Exclusive Enteral Nutrition: Clinical Effects and Changes in Mucosal Cytokine Profile in Pediatric New Inflammatory Bowel Disease

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Abstract

Exclusive Enteral Nutrition (EEN) is the first-line treatment in children with Crohn’s disease (CD) for induction of remission. However, the mode of action remains conjectural. The aim of this study was to investigate whether the effect of EEN is paralleled by changes in the mucosal cytokine profiles (MCP). Twelve children with new onset inflammatory bowel disease (IBD) received induction treatment with a polymeric EEN. We assessed clinical, endoscopic and histologic scoring before and after EEN. Twelve colonic cytokines were analyzed by Polymerase Chain Reaction (PCR) in six of the IBD patients at onset and after EEN as well as in six non-IBD control children at the diagnostic colonoscopy. Twelve children completed 6 weeks of EEN, except from one child who completed 4 weeks. At the control colonoscopy, 83% were in complete clinical remission. Changes were found in the MCPs of individual patients after EEN. In particular, children with IBD showed significantly higher values of Interleukin (IL)-12β ( p = 0.008) and IL-23α ( p = 0.02) compared to non-IBD controls at the diagnostic colonoscopy. Furthermore, an overall change in proinflammatory cytokines was noted in the IBD-group after treatment. Further studies are warranted to understand the role of EEN in MCP.

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Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Isabelle Cleynen, Gabrielle Boucher, Luke Jostins … (2016)

Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10−78), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10−18). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10−4). Interpretation Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time. Funding International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).

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A reproducible grading scale for histological assessment of inflammation in ulcerative colitis.

K. Geboes, R. Riddell, Å. ÓST … (2000)

Evaluation of histological activity in ulcerative colitis needs to be reproducible but has rarely been tested. This could be useful both clinically and in clinical trials. To develop reproducible criteria which are valid in the assessment of acute inflammation (activity) and chronicity, and to evaluate these features in an interobserver variability study. A six grade classification system for inflammation was developed which could also be fine tuned within each grade. The grades were: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin sections from endoscopically inflamed and non-inflamed mucosa from patients with distal ulcerative colitis were assessed in two separate readings by three pathologists independently and without knowledge of the clinical status. Interobserver agreement was compared pairwise using kappa statistics. Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which are too low to be of value. Following development of a semiquantitative pictorial scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For activity defined by neutrophils between epithelial cells, kappa values were 0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils in epithelium correlated with the presence of crypt destruction and ulceration. A histological activity system was developed for ulcerative colitis that showed good reproducibility and modest agreement with the endoscopic grading system which it complemented. It has potential value both clinically and in clinical trials.

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Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease.

J M E Fell, M Paintin, F. Arnaud-Battandier … (2000)

Although enteral nutrition is a recognized form of treatment for intestinal Crohn's disease, there are persisting problems with feed palatability and only limited data as to its mode of action. To assess the effects of a specific oral polymeric diet (CT3211; Nestle, Vevey, Switzerland), which is rich in transforming growth factor beta2, on the mucosal inflammatory process. Twenty-nine consecutive children with active intestinal Crohn's disease were treated with CT3211 as the sole source of nutrition for 8 weeks. Patients were assessed clinically, and endoscopically, whilst cytokine mRNA was measured in mucosal biopsies before and after treatment by quantitative reverse transcriptase polymerase chain reaction. After 8 weeks 79% of children were in complete clinical remission. Macroscopic and histological healing in the terminal ileum and colon was associated with a decline in ileal and colonic interleukin-1beta mRNA (pre-treatment to post-treatment ratio 0.008 and 0.06: P < 0.001, P = 0.006). In the ileum there was also a fall in interferon gamma mRNA (ratio 0.15, P < 0.001) with a rise in transforming growth factor beta1 mRNA (ratio 10, P = 0.04), whilst in the colon interleukin-8 mRNA fell with treatment (ratio 0.06, P < 0.05). The clinical response to oral polymeric diet CT3211 is associated with mucosal healing and a down regulation of mucosal pro-inflammatory cytokine mRNA in both the terminal ileum and colon. In the ileum there was also an increase in transforming growth factor beta1 mRNA.

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Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 15 February 2019

Publication date Collection: February 2019

Volume: 11

Issue: 2

Electronic Location Identifier: 414

Affiliations

[1 ]Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 11883 Stockholm, Sweden; Yigael.finkel@ 123456sll.se

[2 ]Department of Gastroenterology, Sachs’ Children and Youth Hospital, Södersjukhuset, 11883 Stockholm, Sweden

[3 ]Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 14157 Huddinge, Sweden; kerstin.jonsson-videsater@ 123456sll.se

[4 ]Department of Medicine, Huddinge, Karolinska Institutet, 14157 Huddinge, Sweden

[5 ]Department of Women’s and Children’s Health, Karolinska Institutet, 17177 Stockholm, Sweden; ulrika.fagerberg@ 123456ki.se

[6 ]Center for Clinical Research, Västmanland Hospital, Uppsala University, 72189 Västerås, Sweden

[7 ]Department of Gastroenterology, Karolinska University Hospital, 17177 Stockholm, Sweden; Michael.eberhardson@ 123456ki.se

[8 ]Department of Medicine Solna, Karolinska Institutet, 17176 Stockholm, Sweden

Author notes

[* ]Correspondence: helena.jonsson.rolandsdotter@ 123456ki.se ; Tel.: +46-8616-4693

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Helena Rolandsdotter https://orcid.org/0000-0002-5453-6754

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Publisher ID: nutrients-11-00414

DOI: 10.3390/nu11020414

PMC ID: 6412217

PubMed ID: 30781421

SO-VID: 133d2507-4ad9-4f0d-989d-5b6662214dc4

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Exclusive Enteral Nutrition: Clinical Effects and Changes in Mucosal Cytokine Profile in Pediatric New Inflammatory Bowel Disease

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Chinese Journal of School Health

Most cited references 23

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

A reproducible grading scale for histological assessment of inflammation in ulcerative colitis.

Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn's disease.

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