Parenteral Nutrition-Dependent Children With Short-Bowel Syndrome Lack Duodenal-Adaptive Hyperplasia but Show Molecular Signs of Altered Mucosal Function

Autor: Jouko Lohi, Annika Mutanen, Antti Koivusalo, Markku Heikinheimo, Galina Sanaksenaho, Mikko P. Pakarinen, Antti Kyrönlahti, Marjut Pihlajoki, Nimish Godbole
Rok vydání: 2019
Předmět:
Zdroj: JPEN. Journal of parenteral and enteral nutritionReferences. 44(7)
ISSN: 1941-2444
Popis: Background Although adaptive mucosal growth of the remaining small intestine is an essential compensatory mechanism to bowel resection in experimental short-bowel syndrome (SBS), only scarce clinical data are available. We studied structural and molecular mechanisms of intestinal adaptation in children with SBS. Methods Fourteen patients, who had been dependent on parenteral nutrition (PN) since neonatal period for a median (interquartile range)1.4 (0.7-6.5) years, were studied at the age of 1.5 (1.0-6.5) years. Median length of remaining small bowel was 33 (12-60) cm, and 6 patients had their ileocecal valve preserved. Six children without gastrointestinal disorders served as age-matched and gender-matched controls. All patients underwent duodenal biopsies. Mucosal microarchitecture, proliferation, apoptosis, inflammation, and epithelial-barrier function were addressed using histology, immunohistochemistry, and quantitative real-time polymerase chain reaction. Results Villus height, crypt depth, enterocyte proliferation, and apoptosis were similar in patients and matched controls. Messenger RNA (mRNA) expression of numerous genes regulating gut epithelial-barrier function (TGFB2, CAV1, CLDN1, MUC2, and NLRC4) was significantly altered. Of various nutrient transporters studied, only expression of SLC2A1 encoding facilitative glucose transporter GLUT1 was increased among patients, whereas RNA expression of genes encoding sodium-dependent glucose, sterol, fatty-acid, and peptide transport remained unchanged. Conclusion Duodenal mucosal hyperplasia has a limited role in mediating physiological adaptation following intestinal resection among PN-dependent children with SBS. Further clinical studies addressing functional significance of the observed alterations in mucosal RNA expression are warranted.
Databáze: OpenAIRE