Mirikizumab, an anti-interleukin-23 monoclonal antibody targeting the p19 subunit, has shown efficacy in inducing and maintaining clinical remission in patients with moderately-to-severely active ulcerative colitis (UC). This report summarizes the final long-term outcomes from the LUCENT-3 open-label extension (OLE) through week (W)212 of continuous treatment. Among 868 participants who received mirikizumab induction therapy in the LUCENT clinical trial program, 544 achieved clinical response. Of these, 365 were rerandomized to mirikizumab maintenance, with 324 completing W52, 316 entering the OLE, and 182 completing the OLE (4 years of continuous treatment), resulting in 835.3 total patient years of exposure. These analyses include efficacy and safety data from the LUCENT-3 cohort, stratified by LUCENT-1 baseline biologic experience, W52 remitter, and W52 responder status on entering the OLE study. Outcomes were analyzed using modified nonresponder imputation, traditional nonresponder imputation, and observed cases (OC) to handle missing data. At W212, W52 Maintenance Remitters showed 77.7% clinical, 77.7% corticosteroid-free (CSF), 81.3% endoscopic, 66.0% histologic-endoscopic mucosal (HEMR), 94.3% symptomatic, and 73.6% bowel urgency (BU) remission rates (OC); 67.9% achieved histologic-endoscopic mucosal improvement (HEMI), 97.1% sustained clinical response, and 92.9% achieved BU clinically meaningful improvement (CMI). At W212, W52 Maintenance Responders showed 68.7% clinical, 68.7% CSF, 70.2% endoscopic, 55.1% HEMR, 92.7% symptomatic, and 74.8% BU remission rates (OC). For W52 Maintenance Completers, reductions in stool frequency, rectal bleeding, bowel urgency, and abdominal pain from baseline were sustained to W212. W52 Maintenance Remitters and Responders achieved Inflammatory Bowel Disease Questionnaire (IBDQ; quality of life measure) response (70%) and remission (>66%) at W212. Across biologic failed and bionaive subgroups, efficacy results were generally similar. For over 160 weeks of OLE treatment in the safety population, no new safety signals emerged from long-term exposure compared with induction and maintenance treatment. Mirikizumab provided sustained symptomatic, clinical, endoscopic, and histologic benefits over 4 years in responding patients with moderately-to-severely active UC, including those with prior biologic failure. These treatment goals, which are integral to comprehensive disease management, support the long-term use of mirikizumab.

Quyushengxin formula restores the integrity of intestinal barrier by regulating the gut microbiota to ameliorate DSS-induced ulcerative colitis in mice.

Curcumin-QingDai combination for active ulcerative colitis: A cost-effectiveness analysis.

Appendectomy vs. escalation of pharmacotherapy to a JAK inhibitor in patients with active ulcerative colitis: results of the COSTA study after 1 year

Guselkumab (TREMFYA®) is a fully human IgG1λ monoclonal antibody developed by Johnson & Johnson to selectively target the p19 subunit of interleukin (IL)-23, a cytokine that plays a key role in various immune-mediated inflammatory diseases. Guselkumab is approved in multiple countries worldwide, including the USA and those of the EU, for the treatment of adults with moderate-to-severe plaque psoriasis, active psoriatic arthritis, and moderately-to-severely active ulcerative colitis and Crohn's disease. In September 2025, guselkumab received its first pediatric approvals in the USA for the treatment of pediatric patients 6years of age and older and weighing ≥ 40kg who either have moderate-to-severe plaque psoriasis and are candidates for systemic therapy or phototherapy, or who have active psoriatic arthritis. Subsequently, guselkumab was approved in December 2025 in the EU for the treatment of moderate-to-severe plaque psoriasis in children and adolescents from the age of 6 years who are candidates for systemic therapy. Johnson & Johnson is currently undertaking phase III development of guselkumab in pediatric patients with Crohn's disease and ulcerative colitis in various countries. This article summarizes the milestones in the development of guselkumab leading to these first pediatric approvals for plaque psoriasis and psoriatic arthritis.

Ozanimod is a once-daily oral selective sphingosine 1-phosphate receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC) or relapsing multiple sclerosis (RMS). Previous analyses in both indications demonstrated favorable long-term safety profiles of ozanimod. Here we report an integrated analysis of the long-term safety of ozanimod in patients with UC or RMS. Data were pooled in patients with UC who received ozanimod in phase 2, phase 3, and open-label extension (OLE) trials and in patients with RMS who received ozanimod in an OLE trial after completing any phase 1-3 parent trial. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory abnormalities. Overall, 3652 patients with UC or RMS had 16 144 patient-years (PY) of ozanimod exposure over 10 years of follow-up. The most common TEAEs were nasopharyngitis, headache, and coronavirus disease 2019. Rates of TEAEs leading to treatment discontinuation (1.4/100 PY) and TEAEs of special interest, including serious infections (1.0/100 PY), herpes zoster (0.5/100 PY), malignancies (0.4/100 PY), bradycardia (0.1/100 PY), sinus bradycardia (0.04/100 PY), complete atrioventricular block (0.01/100 PY), and macular edema (0.1/100 PY), were low. No serious hepatic events or Hy's law cases occurred. Absolute lymphocyte count of < 200 cells/µL was not temporally associated with serious or opportunistic infections. Long-term exposure to ozanimod is well tolerated in patients with moderate to severe UC or RMS, confirming the previously established safety profile of ozanimod. NCT01647516; NCT02435992; NCT02576717.

Randomized controlled trials have confirmed the efficacy and safety of mirikizumab, an anti-interleukin-23p19 monoclonal antibody, for moderate-to-severe active ulcerative colitis (UC). However, there are no real-world data on the efficacy and safety of mirikizumab for UC as maintenance therapy, especially in difficult-to-treat inflammatory bowel disease (DTT-IBD). This study aimed to evaluate the long-term efficacy and safety of mirikizumab in patients with UC of DTT-IBD. This was a single-center retrospective observational study involving adult patients with UC who received mirikizumab between January 2023 and April 2025 and met the criteria for DTT-IBD (e.g., failure of biologics and advanced small molecule drugs with at least 2 different mechanisms of action). The primary outcome was the clinical response at week 52. Secondary outcomes included steroid-free clinical remission within 52 weeks and the persistency of mirikizumab use. Adverse events were also recorded. Thirty-two patients were included in this study. The median 2-item patient-reported outcome score at baseline was 3 (interquartile range, 2-4). The proportion of patients with a clinical response at week 52 was 33.3% (95% confidence interval, 14.6%-57.0%). Steroid-free clinical remission was achieved in 26.7% (95% confidence interval, 12.3%-45.9%) of the patients. The cumulative continuous rate of mirikizumab use at week 52 was approximately 60%. Only 1 patient developed a serious adverse event requiring hospitalization (pneumonia), and mirikizumab was successfully resumed after recovery. The present study demonstrated real-world data regarding maintenance therapy with mirikizumab for UC among patients with DTT-IBD.

Budesonide rectal foam was approved in Japan in 2017 for mild to moderate active ulcerative colitis (UC). This is the final report of post-marketing surveillance to evaluate real-world safety and effectiveness. This Japanese large-scale, prospective, multicenter, open-label observational study included patients with active-phase mild to moderate UC newly started on budesonide 2 mg rectal foam. Safety was evaluated by adverse drug reactions (ADRs). Effectiveness was evaluated using clinical remission rates and partial Mayo scores. Effectiveness by background (disease phenotype, severity, clinical course, age, prior topical therapy, baseline advanced therapy [biologicals/Janus kinase inhibitors]) was also assessed. There were 633 and 503 patients in the safety and effectiveness analyses, respectively. ADRs occurred in 4.3% (27/633) of patients. Eight glucocorticoid-related ADRs occurred in 7 patients (1.1%). Clinical remission rates were 44.2% (165/373), 72.1% (191/265), and 69.8% (333/477) at week 2, week 6, and the final evaluation, respectively. There were statistically significant changes from baseline in partial Mayo scores at all timepoints (all P< 0.0001 vs. baseline). At 2, 4, 6, and 6-12 weeks, mean± standard deviation changes from baseline in partial Mayo scores were -2.1 ± 1.9, -2.7 ± 2.1, -3.1 ± 2.3, and -3.4 ± 2.3 points, respectively. Statistically significant improvements were maintained at all timepoints in subgroup analyses by background (disease phenotype, severity, clinical course, age, prior topical therapy, baseline advanced therapy). No new safety concerns were identified. Partial Mayo score improved in a variety of patient background factors. Health condition improvements were confirmed in this Japanese post-marketing surveillance. (Japan Registry of Clinical Trials, identifier jRCT1080223802).

Background:PF-06687234 is a novel, human, single-chain variable fragment cytokine fusion protein comprising the antibody fragment F8 and the immunoregulatory cytokine interleukin-10.Objectives:We evaluated the efficacy and safety of PF-06687234 as an add-on therapy to infliximab in participants with active ulcerative colitis (UC).Design:This phase IIa, double-blind, placebo-controlled, parallel-group, multicenter study randomized (1:1) participants with active UC to subcutaneous PF-06687234 20 mg or placebo once weekly, and participants continued intravenous background infliximab every 6 or 8 weeks, for 12 weeks.Methods:The primary endpoint was the proportion of participants who achieved clinical remission determined by the modified total Mayo score at week 12. Safety assessments, including adverse event (AE) reporting and laboratory abnormalities, were also primary endpoints. Secondary endpoints included the proportion of participants achieving endoscopic improvement at week 12, and exploratory endpoints included the concentration of PF-06687234 in colonic mucosal tissue from biopsies.Results:After 20 participants were randomized and treated, this study was stopped early for futility. There were no statistically significant differences between groups for any efficacy endpoint (all p > 0.05), although numerical trends towards efficacy were observed in some secondary endpoints. PF-06687234 was detected at a low concentration in only one colon tissue sample. There were no differences in AEs between the groups. The most frequently reported AE in the PF-06687234-treated group was injection site reaction.Conclusion:PF-06687234 was well tolerated, but when combined with background infliximab, did not meet the primary efficacy endpoint in this cohort of participants with active UC. Efficacious PF-06687234 tissue concentrations may not have been achieved at the dose tested.Trail registration:Efficacy, safety, and tolerability of PF-06687234 as add-on therapy to infliximab in active UC subjects not in remission. https://clinicaltrials.gov/study/NCT03269695. NCT03269695.

We compared the effectiveness of 2 strategies based on the choice of the first biologic owing to either drug efficacy or better acceptability in patients with ulcerative colitis (UC). We collected real-world data of all consecutive UC patients ≥ 18 years starting a first line of biologic for active UC with follow-up > 6 months. Patients were considered as receiving either an effectiveness-based strategy (EBS) if they started with infliximab or vedolizumab, or acceptability-based strategy (ABS) if they started with adalimumab or golimumab. Corticosteroid-free clinical remission (PRO2-CFREM) was defined as the absence of bleeding, normalization of stool frequency and no steroid assessed as a binary criterion each month. All comparisons were adjusted using propensity scores. Overall, 130 patients and 3,355 months were analyzed. The percentage of months spent in PRO2-CFREM within the first 24 months (primary endpoint) was greater in EBS arm than in ABS arm (74.2% vs. 46.6%; P< 0.001), was higher within the first 6 months (60.4% vs. 18.9%), and was not rescued later between months 7 and 12 (73.1% vs. 38.6%), months 13 and 18 (79.9% vs. 57.0%) or M19 and M24 (83.3% vs. 64.6%) (P< 0.001 for all comparisons). EBS group had a lower risk to first-line biologic discontinuation (adjusted hazard ratio [aHR], 6.5; 95% confidence interval [CI], 2.8-15.3: P< 0.001) and a trend for lower risk of colectomy (aHR, 4.5; 95% CI, 0.9-22.3; P= 0.068). The choice of first-line biologic is highly impacting UC outcome and cannot be fully compensated by later treatments, advocating for the use of the most effective therapeutic option as first-line biologic.

Rapid symptom relief is an important consideration for patients with ulcerative colitis (UC) experiencing a flare. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. We evaluated patient-reported symptomatic improvement from patients in the ELEVATE UC program. This study was a post-hoc analysis of pooled daily e-diary data from patients with moderately to severely active UC receiving etrasimod or placebo in the phase III ELEVATE UC 52 and ELEVATE UC 12 trials. During the 12-week induction periods, patients self-reported stool frequency and rectal bleeding on days 1-28. Daily symptomatic response and symptomatic remission were calculated (partial modified Mayo Score). Overall, 787 patients (527 receiving etrasimod, 260 placebo) were included in the analysis. Etrasimod-treated patients had statistically significantly higher rates of symptomatic response and symptomatic remission during the first 28 days of therapy, with adjusted differences (95% CIs) reaching statistical significance from day 2 (5.6% [0.8-10.3], P = .022) to day 11 (4.7% [0.4-9.0], P = .034), respectively. In patients naïve to biologic/Janus kinase inhibitor therapy, symptomatic response was statistically significantly improved with etrasimod vs placebo from day 3 (8.9% [2.3-15.5], P = .008). Symptomatic improvement rates were similar with and without concomitant corticosteroid use. In this post-hoc analysis, improvements in UC symptoms occurred in patients receiving etrasimod vs placebo from as early as day 2. These findings indicate a rapid onset of symptomatic effect with etrasimod treatment for moderately to severely active UC. NCT03945188, NCT03996369.

Inflammatory bowel disease (IBD) is a gastrointestinal, auto-inflammatory disease with a chronic relapsing and remitting course, whose diagnosis is based on several examinations assessing intestinal inflammation and clinical assessment. Furthermore, only 40%-60% of patients respond to therapy, making identification of reliable markers of disease or predictors of disease course and therapy response of great interest to the medical community. The existence of extrachromosomal circular DNA (eccDNA) is well established, and has become a promising biomarker for different types of cancer. Here, we investigate eccDNA in patients affected by IBD. Intestinal biopsies were collected from patients and from healthy controls. Circular DNA was enriched, sequenced, identified with Circle Finder, and annotated with bedtools. Patients were then stratified based on disease type and activity. Intestinal tissue from IBD patients contained significantly higher levels of eccDNAs than tissue from healthy controls. eccDNA production also was significantly increased in patients with active ulcerative colitis compared to patients in remission. In Crohn's disease, eccDNAs were more abundant than in healthy controls, though the difference between active and inactive Crohn's disease was less defined. Furthermore, eccDNAs containing fragments from specific genes were consistently found in a large proportion of patients with IBD, while healthy controls presented with a more stochastic eccDNA pattern. Here, we uncover an IBD-specific pattern of eccDNA production from intestinal biopsies. Furthermore, we have identified genic hotspots that characterize active disease. We propose that eccDNA containing specific gene fragments (eg, NRG1 and ZPMF2) could represent a promising new biomarker tool for patients with IBD.

Efficacy and safety of mirikizumab in paediatric participants with moderately-to-severely active ulcerative colitis (SHINE-1): a multicentre, open-label, non-randomised phase 2 trial.

Abstract Background Individuals with inflammatory bowel disease (IBD) experience mental health disorders at a rate of 1.5 to 2 times higher than the general population. With the rising incidence of IBD, many people are affected by the disease during significant life stages such as pregnancy. Research on the impact of IBD on anxiety and depression in pregnant people is limited. Aims To assess the impact of active IBD on anxiety and depression during pregnancy. Methods This retrospective survey study analyzed data from patients seen at the ‘Preconception and Pregnancy in IBD’ clinic at Mount Sinai Hospital who conceived prior to January 1st, 2022. Standardized pre-visit surveys included validated measures of mental health (General Anxiety Disorder-7 for anxiety; Patient Health Questionnaire-9 for depression) and IBD disease activity (pMayo6 for ulcerative colitis (UC); mHBI for Crohn’s disease (CD)). Demographic data was also collected (age, marital status, occupational status, smoking habits, alcohol use, cannabis use, previous diagnosis of anxiety and/or depression, IBD type, IBD surgical history, and medication use). Linear regression models were used to assess associations between disease activity and anxiety/depression, adjusting for medication type and stratified by trimester and IBD subtype. Results A total of 94 patients were included in this study, 42 patients had UC (44.7%), and 52 patients had CD (55.3%). The median age for the UC group was 32 (IQR 31-35.8), and the median age for the CD group was 32.7 (IQR 30-35.2). Active CD in the second trimester was significantly associated with higher anxiety (p = 0.024) and depression scores (p = 0.021) compared to those in remission. For CD, 6 patients (35.3%) in trimester 1, 8 patients in trimester 2 (25.8%), and 8 patients (26.7%) in trimester 3 had a GAD-7 score of ≥ 5; 5 patients (29.4%) in trimester 1, 6 patients (19.4%) in trimester 2, and 7 patients (23.3%) in trimester 3 had a PHQ-9 score of ≥ 5. Active UC in the second trimester was associated with significantly higher anxiety (p = 0.034) and depression (p = 0.022) scores compared to inactive UC. In the third trimester, this pattern persisted, with active UC again associated with elevated anxiety (p = 0.030) and depression (p = 0.027) scores. For UC, 4 patients (33.3%) in trimester 1, 9 patients (30%) in trimester 2, and 9 patients (31.0%) in trimester 3 had a GAD-7 score of ≥ 5; 4 patients in trimester 1, 4 patients in trimester 2, and 7 patients in trimester 3 had a PHQ-9 score of ≥ 5. Conclusions Active IBD during pregnancy is significantly associated with increased anxiety and depression, therefore, a multidisciplinary approach including mental health support is imperative for pregnant people with IBD. Funding Agencies None

Abstract Background Intestinal ultrasound (IUS) total bowel wall thickness (BWT) correlates well with severity of endoscopic inflammatory bowel disease (IBD) activity. The bowel’s sub-layers are also of interest as additional clues for inflammation. In adults, increased total BWT (&amp;gt;3 mm) and submucosal thickness (SMT) to BWT ratio (&amp;gt;0.50) has been reported in active ulcerative colitis (UC). In children, a thinner total BWT cut-off (&amp;gt;2 mm) has been found for active IBD, but the SMT has not yet been reported. Aims To assess the IUS measured SM and SM/total BWT ratio in pediatric patients with newly diagnosed CD and UC, to help inform cut-offs that distinguish normal vs. inflamed intestine. Methods Pediatric patients (0-18 years) with suspected IBD were prospectively enrolled (between 2019-2024) and underwent baseline IUS, clinical assessment, blood work, calprotectin, and endoscopy. IUS included two total BWT measurements for bowel segment. For this study, IUS images were retrospectively reviewed and the SMT was measured within 0.5 cm of the original total BWT measurements using DiCOM viewer. Statistical analysis included descriptive, Spearman rho correlations, Mann-Whitney U group comparisons, and ROC curve analyses. Results Eight-six patients (n = 431 intestinal segments) were included (n = 55, 64% male), with a median age at diagnosis of 13 years (IQR 11-15, range 3-17), majority with CD (n = 49, 57%). There were significant moderate correlations between endoscopic disease severity and thickness of both the total BWT and SMT for CD (rho=0.58 BWT, rho=0.49 SMT) and ulcerative colitis (rho=0.57 BWT, rho=0.54 SMT) (p &amp;lt; 0.001). SM/BWT ratio weakly correlated with endoscopy in UC (rho=0.27, p &amp;lt; 0.001), and didn’t significantly correlate in CD (rho=0.12, p = 0.09). The median SM was significantly thicker in inflamed intestine (1.1 mm CD, 1.4 mm UC) compared to normal intestine (0.8 mm CD, 0.8 mm UC) (p &amp;lt; 0.001). The optimal cut-off for detecting endoscopic inflammation was a SM ≥ 1.3 mm (for CD) (AUC 0.67, 95th CI 0.59-0.74, p &amp;lt; 0.001) and ≥ 1.1 mm (for UC) (AUC 0.79, 95th CI 0.72-0.86, p &amp;lt; 0.001). The optimal SM/BWT ratio cut-off was ≥0.55 for UC (AUC 0.65, 95th CI 0.56-0.74, p = 0.001). Conclusions Thickening of the SM bowel wall layer was found to be a new helpful indicator of active pediatric IBD, correlating well to endoscopic disease activity. For children, a SM thicker than 1 mm detected active IBD. A SM/BWT ratio &amp;gt;0.55 detected UC inflammation, but was not significant for CD. Possible explanations could be a more uniform thickening of the bowel wall in active CD compared to UC, but future research is needed. Funding Agencies North American Society For Pediatric Gastroenterology, Hepatology &amp; Nutrition (NASPGHAN); Department of Pediatrics, University of Alberta, Canada

Nutritional composition of diets for inducing and maintaining remission in inflammatory bowel diseases: from bedside to plate.

Abstract Background The etiology of ulcerative colitis (UC) remains elusive, with current evidence suggesting weakened mucosal barriers allow noxious luminal stimuli to escape the colonic lumen and trigger inflammation. Escherichia coli pathobionts, particularly of phylogroup B2, have been associated with active UC, however their role in disease is unclear. We previously showed that UC-associated E. coli p19A can penetrate the mucus barrier of UC air-liquid interface (ALI) monolayers. We hypothesize that E. coli pathobionts carried by UC patients degrade their colonic mucosal barriers, thereby contributing to the onset, severity, and chronicity of UC. Aims Using healthy and UC patient biopsy-derived colonic organoids and an ALI monolayer model, we investigated the ability of p19A as well as other E. coli isolates from UC patients to degrade human colonic mucus. Methods ALI monolayers from non-IBD and UC patients were grown, with apical mucus collected, then incubated with secreted proteins from E. coli p19A. Degraded mucus was detected by protein gel and MUC2 western blot. To expand our understanding of UC-isolated E. coli mucus degradation, we analyzed the phylogeny and the mucinases present in the genomes of 92 E. coli strains isolated from UC patients as well as assessed a subset of isolates ability to degrade human mucus. Results We show that p19A degrades human ALI monolayer-derived mucus, with UC ALI-mucus more readily degraded. We identified the known mucinases Pic and Vat in p19A and found a ΔpicΔvat mutant strain retained the ability to degrade mucus, suggesting another secreted protein(s) has mucinase activity. Phylogenetic analysis of 92 clinical E. coli isolates revealed 49% are clustered with IBD pathobionts like p19A. sslE, vat, and pic were the most common mucinase genes, present in 54%, 45%, and 30% of the E. coli isolates, respectively. In addition, nine E. coli isolates derived from four UC patients each harboured three known mucinase genes (pic, vat, and sslE). Mucus degradation assays using secreted proteins from a selected subset of ten phylogenetically distinct isolates (nine from phylogroup B2) revealed that five isolates could degrade both non-IBD and UC-ALI derived mucus, while an additional two isolates could degrade only UC-ALI derived mucus. Conclusions UC patients harbor E. coli strains that contain numerous mucinase genes, many of which can degrade human ALI monolayer-derived mucus, with UC-ALI mucus more easily degraded. Therefore, specific E. coli strains may act as pathobionts, weakening the mucosal barrier in UC patients, thereby contributing to the onset, severity, and/or chronicity of UC. Funding Agencies CCC, CIHRWeston Family Foundation (Canadian National Organoid Network)

Abstract Background Dietary carrageenans are thought to contribute to inflammatory bowel disease (IBD), increasing epithelial permeability and promoting inflammation, but studies have demonstrated conflicting evidence to date. Carrageenans are common food additives derived from red seaweed. In vitro and animal model evidence suggest that carrageenans may promote inflammatory response, altering the gut microbiome and mucosal thickness, disrupting the gut epithelial barrier, and activating innate immune pathways. Here, we investigated how carrageenan exposure in cell lines, human IBD biopsy-derived organoids, and human tissue explant cultures, affects inflammatory signalling, immune activation, and epithelial tight junction integrity and permeability. Aims The specific aims are to examine the impacts of λ, κ, or ι carrageenans on: 1) barrier function, and 2) immune responses. Methods T84 and Caco-2 epithelial cell lines and organoids derived from human colonic biopsies from IBD and non-IBD patients were used to interrogate barrier function and wound healing in response to λ, κ, or ι carrageenan (1mg/mL) using transepithelial electrical resistance (TEER) and FITC-dextran permeability assay, western blotting of cell protein lysates, scratch-wound assays, and Hematoxylin and Eosin (H&amp;E) staining of organoid monolayers. THP-1 macrophages and human tissue explants were cultures with carrageenans to evaluate immune response using multi-plex ELISA and immunohistochemistry. Results Addition of λ, κ, or ι carrageenan resulted in significantly lower TEER as compared to untreated controls, suggesting reduced barrier integrity. This response was exaggerated in organoids derived from active UC patients. Despite the alteration in TEER, there was no significant difference in tight junction proteins including (e.g., Claudin, Occludin). Wound healing was impaired by λ and κ carrageenan but not ι carrageenan. Organoids showed altered cell morphology and reduced crypt heights. All carrageenans induced pro-inflammatory cytokine secretion and immune activation in select gut biopsy explant cultures, although personalized responses were uncovered. Conclusions These findings demonstrate that carrageenans can induce immune activation and inflammation, along with altering epithelial barrier integrity. This highlights the importance of understanding the effects of commonly consumed additives and warrants further investigation into the factors involved in personalized response to carrageenans. Funding Agencies CIHRWeston Family Foundation

BackgroundThis study aimed to evaluate the association between low-cost inflammatory biomarkers and disease severity in ulcerative colitis (UC), with a focus on predicting acute severe ulcerative colitis (ASUC) and active disease (Mayo score >1).MethodsAn analytical cross-sectional study was conducted on 131 patients diagnosed with UC at Imam Khomeini Hospital, Iran, between 2022 and 2024. Demographic, clinical, and laboratory data - including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-to-albumin ratio (CAR), and faecal calprotectin - were collected. Disease activity was evaluated using the Mayo Endoscopic Score (MES). Statistical analyses included chi-square tests, ANOVA, and multivariable logistic regression adjusted for age, sex, and body mass index (BMI).ResultsThe mean age of participants was 45.8± 15.9 years. Elevated inflammatory markers were observed (CRP: 39.1 ± 32.6 mg/L; ESR: 44 .0± 21.5 mm/hr). Defecation frequency S6/day was significantly associated with ASUC (c2(2) = 101.10, p< 0.001). After adjustment, PLR in the third quartile (14-20) was independently associated with ASUC (O R = 2.57, p= 0.034). The percentage of monocytes was significantly higher in ASUC patients (F(1, 30) = 6.52, p= 0.016). No significant associations were found for NLR or CAR. PLR also differed significantly between active and inactive UC groups (median [ IQR] : 133.87 [96.15-190.63] vs. 129.61 [102.15-209.98], p= 0.029), although its discriminatory power was limited.ConclusionsPLR and monocyte percentage may serve as accessible indicators for assessing UC severity and identifying patients at risk for ASUC. These findings support the supplementary use of routine inflammatory blood indices in the management of UC, especially in resource-limited settings.

Our previous study revealed a correlation between fecal leukocyte esterase and fecal calprotectin levels. This study assessed the predictive value of fecal leukocyte esterase compared with fecal calprotectin and C-reactive protein of inflammatory bowel disease. Patients with inflammatory bowel disease who underwent ileocolonoscopy at National Taiwan University Hospital from March 2022 to March 2024 were included. Fecal leukocyte esterase and fecal calprotectin levels from stool samples collected within one month of endoscopy were analyzed. Active ulcerative colitis and Crohn's disease were defined as Mayo endoscopic score≥2 or simple endoscopic score for Crohn's disease≥7, respectively. Sensitivity, specificity, predictive values, and areas under the receiver operating characteristic curve were calculated using IBM SPSS Statistics29. Of the 203 patients (100 with ulcerative colitis and 103 with Crohn's disease), fecal leukocyte esterase levels were significantly correlated with fecal calprotectin levels (r=0.425, p<0.001) and endoscopic severity in ulcerative colitis (r=0.432, p<0.001) and Crohn's disease (r=0.311, p=0.001). For predicting Mayo endoscopic scores≥2 in ulcerative colitis using fecal leukocyte esterase, fecal calprotectin, and C-reactive protein, areas under the curve were 0.731, 0.785, and 0.558, respectively. For predicting simple endoscopic scores for Crohn's disease≥7, areas under the curve were 0.706, 0.800, and 0.770, respectively. No significant difference was observed between fecal leukocyte esterase and fecal calprotectin. Fecal leukocyte esterase correlates with fecal calprotectin and predicts endoscopic severity in inflammatory bowel disease.