Introduction: Teduglutide is used in chronic intestinal failure in order to reduce the need for and to increase time off parenteral nutrition. A trophic effect is induced through GLP-2 stimulation resulting in an improved uptake of water and sodium. It is unclear if the Claudin-10 and -15 mediated sodium selectivity of the paracellular tight junction in the jejunum is influenced. Thus, the effects of Teduglutide were studied in a murine short bowel model.

Methods: By resecting 40 % of the Ileocecal region (ICR) a severe murine short bowel syndrome was simulated. Subcutaneous Teduglutide (0.1 mg/kg BW) or vehicle administration began 36 h postperatively. Survival, development of body weight, stool consistency, plasma aldosterone levels, tight junction protein expression, FITC-4kDa-Dextran-Flux and dilution potentials using an Ussing chamber were analyzed.

Results: Compared to vehicle, the development of body weight in Teduglutide treated animals was more favourable (weight nadir vehicle: 83,6 ± 1,4 % n=15 vs. Teduglutide 87,8 ± 1,4 % n=12, p<0.05). Lower aldosterone levels in Teduglutide treated animals indicated a better volume state in this group (vehicle 988 ± 172 ng/l, n=6 vs. Teduglutide: 512 ± 91.5 ng/l, n=9-11, p<0.05). The transmucosal barrier for macromolecules in the jejunum in short bowel conditions increased independently of Teduglutide administration. Occludin and Claudin-15 mRNA expression was increased after ICR, independent of Teduglutide treatment. In the jejunum of vehicle treated animals, cation permselectivity was impaired. At the same time, Claudin-10 mRNA expression in vehicle treated mice was reduced to 55.2 ± 8.5% of baseline, while it was maintained in Teduglutide treated animals at 109 ± 23.7%, n=3-4, p<0.05. In line with this, tight junction localization of Claudin-10 faded towards the villus tips in vehicle treated mice while permselectivity and Claudin-10 expression up to the villus tip remained constant in Teduglutide treated animals.

Conclusion: Teduglutide alleviates intestinal insufficiency in this mouse model of short bowel syndrome. Teduglutide not only induces trophic effects but retains epithelial function by maintaining Claudin-10 expression. This translates to improved paracellular cation permeability, facilitating sodium recirculation and thus sodium coupled nutrient transport, leading to improved nutrition status.