IBD

Acute severe ulcerative colitis (ASUC) is a life-threatening complication of ulcerative colitis that often requires hospitalisation and urgent therapy. Although intravenous corticosteroids remain the standard first-line treatment, a significant proportion of patients fail to respond and require rescue therapy or colectomy. Janus kinase (JAK) inhibitors, such as tofacitinib and upadacitinib, have emerged as rapidly acting oral immunomodulators and are increasingly being explored as therapeutic options in ASUC. This systematic review and meta-analysis evaluated the effectiveness and safety of JAK inhibitors in ASUC by analysing 35 studies including 664 patients. In the short term (<1 month), clinical response rates were high, reaching 77.9% with tofacitinib and 86.5% with upadacitinib, with colectomy rates around 11% for both drugs. At intermediate follow-up (<3 months), pooled clinical response and remission rates remained moderate, with remission observed in 37.3% (tofacitinib) and 47.4% (upadacitinib) of patients. In the long term (3–12 months), sustained clinical response and remission rates ranged from 33%–41%, while colectomy rates were approximately 22%–23%. Safety outcomes were acceptable. Adverse events included venous thromboembolism (2.2%), herpes zoster infection (3.4%), and major adverse cardiovascular events (0.7%), all occurring at relatively low frequencies. Importantly, high-dose tofacitinib did not demonstrate superior efficacy compared with standard dosing. Overall, the analysis suggests that JAK inhibitors are effective and reasonably safe as adjunct therapy with corticosteroids or as rescue therapy in steroid-refractory ASUC. However, the authors emphasize that well-designed randomized controlled trials are still required to clearly define their optimal role in ASUC management.

Introduction Ulcerative colitis (UC) in children is often aggressive and difficult to manage, with many patients failing conventional therapies such as corticosteroids, immunomodulators, biologics, or JAK inhibitors. Mirikizumab, a humanised monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has demonstrated efficacy in adults with UC and Crohn’s disease. However, evidence in the paediatric population remains limited. The SHINE-1 trial was designed to evaluate the pharmacokinetics, efficacy, and safety of mirikizumab in children with moderately-to-severely active UC who had inadequate response or intolerance to prior therapies. Summary SHINE-1 was a 52-week, multicentre, open-label phase 2 trial conducted across 19 centres in North America, Asia, and Israel. A total of 26 paediatric patients (2–<18 years) with moderate-to-severe UC received weight-adjusted intravenous mirikizumab at weeks 0, 4, and 8, followed by subcutaneous maintenance therapy. At week 12, clinical response rates were encouraging: 69% achieved clinical response, and 38.5% achieved clinical remission based on the modified Mayo score. Endoscopic remission occurred in 53.8%, and symptomatic remission in 46.2% of patients. At week 52, sustained efficacy was observed: 53.8% maintained clinical response 38.5% remained in clinical remission 50% achieved remission based on Pediatric Ulcerative Colitis Activity Index (PUCAI) 38.5% achieved corticosteroid-free remission Safety outcomes were acceptable. Only 12% experienced serious adverse events, and treatment discontinuation occurred in one patient (4%). The most common adverse events included COVID-19 infection, injection-site pain, headache, and fever. Conclusion The SHINE-1 trial demonstrates that mirikizumab is a promising IL-23–targeted therapy for paediatric moderate-to-severe ulcerative colitis, showing meaningful clinical, endoscopic, and symptomatic improvements with an acceptable safety profile. These findings support larger controlled trials to confirm its role in paediatric UC management.

The ACCURE randomised clinical trial investigated whether laparoscopic appendicectomy could improve disease outcomes in ulcerative colitis (UC) when added to standard medical therapy. The rationale for this approach stems from evidence suggesting that the appendix may play an immunomodulatory role in UC, influencing intestinal inflammation and disease relapse. In this multicentre international randomised trial conducted across the Netherlands, Ireland, and the UK, patients with established UC in remission but with a relapse within the previous year were assigned to either: Appendicectomy plus maintenance medical therapy, or Medical therapy alone. After 12 months of follow-up, the appendicectomy group demonstrated significantly better outcomes: Relapse rate: 36% after appendicectomy vs 56% with medical therapy alone. Relative risk reduction: about 35% lower relapse risk. Patients undergoing appendicectomy were also less likely to require escalation to biologic therapy and had improved quality-of-life measures. The procedure was generally safe, with only a small number of postoperative complications and no deaths reported. Key Clinical Message This landmark study provides the first randomised evidence that appendicectomy can reduce relapse rates in ulcerative colitis when added to standard therapy. It suggests that the appendix may contribute to UC pathogenesis and that appendicectomy could become an adjunctive therapeutic strategy, particularly in patients with recurrent disease despite conventional therapy.

Vedolizumab, a gut-selective monoclonal antibody targeting α4β7 integrin, is widely used for the treatment of Crohn’s disease and ulcerative colitis, but safety data during pregnancy have been limited. This prospective observational study from the Vedolizumab Pregnancy Exposure Registry (2015–2022) evaluated pregnancy outcomes among women exposed to vedolizumab. The registry included 275 pregnant women from the United States and Canada, divided into three groups: vedolizumab-exposed (n=99), disease-matched women receiving other biologics (n=76), and healthy unexposed controls (n=100). Mothers and infants were followed for one year postpartum, assessing major birth defects, pregnancy loss, preterm delivery, infections, growth abnormalities, malignancies, and developmental milestones. Among pregnancies resulting in live births, major birth defects occurred in 7.4% of vedolizumab-exposed infants compared with 5.6% in the disease-matched biologic group, showing no statistically significant difference (adjusted risk ratio 1.07). Similarly, rates of spontaneous abortion and preterm delivery were not significantly increased in the vedolizumab group. No increased risk was observed for infections, growth abnormalities, or developmental outcomes in infants. Overall, the registry found no significant safety signals associated with vedolizumab exposure during pregnancy. These findings provide reassuring prospective evidence supporting the continued use of vedolizumab in pregnant women with inflammatory bowel disease when clinically indicated.

Introduction Diet plays an important role in the pathogenesis and management of inflammatory bowel disease (IBD). Among various dietary patterns, the Mediterranean diet (MD)—rich in fruits, vegetables, whole grains, olive oil, legumes, nuts, and fish—has been associated with anti-inflammatory and microbiome-modulating effects. Because chronic intestinal inflammation in IBD is influenced by diet, there is growing interest in evaluating whether the Mediterranean diet could serve as an adjunctive therapeutic strategy alongside standard medical therapy. Summary This systematic review and meta-analysis evaluated the effectiveness of the Mediterranean diet in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Key findings: Eight studies were included in the analysis. Seven studies (223 patients) provided data on remission outcomes. The pooled clinical remission rate with the Mediterranean diet was 62% (95% CI 0.39–0.80). Remission rates were similar between Crohn’s disease and ulcerative colitis: CD: RR 0.67 UC: RR 0.56 When compared with control diets, the Mediterranean diet did not show a statistically significant advantage for inducing remission (OR 0.98). Endoscopic and histological outcomes were not reported in the available studies. Conclusion The Mediterranean diet, when used alongside conventional medical therapy, is associated with a moderate clinical remission rate (~62%) in IBD, with comparable benefits in both CD and UC. However, current evidence is limited by small sample sizes, heterogeneity in study design, and lack of objective outcomes such as endoscopic healing. Further well-designed randomised controlled trials are required to determine the true impact of the Mediterranean diet on mucosal healing, disease activity, and long-term outcomes in IBD.

Introduction Most microbiome studies in inflammatory bowel disease (IBD) are confounded by prior treatment, long disease duration, and inconsistent sequencing/bioinformatic methods—making “core” signatures hard to trust. This systematic review tackles a key unmet question: what does the gut microbiome look like at diagnosis, before therapy starts? The authors go a step further than conventional meta-analysis by reprocessing raw 16S sequence datasets through a single unified pipeline mapped to updated taxonomy, aiming to identify reproducible microbial perturbations in treatment-naïve new-onset Crohn’s disease (CD) and ulcerative colitis (UC). Summary Across 36 eligible studies, 18 contributed raw sequencing data for unified reanalysis and 24 contributed to supplementary meta-analysis. The pooled dataset included samples from 1743 individuals (CD, UC, healthy controls, and symptomatic non-IBD controls), with a large proportion of mucosal biopsies. Standard meta-analysis proved unreliable due to extreme methodological heterogeneity, so the central contribution was the unified QIIME2 reprocessing with multivariable modeling (MaAsLin2) adjusting for sample type, age group, geography, and sequencing differences. Key findings were consistent across CD and UC at disease onset: depletion of obligate anaerobes and enrichment of aerobic, facultative anaerobic, and microaerophilic bacteria, alongside a striking enrichment of orally associated genera in the gut. Importantly, fecal and mucosal biopsy communities were clearly distinct, and geography also shaped community structure—reinforcing why harmonised reanalysis is necessary. The authors interpret the pattern as support for the “oxygen hypothesis” in early IBD—where inflamed mucosa increases luminal oxygenation, disadvantaging anaerobes and enabling oxygen-tolerant and oral taxa to expand. Clinically, these core signatures may aid earlier diagnosis and risk prediction, and therapeutically they point toward microbiome-targeted strategies—potentially including interventions that alter luminal oxygen availability—especially relevant at diagnosis and in high-risk groups.

Why Look Beyond Fecal Calprotectin? Fecal calprotectin (FC) is one of the most widely used noninvasive biomarkers in inflammatory bowel disease (IBD). It reflects intestinal inflammation through the detection of the S100A8/S100A9 heterotetramer, released primarily from neutrophils. However, FC measurement traditionally focuses on the tetrameric complex, without distinguishing between different molecular configurations of its subunits. Emerging evidence suggests that S100A8 and S100A9 homodimers may have distinct biological and inflammatory functions. In particular, fecal S100A9 has attracted attention as a potentially more sensitive indicator of disease activity and chronic intestinal inflammation. This study explores whether analysing these specific subunits can improve disease monitoring and uncover new therapeutic targets in IBD. Summary Using advanced proteomic analysis, investigators characterized the structural forms of S100A8 and S100A9 proteins present in stool from patients with inflammatory bowel disease. Besides the classic calprotectin heterotetramer, high levels of S100A8 and S100A9 homodimers were detected in active disease. Importantly, fecal S100A9 levels correlated strongly with clinical and endoscopic activity, even in patients with relatively low fecal calprotectin concentrations, suggesting added diagnostic sensitivity. Functional experiments demonstrated that oral exposure to recombinant S100A8 or S100A9 homodimers, but not the calprotectin tetramer, aggravated intestinal inflammation in mouse models of colitis. Mechanistic studies showed that these homodimers enhance activation of CD4⁺ and CD8⁺ T cells, thereby amplifying inflammatory responses. Conversely, genetic deletion of S100a9 protected mice from experimental colitis, and pharmacologic inhibition of S100A9 significantly reduced chronic intestinal inflammation. Together, these findings suggest that fecal S100A9 dimers represent both a novel biomarker and a potential therapeutic target in IBD, linking biomarker detection directly with pathogenic mechanisms of chronic intestinal inflammation.

Introduction The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) was developed to standardise the endoscopic assessment of ulcerative colitis activity. It evaluates vascular pattern, bleeding, and erosions/ulcers, generating a score reflecting disease severity. Although initially described with a range of 3–11, subsequent validation rebased the scoring system to 0–8, making a completely normal colonoscopy score 0. Despite this revision, confusion about the correct scoring persists in clinical practice and literature. Summary This commentary highlights ongoing misconceptions regarding the UCEIS scoring system and emphasises the importance of adopting the validated 0–8 scale. The rebasing from 3–11 to 0–8 improved clinical interpretation, so a normal colonoscopy now scores 0 rather than 3. However, surveys among inflammatory bowel disease specialists revealed that over one-third still believe a normal colonoscopy corresponds to a score of 3. Literature review also identified multiple publications, guideline documents, and online calculators continuing to reference the outdated scale. This inconsistency may influence research and clinical decision-making, as UCEIS is increasingly used to guide treatment escalation and predict outcomes, including response to intravenous steroids in acute severe ulcerative colitis. The authors call for universal adoption of the validated scoring system and improved educational resources, including standardised image examples for each descriptor. Establishing a common understanding of UCEIS is essential for reliable communication, accurate disease assessment, and consistency across clinical care and research in ulcerative colitis.