EARLY-LIFE GUT MICROBIOME AND COGNITIVE DEVELOPMENT: A SYSTEMATIC REVIEW AND META ANALYSIS OF GUT–BRAIN MOLECULAR PATHWAYS

Abstract

Background: Early childhood is a critical period for the concurrent development of the gut microbiome and the central nervous system. Emerging evidence suggests that microbial composition, metabolites, immune signalling and neuroplasticity-related mechanisms may be associated with cognitive development. Objective: To examine associations between the early-life gut microbiome and cognitive development, identify potential molecular pathways linking microbial characteristics with neurodevelopment, and quantitatively synthesize comparable microbiome–cognition associations where sufficient data were available. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Searches were undertaken in PubMed, Embase, Web of Science and Scopus for studies examining gut microbial characteristics or related metabolites alongside cognitive, developmental, behavioural or neuropsychological outcomes in infants and children. Extracted information included study characteristics, microbial diversity and composition, metabolites, immune markers, developmental assessments and reported effect estimates. Quantitative synthesis was restricted to sufficiently comparable effect estimates, while heterogeneous findings were summarized narratively. Results: The review identified heterogeneous associations between gut microbial characteristics and cognitive or developmental outcomes. Studies by Carlson et al. (2018) and Tamana et al. (2021) reported associations between Bacteroides/Bacteroidetes-dominant microbial communities and selected cognitive, language and developmental outcomes, whereas Rothenberg et al. (2021) found no significant association between alpha diversity and Bayley developmental scores. An exploratory meta-analysis of two studies, Streit et al. (2021) and van de Wouw et al. (2023), indicated a small negative association between alpha diversity and selected cognitive outcomes ((r=-0.14), 95% CI: −0.22 to −0.06). Microbial metabolites, including short-chain fatty acids and tryptophan-derived compounds, may contribute to gut–brain communication through metabolic, neural and immune pathways. Experimental evidence also implicates microglial regulation and brain-derived neurotrophic factor-related neuroplasticity. However, direct human evidence confirming these mechanisms as mediators of cognitive development remains limited. Conclusion: Early-life gut microbiome characteristics may be associated with cognitive development, but overall microbial diversity is not a consistent indicator of developmental outcomes. Greater methodological consistency, longitudinal research and well-designed intervention studies are needed to clarify the direction, timing and mechanisms of these associations. Quantitative findings further require confirmation using verified primary-study data before definitive conclusions can be drawn.