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

## TL;DR

Long-term exposure to sucrose increases intestinal permeability in lab models, unrelated to taste receptors or osmotic pressure.

## Contribution

The study reveals that sucrose increases intestinal permeability independently of TAS1R3 and osmotic pressure.

## Key findings

- 150 mM sucrose increased paracellular permeability by 259% in Caco-2 monoculture.
- Sucrose altered gene expression of tight junction markers without increasing protein levels.
- Coculture with HT29-MTX-E12 cells showed greater resistance to treatments and osmotic stress.

## Abstract

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.