Age-Specific Ex Vivo Modulation of Gut-Brain Axis-Associated Metabolites by Galacto-Oligosaccharides and Nutrient Blends in Early Childhood.

Background

Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut-brain axis. This ex vivo study assessed how nutritional interventions impact such metabolites during early life, a critical period for neurodevelopment.

Methods

The effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals and amino acids) and their combinations were evaluated in the gut microbiomes of infants (2-4 months, n = 6) and young children (2-3 years old, n = 6) using the ex vivo SIFR® technology.

Results

Baseline microbiome composition was age-dependent, with infants displaying lower α-diversity and greater interpersonal variability. After ex vivo incubation, nutrient blends increased the propionate/butyrate ratio and branched-chain fatty acids in young children and elevated several B-vitamins and amino acid-derived metabolites, including indole-3-carboxaldehyde, imidazoleacetic acid and pipecolinic acid. Combining nutrient blends with GOS exhibited potential synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both age groups). GOS strongly stimulated Bifidobacteriaceae and increased metabolites linked to bifidobacterial metabolism like acetate, HICA, N-acetylated amino acids, aromatic lactic acids and acetylagmatine; in young children, butyrate and γ-aminobutyric acid (GABA) also increased.

Conclusions

Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut-brain axis, with potential synergistic increases of metabolites with emerging roles in neurodevelopment, including GABA, acetylagmatine and HICA. Despite shared bifidogenic effects, differences between age groups indicate that microbiome maturity may influence responses to nutritional intervention. Future clinical studies are needed to determine whether these metabolite changes translate into neurodevelopmental benefits in vivo.