Eytan Wine

• MD, PhD, FRCPC
• University of Alberta

We detect and interactively visualize occurrence, frequency, sequence, and clustering of extraintestinal manifestations (EIM) and associated immune disorders (AID) in 30,334 inflammatory bowel disease (IBD) patients (Crohn’s disease (CD) n = 15924, ulcerative colitis (UC) n = 11718, IBD unclassified, IBD-U n = 2692, 52% female, median age 40 years...

Background/Objectives To examine the relationship between early childhood adiposity, adolescent lifestyles, gut microbiota and steatotic liver disease (SLD) development in adolescents using data from a prospective, longitudinal cohort study. Methods We included 69 adolescents (14–17 years old) with SLD and 69 adolescents without SLD, matched for B...

Context While increased fiber intake may benefit appetite and metabolism in the general population, its effects in individuals with Prader–Willi Syndrome (PWS), a condition characterized by hyperphagia, obesity and metabolic dysregulation, remain to be explored. Objectives This study assessed the effects of a fiber intervention on hyperphagia, met...

Background Crohn’s disease (CD) exclusion diet combined with partial enteral nutrition (CDED + PEN) or exclusive enteral nutrition (EEN) is effective in inducing remission in mild-to-moderate pediatric CD. Although CDED + PEN is better tolerated and has higher compliance compared to EEN, a subset of patients does not achieve remission. Diet-induced...

Background Perianal Crohn’s disease (CD) can be a severe, refractory manifestation of pediatric CD. It is underrecognized, particularly if asymptomatic, which has led to varied reported incidences (10-60%). Earlier detection by pelvic magnetic resonance imaging (pMR) may alter management and outcomes. Aims If performing pMR on newly diagnosed pedi...

Background Indole-3-propionic acid (IPA), a tryptophan metabolite produced by microbes, has demonstrated beneficial effects, including reversing dysbiosis, balancing bacterial populations, and reducing inflammation. However, the mechanisms behind these effects and their impact on pathogenic microbes remain unclear. This study aimed to evaluate the...

Background Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions influenced by genetic, environmental, and microbial factors. Emerging evidence suggests a role for the appendix in IBD with immune and microbe impacts on the colon. Peri-appendicular patch (PAP) inflammation is...

Background Pediatric onset Crohn disease (pCD) tends to be more complicated with a higher likelihood of requiring intestinal resection surgery. Currently there are no predictive tools for surgery in pCD; risk scores and relative survival analysis are available, but these cannot accurately calculate the probability of surgery in children with CD at...

Background We have been investigating the role of viral infections in the development of inflammatory bowel disease (IBD) in genetically predisposed individuals. Using the SvEv IL10 -/- model of colitis, we found evidence of mouse mammary tumor virus (MMTV) infection and modulated the disease with combination antiretroviral therapy. Reducing MMTV R...

Background Vedolizumab (VDZ) is effective to induce remission in children with Crohn disease (CD) and ulcerative colitis (UC), but effectiveness varies. Metabolites produced by interactions between intestinal microbiota and host metabolic processes can be useful to identify metabolome signatures that may preferentially favor response to a specific...

Background The Crohn’s Disease (CD) Exclusion Diet (CDED) is a recognized dietary therapy for managing mild-to-moderate CD in children and adults1,2. This study aimed to compare the effects of CDED on the microbiome in children and adults, based on randomized controlled trials (RCTs) in both cohorts1,2. Methods We analyzed fecal samples from 2 RCT...

Background Pediatric patients with newly diagnosed Crohn’s disease (CD) often undergo magnetic resonance enterography (MRE) to assess bowel not accessible by endoscopy and to evaluate for CD complications. In contrast to intestinal ultrasound (IUS), MRE access is quite limited, expensive, and not feasible for young patients. Little is known about h...

Background Crohn’s disease (CD) exclusion diet with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) effectively induce remission in mild-to-moderate paediatric CD. This has been associated with a shift in gut microbiome and metabolome1. The specific mechanisms driving diet-induced remission remain unclear. Microbial biotr...

Background Perianal Crohn’s disease (CD) can be a severe manifestation of pediatric CD.1,2 It is underrecognized, particularly if asymptomatic, with varied reported incidences (10-60%). Earlier detection by pelvic magnetic resonance imaging (pMR) may alter outcomes.3 The aim of this study was to determine if performing pMR on newly diagnosed pediat...

Background Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions influenced by genetic, environmental, and microbial factors.1,2 Emerging evidence suggests a role for the appendix in IBD with immune and microbe impacts on the colon. Peri-appendicular patch (PAP) inflammation...

Background Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that frequently coexists with inflammatory bowel disease (IBD). Data comparing the paediatric- and adult-onset PSC-IBD are lacking. We compared disease characteristics and the clinical course of PSC-IBD between Canadian children and adults. Methods This was a multi...

Background Indole-3-propionic acid (IPA), a tryptophan metabolite produced by microbes, has demonstrated beneficial effects, including reversing dysbiosis, balancing bacterial populations, and reducing inflammation.1,2,3 However, the mechanisms behind these effects and their impact on pathogenic microbes remain unclear. This study aimed to evaluate...

INTRODUCTION Neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker studied in several autoimmune diseases including inflammatory bowel disease (IBD) in adults but poorly characterized in pediatric IBD (pIBD). We aimed to primarily investigate the relationship between NLR and pIBD endoscopic disease severity. We also examined whether NLR predict...

Dear Editor, We read with interest the article “Formula modifications to the Crohn's disease exclusion diet do not impact therapy success in pediatric Crohn's disease,”1 which addresses a relevant issue but has significant methodological limitations. First, the retrospective design, which should have been mentioned in the title, introduces biases a...

Introduction We investigated relationships between disease activity measures and the gut microbiome in children with Crohn’s disease (CD) and how these were confounded by gastrointestinal transit time. Methods Microbiome was profiled (16S rRNA sequencing) in feces from 196 children with CD. Sixty participants also provided samples after 18 months....

Background: The Crohn's Disease Exclusion Diet (CDED) is a whole-foods regimen that has demonstrated efficacy in inducing remission among children and adults with mild-to-moderate disease. While initial studies predominantly originated from Israel, recent years have witnessed the expansion of experiences to diverse cultures, culminating in the rec...

Objectives Intestinal ultrasound (IUS) is a noninvasive tool in ulcerative colitis (UC), but scoring systems have mostly been developed for adults, Crohn's disease, and flaring UC. Our aim was to evaluate the performance of bowel wall thickness (BWT) and four IUS scores in pediatric patients with newly diagnosed UC. Methods Patients <18 years old...

Given the worldwide epidemic of overweight and obesity among children, evidence-based dietary recommendations are fundamentally important for obesity prevention. Although the significance of the human gut microbiome in shaping the physiological effects of diet and obesity has been widely recognized, nutritional therapeutics for the mitigation of pe...

Background Infants with small bowel stomas (SBstoma) frequently struggle with absorption and rely on parenteral nutrition (PN). Intestinal absorption is difficult to predict based solely on intestinal anatomy. The purpose of this study was to characterize the microbiota and metabolic by‐products within stoma effluent and correlate with clinical fea...

Background and aims We aimed to identify serum metabolites associated with mucosal and transmural inflammation in pediatric Crohn disease (pCD). Methods Fifty-six pCD patients were included through a pre-planned sub-study of the multicenter, prospective, ImageKids cohort, designed to develop the Pediatric Inflammatory Crohn's MRE Index (PICMI). Ch...

Objectives and Study: Crohn's Disease Exclusion Diet (CDED) combined with Partial Enteral Nutrition (PEN) is effective for induction of remission in children. This study evaluated the effectiveness of 2 weeks of Exclusive Enteral Nutrition (EEN) followed by CDED+PEN for maintaining remission for 24 weeks in children with mild-severe disease. Method...

Background Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medic...

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency question...

Parents of young adults with chronic disease are important stakeholders in their child's transition from pediatric to adult care. There remains a gap in characterizing the parent experience during transition. This study describes the experiences of 13 mothers of young adults with inflammatory bowel disease during their child's transition. Most pare...

Background The typical transition from pediatric to adult care in patients with inflammatory bowel disease occurs with an increase in health care utilization and a decrease in adherence to medications and scheduled appointments. An effective transition could reduce negative impacts but requires identifying opportunities to improve this process. Thi...

Dietary fibers are associated with favorable gastrointestinal, immune, and metabolic health outcomes when consumed at sufficient levels. Despite the well-described benefits of dietary fibers, children and adolescents continue to fall short of daily recommended levels. This gap in fiber intake (i.e., “fiber gap”) might increase the risk of developin...

Background The effectiveness of combining biologics for pediatric inflammatory bowel disease (IBD) is under-investigated. Aims To evaluate the effectiveness of dual biologic therapy in children with IBD. Methods Children and adolescents ampersand:003C 17 years old with IBD enrolled in the Canadian Children IBD Network (CIDsCANN) who received any...

Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been previously limited to small samples of patients with no long-term follow up....

Background Neutrophil-to-lymphocyte ratio (NLR) has been recently identified as a potential biomarker for several autoimmune conditions. NLR predicts disease activity in adults with inflammatory bowel diseases (IBD) but had not been studied in pediatric IBD. Aims Investigate the link between NLR and baseline colonoscopic disease activity in UC and...

Background Current treatments for IBD focus on reducing inflammation, mostly through suppression of the immune system. Exclusive enteral nutrition (EEN) is recognized as the first line therapy for mild-to-moderate luminal pediatric Crohn disease patients pCD. Although EEN is safe, as it does not suppress the immune system, it poses considerable cha...

Background Inflammatory bowel diseases (IBD) affect 1:140 Canadians, resulting in significant inflammation and gut damage. Unlike type I and II interferons (IFNs), the most recently discovered IFNs, interferon-lambdas (IFN-λs), uniquely downregulate gut inflammation and promote gut healing in mouse models. However, it remains unknown if the importa...

Background Ustekinumab (UST) is an effective therapy for adults with moderate to severe Crohn’s disease (CD), but data concerning optimal dosing in children are sparse. Aims To examine real-world post-induction PK and efficacy in a prospective multicentre cohort study of paediatric CD (Canadian Children IBD Network (CIDsCaNN)). Methods Children 2...

Background Recent studies indicated that Klebsiella (K) pneumoniae (isolated from the stool of IBD patients) and K. variicola (isolated from the mesenteric tissue of Crohn disease patients) have the potential to induce inflammation in epithelial and preadipocyte cells, exacerbating colitis in murine models. Aims We isolated these strains from pedi...

Background The incidence of patients diagnosed with inflammatory bowel disease (IBD) in childhood/adolescence is increasing worldwide; therefore, in the upcoming years, more patients will need to transition from paediatric to adult care. A smooth transition is essential to ensure continuity of care; however, transition is a difficult time for patie...

Background In the treatment of paediatric Crohn’s disease (CD), the youngest (lightest) children have historically been underdosed by standard weight-based dosing. Paediatric data on optimal dosing and drug levels are sparse. We aimed to examine real-world post-induction pharmacokinetic and effectiveness in a prospective multicentre paediatric CD c...

Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been limited to small samples of patients with no long-term follow up. Our aim is t...

Background Exclusive enteral nutrition (EEN) is the first-line treatment for active Crohn’s disease (CD) in children. CD Exclusion Diet (CDED) combined with Partial Enteral Nutrition (PEN) has demonstrated better tolerance with a comparable effect in inducing remission among children with mild to moderate CD. This study evaluated the effectiveness...

Background The Crohn's Disease (CD) Exclusion Diet (CDED) is an established dietary therapy for children with active mild-to-moderate CD. A recent randomized controlled trial showed efficacy in mild-to-moderate CD in adults. We have previously demonstrated the impact of CDED on the microbiome of children. The aim of this work was to assess if we ca...

Background Recent studies indicated that Klebsiella (K) pneumoniae (isolated from the stool of IBD patients) and K. variicola (isolated from the mesenteric tissue of Crohn disease patients) have the potential to induce inflammation in epithelial and preadipocyte cells, exacerbating colitis in murine models. We isolated these strains from pediatric...

Background Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are effective in inducing remission in mild-to-moderate paediatric CD. While tolerance is higher with CDED+PEN than with EEN, a subset of patients still does not achieve remission. Diet-induced remission at week 6...

Background Patients diagnosed with inflammatory bowel disease (IBD) in childhood/adolescence face additional challenges compared to those diagnosed in adulthood, including more extensive disease and higher risk of complications. The need to undergo transition from paediatric to adult care is associated with an increase in health care utilization an...

Stratified and precision nutrition refers to disease management or prevention of disease onset, based on dietary interventions tailored to a person's characteristics, biology, gut microbiome, and environmental exposures. Such treatment models may lead to more effective management of inflammatory bowel disease (IBD) and reduce risk of disease develo...

Dietary therapy is increasingly recognized for the management of Crohn’s disease (CD) over recent years, including the use of exclusive enteral nutrition (EEN) as first-line therapy for pediatric CD according to current guidelines. The Crohn’s disease exclusion diet (CDED) is a whole-food diet designed to reduce exposure to dietary components that...

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects...

Background This study compared real-world effectiveness between adalimumab (ADA) and infliximab (IFX) in children with Crohn’s disease (CD). Methods Children enrolled into the prospective Canadian Children Inflammatory Bowel Disease Network (CIDsCaNN) National Inception Cohort between 2014 and 2020 who commenced ADA or IFX as first anti-tumor necr...

Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of c...

Aim: To assess contemporary outcomes in children with acute severe ulcerative colitis (ASUC) at initial presentation. Methods: Between 04/2014 and 01/2019, children aged <17 years with new onset ASUC (PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseli...

Introduction: Children who require enteral nutrition often report gastrointestinal symptoms. There is a growing interest in nutrition formulas that meet nutritional requirements and also maintain gut ecology and function. Fiber-containing enteral formulas can improve bowel function, promote the growth of healthy gut microbiota, and improve immune...

Crohn's and Colitis Canada's 2023 Impact of Inflammatory Bowel Disease in Canada Report

Objectives: To examine readiness of adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) to transition to adult care. Study design: A cross-sectional multicenter study evaluating transition readiness in individuals with IBD 16-19-years-old prospectively recruited from 8 Canadian IBD centers using the validated-ON TRAC questi...

Persistent inflammation can trigger altered epigenetic, inflammatory, and bioenergetic states. Inflammatory bowel disease (IBD) is an idiopathic disease characterized by chronic inflammation of the gastrointestinal tract, with evidence of subsequent metabolic syndrome disorder. Studies have demonstrated that as many as 42% of patients with ulcerati...

Background Patients with IBD have an altered microbiome and gut microenvironment leading to changes in their Short-Chain Fatty Acid (SCFA) profile. Pathobionts are commensal organisms that become pathogenic under specific conditions, likely related to microenvironmental gut changes. This is especially relevant to children given that early life expo...

Background Dietary fibers are not digested in the bowel; they are fermented by microbes, typically promoting gut health. However, IBD patients experience sensitivity to consumption of fibers. Our previous findings offered the first mechanistic evidence demonstrating that unfermented dietary β-fructans (inulin and oligofructose) can induce pro-infla...

Background While interferon-lambdas (IFN-λs) were initially discovered for their role in antiviral immunity at mucosal barriers such as the lung and gut, there are many unanswered questions for how IFN-λs uniquely dampen inflammatory immune responses. In mouse colitis models, IFN-λs were shown to play a significant role in promoting epithelial barr...

Background Patients with inflammatory bowel disease (IBD) in childhood are a vulnerable population. Compared to patients diagnosed in adulthood, they may present more often with extensive disease, delayed growth, and more frequently have perianal disease. Eventually, these patients will transfer care from the pediatric to the adult system, which ha...

Background Endoscopy has been the gold standard for assessing activity in Pediatric Crohn disease (pCD); however, it is limited by its invasiveness and partial assessment of small intestine and transmural inflammation. To that end, the Pediatric Inflammatory Crohn's MRE Index (PICMI) is a valid, reliable, non-invasive, and responsive index that inc...

Background Transabdominal bowel ultrasound (TABUS) is an emerging non-invasive tool for monitoring inflammatory bowel disease (IBD). Its use is particularly increasing in pediatric IBD, given the need for anesthesia during endoscopy. The assessment of TABUS in pediatric IBD has been limited to small numbers of patients with no long-term follow-up....

Background Biofilms, aggregated bacteria colonizing the extracellular polymeric substances matrix, are associated with the mucosa of inflammatory bowel diseases (IBD) patients with some studies showing a mean density of the mucosal biofilms 2-fold higher in IBD patients than in controls. The appendix, which is a highly immune organ, seems to be inv...

Background Following viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain-specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-10−/−) model derived from the SvEv...

Background Exclusive enteral Nutrition (EEN) is considered a first line therapy for children with active Crohn disease (CD). CD Exclusion Diet (CDED)+Partial Enteral Nutrition (PEN) is effective for induction of remission in mild-moderate CD at weeks 6 and 12, with better tolerance than EEN. We assessed whether a 2-week course of EEN, followed by C...

Background Barrier disruption leading to impaired intestinal permeability in Crohn’s Disease (CD) has been associated with various processes, including (pro-inflammatory) cytokine production, impaired mucus production and altered tight junction protein expression. A recent study showed that healthy first-degree relatives of CD patients had abnormal...

Background Transabdominal bowel ultrasound (TABUS) is a non-invasive tool that can be used to assess bowel inflammation in ulcerative colitis (UC). It is particularly attractive for use in children, given the need for general anesthesia when undergoing endoscopic assessment of bowel inflammation. A standardized TABUS scoring system in UC has only b...

Background Following viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-I0 -/- ) model derived from the SvE...

Background Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD. Methods Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were cat...

Background: Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn's disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and ch...

Background and AimsChildren with Crohn’s disease have lower response rates to infliximab, lower infliximab levels, and higher infliximab clearance on weight-based dosing than adults. We hypothesize infliximab clearance is a predictive of later outcomes on infliximab in children with Crohn’s disease.Methods In this single-center retrospective study,...

Background and aims: Inflammatory bowel diseases (IBD) are impacted by dietary factors, including non-digestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial but not all fibers are alike and some IBD patients report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-ferme...

Objectives: Transabdominal bowel ultrasound (TABUS) is emerging as an attractive, non-invasive tool in inflammatory bowel disease (IBD). Patient and caregiver experience with TABUS is not well described. We aimed to determine pediatric patient and caregiver satisfaction with TABUS and the impact of IBD severity, gender, age, and a history of anxie...

Background and aims Nutritional therapy with the Crohn’s Disease Exclusion Diet + Partial Enteral Nutrition [CDED+PEN] or Exclusive Enteral Nutrition [EEN] induces remission and reduces inflammation in mild-to-moderate paediatric Crohn’s disease [CD]. We aimed to assess if reaching remission with nutritional therapy is mediated by correcting compos...

To review and discuss recent findings on the associations between pediatric/early-life exposures to ambient air pollution and the risk of pediatric-onset inflammatory bowel diseases (IBD). A scoping review was conducted using the Peters Micah et al. framework. We searched, selected, extracted, and reviewed information from published peer-reviewed p...

LINKED CONTENT This article is linked to Sohouli et al papers. To view these articles, visit https://doi.org/10.1111/apt.17109

The vermiform appendix is generally considered a redundant organ, but recent evidence suggests that the appendix could contribute to the pathogenesis of inflammatory bowel diseases, in particular ulcerative colitis (UC), and may even have a therapeutic role; however, mechanisms of the appendix involvement remain unclear. Here, we highlight current...

Background & Aims Crohn's Disease Exclusion Diet + Partial Enteral Nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) both induce remission in pediatric Crohn's disease (CD). CDED+PEN is better tolerated and able to sustain remission. We characterized the changes in fecal metabolites induced by CDED+PEN and EEN and their relationship with r...

Background: In pediatric Crohn's disease (CD), there is an unmet need to better comprehend the effectiveness of different therapies. This study aimed to compare effectiveness of adalimumab (ADA) or infliximab (IFX) in children with luminal CD. Methods: Children 2-17 years old with newly diagnosed CD were enrolled into a multicenter inception cohor...

Background The transition from pediatric to adult care is associated with changes centered around the patient taking responsibility for their health. As the incidence of childhood-onset inflammatory bowel disease (IBD) is increasing, it is important to address gaps in transition literature—specifically, the indicators signifying achievement of tran...

Background As inflammation can impact microbes, our lab has focused on non-inflamed bowel sections of patients with inflammatory bowel diseases (IBD) and found bacterial alterations in the terminal ileum. We are also interested in the appendix given the involvement of the peri-appendicular region and effects of appendectomy in ulcerative colitis....

Background The pathogenesis of pCD remains poorly understood, but evidence suggests roles for genetics, environment, immune response, and gut microbes. Microbial changes can contribute to chronic inflammation and correlate with disease severity. Metabolomics reflects interactions between host immune and gut microbial function by quantifying compoun...