Age-specific modulation of gut-brain axis metabolites by galacto-oligosaccharides and nutrient blends in early childhood

Abstract

ObjectivesGut microbiome-derived metabolites, including short-chain fatty acids (SCFA) and tryptophan derivatives, are key mediators of the gut-brain axis. We examined how early-life nutritional interventions influence these metabolites during critical neurodevelopmental periods. MethodsUsing a standardized ex vivo fermentation system, we assessed the effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals, amino acids), and their combinations on the gut microbiome of infants (2-4 months, n=6) and young children (2-3 years, n=6). ResultsBaseline microbiome composition differed by age: infants showed low -diversity and high interpersonal variability, while young children exhibited more adult-like profiles. Nutrient blends increased propionate/butyrate ratios and branched-chain fatty acids (BCFA) in young children, alongside B-vitamin and amino acid-derived metabolites, including neuroactive compounds (indole-3-carboxaldehyde, imidazoleacetic acid, pipecolinic acid). Combining nutrient blends with GOS produced synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both groups). GOS-containing treatments strongly promoted Bifidobacteriaceae, driving production of acetate, HICA, N-acetylated amino acids, aromatic lactic acids, and acetylagmatine; in young children, also butyrate and {gamma}-aminobutyric acid (GABA). DiscussionGOS alone and combined with nutrient blends modulated microbiome-derived metabolites linked to the gut-brain axis. Synergistic effects on GABA, acetylagmatine, and HICA suggest roles in neurotransmission, neuroprotection, and immune-brain signaling. Despite shared bifidogenic effects, age-specific differences indicate developmental stage influences intervention outcomes. Further studies should explore neurodevelopmental benefits of these combinations and metabolites.