Intestinal Adaptation in Pediatric Short Bowel Syndrome : Controlled Assessment of Duodenal Mucosa after Extensive Bowel Resection

Background. Although extensively studied in experimental models, human data on intestinal adaptation in short bowel syndrome (SBS) is very limited. Aim of the study. We studied mucosal homeostasis of the duodenum in children with intestinal failure (IF) both during parenteral nutrition (PN) and after achieving intestinal autonomy by weaning off PN in relation to controls. Patients and methods. In total, 58 patients with IF aged from 0.5 to 23 years and 43 controls matched for age and gender without intestinal pathology were included. Duodenal biopsies obtained during clinically indicated gastroscopies were collected. We evaluated duodenal disaccharidase activities, inflammation, structural mucosal hyperplasia, proliferation, apoptosis, epithelial barrier function and nutrient transport by using the glucose oxidase method, histology, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR) for 52 genes. Dilatation of the small bowel was assessed from a contrast small bowel series. Results. Activities of maltase and sucrase were 1.6 times lower and mucosal inflammation more frequent (22% vs 3%) in patients on current PN in comparison with controls (P˂0.05 for both). Disaccharidase activities in patients who had weaned off PN were comparable with controls. In the evaluation of mucosal morphology, proliferation, and apoptosis, PN-dependent and weaned off patients showed similar results to controls. Compared to controls, SBS patients showed a statistically significant (P<0.005 for PN-dependent and weaned off patients) increase in mucosal mRNA expression of Transforming growth factor (TGF)β2 and Caveolin1 (CAV1). In addition, compared to controls, patients on PN demonstrated elevated mRNA expression of Claudin 1 (CLDN1), Mucin 2 (MUC2) and Glucose transporter, GLUT1 (SLC2A1) and decreased expression of NLR family CARD containing 4 (NLRC4) (P<0.005 for all). Weaned-off patients showed increased histologic inflammation of the lamina propria and elevated Tumor necrosis factor (TNF) and TGF-β2 (P<0.05 for all) mRNA expression when compared to controls. Pathologic small bowel dilatation was associated with shorter crypts (P=0.045) and decreased mRNA expression of Interleukin (IL)-6 (P=0.008). Conclusions. In children with IF, current PN was associated with decreased disaccharidase activities and increased inflammation, suggesting that PN requirement negatively affects intestinal adaptation. Duodenal mucosal hyperplasia seemed to have only a limited role in intestinal adaptation after extensive bowel resection in children with SBS and despite weaning off PN, patients showed mucosal inflammation and molecular signs of altered epithelial permeability.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2020

Author dc:creator

• Sanaksenaho, Galina

• lääketiede

Statement dc:rights

• Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
• This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
• Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden.

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/321489

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F321489