​Wang Y, Wu Y, González-Domínguez NP, Boruff JT, Levis B, Cuijpers P, Gilbody S, Harel D, Ioannidis JPA, Markham S, Patten SB, Vigod SN, Ziegelstein RC, Benedetti A, Thombs BD, and the DEPRESsion Screening Data (DEPRESSD) PHQ Collaboration (member of group authorship). Minimal Detectable Change of the Patient Health Questionnaire-9 (PHQ-9), Patient Health Questionnaire-8 (PHQ-8), and Patient Health Questionnaire-2 (PHQ-2): Individual Patient Data Meta-Analysis. British Medical Journal 2026; 2026 Jul 23:394:e100119.

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Objective: To estimate the minimal detectable change (MDC) for the Patient Health Questionnaire-9 (PHQ-9) and its eight item (PHQ-8) and two item (PHQ-2) versions including differences by participant and study characteristics.

Design: Individual participant data meta-analysis.

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Data sources: Medline, Medline In-Process and other non-indexed citations, PsycInfo, and Web of Science, 1 January 2000 to 9 May 2018.

Eligibility criteria for selecting studies: Datasets from articles in any language if participants were aged ≥18 years, were recruited from any non-psychiatric setting, and were not recruited because they were seeking mental healthcare. Eligible datasets had a classification for major depressive disorder or major depressive episode based on a validated semi-structured or fully structured interview conducted within two weeks of administering the PHQ-9, PHQ-8, or PHQ-2.

Results: Pooled MDCs across studies were estimated for the PHQ-9, PHQ-8, and PHQ-2 with random effects meta-analysis for 95% (MDC95), 90% (MDC90), and 67% (MDC67) confidence that change beyond measurement error occurred. PHQ-9, PHQ-8, and PHQ-2 analyses included 42 548 participants (94 studies), 42 592 participants (94 studies), and 44 085 participants (98 studies), respectively. Mean participant age was 49 years (standard deviation 17), and 60% of participants were women. Overall, 10% of participants had major depression (range 1-57% across studies). MDC95 was 5.72 points (95% confidence interval (CI) 5.54 to 5.90, 95% prediction interval (PI) 4.00 to 7.44) for the PHQ-9, 5.51 points (95% CI 5.33 to 5.68, 95% PI 3.87 to 7.15) for the PHQ-8, and 2.26 points (95% CI 2.15 to 2.37, 95% PI 1.20 to 3.32) for the PHQ-2. For the PHQ-9, MDC95 was highest in inpatient healthcare settings at 6.48 (95% CI 6.05 to 6.92) points. MDC95 for the PHQ-9 increased by 0.40 (95% CI 0.25 to 0.55) points for each 10% increase in the proportion of participants with major depression. Sex and age had minimal or no association. Subgroup and meta-regression findings were similar for the PHQ-8 and PHQ-2.

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Conclusions: Based on the pooled estimate, a six point difference on the PHQ-9, the PHQ version most used in clinical practice, could be an appropriate MDC threshold in general practice. A higher threshold may be preferred in specialty mental healthcare. MDC67 or MDC90 thresholds would provide less certainty that change has occurred. Alternative strategies, such as using the upper end of a prediction interval, would provide more certainty but a greater likelihood of not recognising change.

 

 

Xue M, McSHane C, Kim J, Khorasaniha R, Leibovitzh H, Shao J, Chen R, Jeong S, Li Q,. Madsen KL, Griffiths AM, Walters TD, Steinhart AH, Dieleman LA, Huynh HQ, Panaccione R, Aumais GL, Bitton A, Mack D, Jacobson K, Bressler B, Marshall JK, Plotkin L, Focht G, Bernstein CN, El-Matary W, Hyams JS, Otley A, Lee SH, Turner D, Armstrong H, Croitoru K, CCC-GEM consortium, Turpin W. β-Glucan and Inulin Estimated Intake are Associated with Reduced Risk of Crohn’s Disease, Improved Gut Barrier and Systemic Inflammation Markers, and Multi-Omic Signatures in a High-Risk Cohort.  Gastroenterology 2026; Oct;171(4):641-655. 

 

Background & aims: The cause of Crohn's disease (CD) remains unclear; however, evidence suggests fiber intake may play a role. We aimed to investigate the association between intake of total fiber and select fermentable fiber subtypes and future risk of CD in an at-risk population.

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Methods: The Genetic, Environmental, Microbial Project prospectively followed asymptomatic first-degree relatives of individuals with CD. Habitual intake of total fiber and select fiber subtypes was estimated from baseline food frequency questionnaires and biologic samples were collected. Incident CD was confirmed during follow-up. Cox proportional hazards models estimated hazard ratios (HRs) for CD. Associations between fiber subtype intake and urinary fractional excretion of lactulose-mannitol ratio, C-reactive protein, gut microbiota (16S ribosomal RNA sequencing), and serum proteomics (Olink) were evaluated using multivariable regression models.

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Results: During a median follow-up of 8.5 years of 3314 first-degree relatives, 94 developed CD. Higher β-glucan (HR, 0.70; 95% confidence interval, 0.54-0.92) and inulin (HR, 0.68; 95% confidence interval, 0.49-0.96) intake were associated with lower CD risk. Associations were strongest in those with higher baseline relative abundance of Erysipelotrichaceae UCG-003, but weaker with higher Colidextribacter. Higher β-glucan and inulin intake were associated with lower lactulose-mannitol ratio, lower abundance of pathobionts (Ruminococcus torques and Lachnoclostridium), and lower concentrations of inflammation- and barrier-related proteins, including C-reactive protein, triggering receptor expressed on myeloid cells-1, oncostatin M, and matrix metalloproteinase.

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Conclusions: Higher estimated β-glucan and inulin intake was associated with preserved gut barrier function, lower systemic inflammatory markers, and lower CD risk, which was modified by the microbial context. These findings support microbiome-informed dietary strategies and intervention trials for CD prevention.

 

 

Hitchon CA, Bernstein CN, Bolton JM, Dolovich C, El-Gabalawy R, Graff LA, Lix LM, Marriott JJ, Fisk JD, Marrie R.  Impact of depression and anxiety on health-related quality of life changes over time within individuals with rheumatoid arthritis or inflammatory bowel disease: A prospective Canadian cohort study. PLoS One 2026; May 28;21(5):e0349140.

 

Objectives: In individuals with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or primary depressive or anxiety disorders without RA or IBD (DEP/ANX) we aimed to evaluate between-person and within-person changes in physical and mental health-related quality of life (HRQoL) over time. We also aimed to compare the impacts of depression and anxiety symptoms on HRQoL, and to examine the roles of physical and cognitive functioning, fatigue, physical comorbidities, and disease activity, on HRQoL over time.

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Methods: As part of a single centre prospective cohort study, individuals with RA (n = 154), IBD (n = 247), or DEP/ANX (n = 306) recruited between November 2014 and July 2016 were seen annually for 3 years. Participants reported symptoms of depression and anxiety (Hospital Anxiety and Depression Scale), fatigue (Daily Fatigue Impact Scale), HRQoL (RAND-36), and completed functional assessments (physical: nine-hole peg test, timed 25-foot walk test; cognition: Symbol Digit Modalities Test). Generalized linear models with generalized estimating equations tested between-person and within-person associations of depression and anxiety with HRQoL in covariate-adjusted models that included socio-demographic characteristics, health status and medication use. Physical (PCS-36) and mental (MCS-36) HRQoL were assessed separately and comparatively for RA, IBD and DEP/ANX.

 

Results: RA participants were older than IBD or DEP/ANX participants [mean age = 59.49(11.66), 47.45(14.80), 43.87(12.94)]. Most participants (>85%) reported meaningful changes in HRQoL. After adjustment, within-person increased depressive and anxiety symptoms were associated with reduced MCS-36 [depression: -7.91 (-9.45, -6.36), anxiety: -5.62 (-6.85, -4.39)]. Increased fatigue and worse cognition were associated with reduced PCS-36 [-0.33 (-0.38, -0.28); -0.31 (-0.64, 0.022)]. After adjustment, increased physical function, IBD or DEP/ANX diagnosis were associated with higher PCS-36 [1.47 (0.63, 2.30); 2.84 (1.60, 4.08); 5.23 (3.92, 6.55)].

 

Conclusions: Variations in depression, anxiety, fatigue, cognition, and physical function are associated with HRQoL fluctuations in people with RA, IBD and DEP/ANX, highlighting the importance of addressing these issues while treating disease.

 

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Bernstein CN, Kaplan GG, Nugent Z, Ahuja V, Ananthakrishnan AN, Banerjee R, Burisch J, Chen Y, Epstein D, Forbes AJ, Gonczi L , Gu YB, Gunawan J, Hang DV, Kaibullayeva J, Kopylov U, Kotze PG, Iade B, Lakatos PL, Limsrivilai J, Liang J, Mak WYJ, Ng S, Severs M, Shen J, Sood A, Yamamoto-Furusho JK, Yuan S, Wewer MD, Wu K, Windsor JW Gearry RB, and the Globalization Cluster of the International Organization for the Study of IBD.  Inflammatory Bowel Disease Phenotypes in Diverse Populations: A Global Comparative Analysis. Journal of Crohn's and Colitis 2026; May 8;20(5):jjag051.

 

Background: The aim of this study was to determine if Crohn's disease (CD) and ulcerative colitis (UC) manifest similarly in different parts of the world.

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Methods: Investigators of cohort studies from around the world were contacted to provide the most recent data from their CD and UC cohorts. Each cohort provided summated and averaged data on pre-specified variables. The Montreal Classification was used for phenotype assessment. Age at diagnosis was stratified into less than 17 years, 17-39 years, and >39 years. Disease location for CD was stratified as ileum only, colon only, ileocolon, upper gastrointestinal and proximal small bowel disease, and perineal penetrating disease. Disease behavior for CD was stratified into inflammatory disease, stricturing disease, and penetrating disease. Location for UC was stratified into proctitis, left-sided colitis, and extensive including subtotal and pancolitis. Reports were classified geographically as Asia, Latin America, South Africa, and "Western" (ie, North America, Europe, and Oceania). These categories were collapsed to "Western" and "non-Western" for analyses.

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Results: Data from 54 868 patients with IBD were included. For CD, data were available from nine Western cohorts, 12 Asian cohorts, three Latin American cohorts, and one African cohort. For UC, eight Western cohorts were compared with 11 Asian cohorts, three Latin cohorts, and one African cohort. The demographic and phenotypic distribution for CD and UC in comparisons between Western and non-Western countries were no different. Western cohorts had longer disease durations than non-Western cohorts.

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Conclusion: No significant differences were seen in any phenotypic data between the cohorts, suggesting that IBD is similar worldwide.

 

 

Figley T, Kornelsen J, Uddin N, Wong K, Pirzada S, Carter S, Helmick C, O'Grady C, Mazerolle E, Patel R, Bernstein CN, Fisk J, Marrie RA, Figley C.  White matter damage in multiple sclerosis disproportionately targets default mode, executive control, and salience networks. Journal of Neuroscience 2026; Jun 3;46(22):e0278252026.                             

Multiple sclerosis (MS) and several other neurodegenerative disorders affect structurally and functionally connected brain networks. However, the extent of structural damage within specific networks relative to global white matter has not been systematically explored in MS. The aims of this study were therefore to investigate white matter within six brain networks-i.e., dorsal/ventral default mode, left/right executive control, and anterior/posterior salience networks-to (1) determine whether MS white matter lesions are disproportionately prevalent in these regions compared with global white matter; (2) quantify microstructural degradation in these regions among persons with MS (pwMS) compared with healthy controls (HCs); and (3) ascertain whether network degradation is larger than expected compared with global white matter differences between pwMS and HCs. White matter lesion maps, global white matter masks, and whole-brain diffusion MRI maps of mean diffusivity from 104 pwMS (48 ± 12 years; 85 female) and 100 HCs (39 ± 16; 65 female) were analyzed using the UManitoba-JHU Functionally-Defined Human White Matter Atlases. Statistical analyses included parametric t tests and post hoc nonparametric Wilcoxon tests. Among pwMS, 4/6 white matter networks contained disproportionately high lesion volumes (p < 0.008). All six networks exhibited lower microstructure among pwMS compared with HCs (p < 0.008); and even after controlling for subject-specific global white matter values, 5/6 white matter networks exhibited disproportionately reduced tissue microstructure among pwMS compared with HCs (p < 0.008). These findings suggest that MS disproportionately affects white matter structural connections underlying specific intrinsic brain networks, including the default mode, executive control, and salience networks.

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Leibovitzh H, Neustaeter A, Lee SH, Xue M, Espin-Garcia O, Olivera PA,. Huynh HQ, Griffiths AM, Turner D, Madsen KL, Silverberg MS, Steinhart AH, Mack DR, Jacobson K, Moayyedi P, Aumais G, Bernstein CN, Marshall JK, Panaccione R, Xu W, the CCC GEM Project Research Consortium, Turpin W, Croitoru K.  Association of IL-23 receptor genetic variants with risk of Crohn’s disease and gut microbiome and intestinal permeability in a cohort of healthy first-degree relatives of subjects with Crohn’s disease. Clinical Gastroenterology and Hepatology 2026; in press.

 

Background & aims: Single nucleotide polymorphisms in the interleukin23 receptor gene are associated with Crohn's disease, suggesting a role in pathogenesis, and several biologic agents targeting this pathway are now established therapies. Interleukin23 has been suggested to be involved in regulation of intestinal barrier function and may impact gut microbial composition. We investigated whether interleukin23 receptor genetic variants predict Crohn's disease risk and influence gut barrier function and microbiome composition in healthy first-degree relatives.

Methods: A total of 3055 healthy first-degree relatives with genotypic data from the Crohn's and Colitis Canada Genetic, Environmental, Microbial (CCC-GEM) cohort were included. A weighted interleukin23 receptor genetic risk score was generated from 7 Crohn's disease-associated interleukin23 receptor single nucleotide polymorphisms and dichotomized as high (top quintile) vs low interleukin23 receptor genetic risk score. A subset of this cohort was assessed for intestinal permeability (n = 1698) and microbiome profiling (n = 2523). Cox proportional hazards models evaluated Crohn's disease onset risk.

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Results: High interleukin23 receptor genetic risk score was associated with increased Crohn's disease risk (hazard ratio, 1.67; 95% confidence interval, 1.01-2.75; P = .044). This association remained significant after adjusting for fecal calprotectin, indicating genetic risk independent of subclinical inflammation. High interleukin23 receptor genetic risk score was not associated with intestinal permeability (P = .84) but was associated with differences in 15 genera, including decreased Faecalibacterium and increased Akkermansia (q < 0.1).

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Conclusions: High interleukin23 receptor genetic risk score was associated with increased Crohn's disease risk in healthy first-degree relatives and was associated with microbial differences, but not with intestinal permeability. These findings suggest potential clinical applications for interleukin23 receptor genetic risk score in identifying high-risk individuals who may benefit from closer monitoring or future interleukin23 pathway-targeted preventive interventions.

 

 

McIver TA, Bernstein CN, Marrie RA, Fisk JD, Figley C and Kornelsen J. Physical, cognitive, and psychosocial fatigue are differently related to cortical complexity of superior temporal and frontal brain regions in Crohn’s disease. Frontiers in Neuroimaging 2026; 5:1814006.

 

Introduction: Fatigue is common in persons with Crohn's disease, negatively impacting quality of life in both active and remitted disease state. Neural correlates of fatigue in Crohn's disease are understudied, particularly relative to the separate impacts of physical, cognitive, and psychosocial fatigue. The potential moderating role of cortical complexity on the relationship between disease activity and fatigue has yet to be examined.

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Methods: Forty-nine participants with Crohn's disease and 49 healthy control participants completed the Fatigue Impact Scale (which includes physical, cognitive, and psychosocial subscales) and whole-brain T1-weighted magnetic resonance imaging. Cortical complexity analyses were performed in CAT12, including within- and between-group analyses.

 

Results: In the Crohn's disease group, greater fatigue across all domains was associated with lower cortical complexity in the right superior temporal gyrus. Physical and cognitive impacts of fatigue were differently related to cortical complexity in the superior frontal and supramarginal gyri. Cortical complexity in the healthy control group was exclusively, positively, related to the physical impact of fatigue. The relationship between disease activity and fatigue varied relative to cortical complexity in the right superior temporal gyrus (ΔR2 = 0.062, F = 5.558, p = 0.023) and the right superior frontal gyrus (ΔR2 = 0.058, F = 4.059, p = 0.050).

 

Discussion: The present findings expand our understanding of the complex brain-gut interactions linking disease activity and fatigue in Crohn's disease relative to underlying differences in cortical complexity.

 

 

Tsai W, Zhu F, Bar-Or A, Bernstein CN, Bonner C, Graham M, Marrie RA, Mirza A, O’Mahoney J, Yeh EA, Banwell B, Waubant E, Tremlett H on behalf of the Canadian Pediatric Demyelinating Disease Network. The gut microbiome in pediatric-onset acquired demyelinating syndromes by myelin oligodendrocyte glycoprotein antibody status. Multiple Sclerosis and Related Disorders 2026; Jun;110:107216.         

 

Background: Alterations of the gut microbiome have been reported in central nervous system demyelinating diseases. While the gut microbiome in pediatric multiple sclerosis (MS) has been studied, the role of the gut microbiome in other pediatric-onset acquired demyelinating syndromes (ADS) remains unknown. We compared the gut microbiome composition between myelin oligodendrocyte glycoprotein antibody-positive (MOG+) and antibody-negative (MOG-) participants with pediatric-onset ADS.

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Methods: Participants aged ≤21 years enrolled in the Canadian Pediatric Demyelinating Disease Network microbiome study (2015-2018) with a single episode or relapsing non-MS, non-neuromyelitis optica spectrum disease attacks of demyelination with symptom onset <18 years were included. Stool sample-derived DNA underwent 16S rRNA (V4) sequencing. Serum MOG-IgG antibodies were tested within 30 days of first attack onset. Alpha-diversity (Shannon, Margalef's index, Chao1) and beta-diversity (weighted UniFrac) were analysed. Phylum/genus-level taxa were assessed using negative binomial models with false discovery rate correction. Rate ratios were sex- and age-adjusted (aRR).

 

Results: Forty-six participants (18 MOG+/28 MOG-) were included. Mean age at stool sample collection (MOG+/MOG-) was 14.7/17.2 years. Alpha-/beta-diversities did not differ between MOG+/MOG- participants (p > 0.3). At the phylum level, the relative abundance of Proteobacteria was lower in MOG+ than MOG- participants (aRR:0.22;95%CI:0.07-0.69;q = 0.03). At the genus level, the relative abundance of Escherichia/Shigella was lower in MOG+ than MOG- participants (aRR:0.01;95%CI:0.001-0.07;q = 0.001).

 

Conclusions: While alpha/beta-diversities did not differ between MOG+/MOG- participants, taxa-level differences were observed. Our findings suggest that the gut microbiome composition may differ by MOG serostatus among pediatric-onset ADS participants. Future work is warranted, utilizing larger cohorts and longitudinal follow-up.

 

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Machado P, Mazahery H, Black LJ, Tremlett H, Daly A, Pham NM, Tessema GA, Zhu F, Banwell B, Bar-Or A, Marrie RA, Bernstein CN, Mirza AI, Yeh EA, Waubant E, O’Mahony J, Dunlop E on behalf of the Canadian Demyelinating Disease Network Higher ultra-processed food consumption is associated with higher likelihood of paediatric-onset multiple sclerosis. Multiple Sclerosis and Related Diseases 2026 May:109:107159.

 

Background: Diets are increasingly dominated by ultra-processed foods, which have been linked to several chronic diseases. Emerging evidence suggests an association between ultra-processed food consumption and inflammatory diseases, including multiple sclerosis (MS).

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Objective: To assess associations between consumption of ultra-processed foods and paediatric-onset MS (PoMS).

Methods: We used data from the microbiome sub-study of the Canadian Pediatric Demyelinating Disease Network Study for PoMS cases (symptom onset aged <18 years) and unaffected controls. Data on consumption of ultra-processed foods (defined within the Nova system) were derived from dietary intake data collected using the Block Kids Food Screener. Dietary contribution of ultra-processed foods (% of total grams consumed per day) was estimated. Logistic regression models were used to examine associations between ultra-processed food consumption (continuous and tertiles) and likelihood of PoMS. Models were adjusted for age at dietary data collection, sex, race, region of residence, and total energy intake.

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Results: Dietary data were collected from PoMS participants (females=57, males=23) aged 5-28 years and controls (females=30, males=16) aged 8-26 years. Each additional 10% in ultra-processed food consumption was associated with a 35% higher odds of being a PoMS participant (adjusted odds ratio [aOR]=1.35, 95% CI 1.05, 1.73). Participants in the highest (versus lowest) tertile for ultra-processed food consumption had over five times higher odds of being a PoMS participant (aOR=5.30, 95% CI 1.36, 20.70).

 

​Conclusion: Participants with PoMS reported greater consumption of ultra-processed foods compared to unaffected peers. More comprehensive longitudinal dietary histories are required to better understand this observation.

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Semaganda A, Kahia N, Oo MM, Rozenberg D, Nuhu F, Jahan N, Mulhall F, Downing K, Sandberg B, Elands H, Groff R, Altman AD, Robinson C, Keynan Y, Bernstein CN, Poliquin V, Arsenio J, McKinnon LR. Enumeration, Phenotyping, and Clinical Associations of Tissue-Resident T Cells in the Ecto- and Endocervix of Women Attending a Colposcopy Clinic. American Journal of Reproductive Immunology 2026 Mar; 95(3):e70222

 

Problem: Tissue-resident memory (TRM) cells represent important immune sentinels that mount rapid recall responses to pathogens and cancers. However, there are limited data in humans on genital tract TRM collected by clinically feasible sampling methods, limiting a full understanding of their role in immunity and clinical disease.

Method of study: We used flow cytometry and single cell RNA sequencing (scRNAseq) to characterize T cells isolated from ectocervical biopsies and endocervical cytobrushes collected from women attending a colposcopy clinic in Winnipeg, Canada.

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Results: The ectocervix generally contained a higher frequency and abundance of immune cells and T-cells compared to the endocervix. CD4+ and CD8+ TRM were more approximately 5-times more frequent and abundant in the ecto- compared to endocervix, even after accounting for higher T-cell recovery from the ectocervix. Phenotypically, CD4+ TRM showed higher Th17- and comparable regulatory-associated marker expression compared to non-TRM in both the ecto- and endocervix. Cervical dysplasia and ectropion were both associated with several immune cell differences in the ecto- and endocervix including lower CD4+ TRM. Single-cell RNAseq analyses confirmed broad CD69 and core TRM-related gene expression and captured several heterogeneous CD4+ and CD8+ TRM subsets with diverse gene expression and pathways associated with host immunity, homeostasis, and nonimmune cell interactions.

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Conclusions: Our data suggest that TRM are more abundant in ecto- versus endocervical samples, which may reflect differences in commonly used sampling methods. Location and heterogeneous expression profiles underscore the need to better understand their role in microbial interactions, inflammation, and genital infection susceptibility in women.

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Fomenko A, Fischer FH, Marrie RA, Recklitis CJ, Bernstein CN, Hitchon CA, Dawson S, Dümmler D, Hapfelmeier A, Linde K, Schneider A. The screening accuracy of the PROMIS Anxiety measures in adults – A systematic review and multiple-thresholds meta-analysis. Journal of Psychosomatic Research 2026; Mar 2; 205:112611.

 

Aims: To assess the test accuracy of PROMIS® Anxiety measures for screening any anxiety disorder (AAD) and generalised anxiety disorder (GAD), and how it varies by cut-offs.

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Methods: We searched the electronic databases from inception until 15 July 2025 (Embase, MEDLINE, PubMed-not-MEDLINE-subset, PsycINFO). We included test accuracy studies using any PROMIS® anxiety measure and (semi-)structured interviews in adults, and assessed the study quality with the QUADAS-2 instrument. We applied a multiple thresholds model to estimate the summary sensitivities and specificities across cut-offs and the area under the curve (AUC)

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Results: Six studies, each on a different disease, met the inclusion criteria, with a total of 1121 participants. For PROMIS® Short Form-(SF)-Anxiety(A)-8a, we found five studies, two for PROMIS®-CAT-A and one for PROMIS®-SF-A-7a. Meta-analyses for screening AAD and GAD were performed only for PROMIS®-SF-A-8a, identifying the maximised sum of sensitivity and specificity at T-score cut-offs 55.4 and 58.4, respectively. At these cut-offs, summary sensitivity and specificity were 0.76 (95% CI 0.71 to 0.80) and 0.74 (95% CI 0.70 to 0.78) for AAD, and 0.75 (95% CI 0.69 to 0.81) and 0.79 (95% CI 0.77 to 0.80) for GAD. Corresponding AUCs were 0.81 (95% CI 0.79 to 0.84) and 0.84 (95% CI 0.82 to 0.85). Only minor between-study heterogeneity was found.

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Conclusions: The PROMIS®-SF-A-8a results were homogeneous, showing good screening accuracy. However, the limited number of studies - especially for other PROMIS® Anxiety measures - and the lack of replication in settings like primary care highlight the need for further research.

 

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Coward S, Brunet-Mas E, Burisch J, Lakatos PL, Loftus EV Jr, Kaplan GG; Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21 Consortia); (member of group authorship).  Forecasting the incidence and prevalence of inflammatory bowel disease across nine epidemiologic stage 3 nations. Gastroenterology 2026; Jul;171(1):154-157.

 

In this large, contemporary epidemiologic study integrating data from nine distinct stage 3 regions worldwide, a novel Bayesian approach  was applied to aggregate and forecast IBD incidence and prevalence through the first third of the 21st century. Although incidence remains stable, prevalence continues to rise, and the growing proportion of older adults living with IBD is expected to place increasing strain on healthcare systems striving to deliver affordable, accessible, and high-quality care.

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Marrie RA, Maxwell C, Bolton J, Soderling J, Bernstein CN, Krysko K, Mckay K, Rotstein D, Deakin-Harb K, Razzaz N. Incident and Prevalent Peripartum Mental Illness in Mothers with Multiple Sclerosis and Other Chronic Diseases in Sweden Multiple Sclerosis and Related Disorders. Multiple Sclerosis and Related Disorders 2026; Mar; 107: 107041.

 

Background: Findings conflict regarding the risk of peripartum mental illness in women with multiple sclerosis (MS) and how this compares to the risk among women with other chronic diseases. We compared the incidence and prevalence of peripartum mental illness among women with MS, epilepsy, inflammatory bowel disease (IBD), diabetes, and women without any of these diseases (comparators).

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Methods: Using population-based Swedish administrative health data we selected women with MS, epilepsy, IBD, diabetes, and comparators who had deliveries between 2002 and 2019. Using validated case definitions for peripartum mental illness we estimated the incidence and prevalence of mental illness during the period encompassing pregnancy and the first post-partum year. We compared incidence and prevalence between cohorts using crude estimates and unadjusted Poisson regression.

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Results: We included 1096,814 women (1936 MS; 7709 epilepsy; 7731 IBD; 7182 diabetes; 1072,256 comparators). Mean (SD) age at conception was 30.1 (5.1) years. Compared to comparators, mothers with MS had a higher incidence of any mental illness (incidence rate ratio [IRR] 1.36; 1.04-1.78), as did mothers with epilepsy (1.78; 1.58-2.00), IBD (1.46; 1.28-1.66) and diabetes (1.61; 1.41-1.83). Mothers with MS, epilepsy, IBD and diabetes also had a higher incidence and prevalence of depression and bipolar disorder than comparators. Mothers with epilepsy had higher incidence rates of anxiety, and higher prevalence ratios of any mental illness and anxiety than mothers with MS.

 

Conclusions: Women with MS, epilepsy, IBD and diabetes have a similarly elevated incidence and prevalence of peripartum mental illness as compared to mothers without these conditions.

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Fomenko A, Marrie RA, Dummler D, Bernstein CN, Hitchon XA, Tully PT, Dawson S, Schneider A, Hapfelmeier A, Lind K. Test accuracy of the Overall Anxiety Severity and Impairment Scale (OASIS) for screening anxiety in a systematic review and multiple-thresholds meta-analysis. Journal of Affective Disorders 2026; May 1;400:121126.

 

Background: Given the high prevalence of anxiety disorders and their frequent under-recognition, the use of questionnaires for screening anxiety is under debate.

Objective: To evaluate the test accuracy across cut-offs of the Overall Anxiety Severity and Impairment Scale (OASIS) against (semi-)structured interviews for screening any anxiety disorder (AAD) and generalised anxiety disorder (GAD) in adults.

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Methods: We searched Embase, MEDLINE, PubMed-not-MEDLINE subset and PsycINFO up to 15 July 2025. We assessed the internal and external validity using the QUADAS-2-tool. We used the multiple thresholds model to estimate summary sensitivity and specificity across cut-offs, the area under the curve (AUC), and the cut-offs that maximised the Youden-Index.

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Results: We included four studies with 736 participants, all having specific chronic somatic conditions. For the recommended cut-off ≥8, we estimated a summary sensitivity of 0.44 (95% CI 0.27 to 0.63) and a summary specificity of 0.89 (95% CI 0.81 to 0.94) for AAD and a summary sensitivity of 0.58 (95% CI 0.40 to 0.74) and a summary specificity of 0.87 (95% CI 0.79 to 0.93) for GAD. The Youden-Index was maximised at cut-off ≥5 and ≥ 6 in terms of AAD and GAD, respectively. We estimated an AUC of 0.77 (95% CI 0.74 to 0.79) for AAD and 0.81 (95% CI 0.77 to 0.84) for GAD.

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Conclusions: Only a few studies have examined the accuracy of the OASIS in a screening approach, all conducted in populations with somatic diseases. The AUC is comparable to other anxiety questionnaires. The recommended cut-off needs reconsideration.

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O’Mahony SL, Tollenaar SI, Khorasaniha R, Jovel J, Ba I,  Voisin A, Miller R, Olof H, Mahmood R, Marrie RA, Strachan E, Soares LP, Cheng C, Janveaux J, Azaidi D, Bernstein CN, Bonner C, Bar-Or A, Waubant E, Yeh A, Graham M. Arnold DL, Banwell BL, Zhu F, Mirza AI, Karimi-Abdolrezaee S, Tsai S, Tremlett H, McGregor K, Willing BP, Armstrong HK. Reduced fibre-fermenting capacity of gut microbes in multiple sclerosis may result in prebiotic dietary fibre β-fructan promoting inflammation and CNS damage. Gastroenterology 2026; e100296.

 

Background Some people with multiple sclerosis display changes in their gut microbiota with separate evidence suggesting worsened symptoms following a high-fibre diet. We hypothesised that in people with multiple sclerosis whose gut microbiota are less able to adequately ferment fibres, unfermented β-fructans induce inflammation.

Methods Diet data (n=48 multiple sclerosis, n=78 unaffected controls) and stool microbiome data (n=31 multiple sclerosis, n=61 unaffected controls) were previously collected from participants. Daily fibre subtype intakes were calculated and compared with fecal shotgun metagenomic sequencing in pediatric onset multiple sclerosis and unaffected persons. Response to unfermented β-fructans was examined in a germ-free experimental autoimmune encephalomyelitis mouse model (unable to ferment fibres). Mice were fed β-fructans or control fibre diet beginning at symptom onset (day 14). Experimental autoimmune encephalomyelitis scores and weights were recorded daily. Intestinal and central nervous system tissues were collected at two endpoints to examine inflammatory responses and demyelinating lesions.

Results Paediatric onset multiple sclerosis consumed less β-fructans (2.4 g/day±0.3 SD; p<0.05) than unaffected participants (3.6 g/day±0.4), which coincided with differences in the gut microbiota including lower fibre fermenting enzymes. Mice exposed to unfermented β-fructans sustained worsened EAE symptoms (day 20–28; p<0.05), immune activation in the gut and immune activation plus demyelinating lesions in the spinal cord compared with mice on control diet.

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Conclusions  The gut microbiota of pediatric-onset multiple sclerosis had lower fibre fermenting properties, and our animal findings suggest that β-fructans induce worsened demyelination and gut–brain axis immune activation. Lower β-fructan consumption was observed among participants with pediatric-onset multiple sclerosis. Future longitudinal studies are warranted to confirm the findings uncovered in this manuscript.

 

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Bernstein CN, Nugent Z, Panaccione R, Marshall DA, Kaplan GG, Vanner S, Dieleman LA, Graff LA, Otley A, Jones J, Buresi M, Murthy S, Bargaonkar M, Bressler B, Bitton A, Croitoru KC, Sidani S, Fernandes A, Moayyedi P. Patient reported symptoms are independent of extent of disease in longstanding ulcerative colitis: MAGIC in IMAGINE. Journal of Clinical Gastroenterology 2026; May-Jun 01;60(5):442-448. 

 

Background: The Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects Strategy for Patient Oriented Research Network (IMAGINE) has conducted a 5-year multicenter prospective observational cohort study, Mind And Gut Interactions Cohort (MAGIC) in 14 centers across Canada from 2018 to 2022. Herein, we investigated the relationship between ulcerative colitis (UC) phenotypes, demographics and other relevant outcomes, and symptom reporting.

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Methods: At baseline, participants answered surveys assessing disease activity, medications and complementary therapies, lifestyle factors, psychological status, and comorbidities. UC phenotypes were classified by the Montreal Classification. Herein, we describe the association between phenotypes and demographics, medications used, comorbidities, and symptoms experienced in adults with UC. The Inflammatory Bowel Disease Symptom Inventory (IBDSI) was used to assess symptoms.

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Results: The maximal extent phenotypic distribution based on chart review was E1 (proctitis) n=261 (14.5%), E2 (left-sided colitis) n=671 (37.2%), and E3 (subtotal or pancolitis) n=794 (44.0%). More males had E3. Different phenotypes did not lead to differences in the use of complementary therapies. There was greater likelihood of primary sclerosing cholangitis but a lower likelihood of hypertension in E3. Among the 25 different symptoms queried in the IBDSI, there was no difference across phenotypes, except among persons with overall active IBDSI, there was more waking for urges for bowel movements in persons with E3.

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Conclusions: Overall, there was no difference in symptom reporting based on extent of UC except for cohort with overall active IBDSI there were some differences in nocturnal waking based on disease extent.

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Cooper S, Watermeyer G, Levin D, Mhlaba Z, Davidson K, Bernstein CN. McGovern DPB, Epstein D. Challenges and opportunities facing Inflammatory Bowel Disease in Sub-Saharan Africa: Towards a contextually relevant research and practice agenda. Journal of Crohns and Colitis 2026; in press

 

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, has traditionally been considered a disease of Western, industrialized countries. Over the past few decades, however, many Sub-Saharan African (SSA) countries have experienced significant increases in casesYet, IBD remains highly neglected in SSA with most research conducted in high income settings and treatment guidelines geared towards these settings. An emerging body of research on the sub-continent is highlighting several unique realities, dilemmas, and priorities facing IBD, and the need for evidence-based approaches that are more locally relevant and contextually tailored. In this viewpoint article we synthesis the challenges facing IBD in SSA and propose a research and practice agenda for addressing these, building on several promising initiatives already underway. Ultimately, we make a call to the international IBD community, researchers, funders, and policymakers to recognize the importance of IBD in SSA and join efforts to remedy global disparities in the quality, accessibility, and equity of IBD care.

 

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*Sareen J, Prichodko M, Graff LA, Keshavarzian A, Voigt RM, Bernstein CN. Fatigue in inflammatory bowel disease: the role of drug therapy within a holistic management framework. Drugs 2026; in press.

 

Fatigue is one of the most common and disabling symptoms experienced by individuals with inflammatory bowel disease (IBD). Significant fatigue is experienced by approximately 40-80% of adults with IBD, with higher prevalence during active disease states but persisting in up to one third of individuals who are in clinical remission.  Fatigue is not solely a consequence of disease activity, but rather a unique and multifactorial manifestation of IBD. In this narrative review we synthesize evidence on the various mechanisms of fatigue in IBD, as well as pharmacological agents to address fatigue both directly or through secondary contributors including anemia, psychiatric comorbidities, sleep disturbance, and pain. The review further situates pharmacological therapy within a holistic framework that integrates non-pharmacological approaches as part of a multidisciplinary approach to fatigue in IBD. Drug therapy has a meaningful role in this context, both when targeting disease-related inflammation and secondary contributors to fatigue. However, the evidence base for most of these approaches remains weak. It is clear that no single pharmacological agent will resolve IBD-related fatigue in isolation, but effective management should identify a patient’s dominant contributors and address them systematically with both drug and nondrug intervention strategies. This framework should be delivered by a multidisciplinary team through an integrated care approach and optimally be guided by the patient’s priorities and goals.

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Ma C, Ford AC, Hashash JG, Barbara G, Bernstein CN, Brenner DM, Griffiths AM, Keefer L, Long MD, Nurko S, Singh P, Sands BE, Chang L. Recommendations for the Evaluation and Management of Patients with Inflammatory Bowel Disease with Irritable Bowel Syndrome-Like Symptoms: A Joint Rome Foundation and IOIBD Consensus. Gastroenterology 2026; Sep;171(3):504-520. 

 

Background & aims: A substantial proportion of persons with inflammatory bowel disease (IBD) in remission continue to experience abdominal pain, altered bowel habits, and bloating that resemble irritable bowel syndrome (IBS). Lack of standardized definitions and evidence-based management strategies leads to diagnostic ambiguity and potentially unnecessary escalation of IBD therapy. A joint Rome Foundation/International Organization for the Study of Inflammatory Bowel Disease Working Team developed consensus recommendations on nomenclature, evaluation, and treatment of IBD with IBS-like symptoms.

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Methods: A multidisciplinary international panel applied a modified RAND/UCLA Appropriateness Method. Systematic literature reviews informed statement generation across multiple domains: nomenclature, diagnostic and symptom assessment, dietary therapies, drugs, and brain-gut behavioral therapies. Panelists rated the appropriateness of candidate statements independently on a 9-point Likert scale, followed by anonymized feedback, discussion, and re-voting across 2 iterative rounds.

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Results: Thirteen panelists reviewed 133 initial statements; 105 proceeded to final scoring. Of these, 86 were rated appropriate, 16 uncertain, and 3 inappropriate. The preferred term was "IBD with IBS-like symptoms," defined as abdominal pain, bowel habit change, and/or bloating not explained by active inflammation or structural disease. For clinical care, diagnosis should combine Rome clinical criteria with objective exclusion of inflammation. For research, candidate thresholds for endoscopic, histologic, biomarker, and imaging remission were endorsed. Appropriate therapies include psyllium (if no stricture), a short-term low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, targeted drugs, and brain-gut behavior therapies.

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Conclusions: This first joint consensus provides standardized terminology, evaluation strategies, and treatment recommendations for IBD with IBS-like symptoms, supporting improved clinical management and guiding future mechanistic and therapeutic research.

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Bernstein CN, Gearry R, Nugent Z, Witt J, Burisch J, Kaplan GG, and the Global IBD Management Cascades Committee. Global Discrepancies in Inflammatory Bowel Disease Care Reflect Healthcare Expenditure Per Capita. Gastroenterology 2026 Jan;170(1):203-206.

 

In 2010 and 2016, experts published guidelines on management of IBD that accounted for three cascades of available resources ranging from countries with limited resources to those with more extensive capabilities. We conducted an international survey of IBD practitioners to assess real-world patterns of IBD diagnosis and care, examining how practices differed across countries stratified by healthcare expenditure per capita. An English-language survey was disseminated to gastroenterologists in 85 countries, categorized into three tiers based on healthcare expenditure per capita (tier 1 =highest, tier 3 =lowest). An online questionnaire was distributed via multiple organizations, including the World Gastroenterology Organization and the International Organization for the Study of IBD (IOIBD). Survey items included physician demographics, availability of advanced endoscopic and imaging resources, typical test ordering, first-line treatments, access to biologics, and approaches to mental health and dysplasia surveillance.

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Respondents were distributed across tier 1 (42%, n=177), tier 2 (29%, n=123), and tier 3 (29%, n=125) countries. Median healthcare expenditure per capita (USD) was $5738 (range: US$2,499–US$12,012) in tier 1, $1146 (range: US$558–US$2,352) in tier 2, and $180 (range: US$22–US$494) in tier 3. Respondents were predominantly male, with similar years in practice across tiers (Table). While over 80% reported advanced gastroenterology training, specialized IBD training was significantly higher in tier 1 (61%) compared with tier 2 (41%) and tier 3 (32%) (p<0.0001). In tier 3, only one-third worked in IBD specialty clinics, contrasting with two-thirds in tier 1. The limited availability of trained specialists and specialty clinics in lower-expenditure countries is particularly concerning given the growing burden of IBD in these regions.

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Several diagnostic differences emerged. High-resolution endoscopy (81%) and capsule endoscopy (97%) were widely available in Tier 1, with less access in tier 3 (55% and 58%, respectively) (p<0.0001). While colonoscopy was commonly used for new-onset diarrhea across all tiers, tier 1 physicians more often intubated the terminal ileum. C-reactive protein and fecal calprotectin were more frequently ordered in tier 1 (85% and 80%, respectively) than in tier 2 (73% and 65%, respectively) or tier 3 (75% and 64%, respectively) (p<0.04). Radiologic strategies also varied, with small bowel barium studies most commonly ordered in tier 3 (30%) (p=0.04). About 20% of tier 1 respondents reported not using either CT or MRI in investigating suspected or established IBD. Transabdominal ultrasound was used by 70-80% of respondents, with results available within 3 days in 69% of tier 3, 47% of tier 2, and 34% of tier 1 (p<0.0001). Similar test-ordering patterns were seen for both suspected and symptomatic IBD. Capsule endoscopy was significantly more accessible in IBD specialty clinics who see ≥100 IBD patients per year (OR 3.50 95%CI 1.55-7.94). Access to advanced therapies varied widely. Anti-TNF agents were available to 90% in tier 1, 88% in tier 2, but only 63% in tier 3 (p<0.0001). Anti-TNF drug and antibody levels were more available in tier 1 (87%), than tier 2 (74%), and tier 3 (64%, p<0.0001). Vedolizumab and ustekinumab were nearly universal in tier 1 but far less accessible in tier 3, where government or insurance coverage was also less common. Consequently, 5-aminosalicylates and corticosteroids were more frequently used in tier 3 for CD, including moderate to severe disease, likely due to cost and limited capacity to administer and monitor advanced therapies.

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Mental health considerations also differed. While more tier 1 respondents (77%) acknowledged the importance of addressing mental health in IBD, fewer (32%) consistently asked about it, compared to 46% in tier 3 (p=0.008). Tier 3 physicians were more likely to prescribe antidepressant or anti-anxiety medications (46% vs 26% in tier 1, p=0.0007), whereas tier 1 respondents more often referred patients to mental health specialists.

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About one-quarter of tier 1 and half of tier 3 respondents did not routinely screen all colitis patients for cancer. When PSC was present, tier 1 respondents were more likely to provide more frequent colonoscopy surveillance than tier 3 (96% vs 76%). This discrepancy may reflect limited availability of advanced endoscopic techniques or expert pathologists in tier 3, where 70% reported seeing PSC but fewer had specialist pathology services.

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Taken together, these findings highlight important resource discrepancies worldwide. Insufficient access to specialty clinics, advanced imaging, expert histopathology, and biologic therapies remains a challenge in many countries. Tier 1 clinicians, although generally better resourced, nonetheless exhibited inconsistencies in mental health screening and colon cancer surveillance. These results underscore the need for “cascading” clinical guidelines that offer pragmatic recommendations according to economic and resource constraints. They also suggest an opportunity for collaborative programs that expand training and technology in lower-income settings, along with ongoing education to standardize best practices. Improved access to biologic and small-molecule therapies, advanced endoscopic technology, and mental health services is urgently needed in tier 2 and tier 3 countries, where IBD incidence is accelerating. Deficiencies in resources to provide optimal IBD care in Tier 2 and Tier 3 countries must be balanced against other pressing healthcare priorities, such as infectious diseases and maternal-fetal care, which may have a greater impact on population health. Hence enhancing diagnostics and therapeutic resources for IBD should be undertaken in the context of competing health burdens in low income countries.

 

While these findings provide a global snapshot of IBD care, there are limitations. Self-reporting can introduce bias, and single respondents from certain tier 3 countries may not fully represent national practice. Nevertheless, this multinational, survey-based approach offers invaluable insights into real-world patterns across a broad range of economic settings. Ongoing international collaboration among professional organizations is crucial for narrowing gaps in care and ensuring that IBD diagnostic evaluation, therapy selection, and ancillary support—converges toward evidence-based best practices worldwide

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Bernstein CN, Kaplan GG, Nugent Z, Ahuja V, Ananthakrishnan AN, Banerjee R, Burisch J, Chen Y, Epstein D, Forbes AJ, Gonczi L, Gu Y, Gunawan J, Hang DV, Kaibullayeva J, Kopylov U, Kotze PG, Iade B, Lakatos PL, Limsrivilai J, Liang J, Mak JWY, Ng S, Severs M, Shen J, Sood A, Yamamoto-Furusho JK, Yuan S, Wewer MD, Wu K, Windsor JW, Gearry RB; Globalization Cluster of the International Organization for the Study of IBD. Inflammatory bowel disease phenotypes in diverse populations: a global comparative analysis. Journal of Crohn's Colitis 2026 May 8;20(5):jjag051. 

 

Background: The aim of this study was to determine if Crohn's disease (CD) and ulcerative colitis (UC) manifest similarly in different parts of the world.

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Methods: Investigators of cohort studies from around the world were contacted to provide the most recent data from their CD and UC cohorts. Each cohort provided summated and averaged data on pre-specified variables. The Montreal Classification was used for phenotype assessment. Age at diagnosis was stratified into less than 17 years, 17-39 years, and >39 years. Disease location for CD was stratified as ileum only, colon only, ileocolon, upper gastrointestinal and proximal small bowel disease, and perineal penetrating disease. Disease behavior for CD was stratified into inflammatory disease, stricturing disease, and penetrating disease. Location for UC was stratified into proctitis, left-sided colitis, and extensive including subtotal and pancolitis. Reports were classified geographically as Asia, Latin America, South Africa, and "Western" (ie, North America, Europe, and Oceania). These categories were collapsed to "Western" and "non-Western" for analyses.

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Results: Data from 54 868 patients with IBD were included. For CD, data were available from nine Western cohorts, 12 Asian cohorts, three Latin American cohorts, and one African cohort. For UC, eight Western cohorts were compared with 11 Asian cohorts, three Latin cohorts, and one African cohort. The demographic and phenotypic distribution for CD and UC in comparisons between Western and non-Western countries were no different. Western cohorts had longer disease durations than non-Western cohorts.

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Conclusion: No significant differences were seen in any phenotypic data between the cohorts, suggesting that IBD is similar worldwide.

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De Boer NK, Gearry R, Bernstein CN, Banerjee R, Rubin DT, Kaplan GG. The essential medicines list for inflammatory bowel diseases: time to raise the bar of global care. Lancet Gastroenterology and Hepatology 2026; Jan;11(1):7-9.

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Global limitations in the accessibility and affordability of medicines compromise the effective management of IBD. Many essential (advanced) therapies (eg, biologics and oral small molecules) are priced differently between countries and are often prohibitively expensive, particularly in low-income and middle-income countries with underfunded health care and disparate reimbursement systems. The disparities both between and within countries not only limit access to needed treatments but also exacerbate health inequities, contributing to increased morbidity and a diminished quality of life for people with IBD. Without affordable, accessible, and effective medicines, people living with IBD could face uncontrolled symptoms, avoidable hospitalizations, and substantial out-of-pocket expenses, preventing them from leading healthy lives.

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WHO’s Essential Medicines List (EML) identifies medicines that have been deemed crucial to addressing key global health needs. The EML serves to guide countries in selecting the safest and most cost-effective medicines for their health systems, ensuring that treatments are affordable and accessible. The EML also standardizes and informs the appropriate use of medicines among health-care providers, patients, policy-makers, and pharmaceutical companies. By offering essential medicine options that are tailored to prevalent diseases, the EML helps improve health outcomes, reduce health inequalities, and enhance the efficiency of health-care systems globally.

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WHO’s EML has the potential to globally improve the accessibility and affordability of medicines for people with IBD by advocating for the inclusion of these medications in national formularies. By listing essential medicines, the EML can be a catalyst by signaling to governments which medicines should be prioritized for approval, procurement, and distribution, thereby ensuring that key therapies are available where they are needed most. The EML can also help reduce costs by fostering a competitive manufacturing environment that encourages favorable price and accessibility negotiation with pharmaceutical companies.

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Bernstein CN, Nugent Z, Panaccione R, Marshall DA, Kaplan GG, Vanner S, Dieleman LA, Graff LA, Otley A, Jones J, Buresi M, Murthy S, Bargaonkar M, Bressler B, Bitton A, Croitoru KC, Sidani S, Fernandes A, Moayyedi P. Patient reported symptoms are independent of extent of disease in longstanding ulcerative colitis: MAGIC in IMAGINE. Journal of Clinical Gastroenterology 2026; in press.

 

Background: The Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects Strategy for Patient Oriented Research Network (IMAGINE) has conducted a five-year multicenter prospective observational cohort study, Mind And Gut Interactions Cohort (MAGIC) in 14 centres across Canada from 2018-2022. Herein, we investigated the relationship between ulcerative colitis (UC) phenotypes; demographics and other relevant outcomes and symptom reporting.

Methods:  At baseline, participants answered surveys assessing disease activity, medications and complementary therapies, lifestyle factors, psychological status, and comorbidities. UC phenotypes were classified by the Montreal Classification. Herein, we describe the association between phenotypes and demographics, medications used, comorbidities and symptoms experienced in adults with UC. The Inflammatory Bowel Disease Symptom Inventory (IBDSI) was used to assess symptoms

Results: The maximal extent phenotypic distribution based on chart review was E1 (proctitis) n=261 (14.5%), E2 (left sided colitis) n=671 (37.2%), E3 subtotal or pancolitis n=794 (44.0%). More males had E3. Different phenotypes did not lead to differences in the use of complementary therapies. There was greater likelihood of primary sclerosing cholangitis but a lower likelihood of hypertension in E3. Among the 25 different symptoms queried in the IBDSI there was no difference across phenotypes, except among persons with overall active IBDSI there was more waking for urges for bowel movements in persons with E3.

Conclusions Overall, there was no difference in symptom reporting based on extent of UC except for cohort with overall active IBDSI there were some differences in nocturnal waking based on disease extent.

 

 

O’Mahony SL, Tollenaar SI, Khorasaniha R, Jovel J, Ba I,  Voisin A, Miller R, Olof H, Mahmood R, Marrie RA, Strachan E, Soares LP, Cheng C, Janveaux J, Azaidi D, Bernstein CN, Bonner C, Bar-Or A, Waubant E, Yeh A, Graham M. Arnold DL, Banwell BL, Zhu F, Mirza AI, Karimi-Abdolrezaee S, Tsai S, Tremlett H, McGregor K, Willing BP, Armstrong HK. Reduced fibre-fermenting capacity of gut microbes in multiple sclerosis may result in prebiotic dietary fibre β-fructan promoting inflammation and CNS damage. Gastroenterology 2026; e100296 in press.

 

Background Some people with multiple sclerosis display changes in their gut microbiota with separate evidence suggesting worsened symptoms following a high-fibre diet. We hypothesised that in people with multiple sclerosis whose gut microbiota are less able to adequately ferment fibres, unfermented β-fructans induce inflammation.

Methods Diet data (n=48 multiple sclerosis, n=78 unaffected controls) and stool microbiome data (n=31 multiple sclerosis, n=61 unaffected controls) were previously collected from participants. Daily fibre subtype intakes were calculated and compared with fecal shotgun metagenomic sequencing in pediatric onset multiple sclerosis and unaffected persons. Response to unfermented β-fructans was examined in a germ-free experimental autoimmune encephalomyelitis mouse model (unable to ferment fibres). Mice were fed β-fructans or control fibre diet beginning at symptom onset (day 14). Experimental autoimmune encephalomyelitis scores and weights were recorded daily. Intestinal and central nervous system tissues were collected at two endpoints to examine inflammatory responses and demyelinating lesions.

Results Paediatric onset multiple sclerosis consumed less β-fructans (2.4 g/day±0.3 SD; p<0.05) than unaffected participants (3.6 g/day±0.4), which coincided with differences in the gut microbiota including lower fibre fermenting enzymes. Mice exposed to unfermented β-fructans sustained worsened EAE symptoms (day 20–28; p<0.05), immune activation in the gut and immune activation plus demyelinating lesions in the spinal cord compared with mice on control diet.

Conclusions  The gut microbiota of pediatric-onset multiple sclerosis had lower fibre fermenting properties, and our animal findings suggest that β-fructans induce worsened demyelination and gut–brain axis immune activation. Lower β-fructan consumption was observed among participants with pediatric-onset multiple sclerosis. Future longitudinal studies are warranted to confirm the findings uncovered in this manuscript.

 

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