Epigenetic Modulation by Fermented Plant-Based Functional Foods: A New Frontier in Neurodegenerative Disease Prevention

Neurodegenerative diseases, including Alzheimer’s and Parkinson’s, represent an urgent global health challenge marked by progressive cognitive and motor decline. Existing pharmacotherapies largely address symptoms without altering disease progression. Recent advances in epigenetics and nutritional neuroscience suggest novel dietary approaches for neuroprotection. This review investigates the potential of fermented plant-based foods to modulate epigenetic mechanisms involved in neurodegeneration. These foods, enriched through microbial fermentation, produce bioactive metabolites, such as short-chain fatty acids, phenolic derivatives, and peptides that can regulate gene expression via DNA methylation, histone modification, and microRNA activity. Emphasis is placed on the microbiota-gut-brain axis as a critical interface for transmitting dietary signals to the brain. Fermented foods such as kimchi, tempeh, miso, turmeric, and garlic are examined for their capacity to influence neuroprotective epigenetic pathways. Molecular mechanisms, including JAK/STAT, PI3K/Akt, and GLP-1/PGC-1α signaling, are reviewed for their roles in modulating inflammation, synaptic plasticity, and mitochondrial health. The article also evaluates emerging clinical and preclinical evidence supporting these foods’ cognitive benefits. A key focus is the interindividual variability in microbiome-epigenome interactions, which underscores the need for personalized nutrition. Methodological challenges, such as standardizing fermentation protocols and identifying active compounds within complex food matrices, are discussed as barriers to translational research. By integrating findings from nutritional biochemistry, microbiome science, and neuroepigenetics, this review highlights fermented plant-based foods as promising candidates for dietary strategies aimed at preventing or slowing neurodegenerative processes.