Self-Aggregation of Steviol Glycosides Modifies Sweetness Perception via Interactions with Oral Mucosa

Natural sweetener rebaudioside A (Reb A), a major steviol glycoside, exhibits hierarchical self-aggregation behavior in solutions, forming aggregates (Reb A-A) that exhibit reduced bitterness and lingering aftertaste. However, the underlying mechanism of the taste-modifying effects of Reb A-A remains unclear. Here, we investigated the Reb A-mucin interactions, including diffusion and oral retention, and sweetener-receptor binding kinetics. Monomeric Reb A exhibits a strong affinity to mucin, altering mucosal microstructure, diffusion dynamics, and sweetener retention, ultimately leading to a prolonged aftertaste. In contrast, Reb A-A, stabilized by intermolecular hydrophobic interactions and hydrogen bonding, shows a weaker affinity to mucin and a decreased oral retention rate, thereby attenuating the lingering taste. Furthermore, molecular dynamics simulations demonstrate that Reb A in different forms exhibits distinct interactions with taste receptors. These findings demonstrate the significant effect of the physical structural modification of taste compounds and their subsequent interactions with oral mucosa on the final sensory perception.