues to enrich beneficial microbial taxa, enhance short-chain fatty acid production, fortify mucosal immunity, and mitigate inflammatory responses during these critical periods. Preclinical research, primarily in experimental animal models, has demonstrated a causal link between microbiota composition and developmental processes such as myelination, synaptic plasticity, and socio-emotional behaviors, whereas human evidence remains largely associative and heterogeneous. A notable gap exists in the current literature, which typically centers on gastrointestinal, psychiatric, or preterm outcomes, without a focused investigation into neurodevelopmental assessments within the first three years. To bridge this gap, we conducted a systematic review and meta-analysis of randomized controlled trials assessing the impact of probiotics, prebiotics, and synbiotics on neurodevelopment and behavior in infants aged 0-36 months. Our primary objective was to establish whether microbiota-targeted strategies confer discernible neurodevelopmental benefits, alongside elucidating the mechanisms underpinning the relationship between microbial modulation and early brain development.