​​​​​​Narous M, Nugent Z, Rabinovitch-Nikitin I, Kirshenbaum L, Bernstein CN. Cardiac arrhythmia in patients with inflammatory bowel disease: a retrospective, population-based cohort study in Manitoba, Canada. BMJ Open 2025; Mar 21;15(3): e097687. 1-9.

 

Objective: We aimed to characterise the association between inflammatory bowel disease (IBD) and IBD medications and risk of cardiac arrhythmia.

Design, setting and participants: In a retrospective population-based study using the University of Manitoba IBD Epidemiology Database (Manitoba, Canada) from 1984 to 2018, we identified 10,992 IBD cases and 102,875 matched controls.

Analysis: Arrhythmia risk in IBD was adjusted for the presence of comorbidities of the Charlson Comorbidity Index. The effect of IBD medications on the development of arrhythmia was assessed in a nested cohort study of individuals with IBD. Cases were censored at the date of first database identification of a diagnosis of heart failure or myocardial infarction.

Results: The cohort was 48.5% Crohn's disease and 51.5% ulcerative colitis, and 80.5% were incident cases. The median age of incident cases at IBD diagnosis was 35 (interquartile range, IQR, 25 to 49). The median age at arrhythmia diagnosis for persons with IBD was 69 years (IQR, 59 to 77) and for controls 69 years (IQR, 59 to 78). Persons diagnosed with IBD were more likely than controls (HR 1.51; 95% CI, 1.30 to 1.76) to develop arrhythmia. Persons within their sixth decade or younger had increased risk of arrhythmia. When controlling for comorbidities, the significant association between IBD and arrhythmia remains. Medications including 5-aminosalicylates, thiopurines and tumour necrosis factor-α inhibitors were not associated with arrhythmia.

Conclusions: Persons with IBD have a higher risk of arrhythmia prior to a diagnosis with heart disease. Use of IBD medications was not associated with risk of arrhythmia.

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Marrie RA, Maxwell C, Bolton JM, Soderling J, Bernstein CN, Krysko K, McKay K, Rotstein D, Deakin-Harb K, Razaz N. Risk factors for incident peripartum mental illness in multiple sclerosis. Multiple Sclerosis Journal 2025 Jun;31(7):846-855.

 

Background: Mothers with multiple sclerosis face an increased incidence and prevalence of peripartum mental illness as compared to mothers without multiple sclerosis.

Objective: To determine the factors associated with the risk of peripartum mental illness among mothers with multiple sclerosis.

Methods: We identified mothers with multiple sclerosis with live births between 2002 and 2019 using linked population-based administrative data from Ontario, Canada. Using validated definitions, we estimated the incidence of mental illness (depression, anxiety, bipolar disorder) from conception through the first post-partum year (peripartum period). We used multivariable Poisson regression to assess the association between age, delivery year, area-level deprivation (Ontario Marginalization Index), disease duration, disability, and comorbidity and incidence of peripartum mental illness.

Results: Among 1745 mothers with multiple sclerosis, the mean (SD) age at conception was 31.2 (4.8) years. Mothers living in communities that lacked cohesion had increased rates of peripartum depression (incidence rate ratio [IRR] 1.25; 1.11-1.42) and anxiety (IRR 1.20; 1.07-1.33). Elevated multiple sclerosis disability level was associated with elevated peripartum depression rates (IRR 1.51; 1.12-2.04).

Conclusion: Higher area-level deprivation and disability levels are associated with an increased incidence of peripartum mental illness. These findings may assist clinicians in identifying women with MS who may benefit from peripartum mental health support.

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Hracs L, Windsor JW, Gorospe J, Cummings M, Coward S, Buie MJ, Quan J, Goddard Q, Caplan L, Markovinović A, Williamson T, Abbey Y, Abdullah M, Abreu MT, Ahuja V, Affendi R, Ali R, Altuwaijri M, Balderramo D,  Banerjee R, Benchimol EI, Bernstein CN, Brunet-Mas E, Burisch J, Chong VH, Dotan I, Dutta U, El Ouali S, Forbes A, Forss A, Gearry R, Dao VH, Hartono JL, Hilmi I,  Hodges P,  Jones GR, Juliao-Baños F, Kaibullayeva J, Kelly P, Kobayashi T, Kotze PG, Lakatos PL, Lees CW, Limsrivilai J, Loftus EF Jr, Ludvigsson JF, Mak JWY, Miao  YL, Ng KK, Okabayashi S, Olén O, Panaccione R, Paudel MS, Quaresma AB, Rubin DT, Simadibrata M, Sun Y, Suzuki H, Toro M, Turner D, Vergara BI, Wei SC, Yamamoto-Furusho, JK; Yang, SK, Ng SC, Kaplan GG on behalf of the Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) Research Group. Global Evolution of Inflammatory Bowel Disease across Epidemiologic Stages. Nature 2025 Jun; 642(8067): 458-466.

 

During the twentieth century, inflammatory bowel disease was considered a disease of early industrialized regions in North America, Europe and Oceania. At the turn of the twenty-first century, IBD incidence increased in newly industrialized and emerging regions in Africa, Asia and Latin America, while the prevalence in early industrialized regions continued to grow steadily. Changes in the incidence and prevalence denote the evolution of IBD across four epidemiologic stages: stage 1 (emergence), characterized by low incidence and prevalence; stage 2 (acceleration in incidence), marked by rapidly rising incidence and low prevalence; and stage 3 (compounding prevalence), where the incidence decelerates, plateaus or declines while the prevalence steadily increases. A fourth stage (prevalence equilibrium) has been proposed in which the prevalence slope plateaus due to demographic shifts in an ageing IBD population, but it has not yet been evidenced. To date, these stages have remained theoretical, lacking specific numerical indicators to define transition points. Here, using real-world data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920-2024), we show spatiotemporal transitions across stages 1-3 and model stage 4 progression. Understanding the evolution of IBD across epidemiologic stages enables healthcare systems to better anticipate the future worldwide burden of IBD.

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McIver TA, Bernstein CN, Figley C, Patel R, Fisk JD, Marrie RA, Kornelsen J. Impact of fatigue in Crohn's disease is negatively related to resting state functional connectivity between the superior parietal lobule and parahippocampal gyrus/hippocampus. Frontiers in Human Neuroscience 2025 April 25;19: 1561421.

 

Introduction: Crohn's disease is one phenotype of inflammatory bowel disease (IBD). Fatigue is a common and burdensome symptom for persons with Crohn's disease. Despite its detrimental impact on health-related quality of life, the pathophysiology of fatigue in Crohn's disease is not fully understood. Specifically, basic research on the difference in brain functioning associated with fatigue in Crohn's disease is scarce. This study aimed to address this knowledge gap by identifying fatigue-related differences in brain resting state functional connectivity. in Crohn's disease.

Methods: Participants included 49 adults with Crohn's Disease (M age 53 yrs, 35 females) and 49 healthy controls (M age 50 yrs, 31 females). The Fatigue Impact Scale  assessed impact of fatigue across three domains (physical, cognitive, and psychosocial) as well as total impact of fatigue. The Harvey-Bradshaw Inventory (HBI) assessed disease activity. Magnetic Resonance Imaging of brain functional connectivity during resting state (i.e.,: wakeful rest) was assessed in relation to scores on the Fatigue Impact Scale   (total and for each domain). Moderation analyses tested whether brain resting state functional connectivity moderates the relationship between disease activity and fatigue.

Results: The Crohn's disease group reported more severe fatigue than the healthy control group in each domain of the Fatigue Impact Scale. For the Crohn's disease group, increasing fatigue was associated with decreasing synchronicity of brain function (i.e., functional connectivity) between the superior parietal lobule and the parahippocampal gyrus/hippocampus. Unlike in the healthy control group, an increasing impact of physical fatigue was associated with decreasing functional connectivity between these Regions of Interest for the Crohn's disease group (TFCE = 16.88, p-FDR = 0.03). Moderation analyses revealed a significant interaction between disease activity, total fatigue, and functional connectivity of the right superior parietal lobule and left anterior parahippocampal gyrus (ΔR2 = 0.058, F = 5.445, p = 0.0245). Higher scores on the Harvey Bradshaw Index were only associated with higher total scores on the Fatigue Impact Scale   in persons with Crohn's disease who exhibited negative functional connectivity between these brain regions.

Discussion: In people with Crohn's disease, fatigue increases as functional connectivity between brain regions involved in sensorimotor integration and memory processing decreases.

 

 

Cadogan K, Marrie RA, Graff LA, El Gabalawy R, Enns MW, Bolton JM, Sareen J, Bernstein CN. The spectrum of psychiatric comorbidity in individuals with inflammatory bowel disease. Crohn’s and Colitis 360 2025; May 14;7(2):otaf035.

 

Background: Research on psychiatric comorbidity in inflammatory bowel disease  has focused mostly on anxiety and depression. This study aimed to describe the spectrum of psychiatric disorders experienced by individuals with IBD and their overlap.

Methods: Participants were enrolled in a prospective 3-year longitudinal study that assessed psychiatric comorbidity in immune-mediated inflammatory disease. Lifetime prevalence of psychiatric comorbidity was assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-IV), as the DSM-IV was the prevailing classification at the time of study design. Diagnosis was aligned with DSM-5 categorization where possible with available data. Psychiatric burden was categorized as no psychiatric conditions, 1, 2 or 3 or more psychiatric conditions.

Results: Of 154 IBD participants (62% female, 63% Crohn's disease) 57% had at least one psychiatric comorbidity with 27% having >1 psychiatric diagnosis. The prevalence was major depressive disorder (41.7%), anxiety disorders (39.6%; grouped as per DSM-5), substance use disorder (16.2%), posttraumatic stress disorder (5.3%), obsessive-compulsive disorder (4.9%), and bipolar disorder (2.0%). Of participants with major depressive disorder and a comorbid psychiatric disorder, nearly half had substance use disorder. Of those with >1 psychiatric disorder >70% had major depressive disorder and a comorbid anxiety disorder. Persons with ≥1 psychiatric comorbidity were more likely to be current smokers (P < .001) and to have higher IBD disease activity scores (P = .005) than those without a psychiatric comorbidity.

Conclusions: Over half of adults with IBD had >1 diagnosed psychiatric comorbidity from a range of 10 different psychiatric disorders identified. Further research should assess the temporal relationship of IBD and the various psychiatric presentations to better understand the trajectory of co-occurrence, and therapy which may concurrently address the psychiatric disorder and the IBD.

 

 

Solitano V, Ogunsakin RE, Yuan Y, Bernstein CN, Bessissow T, Bressler B, Hoentjen F, van Lierop L, Leun Y, Ma C, Marshall JK, Narua N, Alahmari M, Mccurdy JD, Murthy S, Panaccione R, Rosenfield G, Milgtom R, Silverberg M, Jairath V.  Effectiveness and Safety of Advanced Combination Treatment (ACT) in patients with refractory inflammatory bowel disease or concomitant immune mediated disease or extra-intestinal manifestations: A Multi-Center Canadian Study. American Journal of Gastroenterology 2025; in press. 

 

Introduction: Owing to the therapeutic ceiling associated with inflammatory bowel disease therapies, some patients may require 2 advanced therapeutic agents, known as advanced combination treatment to control disease or treat associated extraintestinal manifestations.

Methods: We included adult patients with IBD from 9 Canadian centers treated with either 2 biological therapies, a biological plus an oral small molecule, or 2 small molecules. Indications for advanced combination treatment   were the following: (i) refractory IBD, (ii) uncontrolled immune mediated diseases, and (iii) uncontrolled extraintestinal manifestations. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 6 and 12 months. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness.

Results: We included 105 IBD patients (76 Crohn's disease, 29 ulcerative colitis) with median age 35 years (Interquartile Range 35.4-40.8). At baseline, 39% had perianal involvement, 58% had failed at least 3 advanced therapies, and 40% had previous surgery. The primary reason for advanced combination treatment   was refractory IBD (63.8%), with the add-on approach used in 97.1% cases. The most frequent combination was antitumor necrosis factor + anti-integrin. At 12 months, cumulative rates of clinical and endoscopic response were 60.0% and 32.4%, respectively, and remission rates were 29.5% and 28.6%. Perianal disease was associated with reduced clinical remission (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.17-0.65, P = 0.001) and endoscopic response (HR = 0.42, 95% CI: 0.12-0.50, P = 0.001). Longer disease duration (HR = 0.96, 95% CI: 0.92-0.99, P = 0.035) and baseline steroid use (HR = 0.39, P = 0.006) was associated with reduced clinical remission. Serious adverse events and infections occurred in 12.4% and 7.6% of patients, respectively.

Discussion: advanced combination treatment was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant immune-mediated diseases/ extraintestinal manifestations, with favorable safety profile.

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Hanžel J, Solitano V, Vuyyuru SK, Panaccione R, Sands BE, Peyrin-Biroulet L, Danese S, D'Haens GR, Atreya R, Allez M, Bernstein CN, Bossuyt P, Bressler B, Bryant RV, Cohen BL, Colombel JF, D'Amico F, Dignass A, Dubinsky M, Fleshner P, Gearry RB, Hanauer SB, Hart AL, Kayal M, Kucharzik T, Lakatos PL, Louis E, Magro F, Narula N, Leong RW, Panés J, Raine T, Ran Z, Regueiro MD, Reinisch W, Singh S, Steinhart AH, Travis S, Ungaro RC, Janneke van der Woude C, Yamamoto T, Ahuja V, Rubin DT, Dulai PS, Cornfield LJ, Hogan M, Sandborn WJ, Feagan BG, Jairath V, Ma C.

An International Consensus on Appropriate Management of Corticosteroids in Clinical Trials in Inflammatory Bowel Disease. Gastroenterology 2025; in press.

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Background & aims: Approval of new therapies for inflammatory bowel disease (IBD) requires rigorously designed and well-executed randomized controlled trials. Corticosteroids remain a cornerstone of IBD induction therapy, and many patients in trials are enrolled while taking corticosteroids. Despite this, approaches to corticosteroid management in randomized controlled trials have been highly heterogeneous, often differing from clinical practice. This negatively impacts patients' willingness to participate due to prolonged corticosteroid exposure and may potentially bias outcomes in the clinical trial. Our aim is to provide comprehensive standardized recommendations on key aspects of corticosteroid use in IBD clinical trials through a multiphase, international expert consensus, with a goal to help inform and standardize practice in future randomized controlled trials.

Methods: The consensus was informed by a systematic review of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, which determined the corticosteroid management rules used in placebo-controlled trials of advanced therapies in IBD. International expert consensus recommendations for all aspects of corticosteroid management in randomized controlled trials s were then developed using a modified Delphi process with 2 rounds of survey questions and a ratification meeting.

Results: These recommendations propose management of corticosteroids during screening, induction, and maintenance phases of pharmacologic trials in IBD and define corticosteroid-related end points. We emphasize the need for minimizing corticosteroid exposure through expedited tapering and shorter fixed-dosing periods that more closely reflect clinical care and provide recommendations for standardized definitions of corticosteroid-free remission.

Conclusions: These recommendations will serve to optimize trial design and facilitate appropriate, acceptable, and standardized randomized controlled trials corticosteroid handling practices.

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Chochinov S, Dolovich C, Ly G, Narvey S, Raiman M, Bernstein CN. A population-based assessment of physical activity and exercise in persons with IBD. Journal of Clinical Gastroenterology 2025; in press.

 

Goals/background: We aimed to assess the physical activity and exercise profiles of persons with IBD, their limitations in undertaking physical activity /exercise, and how physical activity correlates with active disease and fatigue in a Canadian population-based sample.

Study: A cross-sectional survey study was undertaken by participants in the University of Manitoba IBD Research Registry. The survey included sociodemographic factors, PA/exercise, the International Physical Activity Questionnaire (IPAQ), Inflammatory Bowel Disease Symptom Inventory (IBDSI), and Modified Fatigue Impact Scale (MFIS). Bivariate and logistic regression analyses assessed the association between physical activity and disease activity and fatigue.

Results: The survey was completed by 1257 of 2740 invitees (45.8%). Because of 163 missing age or physical activity responses, 1094 were included in the data analysis. The mean age of participants was 60.8+/-13.0 years. Activity status was inactive in 42.5%, moderately active in 32.0%, and highly active in 25.5%. Activity levels were similar for those >55 versus those <55 years. Thirty-eight percent reported that IBD never impacted their physical activity /exercise. Persons with Crohn's disease were more likely to be inactive than persons with ulcerative colitis. Logistic regression analysis showed that the odds of engaging in lower levels of physical activity were greater for persons with active IBDSI versus persons with non-active IBDSI (aOR: 1.51, 95% CI: 1.11-2.04), with an increase in MFIS score (aOR: 1.02, 95% CI: 1.01-1.03), in females with ulcerative colitis, and in those who smoke.

Conclusion: These findings underscore the need for tailored physical activity/exercise guidelines for individuals with IBD. Future research should explore objective measures of physical activity to better understand physical activity /exercise in both younger and older adult populations.

 

 

Manouchehrinia A, Fitzgerald KC, Salter A, Marrie RA, Bernstein CN, Bolton JM, Cutter G, Fisk JD, Graff LA, Hitchon CA, Kockum I, Lu Y, Lublin FD, McKay K, Patten S, Patki A, Riel H, Shchetynsky K, Stridh P, Tiwari HK, Wolinsky JS, Kowalec K. Depression polygenicity and disease activity and disability worsening in multiple sclerosis.  Annals of Neurology 2025;98:1057-1069.

 

Objective: A better understanding of factors associated with multiple sclerosis disease activity and disability is needed. Given the strong link between comorbid depression and multiple sclerosis disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with multiple sclerosis disease activity and disability worsening.

Methods: In this cohort study, we used samples from neurologist-defined adults with multiple sclerosis followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score and tested its association with annualized relapse rate and worsening disability. In the US cohort, we additionally explored the time to relapse, number of enhancing lesions, and confirmed Expanded Disability Status Scale (EDSS) worsening during the study period.

Results: We included 3,420 relapsing-onset adults with multiple sclerosis of European genetic ancestry with a median follow-up of 3 to 5 years. Meta-analyses revealed for each 1-standard deviation increase in the depression polygenic score, the relapse rate increased (incidence rate ratio: 1.23, 95% confidence interval [CI] = 1.01-1.50). In the US cohort, higher depression polygenic score was associated with protocol-defined relapses (hazard ratio [HR] = 1.58, 95% CI = 1.03-2.43), and time to confirmed EDSS worsening (HR = 1.51, 95% CI = 1.03-2.22) with this effect largely direct.

Interpretation: Meta-analyses showed a higher depression genetic burden was associated with increased multiple sclerosis disease activity. In the US clinical trial cohort only, we found a significant association between higher depression polygenic score and time to relapse and confirmed EDSS worsening. These findings may provide insights into MS disease activity and disability worsening.

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Lee SH, Bushra M, Qui L, Griffiths AM, Turpin W, Croitoru K.and the Crohn’s and Colitis Canada-Genetic, Environmental, Microbial (CCC-GEM) Project Research Consortium. Early life exposure to parental Crohn’s disease is associated with offspring’s gut microbiome, gut permeability, and increased risk of future Crohn’s disease. Gastroenterology 2025; 168: 385-388.

 

1,252 offspring of persons with CD were enrolled in which 586 (46.8%) offspring had exposure to parental CD during the perinatal period, and 666 (53.2%) had exposure to parental CD diagnosis after the perinatal period. 14 (1.11%) individuals developed CD, of whom 11 (0.88%) were exposed to parental CD perinatally Participants exposed to a parent’s CD diagnosis during the perinatal period had a 4.31-fold higher risk (95% CI, 1.28–17.46) of developing CD compared to those exposed to a parent who developed CD later in life  In the subgroup of participants with exposure to a mother with CD, we noted a trend toward increased risk (ie, higher HR) of incident CD with earlier exposure to mother’s CD diagnosis. Offspring whose mothers developed CD more than 1 year before birth (ie, before conception) had a 6.3-fold higher risk of developing CD compared to those whose mothers developed CD later in life. Participants exposed to mother’s CD diagnosis within 1 year before birth had a 5.5-fold higher risk of incident CD, those exposed up to 1 year after birth had a 4.7-fold higher risk, and those exposed up to 3 years after birth had a 3.8-fold higher risk However, we did not find this trend in the subgroup exposed to father’s CD diagnosis.

 

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Kornelsen J, McIver T, Figley C, Patel R, Fisk JD, Marrie RA, Bernstein CN. Resting state functional connectivity of the cerebellum differs between persons with inflammatory bowel disease and healthy controls in relation to executive function. Inflammatory Bowel Diseases 2025;31(5):1466-1470. 

 

We hypothesized that there would be a difference between IBD and healthy controls in their relationship between cerebellar resting-state functional connectivity and scores on a separately performed executive function task. Establishing if executive function is associated with different resting-state functional connectivity of cerebellar regions for persons with IBD will expand our understanding of brain–gut axis dysregulation in IBD and support future investigation of executive function impairment as a comorbidity of the disease. We hypothesized that there will be a difference between IBD and healthy controls in their relationship between cerebellar resting-state functional connectivity and scores on a separately performed executive function task. Establishing if executive function is associated with different resting-state functional connectivity of cerebellar regions for persons with IBD will expand our understanding of brain–gut axis dysregulation in IBD and support future investigation of executive function impairment as a comorbidity of the disease. 72 persons with IBD and 90 healthy controls underwent whole-brain anatomical and resting-state functional imaging which were acquired on a 3T Siemens TIM Trio MRI system

The present study provides further support for an association between executive functioning and cerebellar functional connectivity, in addition to highlighting the role of cerebellar VIIa in distinguishing functional connectivity differences between persons with IBD and healthy controls. Limitations of the current study include the participant sample heterogeneity and the use of various disease-modifying medications within the IBD group. Nonetheless, this study provides valuable insight into the role of the cerebellum and the potential neural underpinnings of cognition in IBD.

 

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Bernstein CN, Ly G, Nugent Z, Shaffer SR, Singh H, Graff LA. Research participation in inflammatory bowel disease studies: What do patients want? Crohn’s and Colitis 360 2025; Feb 27; 7(2): otaf016. 

 

Background: We aimed to determine patient perspectives on inflammatory bowel disease (IBD) research participation and potential changes related to the COVID pandemic experience.

Methods: Participants of the population-based University of Manitoba IBD Research Registry were surveyed March 2022 to March 2023. The survey inquired about views on IBD research participation in the pre-, peri- and post-COVID era. Questions included aspects of participation from home or in-person, potential reimbursement, results reporting, and study design. We determined a rank order of reasons for research participation. We assessed willingness to participate in 5 research genres: clinical trials, biospecimen collection research, research involving colonoscopies, research accessing medical records, and research with access to records and samples.

Results: Of 3018 invitees, 1105 (36.6%) completed the survey. Two-thirds reported that pre-pandemic they were unlikely to participate in placebo-controlled clinical trials, and nearly half would participate in a trial if guaranteed to receive active drug. The most important aspect impacting on clinical trial participation was understanding the potential side effects (81%). Post-COVID, 20%-30% reported that their interest in research participation decreased, 15%-20% reported that their interest had increased, with the majority (55%-60%) indicating no change in research participation interest. About 80% would participate in observational research. Payment for participation was not a significant motivator for most.

Conclusions: We found a low rate of interest in participating in placebo-controlled IBD clinical trial research but nearly 50% would participate in clinical trial research receiving active drug and 80% would participate in observational research. Research participation interest, however, was further lessened by the COVID pandemic.

 

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Bernstein CN, Nugent Z, Panacione R, Marshall DA, Kaplan GG, Dieleman LA, Vanner S, Graff LA, Otley A, Jones J, Buresi M, Murthy S, Borgaokar M, Bressler B, Bitton A, Croitoru K, Sidani S, Fernandes, Moayyedi P.  Symptoms in persons with either active or inactive Crohn’s disease are agnostic to disease phenotype-the MAGIC in IMAGINE study. Journal of Clinical Gastroenterology 2025; in press.

 

Background We aimed to examine the relationship between disease symptoms and disease phenotype in a large Canadian cohort of persons with Crohn’s disease

Methods Adults (n=1515) with Crohn’s disease from 14 Canadian centres participated in the Mind And Gut Interactions Cohort (MAGIC) between 2018-2023. Disease activity was measured using the 24-item IBD Symptom Inventory-Short-Form (IBDSI-SF). We compared the symptoms commonly associated with active versus inactive disease, and explored symptoms patterns in relation to disease phenotype, based on the Montreal Classification. To assess psychological status the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 were used.

Results Mean disease duration was 15.6±11.8 years. The 5 most common symptoms were similar for those with active disease, although at higher prevalence (89-98%) versus those with inactive disease (47-79%), and included fatigue, diarrhea, gas, bloating, and urgency. The intensity of symptoms was higher in those with active than inactive IBDSI-SF scores. The rank order and relative distribution of the symptoms and intensity of the symptoms reported were similar between those with different disease phenotypes B1, B2 and B3 and L1, L2 and L3. Persons with active IBDSI-SF had a higher prevalence of anxiety (24.6%) and depression (38/2%) versus persons with inactive IBDSI-SF (6.3% and 8%, respectively)

Conclusions Individuals with Crohn’s disease with active and inactive disease by IBDSI, experience similar symptoms, but the prevalence of symptoms and their intensity is greater in persons with active IBDSI. Persons with inactive IBDSI report many symptoms. There was no difference in symptom reporting by disease behavior or location.

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O'Mahony J, Bernstein CN, Marrie RA. A nested case-control study evaluating the relationship between adverse childhood experiences and immune-mediated inflammatory disease in the Canadian Longitudinal Study on Aging. BMJ Open 2025 Jan 20;15(1):e087133: 1-11.

 

Objectives: Adverse childhood experiences are associated with immune-mediated inflammatory diseases (IMID). We evaluated whether: (i) Adverse childhood experiences associate with psychiatric comorbidity among individuals with IMID, including rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD); (ii) whether psychiatric disorders mediate the relationship between ACE and IMID; and (iii) whether these findings differ from those in individuals with other chronic physical disorders.

Methods: Using data from the Canadian Longitudinal Study on Aging (CLSA) we performed a retrospective case-control study of participants aged 45-85 years recruited between 2010 and 2015. Adverse childhood experiences were queried using questions derived from the Childhood Experiences of Violence Questionnaire-Short Form and the National Longitudinal Study of Adolescent to Adult Health Wave III questionnaire. We used multivariable logistic regression and causal mediation analysis to address our objectives.

Results: We included 13,977 CLSA participants. Among the 31 % of IMID participants who reported a comorbid psychiatric disorder, 79 % reported a history of Adverse childhood experiences. Adverse childhood experiences associated with increased odds (OR [95 % CI]) of a psychiatric disorder (2.55 [1.02-6.35]) among participants with IMID; this did not differ across IMID. The total effect (OR [95 % CI]) of ACE on IMID was 1.11 (1.07-1.16), of which 10.60 % (8.04-17.47) was mediated by psychiatric disorders. We found similar associations among participants with other chronic physical disorders.

Conclusion: Our findings suggest that psychiatric disorders partially mediate the association between adverse childhood experiences and IMID. Most participants with IMID and comorbid psychiatric disorders report a history of adverse childhood experiences and may benefit from trauma-informed mental health care.

 

 

Lee SH, Turpin W, Espin-Garcia O, Xu W, Croitoru K; Crohn's and Colitis Canada-Genetic, Environmental, Microbial (CCC-GEM) Project Research Consortium. Development and Validation of an Integrative Risk Score for Future Risk of Crohn's Disease in Healthy First-Degree Relatives: A Multicenter Prospective Cohort Study. Gastroenterology 2025 Jan;168(1):150-153.

 

Despite advances in medical therapy, approximately one-half of patients with Crohn’s disease develop complications ultimately requiring surgery. Currently, no treatment offers a chance of cure. The increasing incidence and prevalence of Crohn’s disease globally pose a substantial burden at the population and individual levels. Thus, a better understanding of the early triggers of Crohn’s disease is desperately needed to enhance early detection, improve medical therapy, and offer a possibility of interventions that prevent development of Crohn’s disease. Previous studies have reported candidate predisease biomarkers associated with future development of Crohn’s disease, supporting the concept of a preclinical phase. However, these studies lack integration of individual predisease signatures and the multidimensional mechanisms of disease pathogenesis. To date, no risk-stratification model has combined multiple predictive biomarkers to predict future risk of developing Crohn’s disease in healthy at-risk individuals.

In this study, we leveraged a large prospective multicenter cohort of healthy first-degree relatives of people with Crohn’s disease —the Crohn’s and Colitis Canada-Genetic, Environmental, Microbial (GEM) study. Using available demographic characteristics, physiologic biomarkers, and fecal microbiome data, we developed an integrative multidimensional risk model—the GEM integrative risk score (IRS)—that predicts an first-degree relatives future risk of developing Crohn’s disease. We subsequently validated the performance of GEM-IRS in 2 testing cohorts.

We included participants with a minimum 3 months of follow-up duration as of February 28, 2021; participants recruited from countries with sufficient median follow-up duration of at least 5 years (ie, Canada, United States, and Israel). Fecal microbial profiling was performed by 16S ribosomal RNA sequencing; microbial function was imputed using PICRUSt2. Fecal calprotectin (FCP) was measured as a biomarker of gut inflammation and intestinal barrier function was assessed by the ratio of the urinary fractional excretion of lactulose over that of mannitol (LMR).

After quality control of microbiome data and removal of missing data, there were 2619 participants (1170 North American training set, 1141 North American test set, and 308 from Israel), which we used for subsequent analyses. During a median follow-up duration of 6.8 years (interquartile range 4.2–9.6 years), 61 of 2619 participants (2.3%) developed Crohn’s disease.

The GEM-IRS, built with random survival forest, resulted in a predictive performance measured by a Harrell’s concordance index of 0.951 (95% CI, 0.925–0.976) in the North American training cohort. On validation, the GEM-IRS had a concordance index of 0.789 (95% CI, 0.713–0.865) in the pooled testing cohort. Of note, the performance was higher compared with the other models tested (ie, 0.777 for gradient boosting survival and 0.717 for penalized Cox proportional hazards model).

The cumulative incidence of CD in the 2 testing cohorts was assessed using the quartiles of the GEM-IRS from the training cohort. The fourth quartile compared with the lower 3 quartiles showed a significantly increased risk of Crohn’s disease onset (hazard ratio, 6.42; 95% CI, 3.10–13.30) in the pooled testing cohort.

 

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Olivera PA, Martinez-Lozano H, Leibovitzh H, Xue M, Neustaeter A, Espin-Garcia O, Xu W, Madsen KL, Guttman DS, Bernstein CN, Yerushalmi B, Hyams JS, Abreu MT, Marshall JK, Wrobel I, Mack DR, Jacobson K, Bitton A, Aumais G, Panacionne R, Dieleman LA, Silverberg MS, Steinhart AH, Moayyedi P, Turner D, Griffiths AM, Turpin W, Lee SH, Croitoru K; Crohn’s and Colitis Canada (CCC) Genetic, Environmental, Microbial (GEM) Project Research Consortium. Healthy first-degree relatives from multiplex families versus simplex families have a higher subclinical intestinal inflammation, a distinct fecal microbial signature, and harbor a higher risk of developing Crohn's disease. Gastroenterology 2025; 168 (1):99-110.

 

Background & aims: Unaffected first-degree relatives from families with at least 2 affected first-degree relatives with Crohn's disease (multiplex families) have a high risk of developing Crohn’s disease, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between first-degree relatives from multiplex vs simplex families and investigate the risk of future Crohn’s disease onset accounting for potential confounders.

Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial (GEM) cohort of healthy first-degree relatives of patients with Crohn’s disease. Genome-wide Crohn’s disease-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between Crohn’s disease multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future Crohn’s disease onset.

Results: There were 4051 participants from simplex families and 334 from Crohn’s disease multiplex families. Crohn’s disease multiplex status was significantly associated with higher baseline FCP (P = .026) but not with baseline Crohn’s disease-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. Crohn’s disease multiplex status at recruitment was independently associated with an increased risk of developing Crohn’s disease (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18-6.11, P < .001).

Conclusion: Within first-degree relatives of patients with Crohn’s disease, participants from multiplex families had a 3-fold increased risk of Crohn’s disease onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in first-degree relatives from multiplex families.

 

 

Bernstein CN, Panaccione R, Nugent Z, Marshall DA, Kaplan GG, Vanner S, Dieleman LA, Graff LA, Otley A, Jones J, Buresi M, Murthy S, Borgaonkar M, Bressler B, Bitton A, Croitoru K, Sidani S, Fernandes A, Moayyedi P. Crohn's Disease Phenotypes and Associations With Comorbidities, Surgery Risk, Medications and Nonmedication Approaches: The MAGIC in IMAGINE Study.  Inflammatory Bowel Diseases 2025 Jan 6;31(1):113-122

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Background: We aimed to establish a cohort of persons with Crohn's disease enrolled from 14 Canadian centers to describe the contemporary presentation of Crohn's disease in Canada.

Methods: All enrollees were at least 18 years old and underwent chart review for phenotype documentation by Montreal Classification at time of enrollment, comorbidities, IBD and other surgeries, and use IBD and other therapies.

Results: Of 2112 adults, 59% were female, and the mean age was 44.1 (+/-14.9SD) years. The phenotype distribution was B1 (inflammatory)= 50.4%, B2 (fibrostenotic)= 22.4%, B3 (penetrating)= 17.3%, and missing information = 9.9%. Perineal disease was present in 14.2%. Pertaining to disease location, 35.2% of patients had disease in L1 (ileal only), 16.8% in L2 (colonic only), 48% in L3 (ileocolonic), and 0.4% in L4 (upper gastrointestinal). There was no difference in phenotype by gender, anxiety score, depression score. Disease duration was significantly different depending on disease behavior type (B1 = 12.2 ± 10.1; B2 = 19.4 ± 12.9; B3 = 18.9 ± 11.8, P < .0001). Isolated colonic disease was much less likely to be fibrostenotic or penetrating than inflammatory disease. Penetrating disease was more likely to be associated with ileocolonic location than other locations. Perineal disease was most commonly seen in persons with B3 disease behavior (24%) than other behaviors (11% B1; 20% B2 disease, P < .0001) and more likely to be seen in ileocolonic disease (L3;19%) vs L2 (17%) and L1 (11%; P < .0001). Surgery related to IBD occurred across each behavior types at the following rates: B1 = 23%, B2 = 64%, and B3 = 74%. Inflammatory bowel disease-related surgery rates by location of disease were L1 = 48%, L2 = 21%, and L3 = 51%.

Conclusions: In exploring this large contemporary Crohn’s disease cohort we have determined that inflammatory disease is the main Crohn’s disease phenotype in Canada and that Crohn’s disease-related surgery remains very common.

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Olivera PA, Martinez-Lozano H, Leibovitzh H, Xue M, Neustaeter A, Espin-Garcia O, Xu W, Madsen KL, Guttman DS, Bernstein CN, Yerushalmi B, Hyams JS, Abreu MT, Marshall JK, Wrobel I, Mack DR, Jacobson K, Bitton A, Aumais G, Panacionne R, Dieleman LA, Silverberg MS, Steinhart AH, Moayyedi P, Turner D, Griffiths AM, Turpin W, Lee SH, Croitoru K; Crohn’s and Colitis Canada (CCC) Genetic, Environmental, Microbial (GEM) Project Research Consortium. Healthy first-degree relatives from multiplex families versus simplex families have a higher subclinical intestinal inflammation, a distinct fecal microbial signature, and harbor a higher risk of developing Crohn's disease. Gastroenterology 2025; 168 (1):99-110. 

 

Background: Unaffected first-degree relatives from families with at least 2 affected first-degree relatives with Crohn's disease (multiplex families) have a high risk of developing Crohn’s disease, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between first-degree relatives from multiplex vs simplex families and investigate the risk of future Crohn’s disease onset accounting for potential confounders.

Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy first-degree relatives of patients with Crohn’s disease. Genome-wide Crohn’s disease-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin, and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between Crohn’s disease multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future Crohn’s disease onset.

Results: There were 4051 participants from simplex families and 334 from Crohn’s disease multiplex families. Crohn’s disease multiplex status was significantly associated with higher baseline fecal calprotectin (P = .026) but not with baseline Crohn’s disease-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. Crohn’s disease multiplex status at recruitment was independently associated with a 3-4-fold increased risk of developing Crohn’s disease (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18-6.11, P<.001).

Conclusion: Within first-degree relatives of patients with Crohn’s disease, participants from multiplex families had a 3-4-fold increased risk of Crohn’s disease onset, a higher fecal calprotectin, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in first-degree relatives from multiplex families.
 

 

Bernstein CN, Fisk JD, Walld R, Bolton JM, Sareen J, Patten SB, Singer A, Lix LM, Hitchon CA, El-Gabalawy R, Katz A, Graff LA, Marrie RA. Psychiatric comorbidity does not enhance prescription opioid use in inflammatory bowel disease as it does in the general population. Inflammatory Bowel Disease 2025 Feb 10;31(2):386-393.

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Background: Little is known about patterns of opioid prescribing in IBD, but pain is common in persons with IBD. We estimated the incidence (new prescriptions) and prevalence of opioid use in adults with IBD and an unaffected reference cohort and assessed factors that modified opioid use.

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Methods: Using population-based health administrative data from Manitoba, Canada, we identified 5233 persons with incident IBD and 26150 persons without IBD matched 5:1 on sex, birth year, and region from 1997 to 2016. New and prevalent opioid prescription dispensations were quantified, and patterns related to duration of use were identified. Generalized linear models were used to test the association between IBD, psychiatric comorbidity, and opioid use adjusting for sociodemographic characteristics, physical comorbidities, and healthcare use.

Results: Opioids were dispensed to 27% of persons with IBD and to 12.9% of the unaffected reference cohort. The unadjusted crude incidence per 1000 person-years of opioid use was nearly twice as high for the IBD cohort (88.63; 95% CI, 82.73-91.99) vs the reference cohort (45.02; 95% CI, 43.49-45.82; relative risk 1.97; 95% CI, 1.86-2.08). The incidence rate per 1000 person-years was highest in those 18-44 years at diagnosis (98.01; 95% CI, 91.45-104.57). The relative increase in opioid use by persons with IBD compared to reference cohort was lower among persons with psychiatric comorbidity relative to the increased opioid use among persons with IBD and reference cohort without psychiatric comorbidity.

Discussion: The use of opioids is more common in people with IBD than in people without IBD. This does not appear to be driven by psychiatric comorbidity.

 

 

Venner JM, Bernstein CN. Current Endoscopic Scoring Systems in Inflammatory Bowel Disease: Strengths and Limitations. Gastrointestinal Endoscopy Clinics North America 2025 Jan; 35(1):19-39.

 

There are several available endoscopic scoring systems that are designed to assess disease activity in inflammatory bowel disease. The most widely known is the Mayo endoscopic subscore for ulcerative colitis. These schemas are not routinely used in clinical practice, largely due to their complexity or lack of granularity, although they are standard for outcomes measurement in large clinical trials. While some schemas have been validated using independent cohorts, there is high inherent interobserver variation. Furthermore, derivation of these scoring systems has been subject to selection bias and limited challenge bias. In this article we review endoscopic scoring systems used in IBD, their strengths and weaknesses.

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Tshikudi DM, Bernstein CN, Mishra S, Ghia JE, Armstrong HK. Influence of sex in inflammatory bowel diseases. Nature Reviews Gastroenterology and Hepatology 2025 Jun 22; (6):415-437.

 

The incidence rate of IBD has risen in the past decades and has emerged as a global health issue. IBD is characterized by chronic inflammation of the gastrointestinal tract. There is compelling evidence for the role of biological sex in IBD epidemiology, pathophysiology, disease progression, symptoms and extraintestinal diseases. IBD disease course, management and therapies differ between men and women, yet there is a paucity of analysis of sex as a factor. This review discusses the known influence of sex-linked genetic factors, hormones, and hormone receptors in IBD incidence, prevalence, disease burden, and clinical manifestation. Furthermore, we review the mechanisms underlying these sex-dependent effects on the dysregulation of gastrointestinal mucosal immunity (immune, epithelial barrier, and microbiota) in IBD. To support the progressive inclusion of sex in the study of IBD, we summarize the current standard research methodology that should be implemented to investigate sex as a biological variable in IBD studies. Enhanced comprehension of the influence of sex in IBD pathophysiology will advance the development of targeted therapies and improve patient care.

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Marrie RA, Bolton JM, Ling V, Bernstein CN, Krysko K, Li P, McKay L, Pequeno P, Razaz N, Rotstein D, Deakin-Harb K, Maxwell C. Comparing Peripartum Mental Illness Rates in Mothers with Multiple Sclerosis and Other Chronic Diseases in Ontario, Canada. Neurology 2025 Feb 25; 104(4):e210170.

 

Background: Peripartum mood and anxiety disorders constitute the most frequent form of maternal morbidity in the general population but little is known about peripartum mental illness in mothers with multiple sclerosis. We compared the incidence and prevalence of peripartum mental illness among mothers with multiple sclerosis, epilepsy, IBD, diabetes, and women without these conditions.

Methods: We used population-based administrative health data from Ontario, Canada to identify mothers with multiple sclerosis, epilepsy, IBD, diabetes, and without these diseases (controls) with index dates between 2003 and 2018. Using validated definitions, we estimated the incidence (new diagnoses) and prevalence of mental illness (any, depression, anxiety, bipolar disorder, psychosis, substance use, suicide attempt) during the prenatal period, and for three years post-partum. We compared incidence and prevalence estimates between groups using incidence ratios and prevalence ratios with 95% confidence intervals (95%CI). We also compared incidence between groups using Poisson models adjusting for potential confounders. 

Results: We included 894,852 mothers (1,745 multiple sclerosis; 5,954 epilepsy; 4,924 IBD; 13,002 diabetes; 869,227 controls).  At conception, mean (SD) maternal age was 28.6 (5.7) years. One-third of mothers gave birth from 2014 to 2019, and 98.1% of births were singleton births. Any incident mental illness affected 8.4% of mothers with multiple sclerosis prenatally and 14.2% during the first post-partum year; depression and anxiety were the most common incident disorders, and the first post-partum year was a higher risk period than the prenatal period. On multivariable regression mothers with multiple sclerosis had an increased incidence of all disorders except suicide attempt during the prenatal (RR 1.26-4.31) and post-partum periods (RR 1.24-2.92 in first year) compared to control mothers. Any prevalent mental illness affected 42% of mothers with multiple sclerosis prenatally, and 50.3% in the first post-partum year. Mothers with epilepsy, IBD and diabetes also had an increased incidence and prevalence of mental illness compared to control mothers.

Conclusions: Mothers with chronic illnesses, including multiple sclerosis, have an elevated incidence and prevalence of peripartum mental illness compared to controls. Given the adverse effects of peripartum mental illness, these findings emphasize the need for preventive interventions and early treatment of mental illness.

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Keunzig EA, Walters TD, Mack DR, Griffiths AM, Duchen R, Bernstein CN, Kaplan GG Kaplan, Otley AR, El Matary W, Yu W, Wang X, Guan J, Crowley E, Sherlock M, Carman N, Fung SG, Benchimol EI. High healthcare costs in childhood inflammatory bowel disease: Development of a prediction model using linked clinical and health administrative data. Inflammatory Bowel Disease 2025 Apr 10;31(4):1018-1031.

 

Background: The incidence of pediatric-onset inflammatory bowel disease (IBD) and the costs of caring for individuals with IBD are both increasing. We calculated the direct healthcare costs of pediatric IBD in the first year after diagnosis and developed a model to predict children who would have high costs (top 25th percentile).

Methods: Using data from the Canadian Children IBD Network inception cohort (16 years of age or younger, diagnosed between 2013 and 2019) deterministically linked to health administrative data from Ontario, Canada, we estimated direct healthcare and medication costs accrued between 31 and 365 days after diagnosis. Candidate predictors included age at diagnosis, sex, rural/urban residence location, distance to pediatric center, neighborhood income quintile, IBD type, initial therapy, disease activity, diagnostic delay, health services utilization or surgery around diagnosis, regular primary care provider, and receipt of mental health care. Logistic regression with stepwise elimination was used for model building; 5-fold nested cross-validation optimized and improved model accuracy while limiting overfitting.

Results: The mean cost among 487 children with IBD was CA$15168 ± 15305. Initial treatment (anti-tumor necrosis factor therapy, aminosalicylates, or systemic steroids), having a mental health care encounter, undergoing surgery, emergency department visit at diagnosis, sex, and age were predictors of increased costs, while having a regular primary care provider was a predictor of decreased costs. The C-statistic for our model was 0.71.

Conclusions: The cost of caring for children with IBD in the first year after diagnosis is immense and can be predicted based on characteristics at diagnosis. Efforts that mitigate rising costs without compromising quality of care are needed.​

 

 

Shaffer S, Nugent Z, Schaeffer D, Chu J, Bernstein CN. Medication Withdrawal with Normal or Near-Normal Histology in Ulcerative Colitis is Associated with Clinical Relapse. Journal of Clinical Gastroenterology 2025; in press.

 

Introduction: Histologic inflammation has been shown to be a predictor of worse clinical outcomes in persons with ulcerative colitis. Some people with ulcerative colitis can develop completely normal colon biopsies without acute or even chronic changes. It is felt that achieving normal, or near-normal histology in ulcerative colitis, is associated with improved clinical outcomes along with a likely decreased risk of dysplasia. We sought to understand the clinical course and risk of dysplasia in persons with ulcerative colitis who achieve near or complete normalization of histology.
Methods: We performed a retrospective chart review in a single centre in Winnipeg, Canada. We identified patients in complete endoscopic remission with a normal pathology report (no changes of acute or chronic inflammation). Slides were sent to a gastroenterology-expert pathologist to score the slides and report them using the Geboes score, evaluating the right and left colon separately. The primary outcome was rate of clinical relapse from the index colonoscopy until the date of last follow-up. Secondary outcomes included events of low- or high-grade dysplasia, colon cancer, and colectomy. Continuous variables were analyzed using means and T-test, Fisher’s Exact test was used for 2x2 tables. Survival analysis was performed using proportional hazards regression model.

Results: There were 78 persons included in the study. Approximately one-fifth of persons had clinical relapse in follow-up. Only 2 people in this cohort had completely normal pathology in both the right and left colon after reassessment by a gastroenterologist-expert pathologist. Mean time to clinical relapse was 4.7 years (standard deviation 3.1 years). All persons with clinical relapse had chronic inactive disease in the left colon. There were no predictors of clinical relapse regarding right colon pathology. Persons who withdrew off therapy were nearly 5 times more likely to clinically relapse than those who remained on IBD-therapy (HR 4.89, 95%CI 1.32-18.08). There were zero episodes of dysplasia or colon cancer in follow-up. There were two episodes of colectomy due to medically-refractory disease both who had normal right sided pathology and chronic inactive disease in the left colon.

Conclusion: We found that histologic near-normalization as defined by Geboes score, is associated with no risk for dysplasia over a mean of 7.3 years. Hence surveillance colonoscopy intervals can be lengthened in persons with such histology. Persons with ulcerative colitis who achieve normal or near-normal histology have moderate rates of clinical relapse, and physicians should be cautious when considering withdrawing their therapy.

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Anand R, George AT, Rubin DT, Spiegel BMR, Bernstein CN. The Role of Virtual Reality in Managing Inflammatory Bowel Disease: A Novel Approach to Bridging Mental and Physical Health. Journal of Canadian Association of Gastroenterology 2025 Feb 21;8(Suppl 2):S15-S20.

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IBD encompassing Crohn’s disease and ulcerative colitis, is characterized by symptoms such as fatigue, abdominal pain, and diarrhea, which may persist even when inflammation is controlled. These symptoms are further exacerbated by psychological stress, which may complicate disease management that involves the gut-brain axis—a bidirectional communication pathway linking the gastrointestinal system and the central nervous system. While stress, anxiety, and depression are prevalent among patients with IBD, access to comprehensive mental health care is often limited, particularly in rural and underserved areas. Virtual reality has emerged as a promising tool in managing psychological comorbidities and enhancing the overall care of patients with IBD.

This review explores the potential of virtual reality interventions for pain and anxiety management in patients with IBD. Virtual reality also shows promise in patient education and as a tool for mental health interventions, providing immersive environments for relaxation and mindfulness. The integration of virtual reality in IBD care offers a novel, accessible approach to addressing both physical and mental health challenges, potentially improving quality of life and clinical outcomes for IBD patients. Further research is warranted to evaluate the long-term benefits and broader applicability of virtual reality-based interventions in diverse patient populations.

 

 

Lee SH, Turpin W, Espin-Garcia O, Xu W, Croitoru K; Crohn's and Colitis Canada-Genetic, Environmental, Microbial (CCC-GEM) Project Research Consortium. Development and Validation of an Integrative Risk Score for Future Risk of Crohn's Disease in Healthy First-Degree Relatives: A Multicenter Prospective Cohort Study. Gastroenterology 2025 Jan;168(1):150-153.

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Background: Although the cause of Crohn’s disease is unknown, recent studies have identified a number of biomarkers associated with the risk of developing Crohn’s disease in healthy at-risk individuals. Establishing a combined prediction model that accurately stratifies healthy at-risk individuals’ future risk of Crohn’s disease is the first step towards disease prevention and will advance our understanding of pathogenesis.

Methods: We recruited healthy first-degree relatives of patients with Crohn’s disease from 2008-2017 as part of the global multicenter Crohn’s and Colitis Canada Genetic Environmental Microbial (CCC-GEM) Project. After collecting demographic information, blood, urine, and stool samples at recruitment, participants were followed prospectively for the development of Crohn’s disease. A GEM-integrative risk score (GEM-IRS), using random survival forest modeling that combined the baseline variables (demographics, measures of gut inflammation, intestinal barrier function, and fecal microbiome composition) to estimate time-to- Crohn’s disease onset, was derived and subsequently validated in two independently ascertained testing cohorts.

Findings: Of 2,619 first-degree relatives followed for a median of 6.8 years, 61 (2.3%) developed Crohn’s disease. The GEM-IRS, developed on the training cohort, had a predictive performance (concordance index) of 0.789 and a hazard ratio of 2.69 per SD increase (95% CI 2.06-3.53) for development of Crohn’s disease in the pooled-testing cohorts. Furthermore, the GEM-IRS predicted Crohn’s disease in pre-specified subgroups of first-degree relatives with minimal subclinical inflammation or normal barrier function measures, and up to 7 years before diagnosis in the pooled-testing cohorts.

Interpretation: The GEM-IRS, includes biomarkers of gut inflammation, intestinal barrier function, and the gut microbiome, is a valid risk stratification tool for predicting future development of CD in healthy FDR population. The score may be used to guide preventative care for the healthy FDR population.

 

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