Compromised duodenal mucosal integrity in children with short bowel syndrome after adaptation to enteral autonomy

Galina Sanaksenaho; Annika Mutanen; Nimish Godbole; Maria Hukkinen; Laura Merras-Salmio; Reetta Kivisaari; Antti Kyrönlahti; Marjut Pihlajoki; Jouko Lohi; Markku Heikinheimo; Mikko P Pakarinen

doi:10.1016/j.jpedsurg.2020.09.065

Compromised duodenal mucosal integrity in children with short bowel syndrome after adaptation to enteral autonomy

J Pediatr Surg. 2021 May;56(5):966-974. doi: 10.1016/j.jpedsurg.2020.09.065. Epub 2020 Oct 8.

Affiliations

¹ Division of Pediatric Surgery, Pediatric Liver and Gut Research Group, Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
² Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Department of Pediatric Gastroenterology, Pediatric Liver and Gut Research Group, Children's Hospital, Pediatric Research Centre, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
⁴ HUS Medical Imaging Center, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁵ Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁶ Division of Pediatric Surgery, Pediatric Liver and Gut Research Group, Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address: mikko.pakarinen@hus.fi.

PMID: 33131778
DOI: 10.1016/j.jpedsurg.2020.09.065

Abstract

Background: Intestinal adaptation has been extensively studied experimentally, but very limited data is available on human subjects. In this study we assessed intestinal adaption in humans with short bowel syndrome (SBS).

Methods: We comparatively evaluated mucosal hyperplasia, inflammation, barrier function and nutrient transport using histology, immunohistochemistry and qPCR for selected 52 key genes in duodenal biopsies obtained from children with SBS after weaning off parenteral nutrition (n = 33), and matched controls without intestinal pathology (n = 12). Small bowel dilatation was assessed from contrast small bowel series.

Results: Duodenal mucosa of SBS children showed increased histologic inflammation of lamina propria (p = 0.033) and mucosal mRNA expression of tumor necrosis factor (p = 0.027), transforming growth factor (TGF)-β2 (p = 0.006) and caveolin-1 (CAV1; p = 0.001). Villus height, crypt depth, enterocyte proliferation, apoptosis and expression of proliferation and nutrient transport genes remained unchanged. Pathologic small bowel dilatation reduced crypt depth (p = 0.045) and downregulated mRNA expression of interleukin (IL)-6 by three-fold (p = 0.008), while correlating negatively with IL6 (r = -0.609, p = 0.004). Loss of ileocecal valve (ICV) upregulated mRNA expression of toll-like receptor 4 (TLR4), TGF-β1, CAV1, several apoptosis regulating genes, and mRNA expression of zonulin (p < 0.05 for all).

Conclusions: Despite successful adaptation to enteral autonomy, duodenal mucosa of SBS children displayed histologic and molecular signs of abnormal inflammation and regulation of epithelial permeability, whereas no structural or molecular signs of adaptive hyperplasia or enhanced nutrient transport were observed. Excessive dilatation of the remaining small bowel paralleled impaired duodenal crypt homeostasis, while absence of ICV modified regulation of mucosal inflammation, regeneration and permeability.

Level of evidence: II.

Keywords: caveolin; ileocecal valve; interleukin-6; intestinal failure; small bowel dilatation; transforming growth factor.

MeSH terms

Adaptation, Physiological
Animals
Child
Disease Models, Animal
Humans
Intestinal Mucosa
Intestine, Small
Rats
Rats, Sprague-Dawley
Short Bowel Syndrome*