Introduction:

Teduglutide, an analog of glucagon-like peptide 2, improves intestinal rehabilitation in chronic intestinal failure frequently caused by short bowel syndrome (SBS). However, the mechanisms in the intestinal barrier related to regulation of intestinal permeability (IP) during adaptive response or therapy are not well understood. We analyzed whether measurement of IP or gene expression analysis from mucosal biopsies of selected candidate genes likely associated with IP are useful biomarkers to describe the regulation mechanisms in the intestinal barrier in patients with SBS with or without teduglutide therapy.

Methods:

IP was assessed using a sugar drink test containing lactulose and mannitol and urinary recovery rate was used to determine lactulose/mannitol ratio. Gene expression analyses of mucosal biopsies was performed using qRT-PCR Quantitec Primer Assays for tight junction genes and epithelial markers.

Results:

SBS patients showed increased Lac/Man ratio compared to healthy controls (HC), (n=29/34, p=0.0001). Mannitol recovery was decreased in SBS (Mean HC 13.8% vs. SBS 5.4%, p= 0.0001), whereas lactulose recovery was similar to HC (mean HC 0.21% vs. SBS 0.36% p= 0.2). qRT-PCR analyses showed significant differences in gene expression between SBS patients and HC (n=30/7) for YBX3 p=0.048, CRB3 p=0.009, CDK4 p=0.048, CASK p=0.03, and SI p=0.02.

For 12 patients, gene expression data were analyzed before and after up to 12 month of teduglutide treatment. Significant differences in gene expression were received for CASK p=0.01 and SI p=0.028. Further, analysis of citrullin levels in this cohort showed increased citrullin levels in patients with teduglutide therapy (p=0.012).

Conclusions:

The analysis of IP gave first insights into changes of intestinal sugar absorption but has not yet been established in SBS patients. Further paired and controlled studies are required to evaluate the specifc influence of both altered bowel anatomy and/or changes in barrier function. Furthermore, altered specific gene expression was shown for both, tight junction formation and genes involved in nutrient transport and should be further analyzed.