Dietary Polyphenols in Non-Communicable Chronic Diseases: Neuro-Enteric Mechanisms, Multi-Omics Biomarkers and Translational Opportunities.

Polyphenols from plant foods (tea, cocoa, berries, grapes, and extra-virgin olive oil) modulate oxidative stress, inflammation, vascular function, and the gut microbiome-axes central to non-communicable chronic diseases (NCCDs) that involve the brain and enteric nervous system (ENS). Recent randomized trials and longitudinal studies report modest but reproducible benefits on cognitive domains and vascular/endothelial function with berry/grape extracts, matcha/green tea, and high-polyphenol extra-virgin olive oil; effects appear stronger in older adults or those with metabolic risk. Complementary evidence in irritable bowel syndrome (IBS)-a prototypical gut-brain disorder-suggests polyphenol-based combinations (often with probiotics/fiber) can improve quality of life and inflammatory markers, supporting enteric-central crosstalk. Emerging genetics (Mendelian randomization) and multi-omics readouts strengthen causal inferences for tea polyphenols in neurodegeneration-adjacent outcomes and outline mechanistic mediators (endothelial/BBB function, cytokine tone, microbiome-derived metabolites). Key gaps remain: heterogeneous formulations/doses, limited head-to-head trials, sparse target engagement biomarkers, and uncertain durability after discontinuation. We synthesize clinical and mechanistic advances, propose a standardized biomarker set (neurocognitive, endothelial, immune, and microbiome-metabolome), and outline designs for mechanism-anchored RCTs that integrate ENS endpoints with brain outcomes to translate associative signals into precision nutrition strategies for NCCDs.