Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome

Introduction: The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel synd...

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Main Authors: Janine Büttner, Elisabeth Blüthner, Sophie Greif, Anja Kühl, Sefer Elezkurtaj, Jan Ulrich, Sebastian Maasberg, Christoph Jochum, Frank Tacke, Ulrich-Frank Pape
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/19/4220
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author Janine Büttner
Elisabeth Blüthner
Sophie Greif
Anja Kühl
Sefer Elezkurtaj
Jan Ulrich
Sebastian Maasberg
Christoph Jochum
Frank Tacke
Ulrich-Frank Pape
author_facet Janine Büttner
Elisabeth Blüthner
Sophie Greif
Anja Kühl
Sefer Elezkurtaj
Jan Ulrich
Sebastian Maasberg
Christoph Jochum
Frank Tacke
Ulrich-Frank Pape
author_sort Janine Büttner
collection DOAJ
description Introduction: The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. Methods: Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. Results: The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. Conclusions: Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide.
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spelling doaj.art-e417db28f76b45a58f4977d2020901192023-11-19T14:51:52ZengMDPI AGNutrients2072-66432023-09-011519422010.3390/nu15194220Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel SyndromeJanine Büttner0Elisabeth Blüthner1Sophie Greif2Anja Kühl3Sefer Elezkurtaj4Jan Ulrich5Sebastian Maasberg6Christoph Jochum7Frank Tacke8Ulrich-Frank Pape9Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow Klinikum, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow Klinikum, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow Klinikum, 10117 Berlin, GermanyiPATH.Berlin, Core Unit der Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt, Campus Benjamin Franklin, 12203 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Pathology, Campus Mitte, 10117 Berlin, GermanyDepartment of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, 20099 Hamburg, GermanyDepartment of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, 20099 Hamburg, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow Klinikum, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow Klinikum, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow Klinikum, 10117 Berlin, GermanyIntroduction: The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. Methods: Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. Results: The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. Conclusions: Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide.https://www.mdpi.com/2072-6643/15/19/4220short bowel syndromechronic intestinal failureglucagon-like peptide-2teduglutideintestinal permeability
spellingShingle Janine Büttner
Elisabeth Blüthner
Sophie Greif
Anja Kühl
Sefer Elezkurtaj
Jan Ulrich
Sebastian Maasberg
Christoph Jochum
Frank Tacke
Ulrich-Frank Pape
Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome
Nutrients
short bowel syndrome
chronic intestinal failure
glucagon-like peptide-2
teduglutide
intestinal permeability
title Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome
title_full Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome
title_fullStr Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome
title_full_unstemmed Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome
title_short Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome
title_sort predictive potential of biomarkers of intestinal barrier function for therapeutic management with teduglutide in patients with short bowel syndrome
topic short bowel syndrome
chronic intestinal failure
glucagon-like peptide-2
teduglutide
intestinal permeability
url https://www.mdpi.com/2072-6643/15/19/4220
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