Early-life cognitive effects of prebiotics and probiotics: A cross-species systematic review

This systematic review evaluated the effects of prebiotic and probiotic interventions on early-life cognitive development in animal models and humans. Following PRISMA 2020 guidelines, 39 studies published between 2015 and 2025 were included from PubMed, Scopus, and Web of Science. In rodents, probiotics -mainly Lactobacillus and Bifidobacterium strains- consistently improved spatial learning, working memory, and cognitive flexibility, particularly under conditions of early-life stress and neuroinflammation. Porcine models showed partial benefits in learning and memory, though several studies reported neutral outcomes. Human trials yielded mixed findings: some demonstrated improvements in language, attention, or adaptive behavior, while others observed no significant cognitive effects. Proposed mechanisms include modulation of neurotransmitter systems, reduced neuroinflammation, restoration of blood-brain barrier integrity, and regulation of the hypothalamic-pituitary-adrenal axis. Overall, preclinical evidence strongly supports the cognitive benefits of microbiota-targeted interventions, but translation to humans remains uncertain due to methodological heterogeneity, species differences, and the limited number of pediatric studies. Future research should focus on longitudinal human trials, direct comparisons between prebiotic, probiotic, and synbiotic approaches, and the inclusion of sex as a biological variable.