Akademik Veri Yönetim Sistemi
World Immune Regulation Meeting XVIII 2024, Chur, İsviçre, 12 - 16 Mart 2024, cilt.18, sa.51, ss.65
Westernized lifestyle exposes individuals to a wide range of harmful substances and chemicals. There is increasing evidence that even at low levels, these chemicals can disrupt the intestinal barrier. Furthermore, the consumption of non-nutritive sweeteners as a substitute for sugar is on the rise globally. This study aimed to examine the impact of commonly used non-nutritive sweeteners on the intestinal barrier. Colon organoid organ-on-a-chip and the human epithelial Caco-2 were exposed to sucralose, sodium saccharin (NaSA), stevia-extract (STVE), and steviol (STVO) at doses relevant to consumers. Cytotoxicity and transepithelial electrical resistance (TEER) of the cells were analyzed. Targeted proteomics using proximity extension assay and RNA-seq were performed to analyze the effects of these sweeteners on the gut epithelial barrier. Our findings indicate that sodium saccharin (NaSA), sucralose, stevia extract (STVE), and steviol (STVO) demonstrated dose-dependent toxicity in Caco-2 cell layers, with cytotoxicity levels exceeding 20% at 1.56 mg/ml of NaSA, 0.075 mg/ml of sucralose, over 30% at 5 mg/ml of STVE, and 0.318 mg/ml of STVO. Furthermore, these sweeteners caused a dose- and time-dependent reduction in relative transepithelial electrical resistance (TEER). The evaluation of NaSA using targeted proteomics revealed an upregulation of the MAPK cascade, chemokines associated with granulocyte chemotaxis, and cellular response to interleukin-1. Similarly, the proteomic analysis of sucralose exposure showed an upregulation of cellular response to oxidative stress, innate immune response, and natural killer cell activation. Transcriptomic data after NaSA exposure revealed upregulated pathways related to the cellular response to stress, apoptosis, and programmed cell death. In the case of sucralose exposure, transcriptomic data revealed upregulation of the apoptotic process, cell differentiation, inflammatory response, and positive regulation of the neuron apoptotic process. The evidence indicates that commonly used non-nutritive sweeteners lead to dysfunction of the gut barrier and inflammation through multiple cellular stress mechanisms in vitro.