Jan de Laffolie1, Diana Sheridan2, Konrad Reinshagen3, Lucas Wessel4, Christian Zimmermann1, Sebastian Stricker1, Markus M Lerch5, Markus Weigel6,7, Torsten Hain6,7, Eugen Domann6,7, Silvia Rudloff1, Buford L Nichols8, Hassan Y Naim9, Klaus-Peter Zimmer1. 1. Department of Paediatrics, Justus-Liebig-University Giessen, Giessen, Germany. 2. Department of Pathology, Justus-Liebig-University Giessen, Giessen, Germany. 3. Department of Pediatric Surgery, UKE: University Hospital Eppendorf, Altona Children's Hospital, Hamburg, Germany. 4. Department of Pediatric Surgery, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany. 5. Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany. 6. Institute of Medical Microbiology, Justus-Liebig-University Giessen, Giessen, Germany. 7. German Centre for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus Liebig University Giessen, Giessen, Germany. 8. Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA. 9. Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
Abstract
BACKGROUND AND AIMS: Intestinal adaptation in short bowel syndrome (SBS) includes morphologic processes and functional mechanisms. This study investigated whether digestive enzyme expression in the duodenum and colon is upregulated in SBS patients. METHOD: Sucrase-isomaltase (SI), lactase-phlorizin hydrolase (LPH), and neutral Aminopeptidase N (ApN) were analyzed in duodenal and colonic biopsies from nine SBS patients in a late stage of adaptation as well as healthy and disease controls by immunoelectron microscopy (IEM), Western blots, and enzyme activities. Furthermore, proliferation rates and intestinal microbiota were analyzed in the mucosal specimen. RESULTS: We found significantly increased amounts of SI, LPH, and ApN in colonocytes in most SBS patients with large variation and strongest effect for SI and ApN. Digestive enzyme expression was only partially elevated in duodenal enterocytes due to a low proliferation level measured by Ki-67 staining. Microbiome analysis revealed high amounts of Lactobacillus resp. low amounts of Proteobacteria in SBS patients with preservation of colon and ileocecal valve. Colonic expression was associated with a better clinical course in single cases. CONCLUSION: In SBS patients disaccharidases and peptidases can be upregulated in the colon. Stimulation of this colonic intestinalization process by drugs, nutrients, and pre- or probiotics might offer better therapeutic approaches.
BACKGROUND AND AIMS: Intestinal adaptation in short bowel syndrome (SBS) includes morphologic processes and functional mechanisms. This study investigated whether digestive enzyme expression in the duodenum and colon is upregulated in SBSpatients. METHOD:Sucrase-isomaltase (SI), lactase-phlorizin hydrolase (LPH), and neutral Aminopeptidase N (ApN) were analyzed in duodenal and colonic biopsies from nine SBSpatients in a late stage of adaptation as well as healthy and disease controls by immunoelectron microscopy (IEM), Western blots, and enzyme activities. Furthermore, proliferation rates and intestinal microbiota were analyzed in the mucosal specimen. RESULTS: We found significantly increased amounts of SI, LPH, and ApN in colonocytes in most SBSpatients with large variation and strongest effect for SI and ApN. Digestive enzyme expression was only partially elevated in duodenal enterocytes due to a low proliferation level measured by Ki-67 staining. Microbiome analysis revealed high amounts of Lactobacillus resp. low amounts of Proteobacteria in SBSpatients with preservation of colon and ileocecal valve. Colonic expression was associated with a better clinical course in single cases. CONCLUSION: In SBSpatients disaccharidases and peptidases can be upregulated in the colon. Stimulation of this colonic intestinalization process by drugs, nutrients, and pre- or probiotics might offer better therapeutic approaches.