Capillary Flow Rates in the Duodenum of Pediatric Ulcerative Colitis Patients Are Increased and Unrelated to Inflammation

Zaidi, Deenaz; Churchill, Lucas; Huynh, Hien Q.; Carroll, Matthew; Persad, Rabin; Wine, Eytan

doi:10.1097/mpg.0000000000001495

Cited by 12 publications

(11 citation statements)

References 26 publications

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Patients aged 3–18 years, with histological and endoscopic confirmed diagnosis of CD or UC, based on the revised Porto criteria [70] and the Paris classifications [66] were eligible to participate; non-IBD controls underwent colonoscopy for abdominal pain and/or diarrhea, but endoscopy and histology were completely normal, excluding the possibility of IBD. Detailed inclusion and exclusion criteria were described previously [27, 71]. UC subjects endoscopically or histologically diagnosed with backwash ileitis were excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

et al. 2019

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BackgroundInflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis.ResultsIgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not.ConclusionUsing IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0604-3) contains supplementary material, which is available to authorized users.

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“…The cut-off point for normal gap density and capillary flow was determined based on a similar previous study [5]. Epithelial gap densities and capillary flow rates above the estimated 94 th percentile of the non-IBD group were considered to be abnormal (this cutoff has been used previously for the gaps [5], but there are no published papers on normal cutoffs for capillary flows, as we were the first to describe this method [9]; therefore, we decided to use the same methods for this analysis). Kaplan-Meier plots were used to determine event-free survival probabilities, with log-rank tests to determine the differences between study groups.…”

Section: Discussionmentioning

confidence: 99%

“…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. In another study, we reported increased capillary flow rates in the non-inflamed duodenum of UC patients, also measured with pCLE [9]. Further probing the outcomes of these significant features in IBD patients, we wanted to analyze if the presence of increased epithelial gap density and vascular flow could predict disease course and/or response to therapy, especially since they were found in unaffected areas.…”

Section: Discussionmentioning

confidence: 99%

“…Further probing the outcomes of these significant features in IBD patients, we wanted to analyze if the presence of increased epithelial gap density and vascular flow could predict disease course and/or response to therapy, especially since they were found in unaffected areas. Thus, we conducted a follow up of the patients enrolled in our previous studies [8,9], in order to determine the clinical course of patients who had increased epithelial gaps and capillary flow rates in the duodenum, as measured using pCLE. Our objective was to analyze if patients with higher epithelial gaps and/or capillary flow had increased incidences of clinical complications (described as IBD-related hospitalization, surgeries, or flares), changes in disease activity indices, or altered inflammatory markers (CRP and ESR) over a period of at least 24 months.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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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Capillary Flow Rates in the Duodenum of Pediatric Ulcerative Colitis Patients Are Increased and Unrelated to Inflammation

Abstract: This pilot study shows, for the first time, increased capillary blood flow in the duodenum of UC patients that was unrelated to inflammatory markers or disease activity. Thus, early vascular changes can be assessed using pCLE during endoscopy.

Cited by 12 publications

References 26 publications

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

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

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases

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

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