Long-Term Exposure to Sucrose during the Differentiation Process Increases Permeability Independently of TAS1R3 in In Vitro Models of the Intestinal Barrier Function

While some studies report negative effects of noncaloric sweeteners and high glucose on models for the intestinal barrier function, the long-term effects of noncaloric sweeteners and sucrose remain unclear. Here, we investigated the impact of a long-term treatment with caloric and noncaloric sweeteners on two in vitro models for the intestinal barrier function. A Caco-2 monoculture and a coculture with mucus-producing HT29-MTX-E12 cells were treated with equi-sweet and equi-molar concentrations of sucrose, sucralose, rebaudioside M, and neohesperidin dihydrochalcone during the differentiation period of 21 days. Only treatment with 150 mM sucrose increased the paracellular permeability by up to 259% in the monoculture independent of the sweet taste receptor subunit TAS1R3 and osmotic pressure. Sucrose treatment decreased the gene expression of pore-forming markers while increasing sealing tight junctions without increasing tight junction protein 1 on the protein level. The coculture with HT29-MTX-E12 cells was more resistant toward the treatments and osmotic stress than the Caco-2 monoculture, suggesting a beneficial effect of the produced mucus by the HT29-MTX-E12 cells. In conclusion, treatment with sucrose showed a time-dependent effect on markers of intestinal permeability independent of TAS1R3 and osmotic pressure, with a potential protective effect of the mucus layer.