Akademik Veri Yönetim Sistemi
World Immune Regulation Meeting XIX 2025, Chur, İsviçre, 12 - 15 Mart 2025, ss.64, (Özet Bildiri)
The global consumption of non-nutritive sweeteners (NNS) as sugar alternatives has increased considerably in recent years to reduce caloric intake; however, emerging evidence suggests that even small amounts of NNS may negatively impact gut health. As demonstrated in previous analyses, the adverse effects of NNS on the intestinal epithelial barrier have been observed at consumer-relevant doses in an acute exposure setting. In the present study, a chronic exposure model was employed, in which low doses were administered every two days in the culture medium over an eight-day period. A microfluidic organ-on-a-chip platform was used to generate three-dimensional intestinal tubules from the human epithelial cell line Caco-2, enabling investigation of the effects of sodium saccharin (NaSA), sucralose, stevia extract (STVE), and steviol (STVO) at doses below estimated consumption exposure levels. Transepithelial electrical resistance (TEER) was assessed to evaluate cellular responses, and the effects of NNS on the gut epithelial barrier were further analyzed using RNA sequencing. Our findings indicate that NaSA and STVE, at low cumulative doses, did not result in a significant reduction in TEER, whereas sucralose and STVO induced a significant dose- and time-dependent decrease in TEER. Furthermore, transcriptomic analysis following chronic low-dose exposure to all studied NNS revealed upregulation of pathways associated with cellular stress responses, including oxidative stress, endoplasmic reticulum stress, response to unfolded proteins, mitochondrial stress, response to damage stimuli, telomere maintenance, innate immune responses, and cell death. Collectively, these results indicate that commonly used non-nutritive sweeteners, even at relatively low and daily used doses, have the capacity to disrupt gut barrier function and induce inflammatory and stress-related responses through multiple cellular mechanisms in vitro, raising potential concerns regarding the widespread and chronic consumption of NNS and their implications for gut and systemic health.