Inflammatory Bowel Disease

CHEO’s IBD Centre conducts clinical and translational research to add to the growing literature on how to improve clinical care and to bring findings we have discovered in the research laboratories to patient care Our research is conducted at CHEO, the University of Ottawa

Canada has amongst the highest rates of IBD in the world. IBD is a chronic lifelong gastrointestinal disease for which the cause is unknown. The rate of IBD in children has increased by 50% since 1994. These statements provide the incentives for the CHEO IBD Centre Research Team. Greater understanding of disease process, predictors of outcomes and improving care are common themes of the local, national and international collaborations underway. Funding is currently through a number of sources including Ontario Genomics, Genome Canada, the Ontario Government, the Canadian Institutes of Health Research, and C.H.I.L.D. Foundation as well as local donors.

“We work on a greater understanding of children and young people with Crohn’s disease and ulcerative colitis, how better to care and treat these diseases and to determine how to improve outcomes. Fostering the development of clinical and research expertise both locally and beyond is an important avenue to both gain access and share improvement IN IBD health care practices. At the CHEO IBD Centre, we strongly believe in collaborative efforts and strive to be strong partners in North American and international IBD studies and initiatives. Our hope is that this will allow for a more rapid gain in knowledge, earlier implementation of the best new practices and improvements in pediatric IBD care which is a consistent goal and expectation of our research activities.”

Dr. David Mack – Director, CHEO IBD Centre

Research Projects

Mediterranean-Like Dietary Pattern Associations With Gut Microbiome Composition and Subclinical Gastrointestinal Inflammation
01/09/2022

No single food item was associated with microbial clusters or with the level of gut inflammation. However, we found that the consumption of a Mediterranean-like diet was strongly associated with decreased subclinical intestinal inflammation.
Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn’s Disease
16/07/2022

To our knowledge, this study is the first to assess human microbial associations with gut barrier function in vivo, and our large sample is a considerable strength of our study.
Indirect and Out-of-Pocket Disease-associated Costs in Pediatric Inflammatory Bowel Disease: A Cross-sectional Analysis
27/06/2022

Indirect and OOP IBD-associated costs are substantial and more likely to affect families living in remote communities.
Hospitalization With Clostridioides difficile in Pediatric Inflammatory Bowel Disease: a Population-Based Study
07/06/2022

Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.
Targeted Assessment of Mucosal Immune Gene Expression Predicts Clinical Outcomes in Children with Ulcerative Colitis
04/06/2022

Targeted assessment of rectal mucosal immune gene expression predicts 52-week CSFR in treatment-naïve paediatric UC patients. Further exploration of IL-13Rɑ2 as a therapeutic target in UC and future studies of the epithelial-specific role of RORC in UC pathogenesis are warranted.
Thromboprophylaxis use in paediatric inflammatory bowel disease: an international RAND appropriateness panel
24/05/2022

This work therefore constitutes neither a guideline nor a consensus; however, the findings suggest a need to re-evaluate the role of thromboprophylaxis in future guidelines.
Serological responses to three doses of SARS-CoV-2 vaccination in inflammatory bowel disease
23/05/2022

In total, 232 participants (mean age 52.7 years;42.7% male) with IBD and three doses of an mRNA vaccine were included (table 1). The seroconversion rate among this sample was 99.6% and the GMT was 14 569 AU/mL (95% CI 12 846 to 16 472 AU/mL). Multivariable linear regression identified significantly increased log anti-S concentration for prior SARS-CoV-2 infection (FC: 1.97 (95% CI 1.22 to 3.18)) and decreased log anti-S concentration for corticosteroid use (FC: 0.07 (95% CI 0.03 to 0.20))
Meta-analysis of multi-jurisdictional health administrative data from distributed networks approximated individual-level multivariable regression
20/05/2022

This study validates a privacy-preserving method when conducting multi-jurisdictional multi-database studies using real-world health administrative data. This is increasingly important as multi-jurisdictional research becomes more common in parallel with rising availability of routinely collected health data. Our findings are consistent with those of previous validation studies.
Multimodal intervention to improve the transition of patients with inflammatory bowel disease from pediatric to adult care: protocol for a randomized controlled trial.
18/05/2022

This multi-component prospective transition intervention study for pediatric onset IBD builds on the existing literature of observational research to improve patient outcomes, as well as RCTs in other pediatric chronic diseases. It offers a unique focus on implementation science and a credible opportunity for national and international dissemination of positive findings. When this RCT is complete, it will represent the highest-level evidence for a transition intervention for IBD patients.
Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopists and Endoscopists in Training: A Joint NASPGHAN/ESPGHAN Guideline
01/03/2022

It is recommended that all facilities and individual providers performing pediatric endoscopy worldwide initiate and engage with the procedure-related standards and indicators developed by PEnQuIN to identify gaps in quality and drive improvement.
Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy Facilities: A Joint NASPGHAN/ESPGHAN Guideline
01/03/2022
Overview of the Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline
01/03/2022
Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopic Procedures: A Joint NASPGHAN/ESPGHAN Guideline
01/03/2022

The goal of the PEnQuIN working group in this document was to achieve consensus on a list of key standards that should be applied to all gastrointestinal endoscopic procedures that are performed in children. In addition, the working group defined indicators that can be used to measure the quality of procedures at an individual provider, group of providers or facility level, as appropriate.
Pediatric Endoscopy Quality Improvement Network Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline
03/01/2022

It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy.
Early Change in Fecal Calprotectin Predicts One-Year Outcome in Children Newly Diagnosed With Ulcerative Colitis
01/01/2022

Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.
Tolerability and SCFA production after resistant starch supplementation in humans: a systematic review of randomized controlled studies
06/12/2021

Available evidence suggests that RS supplementation is tolerated in both healthy subjects and in those with an underlying medical condition. In addition, SCFA production was increased in most of the studies.
The Rest of my Childhood was Lost”: Canadian Children and Adolescents’ Experiences Navigating Inflammatory Bowel Disease
24/11/2021
Crohn’s and Colitis Canada’s 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Executive Summary
05/11/2021

Crohn’s and Colitis Canada’s COVID-19 and IBD Taskforce produced online tools and webinars that served to rapidly synthesize and communicate scientific knowledge on COVID-19’s impact on the IBD community.
Crohn’s and Colitis Canada’s 2021 Impact of COVID-19 & Inflammatory Bowel Disease in Canada: A Knowledge Translation Strategy
05/11/2021

CCC was able to quickly assemble the COVID-19 and IBD Taskforce at the outset of the global pandemic. The Taskforce members have met and continue to meet regularly in an effort to ensure that the IBD community has the best available information to support them as they navigate a new reality with COVID-19. Direct communication from the Taskforce and the expert community in Canada to people with IBD and caregivers through a webinar series was an effective and efficient knowledge translation vehicle.
Crohn’s and Colitis Canada’s 2021 Impact of COVID-19 and Inflammatory Bowel Disease in Canada: Children and Expectant Mothers With Inflammatory Bowel Disease
05/11/2021

The pandemic has significantly affected the mental health and sense of well-being of children and their families, as well as pregnant people with IBD.
Safety of Venous Thromboprophylaxis With Low-molecular-weight Heparin in Children With Ulcerative Colitis
01/11/2021

Conclusions: There was no difference in Hb levels or need for blood transfusions in children hospitalized for severe UC (PUCAI ≥65) whether or not they received enoxaparin for thromboembolism prophylaxis.
Elevated colonic microbiota-associated paucimannosidic and truncated N-glycans in pediatric ulcerative coliti
30/10/2021
Stratification of risk of progression to colectomy in ulcerative colitis via measured and predicted gene expression
02/09/2021

In order to more explicitly model progression to colectomy observed in 6% (25 of 400) of the UC-affected individuals within 1 year of diagnosis, we performed differential expression analysis between baseline rectal RNA-seq biopsies of 21 affected individuals who progressed to colectomy and 310 who did not.
Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment
23/08/2021
Anti-Microbial Antibody Response is Associated With Future Onset of Crohn’s Disease Independent of Biomarkers of Altered Gut Barrier Function, Subclinical Inflammation, and Genetic Risk
19/07/2021

In this study, we investigated the early events of CD pathogenesis in a multicenter prospective cohort of asymptomatic FDRs of patients with CD. In other chronic immune-mediated diseases (eg, type 1 diabetes, rheumatoid arthritis), serologic markers have been used to help stratify early and late preclinical phase subjects as a basis for intervention trials aiming to prevent the onset of disease;27,28 however, no such evidence has supported the role of serologic markers in the context of preclinical CD.
Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children
24/08/2020

Conclusions: A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores.
Widespread protein lysine acetylation in gut microbiome and its alterations in patients with Crohn’s disease
17/08/2020

In this study, the proteolytic peptides generated from each microbiome sample were aliquoted for both metaproteomics and lysine acetylomics analysis. Kac peptides from the first aliquot were enriched using a seven-plex anti-Kac peptide antibody cocktail; the second aliquot was directly analyzed for metaproteome profiling
Increased Intestinal Permeability is Associated with Later Development of Crohn’s Disease
10/08/2020

Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.
Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis
30/07/2020

Liver biochemistry worsened over time in IBD unresponsive to VDZ, but remained unchanged in IBD patients in remission. VDZ did not improve liver biochemistry in pediatric PSC-IBD. Progressive liver disease may be more common in patients with medically-refractory IBD.
Phenotypic Variation in Paediatric Inflammatory Bowel Disease by Age: A Multicentre Prospective Inception Cohort Study of the Canadian Children IBD Network
21/05/2020

Paris classification of age at diagnosis is supported by age-related increases in ileal disease until age 10 years. Other phenotypic features, including severity, are similar across all ages. Linear growth is less impaired in CD than in historical cohorts, reflecting earlier diagnosis.
Fecal Markers of Inflammation and Disease Activity in Pediatric Crohn Disease: Results from the ImageKids Study
15/05/2020

This study has confirmed that FC is useful, and overall best, marker to monitor mucosal inflammation in inflammatory bowel disease. FA12, however, appears to be a more suitable maker for prediction of mucosal healing in children.
CpG Methylation in TGFβ1 and IL-6 Genes as Surrogate Biomarkers for Diagnosis of IBD in Children
14/05/2020

We found that CpG methylation in the promoter of the TGFβ1 gene has high discriminative power for identifying CD and UC and could serve as an important diagnostic marker
SMAC mimetics and RIPK inhibitors as therapeutics for chronic inflammatory diseases
18/02/2020

This may benefit and guide the development of SMs or selective RIPK inhibitors as anti-inflammatory therapeutics for various chronic inflammatory conditions.
Dietary strategies and food practices of pediatric patients, and their parents, living with inflammatory bowel disease: a qualitative interview study
15/12/2019

Our findings have important implications for the clinical care of pediatric IBD. Notably, IBD not only influenced the food practices of the pediatric patients, but also their parents and other family members. Healthcare professionals should consider the family unit when giving nutritional advice or developing nutritional guidelines. Personalized nutritional counselling and ongoing nutritional assessment are also warranted.
Analysis of Genetic Association of Intestinal Permeability in Healthy First-degree Relatives of Patients with Crohn’s Disease
19/10/2019

Excessive intestinal permeability or intestinal barrier dysfunction as measured by various assays has been observed in various diseases. However, little is known about the factors contributing to altered gut permeability in these diseases.
Anticipatory care of children and adolescents with inflammatory bowel disease: a primer for primary care providers
19/10/2019

High-quality care in pediatric IBD requires coordination between pediatric gastroenterologists and primary care providers, with careful attention paid to the specific needs of children with IBD.
Canadian Association of Gastroenterology Clinical Practice Guideline for the Medical Management of Pediatric Luminal Crohn’s Disease
15/08/2019

Evidence-based medical treatment of Crohn's disease in children is recommended, with thorough ongoing assessments to define treatment success.
Clinical disease activity and endoscopic severity correlate poorly in children newly diagnosed with Crohn’s disease
01/02/2019

In children with newly diagnosed CD, wPCDAI correlates poorly with endoscopic disease activity. As treatment paradigms evolve to target mucosal healing, clinical markers should not be used in isolation to determine disease activity.
Symptoms do not correlate with findings from colonoscopy in children with inflammatory bowel disease and primary sclerosing cholangitis
01/07/2018

Children with PSC-IBD in clinical remission, based on PUCAI scores, have a significantly higher risk of active endoscopic and histologic disease than children with colitis without PSC. Fecal levels of calprotectin correlate with endoscopic findings in pediatric patients with PSC-IBD; levels below 93 μg/g are associated with mucosal healing.
Trends in Epidemiology of Pediatric Inflammatory Bowel Disease in Canada: Distributed Network Analysis of Multiple Population-Based Provincial Health Administrative Databases
01/07/2017

Canada has amongst the highest incidence of childhood-onset IBD in the world. Prevalence significantly increased over time. Incidence was not statistically changed with the exception of a rapid increase in incidence in the youngest group of children.
ACTIVE RESEARCH – Microbiome-based Precision Medicine in Inflammatory Bowel Diseases

Active Research - The primary objective of our proposed research program is to establish prognostic and risk stratification models for personalizing IBD therapy.