Astringent Gallic Acid in Red Wine Regulates Mechanisms of Gastric Acid Secretion via Activation of Bitter Taste Sensing Receptor TAS2R4

Abstract

Red wine is rich in phenolic compounds, which chiefly determine its characteristic taste. One of its major phenolic acid constituents for which an astringency, yet no clear contribution to bitter taste has been reported, is gallic acid (GA). In previous studies, we have demonstrated bitter-tasting constituents to regulate cellular proton secretion (PS) as a key mechanism of gastric acid secretion via activation of bitter taste sensing receptors (TAS2Rs). Here, we hypothesized a contributing role of GA to the red wine-stimulated effect on PS in human gastric tumor cells (HGT-1 cells). Sensory analyses revealed that 10 μM GA as the lowest concentration tested more bitter than tap water, with increasing bitter ratings up to 1000 μM. In HGT-1 cells, the concentration of 10 μM GA evoked the most pronounced effect on PS secretion, either when added to cells as in-water solution or when spiked to a red wine matrix. GA-spiking of Zweigelt and Blaufränkisch red wine samples up to a concentration of 10 μM resulted in an equally stimulated PS, whereas the non-GA-spiked wine samples demonstrated contrary effects on PS, indicating a functional role of GA on PS. Involvement of TAS2R4 in the GA-induced PS was verified by means of an HGT-1 homozygote CRISPR-Cas9 TAS2R4 knockout approach. Moreover, gene expression analyses revealed GA to increase <i>TAS2R4</i>. These results demonstrate a functional role of TAS2R4 in GA-evoked PS as a key mechanism of gastric acid secretion aiding digestion. Moreover, our data provide mechanistic insights, which will help to produce stomach-friendly red wines.