Early-life gastrointestinal inflammation and the developing brain: Unravelling the pathways to long-term cognitive dysfunction

Table 1 Co-development in of gut microbiome, immune system and brain and cognitive functions in early life (the critical window)

Time frame	Gut microbiome development	Immune system development	Brain/cognitive development
Prenatal (in utero)	Microbiome density increases rapidly leading up to birth	Immature: Components are developing but not fully functional	Foundation laid: Neurulation, neural proliferation, neuronal migration, and initial axon growth are active
Birth – 3 months	Rapid colonization: Window of opportunity for microbial assembly. Diversity is fluctuating	Education/expansion: Immune system begins learning to repel new bacterial strains. IgG/IgM are developing	High activity: Synapse formation (synaptogenesis) is highly active. Myelination begins
Birth – 2 years	Assembling/fluctuating: Gut microbiota is actively assembling. Microbial density is high but composition is unstable	Developing: Natural killer cells are above adult levels. Key immunoglobulin levels (IgG, IgA) are developing but not yet mature. T cell independent antibody response is immature	Peak proliferation (first 1000 days): Synapses intensely proliferate. Brain metabolism increases. Sensory pathways (vision, hearing) peak, and language develops rapidly
Year 2-3	Stabilization phase: Composition begins to settle toward an adult-like state	Transition: Continues developing toward adult levels, including Th1 mediated immunity	Pruning begins: Synapses are pruned (eliminated). Metabolism decreases, and higher cognitive function development approaches its peak

It effectively highlights the synchronization of these three major biological systems during the first 1000 days of life, illustrating why early-life gastrointestinal inflammation is such a significant neurodevelopmental risk factor. Ig: Immunoglobulin.