Publications by authors named "Johan Van Limbergen"

60 Publications

Withdrawal of Combination Immunotherapy in Paediatric Inflammatory Bowel Disease - An International Survey of Practice.

J Pediatr Gastroenterol Nutr 2021 Mar 1. Epub 2021 Mar 1.

Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, United Kingdom Child Life and Health, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, the Netherlands Edmonton Pediatric IBD Clinic (EPIC), Department of Pediatrics, University of Alberta, Edmonton, Canada.

Objectives: To assess current practices around the use of combination immunosuppression in paediatric inflammatory bowel disease (PIBD) with a focus on the subsequent withdrawal process.

Methods: A web-based, 43 question survey.

Results: Surveys were completed by 70 paediatric gastroenterologists (PG) from 27 nations across Europe, North America, Oceania and Asia from 62 centres covering approximately 15,000 PIBD patients (median of 200 patients (IQR 130-300) per centre). Routine use of co-immunosuppression was significantly higher with infliximab (IFX) versus adalimumab (ADL) {(61/70, 87.1%) compared with (23/70, 32.9%) [p < 0.01]}. Thiopurines [azathioprine (AZA) or 6-mercaptopurine] were the preferred option overall for co-immunosuppression. They were favoured with either IFX or ADL, (76% and 77% respectively) and in both ulcerative colitis (UC) and Crohn's disease (CD) (84% and 69%) compared with methotrexate (MTX).Immunomodulators were the preferred choice as the initial drug to be withdrawn from the combination therapy rather than anti-Tumour Necrosis Factor-alpha (anti-TNF) therapy (59/67, 88% [p < 0.01]). The most common withdrawal time was after 6-12 months, with this decision usually based on clinical assessment rather than a scheduled withdrawal time (51/67, 76% versus 16/67, 24%). Indicators of mucosal healing and therapeutic drug monitoring (TDM) results tended to be the most important "clinical factors" in the withdrawal decision. [p = 0.05].

Conclusion: Most PG's favour initial withdrawal of immunomodulator (usually thiopurines) rather than biologic therapy in the step-down process, usually after 6-12 months based on sustained clinical remission. This survey precedes an in-depth, multicentre study of clinical outcomes of withdrawal of co-immunosuppression in PIBD.
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http://dx.doi.org/10.1097/MPG.0000000000003098DOI Listing
March 2021

Adverse Events of Thiopurine Therapy in Pediatric Inflammatory Bowel Disease and Correlations with Metabolites: A Cohort Study.

Dig Dis Sci 2021 Feb 3. Epub 2021 Feb 3.

Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam, UMC, Vrije Universiteit Amsterdam, 1105 AZ, Amsterdam, The Netherlands.

Background: In the recent era of growing availability of biological agents, the role of thiopurines needs to be reassessed with the focus on toxicity.

Aims: We assessed the incidence and predictive factors of thiopurine-induced adverse events (AE) resulting in therapy cessation in pediatric inflammatory bowel disease (IBD), related to thiopurine metabolites and biochemical abnormalities, and determined overall drug survival.

Methods: We performed a retrospective, single-center study of children diagnosed with IBD between 2000 and 2019 and treated with thiopurine therapy. The incidence of AE and overall drug survival of thiopurines were evaluated using the Kaplan-Meier method. Correlations between thiopurine metabolites and biochemical tests were computed using Spearman's correlation coefficient.

Results: Of 391 patients with IBD, 233 patients (162 Crohn's disease, 62 ulcerative colitis, and 9 IBD-unclassified) were prescribed thiopurines (230 azathioprine and 3 mercaptopurine), of whom 50 patients (22%) discontinued treatment, at least temporary, due to thiopurine-induced AE (median follow-up 20.7 months). Twenty-six patients (52%) were rechallenged and 18 of them (70%) tolerated this. Sixteen patients (6%) switched to a second thiopurine agent after azathioprine intolerance and 10 of them (63%) tolerated this. No predictive factors for development of AE could be identified. Concentrations of 6-thioguanine nucleotides (6-TGN) were significantly correlated with white blood cell and neutrophil count, 6-methylmercaptopurine (6-MMP) concentrations with alanine aminotransferase and gamma-glutamyltranspeptidase.

Conclusions: Approximately 20% of pediatric patients with IBD discontinued thiopurine treatment due to AE. A rechallenge or switch to mercaptopurine is an effective strategy after development of AE. Concentrations of 6-TGN and 6-MMP are associated with biochemical abnormalities.
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http://dx.doi.org/10.1007/s10620-021-06836-3DOI Listing
February 2021

Nutritional Therapy Strategies in Pediatric Crohn's Disease.

Nutrients 2021 Jan 13;13(1). Epub 2021 Jan 13.

Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands.

The increase in incidences of pediatric Crohn's Disease (CD) worldwide has been strongly linked with dietary shifts towards a Westernized diet, ultimately leading to altered gut microbiota and disturbance in intestinal immunity and the metabolome. Multiple clinical studies in children with CD have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission with an excellent safety profile. However, EEN is poorly tolerated, limiting its compliance and clinical application. This has spiked an interest in the development of alternative and better-tolerated nutritional therapy strategies. Several nutritional therapies have now been designed not only to treat the nutritional deficiencies seen in children with active CD but also to correct dysbiosis and reduce intestinal inflammation. In this review, we report the most recent insights regarding nutritional strategies in children with active CD: EEN, partial enteral nutrition (PEN), Crohn's disease exclusive diet (CDED), and CD treatment-with-eating diet (CD-TREAT). We describe their setup, efficacy, safety, and (dis)advantages as well as some of their potential mechanisms of action and perspectives. A better understanding of different nutritional therapeutic options and their mechanisms will yield better and safer management strategies for children with CD and may address the barriers and limitations of current strategies in children.
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http://dx.doi.org/10.3390/nu13010212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828385PMC
January 2021

Clinical Genomics for the Diagnosis of Monogenic Forms of Inflammatory Bowel Disease: A Position Paper From the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

J Pediatr Gastroenterol Nutr 2021 Mar;72(3):456-473

Child Life and Health, University of Edinburgh, Department of Paediatric Gastroenterology, The Royal Hospital for Sick Children, Edinburgh.

Background: It is important to identify patients with monogenic IBD as management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups.

Methods: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists).

Results: We recommend next-generation DNA-sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, paediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We developed a diagnostic algorithm that includes a gene panel of 75 monogenic IBD genes. Considerations are provided also for low resource countries.

Conclusions: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD.
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http://dx.doi.org/10.1097/MPG.0000000000003017DOI Listing
March 2021

Investigating the gut microbial community and genes in children with differing levels of change in serum asparaginase activity during pegaspargase treatment for acute lymphoblastic leukemia.

Leuk Lymphoma 2021 Apr 1;62(4):927-936. Epub 2020 Dec 1.

Department of Pediatrics, Division of Hematology/Oncology, IWK Health Centre, Halifax, Canada.

Asparaginase (ASNase) is an effective treatment of pediatric acute lymphoblastic leukemia (ALL). Changes in ASNase activity may lead to suboptimal treatment and poorer outcomes. The gut microbiome produces metabolites that could impact ASNase therapy, however, remains uninvestigated. We examined gut-microbial community and microbial-ASNase and asparagine synthetase (ASNS) genes using 16SrRNA and metagenomic sequence data from stool samples of pediatric ALL patients. Comparing ASNase activity between consecutive ASNase-doses, we found microbial communities differed between decreased- and increased-activity samples. predominated in the decreased-activity community while and predominated in the increased-activity community. In addition microbial ASNS was significantly (=.004) negatively correlated with change in serum ASNase activity. These preliminary findings suggest microbial communities prior to treatment could affect serum ASNase levels, although the mechanism is unknown. Replication in an independent cohort is needed, and future research on manipulation of these communities and genes could prove useful in optimizing ASNase therapy.
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http://dx.doi.org/10.1080/10428194.2020.1850718DOI Listing
April 2021

SuRF: A new method for sparse variable selection, with application in microbiome data analysis.

Stat Med 2021 Feb 20;40(4):897-919. Epub 2020 Nov 20.

Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia, Canada.

In this article, we present a new variable selection method for regression and classification purposes, particularly for microbiome analysis. Our method, called subsampling ranking forward selection (SuRF), is based on LASSO penalized regression, subsampling and forward-selection methods. SuRF offers major advantages over existing variable selection methods in terms of both sparsity of selected models and model inference. We provide an R package that can implement our method for generalized linear models. We apply our method to classification problems from microbiome data, using a novel agglomeration approach to deal with the special tree-like correlation structure of the variables. Existing methods arbitrarily choose a taxonomic level a priori before performing the analysis, whereas by combining SuRF with these aggregated variables, we are able to identify the key biomarkers at the appropriate taxonomic level, as suggested by the data. We present simulations in multiple sparse settings to demonstrate that our approach performs better than several other popularly used existing approaches in recovering the true variables. We apply SuRF to two microbiome datasets: one about prediction of pouchitis and another for identifying samples from two healthy individuals. We find that SuRF can provide a better or comparable prediction with other methods while controlling the false positive rate of variable selection.
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http://dx.doi.org/10.1002/sim.8809DOI Listing
February 2021

Fool me once… treatment exposure to achieve remission in pediatric IBD.

Eur J Pediatr 2020 12;179(12):1921-1924

Department of Pediatrics, Spaarne Gasthuis, Hoofddorp, Haarlem, The Netherlands.

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http://dx.doi.org/10.1007/s00431-020-03862-7DOI Listing
December 2020

The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update.

J Crohns Colitis 2020 Oct 7. Epub 2020 Oct 7.

Assistance Publique- Hôpitaux de Paris, Hôpital Necker Enfants Malades, Pediatric Gastroenterology, Paris, France.

Objective: We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD].

Methods: We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained.

Results: We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone.

Conclusions: We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa161DOI Listing
October 2020

Assessing the Variation within the Oral Microbiome of Healthy Adults.

mSphere 2020 09 30;5(5). Epub 2020 Sep 30.

Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.

More than 1,000 different species of microbes have been found to live within the human oral cavity, where they play important roles in maintaining both oral and systemic health. Several studies have identified the core members of this microbial community; however, the factors that determine oral microbiome composition are not well understood. In this study, we exam the salivary oral microbiome of 1,049 Atlantic Canadians using 16S rRNA gene sequencing to determine which dietary, lifestyle, and anthropometric features play a role in shaping microbial community composition. Features that were identified as being significantly associated with overall composition then were additionally examined for genera, amplicon sequence variants, and predicted pathway abundances that were associated with these features. Several associations were replicated in an additional secondary validation data set. Overall, we found that several anthropometric measurements, including waist-hip ratio (WHR), height, and fat-free mass, as well as age and sex, were associated with overall oral microbiome structure in both our exploratory and validation data sets. We were unable to validate any dietary impacts on overall taxonomic oral microbiome composition but did find evidence to suggest potential contributions from factors such as the number of vegetable and refined grain servings an individual consumes. Interestingly, each one of these factors on its own was associated with only minor shifts in the overall taxonomic composition of the oral microbiome, suggesting that future biomarker identification for several diseases associated with the oral microbiome can be undertaken without the worry of confounding factors obscuring biological signals. The human oral cavity is inhabited by a diverse community of microbes, known as the human oral microbiome. These microbes play a role in maintaining both oral and systemic health and, as such, have been proposed to be useful biomarkers of disease. However, to identify these biomarkers, we first need to determine the composition and variation of the healthy oral microbiome. In this report, we investigate the oral microbiome of 1,049 healthy individuals to determine which genera and amplicon sequence variants are commonly found between individual oral microbiomes. We then further investigate how lifestyle, anthropometric, and dietary choices impact overall microbiome composition. Interestingly, the results from this investigation showed that while many features were significantly associated with oral microbiome composition, no single biological factor explained a variation larger than 2%. These results indicate that future work on biomarker detection may be encouraged by the lack of strong confounding factors.
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http://dx.doi.org/10.1128/mSphere.00451-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529435PMC
September 2020

Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn's Disease.

J Crohns Colitis 2021 Mar;15(3):419-431

SickKids Hospital, University of Toronto, Toronto, ON, Canada.

Background: Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay.

Methods: We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression.

Results: Overall (64% Crohn's disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0-9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41-4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005-0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay.

Conclusions: Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD.

Podcast: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944510PMC
March 2021

IPEX Syndrome with Normal FOXP3 Protein Expression in Treg Cells in an Infant Presenting with Intractable Diarrhea as a Single Symptom.

Case Reports Immunol 2020 9;2020:9860863. Epub 2020 Sep 9.

Department of Paediatrics, Faculty of Medicine, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada.

IPEX (immune dysregulation-polyendocrinopathy-enteropathy-X-linked) syndrome is a rare, potentially fatal multisystem disorder caused by mutations in the gene. This can lead to quantitative or functional deficiency of regulatory T cells (Treg), thereby affecting their immune-suppressive actions which can in turn cause autoimmune and inflammatory disorders. We describe an infant with IPEX syndrome with unremarkable maternal family history whose only presentations were severe diarrhea and malnutrition. The patient had a normal percentage of Treg cells and FOXP3 protein expression, but further testing revealed a hemizygous missense mutation in the gene. IPEX syndrome should be considered in young children even if severe intractable diarrhea is the only symptom with no other autoimmune manifestations. Sequencing of the gene should always be considered for accurate diagnosis to look for mutations even in the face of normal FOXP3 protein expression in the Treg cell.
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http://dx.doi.org/10.1155/2020/9860863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499275PMC
September 2020

Nutritional Therapy to Modulate Tryptophan Metabolism and Aryl Hydrocarbon-Receptor Signaling Activation in Human Diseases.

Nutrients 2020 Sep 17;12(9). Epub 2020 Sep 17.

Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Emma Children's Hospital, 1105 AZ Amsterdam, The Netherlands.

The aryl hydrocarbon receptor (AhR) is a nuclear protein which, upon association with certain endogenous and exogenous ligands, translocates into the nucleus, binds DNA and regulates gene expression. Tryptophan (Trp) metabolites are one of the most important endogenous AhR ligands. The intestinal microbiota is a critical player in human intestinal homeostasis. Many of its effects are mediated by an assembly of metabolites, including Trp metabolites. In the intestine, Trp is metabolized by three main routes, leading to kynurenine, serotonin, and indole derivative synthesis under the direct or indirect involvement of the microbiota. Disturbance in Trp metabolism and/or AhR activation is strongly associated with multiple gastrointestinal, neurological and metabolic disorders, suggesting Trp metabolites/AhR signaling modulation as an interesting therapeutic perspective. In this review, we describe the most recent advances concerning Trp metabolism and AhR signaling in human health and disease, with a focus on nutrition as a potential therapy to modulate Trp metabolites acting on AhR. A better understanding of the complex balance between these pathways in human health and disease will yield therapeutic opportunities.
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http://dx.doi.org/10.3390/nu12092846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551725PMC
September 2020

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn's Disease.

Inflamm Bowel Dis 2020 Sep 18. Epub 2020 Sep 18.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Background: The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations.

Methods: We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn's disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP <250 µg/g, with clinical response defined as a weighted Pediatric Crohn's Disease Activity Index <12.5 or Δ>17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs).

Results: Among 56 CD patients, ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934, P < 0.001) and nCD64 <6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of >9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP <250 and FCP <100, respectively. We found patients achieving end of induction trough >5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels <5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031).

Conclusions: This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.
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http://dx.doi.org/10.1093/ibd/izaa241DOI Listing
September 2020

Teaching Families of Children with Celiac Disease about Gluten-Free Diet Using Distributed Education: a Pilot Study.

Can J Diet Pract Res 2021 Mar 9;82(1):38-40. Epub 2020 Sep 9.

Division of Gastroenterology and Nutrition, Department of Paediatrics, Faculty of Medicine, Dalhousie University, Halifax, NS.

Treatment of celiac disease is a strict life-long gluten-free diet (GFD). The GFD is complex, and counseling by a dietitian is essential. The number of new referrals for GFD education has increased. We studied the feasibility of GFD teaching using distributed education. The IWK Health Center in Halifax is the only tertiary-care pediatric hospital in the 3 Maritime provinces with GFD experienced dietitians. Families travel long distances to attend teaching sessions. Families outside the Halifax area were offered to participate in the 2.5-hour education sessions held once a month via live videoconference link at their regional hospitals. All participants were surveyed with a 10-item questionnaire assessing the content and delivery and usefulness of information. Over a 6-month period, 39 families attended the sessions, 21 locally and 18 at distributed sites across the Maritimes. The survey was completed by 26 participants (67%). All participants at both sites strongly agreed or agreed that their setting was good for learning and the information provided was easy to understand. There were no significant differences between the 2 groups on any individual questions in the 2 domains assessed (all  > 0.06). Distributed education on GFD is feasible and as effective as in person education. It affords convenience and savings to families by reducing travel costs.
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http://dx.doi.org/10.3148/cjdpr-2020-021DOI Listing
March 2021

Natural History of  Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study.

Inflamm Bowel Dis 2021 Feb;27(3):295-302

University of North Carolina in Chapel Hill, Chapel Hill, NC, United States.

Background: The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described.

Methods: We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years.

Results: The study population included 269 children (105 [39%] Crohn's disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9-5.2). Most (94%) Crohn's disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn's disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis.

Conclusions: Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%-15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.
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http://dx.doi.org/10.1093/ibd/izaa080DOI Listing
February 2021

Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn's Disease.

Clin Gastroenterol Hepatol 2021 Apr 14;19(4):752-759. Epub 2020 Apr 14.

Wolfson Medical Center, Pediatric Gastroenterology, Holon, Israel; The Sackler Faculty of medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background & Aims: Dietary therapies based on exclusion of usual dietary elements induce remission in children with Crohn's disease (CD), whereas re-exposure induces rebound inflammation. We investigated whether a short trial of dietary therapy, to identify patients with and without a rapid response or remission on the diet (DiRe), can be used to predict success or failure of long-term dietary therapy.

Methods: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2 ± 2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (n = 39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein.

Results: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a DiRe. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P < .001). Among the 49 patients in remission at week 6, 46 patients (94%) had a DiRe and 81% were in clinical remission by week 3. In multivariable analysis, remission at week 3 increased odds of remission by week 6 (odds ratio, 6.37; 95% CI, 1.6-25; P = .008) whereas poor compliance reduced odds of remission at week 6 (odds ratio, 0.75; 95% CI, 0.012-0.46; P = .006).

Conclusions: For pediatric patients with active CD, dietary therapies (CDED and EEN) induce a rapid clinical response (by week 3). Identification of patients with and without a rapid response to diet might help identify those who, with compliance, will be in clinical remission by week 6 of the diet. ClinicalTrials.gov no: NCT01728870.
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http://dx.doi.org/10.1016/j.cgh.2020.04.006DOI Listing
April 2021

A Case-Based Approach to New Directions in Dietary Therapy of Crohn's Disease: Food for Thought.

Nutrients 2020 Mar 24;12(3). Epub 2020 Mar 24.

Amsterdam University Medical Centres, Emma Children's Hospital, 1105 AZ Amsterdam, The Netherlands.

Recent evidence has demonstrated that Crohn's disease may have its roots in dysbiosis of the microbiome and other environmental factors. One of the strongest risk factors linked to immune activation appears to be diet. Exclusion diets have been shown to ameliorate inflammation and induce remission in 70-80% of treatment-naïve children at disease onset, and to induce remission in patients that lose response or are refractory to currently recommended medical therapy. Recent studies have also linked dietary modulation of the microbiome with clinical remission, while reintroduction of the previous habitual diet led to reactivation of inflammation and reversion of the dysbiotic state. While dietary therapy has usually been used as a first line therapy as a bridge to immunomodulators, newer insights suggest that new treatment paradigms involving dietary therapy may allow different treatment strategies. This case-based narrative review will discuss the Crohn's disease exclusion diet (CDED) as monotherapy, combination therapy with drugs, as a rescue therapy in refractory patients and for de-escalation from medical therapy.
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http://dx.doi.org/10.3390/nu12030880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146196PMC
March 2020

Bacterial Taxa and Functions Are Predictive of Sustained Remission Following Exclusive Enteral Nutrition in Pediatric Crohn's Disease.

Inflamm Bowel Dis 2020 06;26(7):1026-1037

Department of Pediatrics, Dalhousie University, Halifax, Canada.

Background: The gut microbiome is extensively involved in induction of remission in pediatric Crohn's disease (CD) patients by exclusive enteral nutrition (EEN). In this follow-up study of pediatric CD patients undergoing treatment with EEN, we employ machine learning models trained on baseline gut microbiome data to distinguish patients who achieved and sustained remission (SR) from those who did not achieve remission nor relapse (non-SR) by 24 weeks.

Methods: A total of 139 fecal samples were obtained from 22 patients (8-15 years of age) for up to 96 weeks. Gut microbiome taxonomy was assessed by 16S rRNA gene sequencing, and functional capacity was assessed by metagenomic sequencing. We used standard metrics of diversity and taxonomy to quantify differences between SR and non-SR patients and to associate gut microbial shifts with fecal calprotectin (FCP), and disease severity as defined by weighted Pediatric Crohn's Disease Activity Index. We used microbial data sets in addition to clinical metadata in random forests (RFs) models to classify treatment response and predict FCP levels.

Results: Microbial diversity did not change after EEN, but species richness was lower in low-FCP samples (<250 µg/g). An RF model using microbial abundances, species richness, and Paris disease classification was the best at classifying treatment response (area under the curve [AUC] = 0.9). KEGG Pathways also significantly classified treatment response with the addition of the same clinical data (AUC = 0.8). Top features of the RF model are consistent with previously identified IBD taxa, such as Ruminococcaceae and Ruminococcus gnavus.

Conclusions: Our machine learning approach is able to distinguish SR and non-SR samples using baseline microbiome and clinical data.
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http://dx.doi.org/10.1093/ibd/izaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301407PMC
June 2020

The relationship between fecal bile acids and microbiome community structure in pediatric Crohn's disease.

ISME J 2020 03 3;14(3):702-713. Epub 2019 Dec 3.

Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.

Gut microbiome community structure is associated with Crohn's disease (CD) development and response to therapy. Bile acids (BAs) play a central role in modulating intestinal immune responses, and changes in gut bacterial communities can profoundly alter the intestinal BA pool. The liver synthesizes and conjugates primary bile acids (priBAs) that are then deconjugated, epimerized, and dehydroxylated by gut bacteria to produce secondary bile acids (secBAs). We investigated the relationship between the gut microbiome and the fecal BA pool in stool samples obtained from a well-characterized cohort of pediatric CD patients undergoing nutritional therapy to induce disease remission. We found that fecal BA composition was altered in a sub-group of CD patients who did not sustain remission. The microbial community structures associated with priBA and secBA-dominant profiles were distinct. In addition, the fecal BA concentrations were correlated with the abundance of distinct bacterial taxonomic groups. Finally, priBA dominant samples were associated with community-level decreases in enzymes for dehydroxylation but not deconjugation.
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http://dx.doi.org/10.1038/s41396-019-0560-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031364PMC
March 2020

Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial.

Gastroenterology 2019 08 4;157(2):440-450.e8. Epub 2019 Jun 4.

IWK Health Centre, Dalhousie University, Halifax, Canada; Amsterdam University Medical Centers, Emma Children's Hospital, Amsterdam, the Netherlands; Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address:

Background & Aims: Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn's disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier.

Methods: We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestlé) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n = 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n = 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12.

Results: Four patients withdrew from the study because of intolerance by 48 hours, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P = .002; odds ratio for tolerance of CDED and PEN, 13.92; 95% confidence interval [CI] 1.68-115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission vs 20 (59%) of 34 children given EEN (P = .38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given EEN and then PEN (P = .01; odds ratio for remission in children given CDED and PEN, 3.77; CI 1.34-10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria.

Conclusion: CDED plus PEN was better tolerated than EEN in children with mild to moderate CD. Both diets were effective in inducing remission by week 6. The combination CDED plus PEN induced sustained remission in a significantly higher proportion of patients than EEN, and produced changes in the fecal microbiome associated with remission. These data support use of CDED plus PEN to induce remission in children with CD. Clinicaltrials.gov no: NCT01728870.
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http://dx.doi.org/10.1053/j.gastro.2019.04.021DOI Listing
August 2019

Infectious Complications Are Associated With Alterations in the Gut Microbiome in Pediatric Patients With Acute Lymphoblastic Leukemia.

Front Cell Infect Microbiol 2019 19;9:28. Epub 2019 Feb 19.

Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.

Acute lymphoblastic leukemia is the most common pediatric cancer. Fortunately, survival rates exceed 90%, however, infectious complications remain a significant issue that can cause reductions in the quality of life and prognosis of patients. Recently, numerous studies have linked shifts in the gut microbiome composition to infection events in various hematological malignances including acute lymphoblastic leukemia (ALL). These studies have been limited to observing broad taxonomic changes using 16S rRNA gene profiling, while missing possible differences within microbial functions encoded by individual species. In this study we present the first combined 16S rRNA gene and metagenomic shotgun sequencing study on the gut microbiome of an independent pediatric ALL cohort during treatment. In this study we found distinctive differences in alpha diversity and beta diversity in samples from patients with infectious complications in the first 6 months of therapy. We were also able to find specific species and functional pathways that were significantly different in relative abundance between samples that came from patients with infectious complications. Finally, machine learning models based on patient metadata and bacterial species were able to classify samples with high accuracy (84.09%), with bacterial species being the most important classifying features. This study strengthens our understanding of the association between infection and pediatric acute lymphoblastic leukemia treatment and warrants further investigation in the future.
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http://dx.doi.org/10.3389/fcimb.2019.00028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389711PMC
November 2019

The Role of Succinate in the Regulation of Intestinal Inflammation.

Nutrients 2018 Dec 22;11(1). Epub 2018 Dec 22.

Division of Gastroenterology, IWK Health Centre, Halifax, NS B3K 6R8, Canada.

Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle within host cells. Succinate is also produced in large amounts during bacterial fermentation of dietary fiber. Elevated succinate levels within the gut lumen have been reported in association with microbiome disturbances (dysbiosis), as well as in patients with inflammatory bowel disease (IBD) and animal models of intestinal inflammation. Recent studies indicate that succinate can activate immune cells via its specific surface receptor, succinate receptor 1(SUCNR1), and enhance inflammation. However, the role of succinate in inflammatory processes within the gut mucosal immune system is unclear. This review includes current literature on the association of succinate with intestinal inflammation and the potential role of succinate⁻SUCNR1 signaling in gut immune functions.
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http://dx.doi.org/10.3390/nu11010025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356305PMC
December 2018

Clinical disease activity and endoscopic severity correlate poorly in children newly diagnosed with Crohn's disease.

Gastrointest Endosc 2019 02 28;89(2):364-372. Epub 2018 Sep 28.

The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Canada.

Background And Aims: Treatment goals in Crohn's disease (CD) have evolved to target mucosal healing. There is now a drive to determine if noninvasive measures can adequately identify the attainment and persistence of this goal. Currently, data describing the relationship between clinical indices and endoscopic appearance in pediatric CD are sparse. Our aim was to compare endoscopic severity with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI) in children with newly diagnosed CD.

Methods: All children aged ≤17 years newly diagnosed with CD enrolled in an inception cohort at sites of the Canadian Children Inflammatory Bowel Disease Network were eligible. Clinical disease activity at presentation was evaluated by the wPCDAI and conventional biochemical parameters. Severity of disease at ileocolonoscopy was assessed by the simple endoscopic score for CD (SES-CD), with segmental subscores noted. We evaluated the association of SES-CD and disease activity markers using the Pearson test of correlation, the Spearman rank coefficient, and linear regression models.

Results: Two hundred eighty patients from 11 centers were included in the analysis. The median wPCDAI score was 60 (interquartile range, 40-80; 53% severe). Median SES-CD was 16 (interquartile range 10-22; 51% severe). The wPCDAI correlated weakly with SES-CD (r = .39, P < .001). Examination of the individual components that contribute to the wPCDAI demonstrated weak correlation with the SES-CD for all items apart from stooling (moderate correlation, r = .50, P < .001). Routine blood tests did not correlate well with the SES-CD. In regression models, variation in clinical symptoms accounted for most of the variation in both the wPCDAI and SES-CD, with no additional benefit from routine blood tests.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.gie.2018.09.025DOI Listing
February 2019

The anaphylatoxin C3a primes model colonic epithelial cells for expression of inflammatory mediators through Gαi.

Mol Immunol 2018 11 24;103:125-132. Epub 2018 Sep 24.

Department of Microbiology & Immunology, Dalhousie University, 5850 College Street, Room 7-C, Halifax, NS, B3H 4R2, Canada; Department of Pediatrics, Dalhousie University, IWK Health Centre, 5850 University Avenue, Halifax, NS, B3K 6R8, Canada. Electronic address:

Multiple studies have identified that complement becomes activated during inflammation of the intestines yet it is unclear what roles the split complement molecules play. The epithelium, in particular, may be impacted and accordingly, we first discovered that colonic cell lines indeed possess the C5aR. Here we examined whether these cells also possess the C3aR. We determined that T84, HT-29 and Caco2 all possess C3aR mRNA and protein; T84 and HT29 were used to further explore the consequence of C3a binding the C3aR. C3a led to increased mRNA for CXCL2, CXCL8 and CXCL11. Polarized T84 monolayers responded to apically applied C3a with increased CXCL8 mRNA more rapidly than if the C3a was applied basolaterally. Polarized monolayers also increased permeability when treated with C3a. ERK1/2 was activated by C3a and the increase in CXCL8 mRNA was ERK-dependent in both T84 and HT-29. C3a resulted in activation of Gαi, determined by the ERK1/2 signal showing sensitivity to pertussis toxin. The transmembrane signal was further mapped to include Ras and c-Raf. Finally, we show that the C3aR is expressed by primary cells in mouse enteroids. We conclude that complement activation will contribute to the epithelial response during inflammation through C3a binding to the C3aR including by priming the cells to upregulate mRNA for selected chemokines.
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http://dx.doi.org/10.1016/j.molimm.2018.09.008DOI Listing
November 2018

Differences in adiposity and diet quality among individuals with inflammatory bowel disease in Eastern Canada.

PLoS One 2018 19;13(7):e0200580. Epub 2018 Jul 19.

Department of Pediatrics, Division of Pediatric Gastroenterology & Nutrition, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.

The objective of the current study was to characterize the relationship between diet quality and body composition in participants living with IBD, specifically Crohn's disease (CD) or ulcerative colitis (UC), in Atlantic Canada. Participants from the Atlantic Partnership for Tomorrow's Health (PATH) study are residents of one of the four Atlantic Canada provinces. Participants who completed the dietary questionnaire and had body composition measured were included in the study (n = 12,462 without IBD, n = 111 CD, n = 119 UC). A greater number of participants with IBD reported having multiple chronic conditions compared to those without IBD. Those with UC had statistically higher body weight and body mass index (BMI) compared to those without IBD. Overall, significant positive correlations were observed between adiposity and servings of refined grains, and meats and alternatives such as eggs and fish, whereas negative correlations were observed with servings of vegetables, fruit, whole grains, and alternatives such as tofu, and nuts/seeds. Participants with IBD (both CD and UC) consumed more refined grains than those without IBD. Using logistic regression analysis, participants consuming more servings of vegetables and whole grains were less likely to have CD where as those consuming more serving of fruit and bean/legumes were less likely to have UC. In the Atlantic PATH cohort, which includes a region of the world with a high incidence of IBD, distinct differences in adiposity and diet quality were observed in individuals with specific types of IBD compared to those without. There is a need for collaborative efforts to address weight management and diet quality issues in those living with IBD in the Atlantic Canadian region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200580PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053167PMC
January 2019

Nutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition.

J Pediatr Gastroenterol Nutr 2018 04;66(4):687-708

Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy.

Background And Aims: A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients.

Methods: A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature.

Results: A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment; macronutrients needs; trace elements, minerals, and vitamins; nutrition as a primary therapy of pediatric IBD; probiotics and prebiotics; specific dietary restrictions; and dietary compounds and the risk of IBD.

Conclusions: This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD.
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http://dx.doi.org/10.1097/MPG.0000000000001896DOI Listing
April 2018

An Omental Lymphatic Malformation Mimicking Ascites in a 2-Year-Old Boy.

J Pediatr Gastroenterol Nutr 2018 07;67(1):e14-e15

Department of Surgery, Division of Pediatric General and Thoracic Surgery.

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http://dx.doi.org/10.1097/MPG.0000000000001939DOI Listing
July 2018

Multi-omics differentially classify disease state and treatment outcome in pediatric Crohn's disease.

Microbiome 2018 01 15;6(1):13. Epub 2018 Jan 15.

Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.

Background: Crohn's disease (CD) has an unclear etiology, but there is growing evidence of a direct link with a dysbiotic microbiome. Many gut microbes have previously been associated with CD, but these have mainly been confounded with patients' ongoing treatments. Additionally, most analyses of CD patients' microbiomes have focused on microbes in stool samples, which yield different insights than profiling biopsy samples.

Results: We sequenced the 16S rRNA gene (16S) and carried out shotgun metagenomics (MGS) from the intestinal biopsies of 20 treatment-naïve CD and 20 control pediatric patients. We identified the abundances of microbial taxa and inferred functional categories within each dataset. We also identified known human genetic variants from the MGS data. We then used a machine learning approach to determine the classification accuracy when these datasets, collapsed to different hierarchical groupings, were used independently to classify patients by disease state and by CD patients' response to treatment. We found that 16S-identified microbes could classify patients with higher accuracy in both cases. Based on follow-ups with these patients, we identified which microbes and functions were best for predicting disease state and response to treatment, including several previously identified markers. By combining the top features from all significant models into a single model, we could compare the relative importance of these predictive features. We found that 16S-identified microbes are the best predictors of CD state whereas MGS-identified markers perform best for classifying treatment response.

Conclusions: We demonstrate for the first time that useful predictors of CD treatment response can be produced from shotgun MGS sequencing of biopsy samples despite the complications related to large proportions of host DNA. The top predictive features that we identified in this study could be useful for building an improved classifier for CD and treatment response based on sufferers' microbiome in the future. The BISCUIT project is funded by a Clinical Academic Fellowship from the Chief Scientist Office (Scotland)-CAF/08/01.
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http://dx.doi.org/10.1186/s40168-018-0398-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769311PMC
January 2018

Allied Health Professional Support in Pediatric Inflammatory Bowel Disease: A Survey from the Canadian Children Inflammatory Bowel Disease Network-A Joint Partnership of CIHR and the CH.I.L.D. Foundation.

Can J Gastroenterol Hepatol 2017 16;2017:3676474. Epub 2017 May 16.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, ON, Canada.

Objectives: The current number of healthcare providers (HCP) caring for children with inflammatory bowel disease (IBD) across Canadian tertiary-care centres is underinvestigated. The aim of this survey was to assess the number of healthcare providers (HCP) in ambulatory pediatric IBD care across Canadian tertiary-care centres.

Methods: Using a self-administered questionnaire, we examined available resources in academic pediatric centres within the Canadian Children IBD Network. The survey evaluated the number of HCP providing ambulatory care for children with IBD.

Results: All 12 tertiary pediatric gastroenterology centres participating in the network responded. Median full-time equivalent (FTE) of allied health professionals providing IBD care at each site was 1.0 (interquartile range (IQR) 0.6-1.0) nurse, 0.5 (IQR 0.2-0.8) dietitian, 0.3 (IQR 0.2-0.8) social worker, and 0.1 (IQR 0.02-0.3) clinical psychologists. The ratio of IBD patients to IBD physicians was 114 : 1 (range 31 : 1-537 : 1), patients to nurses/physician assistants 324 : 1 (range 150 : 1-900 : 1), dieticians 670 : 1 (range 250 : 1-4500 : 1), social workers 1558 : 1 (range 250 : 1-16000 : 1), and clinical psychologists 2910 : 1 (range 626 : 1-3200 : 1).

Conclusions: There was a wide variation in HCP support among Canadian centres. Future work will examine variation in care including patients' outcomes and satisfaction across Canadian centres.
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http://dx.doi.org/10.1155/2017/3676474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448041PMC
April 2018

Exclusive Enteral Nutrition Therapy in Paediatric Crohn's Disease Results in Long-term Avoidance of Corticosteroids: Results of a Propensity-score Matched Cohort Analysis.

J Crohns Colitis 2017 Sep;11(9):1063-1070

Division of Gastroenterology, IWK Health Centre, Halifax, Nova Scotia, Canada.

Background And Aims: Exclusive enteral nutrition [EEN] is recommended as a first-line induction therapy for paediatric Crohn's disease [CD] although corticosteroids [CS] are still used commonly. Our aim was to compare short- and long-term disease outcomes of paediatric CD patients initially managed with either EEN or CS.

Methods: Medical records of newly diagnosed paediatric CD patients treated with EEN or CS as induction therapy were retrospectively reviewed. To minimise selection bias inherent in observational cohort studies, propensity analysis was carried out. Data on anthropometrics, medical history, and presenting phenotype were collected at time of diagnosis [baseline]; outcomes of interest, including medication use, hospitalisation, surgical procedures, and disease progression were assessed up to 6 years following diagnosis.

Results: Of 127 patients reviewed, a total of 111 propensity-score matched CD patients receiving EEN [n = 76] or CS [n = 35] were analysed. By 4-12 weeks of induction therapy, 86.6% of EEN-treated patients achieved remission (Paediatric Crohn's Disease Activity Index [PCDAI] ≤ 7.5) compared with 58.1% of patients in the CS-treated group [p < 0.01]. Choice of EEN over CS for induction was associated with avoidance of corticosteroids over a 6-year follow-up period. Analysis of long-term linear growth, hospitalisation, need for biologic therapy, or surgical intervention did not reveal any significant differences.

Conclusions: These findings suggest that EEN induction therapy is more effective in achieving early remission and is associated with long-term steroid avoidance without increased use of biologics or need for surgery.
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http://dx.doi.org/10.1093/ecco-jcc/jjx060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881686PMC
September 2017