Prebiotics/synbiotics as natural alternatives for brain development and aging – focus on nutrigenomic and direct effects: a systematic review

OBJECTIVES: This review highlights the importance of prebiotics and their combination with probiotics as essential nutrients for brain development and as potential therapeutic alternatives for neurodegenerative diseases. It further highlights the nutrigenomic action of prebiotics or synbiotics. METHODS: A literature search of PubMed, Scopus, and Web of Science was conducted for studies published from 2010 to 2025. Key search terms included ('prebiotics' OR 'synbiotics)' AND ('brain development' OR 'neurodevelopment' OR 'cognition' OR 'neuroplasticity' OR 'brain aging)' AND ('epigenetics' OR 'nutrigenomics' OR 'gene expression' OR 'DNA methylation' OR 'histone modification' OR 'microRNA)'. RESULTS: studies and 13 human studies) have been selected to be reviewed. Despite the importance of prebiotics or synbiotics as a prime source of energy, their diverse direct or indirect mechanisms of action have only recently been described, especially those involving these nutraceuticals as substrates for epigenetic effects. DISCUSSION: The literature shows that further studies are necessary to elucidate mechanisms and strategies for prebiotic intervention in the brain epigenome during brain development, adulthood and aging. Notwithstanding, the current data can help to initiate novel health approaches for treating brain disorders. The development of targeted therapy, using prebiotics or synbiotics as nutrigenomic substrates, seems to restore normal interaction between systemic diseases and brain function.