Microbiome-gut-brain axis in brain development, cognition and behavior during infancy and early childhood

The gut microbiota is increasingly recognized as a modulator of brain and behavior but its role in early childhood, when the microbiome and the brain are both undergoing rapid development, is poorly understood. Preclinical work suggests there are critical windows during early life when bacterial signals are required for normal neurobehavioral development, whereas gut microbial dysfunction has been observed in patients with certain neurodevelopmental disorders. Here, we review the evidence that gut bacterial diversity and community composition affect brain structure/function and behavior in typically developing pre-school children. Following narrative synthesis, we report that twenty studies suggest the microbiome-gut-brain axis may operate across three domains in infancy and early childhood: general neurocognitive development, socio-emotional behaviors, and brain structure and function inferred from neuroimaging. However, there is substantial variation in the bacteria-brain/behavior relationships reported. We identified sources of clinical and methodological heterogeneity in the studies, including participant characteristics, small sample sizes, variations in DNA extraction and sequencing, and statistical analysis approaches. We propose that harmonization of sample collection and data processing pipelines, longitudinal assessments, and mechanistic insights from whole metagenome analyses could improve understanding of the role of gut microbiome in brain development during early development. This will also promote comparability between studies and increase study power by allowing for meta-analyses. Greater knowledge of the role of gut microbiome in brain development may ultimately offer new avenues for promoting brain health in early life.