2. Academic Validation
  3. Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

  • Dig Dis Sci. 2020 Dec;65(12):3521-3537. doi: 10.1007/s10620-020-06140-6.
Johannes Reiner 1,  Peggy Berlin 1,  Jakob Wobar 1,  Holger Schäffler 1,  Karen Bannert 1,  Manuela Bastian 2,  Brigitte Vollmar 3,  Robert Jaster 1,  Georg Lamprecht 4,  Maria Witte 5
Affiliations

Affiliations

  • 1 Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Ernst-Heydemann-Str. 6, 18057, Rostock, Germany.
  • 2 Institute for Clinical Chemistry and Laboratory Medicine, Rostock University Medical Center, Ernst-Heydemann-Str. 6, 18057, Rostock, Germany.
  • 3 Rudolf-Zenker-Institute of Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18057, Rostock, Germany.
  • 4 Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Ernst-Heydemann-Str. 6, 18057, Rostock, Germany. georg.lamprecht@med.uni-rostock.de.
  • 5 Department of General, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center, Schillingallee 35, 18057, Rostock, Germany.
PMID: 32072437 DOI: 10.1007/s10620-020-06140-6
Abstract

Background: In short bowel syndrome, epithelial surface loss results in impaired nutrient absorption and may lead to intestinal insufficiency or intestinal failure. Nucleotide oligomerization domain 2 (NOD2) dysfunction predisposes to the development of intestinal failure after intestinal resection and is associated with intestinal barrier defects. Epithelial barrier function is crucial for intestinal absorption and for intestinal adaptation in the short bowel situation.

Aims: The aim of the study was to characterize the effects of the GLP-2 analogue Teduglutide in the small intestine in the presence and absence of NOD2 in a mouse model of short bowel syndrome.

Methods: Mice underwent 40% ICR and were thereafter treated with Teduglutide versus vehicle injections. Survival, body weight, stool water, and sodium content and plasma aldosterone concentrations were determined. Intestinal and kidney tissue was examined with light and fluorescence microscopy, Ussing chamber studies and quantitative PCR in wild type and transgenic mice.

Results: Teduglutide reduced intestinal failure incidence in NOD2 k.o. mice. In wt mice, Teduglutide attenuated intestinal insufficiency as indicated by reduced body weight loss and lower plasma aldosterone concentrations, lower stool water content, and lower stool sodium losses. Teduglutide treatment was associated with enhanced epithelial paracellular pore function and enhanced claudin-10 expression in tight junctions in the villus tips, where it colocalized with sodium-glucose cotransporter 1 (SGLT-1), which mediates Na-coupled glucose transport.

Conclusions: In the SBS situation, Teduglutide not only maximizes small intestinal mucosal hypertrophy but also partially restores small intestinal epithelial function through an altered distribution of claudin-10, facilitating sodium recirculation for Na-coupled glucose transport and water absorption.

Keywords

Barrier function; Mouse model; Nucleotide oligomerization domain 2; Short bowel syndrome; Teduglutide; Ussing chamber.

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