Increased Epithelial Gap Density in the Noninflamed Duodenum of Children With Inflammatory Bowel Diseases

Zaidi, Deenaz; Bording-Jorgensen, Michael; Huynh, Hien Q.; Carroll, Matthew; Turcotte, J.; Sergi, Consolato; Liu, Julia; Wine, Eytan

doi:10.1097/mpg.0000000000001182

Cited by 24 publications

(18 citation statements)

References 35 publications

(45 reference statements)

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“…Increased epithelial gaps in the duodenum of adult IBD patients were reported by Lim, et al [7]. We also found increased epithelial gap density, defined as the number of epithelial gaps per 1000 epithelial cells, in the unaffected duodenum of both CD and UC patients [8]. Epithelial gaps were unrelated to local inflammation or disease activity in our study, suggesting that these gaps could represent a baseline defect in the gut barrier in pediatric IBD patients and that they are not secondary to inflammation.…”

Section: Discussionsupporting

confidence: 87%

Prognostic Value of Probe-Based Confocal Laser Endomicroscopy in Pediatric Inflammatory Bowel Diseases

Zaidi¹,

Huynh²,

Carroll³

et al. 2018

J Gastroenterol Res

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The incidence of inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is increasing in children. We recently demonstrated increased epithelial gaps in the non-inflamed duodenum of CD and UC patients, and high capillary flow rates in the duodenum of UC patients using probe-based confocal laser endomicroscopy (pCLE). The aim of the present study was to determine if increased epithelial gap density or capillary flow could predict the clinical course of IBD patients and response to therapy.A total of 26 patients (16 CD and 10 UC cases for the epithelial gap study and 9 UC patients for the vascular flow study -all also included in the gap study) were followed from the time of initial pCLE imaging for a minimum of 24 months. Clinical outcomes analysed included the occurrence of significant clinical events (hospitalizations, surgeries, disease flares), alterations in inflammatory parameters, and disease activity indices.High epithelial gaps and capillary flow rates did not predict the risk of clinical events or alterations in inflammatory parameters in IBD patients. CD patients with high gap density who were treated with infliximab had a significant reduction in ESR levels at 12 months.The study did not support an ability for pCLE to predict hospitalizations or flares. Future studies evaluating epithelial gap density and vascular changes in pediatric IBD patients and their relation with inflammatory parameters and sub-clinical molecular changes might be helpful in determining disease pathogenesis and better defining treatment options.

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Section: Discussionsupporting

confidence: 87%

Prognostic Value of Probe-Based Confocal Laser Endomicroscopy in Pediatric Inflammatory Bowel Diseases

Zaidi¹,

Huynh²,

Carroll³

et al. 2018

J Gastroenterol Res

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“…However, in the present study, ulcerative colitis was associated with the clearest alterations in duodenal microbiota composition, despite the fact that in this disease, the inflammation primarily affects the colon. Still, epithelial barrier, and permeability defects have been detected in the duodenal biopsies from patients with IBD [ 43 , 44 ], along with markers of local inflammation that were not reflected in general disease activity [ 44 , 45 ]. Furthermore, although we excluded all children whose diet had been modified due to the disease, as well as those treated with antacids, antibiotics or other medication, bacterial richness might be influenced by transit time, anemia and overall lower food intake that may reduce acid and bile secretion.…”

Section: Discussionmentioning

confidence: 99%

Low-complexity microbiota in the duodenum of children with newly diagnosed ulcerative colitis

et al. 2017

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BackgroundInflammatory bowel disease (IBD) is characterized by gut dysbiosis. To date, the large bowel microbiota has been in focus. However, the microbiota of the small intestine may also be of importance, as the small bowel is a site for the induction and control of mucosal immune responses, which can be modulated by constituents of the local microbiota.MethodsDuodenal fluids were collected during diagnostic work-up of treatment-naïve children who were suspected of having IBD. The duodenal fluids were analyzed by pyrosequencing (average of 32,000 reads/sample, read length of 500 nucleotides). After diagnosis, the duodenal microbiota of subjects with ulcerative colitis (N = 8) or Crohn’s disease (N = 5), and non-IBD controls (N = 8) were compared.ResultsPyrosequencing revealed that the duodenal microbiota of children with ulcerative colitis contained fewer Operational Taxonomic Units (OTUs) per individual than the duodenal microbiota of the controls (P = 0.005). This reduction in richness of the duodenal microbiota was seen for three major phyla: Firmicutes, Actinobacteria, and Bacteroidetes. Several bacterial genera were detected less frequently in the children with ulcerative colitis than in the non-IBD controls, including Collinsella (P = 0.001), Lactobacillus (P = 0.007), and Bacillus (P = 0.007), as well as a non-identified member of the order Sphingobacteriales (P = 0.007).ConclusionsIn this pilot study, we show that the duodenal microbiota of children with ulcerative colitis exhibits reduced overall richness, despite the fact that the inflammation is primarily localized to the colon. These results should be corroborated in a larger study.

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“…Impaired epithelial barrier function, alterations of normal gut microbiota composition and translocation of bacteria through the intestinal epithelium have all been described in IBD and thus in CD [ 13 , 124 , 125 , 126 ]. Despite the wide availability of data regarding EEN utilization for the induction of remission in CD, there is a considerable knowledge gap in our understanding of its exact mechanism of action.…”

Section: Nutritional Therapiesmentioning

confidence: 99%

Dietary Management in Pediatric Patients with Crohn’s Disease

Scarallo

Lionetti

2021

Nutrients

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It has been widely endorsed that a multifactorial etiology, including interaction between genetic and environmental factors, can contribute to Crohn’s Disease (CD) pathogenesis. More specifically, diet has proven to be able to shape gut microbiota composition and thus is suspected to play a significant role in inflammatory bowel disease (IBD) pathogenesis. Moreover, poor nutritional status and growth retardation, arising from several factors such as reduced dietary intake or nutrient leakage from the gastrointestinal tract, represent the hallmarks of pediatric CD. For these reasons, multiple research lines have recently focused on the utilization of dietary therapies for the management of CD, aiming to target concurrently mucosal inflammation, intestinal dysbiosis and optimization of nutritional status. The forerunner of such interventions is represented by exclusive enteral nutrition (EEN), a robustly supported nutritional therapy; however, it is burdened by monotony and low tolerance in the long term. Novel dietary interventions, such as Crohn’s Disease Exclusion Diet or Crohn’s Disease treatment with eating, have shown their efficacy in the induction of remission in pediatric patients with CD. The aim of the present narrative review is to provide a synopsis of the available nutritional strategies in the management of pediatric CD and to discuss their application in the dietary management of these patients.

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Increased Epithelial Gap Density in the Noninflamed Duodenum of Children With Inflammatory Bowel Diseases

Abstract: Duodenal epithelial gaps are increased in pediatric patients with IBD (including UC) but are unrelated to inflammation. This suggests that altered epithelial barrier is an important systemic feature of pediatric IBD and is not only secondary to inflammation.

Cited by 24 publications

References 35 publications

Prognostic Value of Probe-Based Confocal Laser Endomicroscopy in Pediatric Inflammatory Bowel Diseases

Prognostic Value of Probe-Based Confocal Laser Endomicroscopy in Pediatric Inflammatory Bowel Diseases

Low-complexity microbiota in the duodenum of children with newly diagnosed ulcerative colitis

Dietary Management in Pediatric Patients with Crohn’s Disease

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