Chemosensate-Induced Modulation of the Salivary Proteome and Metabolome Alters the Sensory Perception of Salt Taste and Odor-Active Thiols.

Oral stimulation with chemosensates was found to trigger changes in the composition of the salivary proteome and metabolome, which translate into a functional modulation of odor and taste perception. Orosensory intervention with 6-gingerol induced a significant increase in the abundance of salivary sulfhydryl oxidase 1, which was found to catalyze the oxidative decline of odor-active 2-furfurylthiol, thus resulting in a decrease in the odorant levels in exhaled breath, as shown by PTR-MS, and a reduction of the perceived sulfury after-smell. Therefore, sulfhydryl oxidase 1 may be considered as a component of a molecular network triggering oral cleansing mechanisms after food ingestion. Moreover, oral stimulation with citric acid, followed by targeted metabolomics, was found to induce a strong increase in salivary concentrations of minerals and, in particular, sodium ions, whereas the other metabolites were rather unaffected. Because of the elevated basal levels of salivary sodium after citric acid stimulation, NaCl test stimuli were perceived as significantly less salty, most likely due to the decreased sensory contrast. This indicates the modulation of the salivary proteome and metabolome to be a major perireceptor event in fine-tuning odor and taste sensitivity.

Quantitative proteomics and SWATH-MS to elucidate peri-receptor mechanisms in human salt taste sensitivity.

Recently, studies on human salt taste sensitivity demonstrated that sodium chloride (NaCl) sensitive and non-sensitive subjects differed in their salivary proteome and, in particular, in endopeptidase activity. In order to investigate individual's NaCl sensitivity and the role of endoprotease activity in salt taste perception, 20 panellists were classified according to NaCl sensitivity and saliva samples collected. A targeted protein quantitation by means of selected-reaction-monitoring (SRM) mass spectrometry and stable-isotope incorporation revealed the joint abundance of lysozyme C and lipocalin-1 to be indicative for non-sensitive subjects. Sensory studies performed after oral challenge with the serine-type endopeptidase trypsin demonstrated a salt enhancing effect which was assumed to be due to an in-vivo generation of salt-modulating peptides as shown by LC-SWATH-MS. Amongst those, the tetrapeptide PLWR was found to elicit salty taste enhancing activity above an extraordinarily low taste threshold concentration of 6.5 µmol/L.

Salivary Proteome Patterns Affecting Human Salt Taste Sensitivity.

To investigate the role of perireceptor events in inter-individual variability in salt taste sensitivity, 31 volunteers were monitored in their detection functions for sodium chloride (NaCl) and classified into sensitive (0.6-1.7 mmol/L), medium-sensitive (1.8-6.9 mmol/L), and nonsensitive (7.0-11.2 mmol/L) subjects. Chemosensory intervention of NaCl-sensitive (S+) and nonsensitive (S-) panellists with potassium chloride, ammonium chloride, and sodium gluconate showed the salt taste sensitivity to be specific for NaCl. As no significant differences were found between S+ and S- subjects in salivary sodium and protein content, salivary proteome differences and their stimulus-induced dynamic changes were analyzed by tryptic digestion, iTRAQ labeling, and liquid chromatography-tandem mass spectrometry analysis. Differences in the salivary proteome between S+ and S- subjects were found primarily in resting saliva and were largely independent of the dynamic alterations observed upon salt stimulation. Gene ontology enrichment analysis of key proteins, i.e., immunoglobulin heavy constant y1, myeloblastin, cathepsin G, and kallikrein, revealed significantly increased serine-type endopeptidase activity for the S+ group, while the S- group exhibited augmented cysteine-type endopeptidase inhibitor activity by increased abundances in lipocalin-1 and cystatin-D, -S, and -SN, respectively. As proteases have been suggested to facilitate transepithelial sodium transport by cleaving the y-subunit of the epithelial sodium channel (ENaC) and protease inhibitors have been shown to reduce ENaC-mediated sodium transport, the differentially modulated proteolytic activity patterns observed in vivo for S+ and S- subjects show evidence of them playing a crucial role in affecting human NaCl sensitivity.