Inflammation-related Proteins Support Diagnosis of Inflammatory Bowel Disease and Are Modified by Exclusive Enteral Nutrition in Children With Crohn’s Disease, Especially of Ileal Phenotype

Author:

White Bernadette1,Svolos Vaios1,Gervais Lisa2,Jatkowska Aleksandra1ORCID,Nichols Ben1,MacDonald Jonathan3,Seenan John Paul3,Hansen Richard4,Russell Richard K5,Milling Simon6ORCID,Gerasimidis Konstantinos1ORCID

Affiliation:

1. Department of Human Nutrition, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary , Glasgow , United Kingdom

2. Department of Paediatric Gastroenterology, Royal Hospital for Children , Glasgow , United Kingdom

3. Department of Gastroenterology, Queen Elizabeth University Hospital , Glasgow , United Kingdom

4. Division of Clinical and Molecular Medicine, School of Medicine, University of Dundee , Dundee , United Kingdom

5. Department of Paediatric Gastroenterology, Royal Hospital for Children & Young People , Edinburgh , United Kingdom

6. School of Infection & Immunity, College of Medical, Veterinary, and Life Sciences, University of Glasgow , Glasgow , United Kingdom

Abstract

Abstract Background The immunological effects of treatment with exclusive enteral nutrition (EEN) in Crohn’s disease (CD) remain unknown. We characterized the plasma levels of inflammation-related proteins (IRPs) in children with CD and ulcerative colitis (UC) compared with noninflammatory controls (non-IBD) and explored the effect of EEN in CD. Methods Ninety-two IRPs were quantified using Olink proteomics in children with CD (n = 53), UC (n = 11), and non-IBD (n = 19). For 18 children with active CD, IRPs were measured before and after 8 weeks of EEN. Relationships with disease phenotype and response to EEN were studied. Results Compared with non-IBD, patients with active UC and CD had different levels of 27 (24 raised, 3 decreased) and 29 (26 raised, 3 decreased) IRPs, respectively. Exclusive enteral nutrition modified the levels of 19 IRPs (13 increased, 6 decreased including CCL23, interleukin-24, interleukin-6, and MMP-1). More pronounced changes in IRP profile were observed in patients with ileal involvement and a ≥50% decrease in fecal calprotectin during EEN compared with those with colonic involvement and a <50% decrease in fecal calprotectin, respectively. A machine-learning model utilizing baseline IRP profile predicted response to EEN with a sensitivity of 89%, specificity of 57%, and accuracy of 73%. Thymic stromal lymphopoietin was the most important IRP in the model, this being higher in responders. Conclusions Inflammation-related proteins may be useful in the differential diagnosis of IBD. Exclusive enteral nutrition extensively modulated IRPs levels in children with active CD with more pronounced effects observed in patients who showed a reduction in FC and had ileal disease involvement.

Funder

The Glasgow Children Hospital Charity, Nestle Health Science, The Leona and Harry Helmsley Charitable Trust, and The Catherine McEwan Foundation

Publisher

Oxford University Press (OUP)

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