The relationship between the gut microbiota and neuropsychological development and behaviour during childhood and adolescence: a systematic review of epidemiological studies

Mounting evidence suggests that early-life microbial colonization might shape cognitive development and behaviour. This systematic review summarizes current research on the relationship between the gut microbiota and neuropsychological development and behaviour in children and adolescents (0-18 years). Following PRISMA guidelines, we conducted a comprehensive search across MEDLINE, Scopus, and Web of Science, identifying 78 eligible studies covering both clinical neurodevelopmental disorders and general-population neuropsychological outcomes. We observed a high heterogeneity across studies regarding study design, statistical analyses and the consideration of confounding factors (e.g., diet, medication use), gut microbiota determinations and the assessment of neurobehavioural outcomes. Only 42% of studies used longitudinal designs, and confounding factors were frequently unaddressed. Microbiome alterations in autism spectrum disorder (n = 23 studies) included community structure shifts, elevated <i>Clostridium</i> and <i>Sutterella</i>, and reduced <i>Blautia, Lactobacillus,</i> and <i>Bifidobacterium</i>. Functional and metabolomic analyses suggest immunomodulatory and neuroactive processes as main contributors, including elevated levels of the short-chain fatty acids propionate and valerate. For attention-deficit/hyperactivity disorder (n = 7) findings were less consistent. Associations were modest in the general paediatric population, with <i>Veillonella</i> and <i>Bifidobacterium</i> appearing across multiple studies being more abundant in children with enhanced neuropsychological development. Overall, the evidence highlights potential microbial signatures associated with neurodevelopment, yet methodological limitations constrain causal inference. Most of the studies were of poor to fair quality, often due to technical shortcomings in microbiome assessment and statistical limitations. Future research should prioritize standardized exposure/outcome assessment protocols and multi-omics integration, while underlining the potential of methodological rigour in translating findings into clinically actionable knowledge.