Sweetener System Intervention Shifted Neutrophils from Homeostasis to Priming

• Published in: Nutrients Vol. 15; no. 5; p. 1260
• Main Authors: Skurk, Thomas, Krämer, Tamara, Marcinek, Patrick, Malki, Agne, Lang, Roman, Dunkel, Andreas, Krautwurst, Tiffany, Hofmann, Thomas F., Krautwurst, Dietmar
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.03.2023; MDPI
• Subjects: acesulfame potassium; Artificial sweeteners; Beverages; Bioavailability; calcium; clinical trials; Cytokines; Food; Food Additives; gene expression; glycemic control; Health aspects; Homeostasis; Humans; Immune system; Inflammation; ingestion; Mineral water; Neutrophils; Non-Nutritive Sweeteners; nutrition; Nutrition research; Physiological aspects; Physiology; saccharin; Sodium; Sugar substitutes; Sweetening Agents; Tandem Mass Spectrometry; taste; taste receptors; transcription (genetics); Germany; St Louis Missouri; Ann Arbor Michigan; United States > US; taste receptors; acesulfame-K; cyclamate; healthy subjects; GPCR; cytokines; chemokines; chemoreception; polymorphonuclear neutrophils; saccharin
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15051260

Background: Non-nutritive sweeteners (NNS) are part of personalized nutrition strategies supporting healthy glycemic control. In contrast, the consumption of non-nutritive sweeteners has been related to person-specific and microbiome-dependent glycemic impairments. Reports on the effects of NNS on our highly individual cellular immune system are sparse. The recent identification of taste receptor expression in a variety of immune cells, however, suggested their immune-modulatory relevance. Methods: We studied the influence of a beverage-typical NNS system on the transcriptional profiling of sweetener-cognate taste receptors, selected cytokines and their receptors, and on Ca2+ signaling in isolated blood neutrophils. We determined plasma concentrations of saccharin, acesulfame-K, and cyclamate by HPLC-MS/MS, upon ingestion of a soft drink-typical sweetener surrogate. In an open-labeled, randomized intervention study, we determined pre- versus post-intervention transcript levels by RT-qPCR of sweetener-cognate taste receptors and immune factors. Results: Here we show that the consumption of a food-typical sweetener system modulated the gene expression of cognate taste receptors and induced the transcriptional regulation signatures of early homeostasis- and late receptor/signaling- and inflammation-related genes in blood neutrophils, shifting their transcriptional profile from homeostasis to priming. Notably, sweeteners at postprandial plasma concentrations facilitated fMLF (N-formyl-Met-Leu-Phe)-induced Ca2+ signaling. Conclusions: Our results support the notion of sweeteners priming neutrophils to higher alertness towards their adequate stimuli.