Beyond Sensory Properties: Molecular Interactions of Antioxidant Flavour-Active Polyphenols Across the Food-Oral-Gut Axis

Dietary antioxidants are widely valued for their potential health benefits, but incorporating them into functional foods is not straightforward. Polyphenols are among the most abundant and important antioxidants in foods, and this review focuses on them because the same structural features linked to their health-promoting effects can also cause pronounced bitterness and astringency, ultimately limiting consumer acceptance. This review examines how these challenges are interconnected across three levels: food matrix interactions, bioavailability, and consumer psychobiology. We describe how non-covalent interactions between polyphenols, proteins, and polysaccharides can have both positive and negative effects. While these interactions may alter oral lubrication and flavour release, they also protect highly reactive bioactive compounds from gastric degradation. Furthermore, we broaden the concept of bioavailability by exploring the microbiota-mediated "colonic rescue" of polyphenols that are not released during earlier digestion. We also highlight the role of extraoral bitter taste receptors (TAS2Rs) along the gastrointestinal (GI) tract. Activation of these receptors during digestion can trigger relevant metabolic and endocrine responses, indicating that systemic absorption is not the only pathway to bioactivity. Finally, we connect these mechanisms to individual differences in food acceptance, showing that genetic factors (e.g., TAS2R38 and the salivary proteome) and psychological traits (such as neophobia and reward sensitivity) can shape rejection or flavour-nutrient learning. Overall, the successful development of functional foods will require a "sensory-by-design" approach. This strategy utilises matrix interactions strategically to improve both consumer acceptance and physiological efficacy.