{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:10:00Z","timestamp":1792789800793,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nestl\u00e9 Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut\u2013brain 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\u20134 months, n = 6) and young children (2\u20133 years old, n = 6) using the ex vivo SIFR\u00ae technology. Results: Baseline microbiome composition was age-dependent, with infants displaying lower \u03b1-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 \u03b3-aminobutyric acid (GABA) also increased. Conclusions: Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut\u2013brain 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.<\/jats:p>","DOI":"10.3390\/metabo16040255","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T13:16:17Z","timestamp":1775826977000},"page":"255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age-Specific Ex Vivo Modulation of Gut\u2013Brain Axis-Associated Metabolites by Galacto-Oligosaccharides and Nutrient Blends in Early Childhood"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2981-7375","authenticated-orcid":false,"given":"Laurent","family":"Ferrier","sequence":"first","affiliation":[{"name":"Nestl\u00e9 Institute of Health Sciences, Nestl\u00e9 Research, Route du Jorat 57, 1000 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-4313","authenticated-orcid":false,"given":"Shaillay Kumar","family":"Dogra","sequence":"additional","affiliation":[{"name":"Nestl\u00e9 Institute of Health Sciences, Nestl\u00e9 Research, Route du Jorat 57, 1000 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam Dai","family":"Vu","sequence":"additional","affiliation":[{"name":"Cryptobiotix SA, Technologiepark-Zwijnaarde 82, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2094-7491","authenticated-orcid":false,"given":"Alexandros K.","family":"Kanellopoulos","sequence":"additional","affiliation":[{"name":"Nestl\u00e9 Institute of Health Sciences, Nestl\u00e9 Research, Route du Jorat 57, 1000 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Poppe","sequence":"additional","affiliation":[{"name":"Cryptobiotix SA, Technologiepark-Zwijnaarde 82, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Biehl","sequence":"additional","affiliation":[{"name":"Nestl\u00e9 Product Technology Center, Nestl\u00e9 Strasse 3, 3510 Konolfingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4872-6875","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Baudot","sequence":"additional","affiliation":[{"name":"Cryptobiotix SA, Technologiepark-Zwijnaarde 82, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-6332","authenticated-orcid":false,"given":"Pieter","family":"Van den Abbeele","sequence":"additional","affiliation":[{"name":"Cryptobiotix SA, Technologiepark-Zwijnaarde 82, 9052 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","first-page":"203","article-title":"The Gut-Brain Axis: Interactions between Enteric Microbiota, Central and Enteric Nervous Systems","volume":"28","author":"Carabotti","year":"2015","journal-title":"Ann. 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