Trending Topics in Gastroenterology | GastroAGI

Mirikizumab in Paediatric UC (SHINE-1 Trial): Lancet Gastroentrol Hepatolo, February 2026

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.

ACCURE Trial (Appendectomy and UC): Lancet Gastro Hepato, March 2026

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 and Pregnancy: Am J Gastro, March 2026

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.

Mediterranean Diet in IBD: IJG March 2026

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.

Microbiome Signature at IBD Onset: Gastroenterology | March 2026

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.

Faecal S100A9- A new IBD Biomarker: Gastroenterology | March 2026

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.

A Normal UCEIS Is Zero, not Three: Gastroenterology | March 26

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.

VECTORS Trial - BMJ Open Gastro Feb. 26

The VECTORS trial, a landmark phase 4 randomized controlled trial (RCT), was recently published in *BMJ Open Gastroenterology* on February 26. This trial represents a significant step forward in the treatment of Crohn’s disease (CD) by evaluating transmural healing (TMH) as a novel treatment target. The trial explores the potential benefits of targeting deeper levels of disease control beyond the traditional focus on mucosal healing. ### Key Highlights of the VECTORS Trial: #### Purpose and Rationale: - **Transmural Disease in Crohn's**: CD is a transmural inflammatory disease, meaning it affects the entire bowel wall, not just the mucosal lining. Historically, treatment targets have focused on symptom relief or mucosal healing seen through colonoscopy. However, these targets may not address the deeper, transmural nature of the disease. - **Transmural Healing (TMH)**: The trial aims to evaluate TMH as a treatment goal, hypothesising that it could offer more comprehensive disease control, reduce complications, and improve long-term outcomes. #### Trial Design: - **Phase**: Phase 4, multicenter RCT. - **Participants**: 304 patients with moderately to severely active Crohn’s disease. - **Sites and Countries**: Conducted across 66 sites in 13 countries. - **Novel Monitoring Tool**: The trial uses intestinal ultrasound (IUS), a non-invasive, radiation-free, and repeatable imaging tool to monitor TMH. IUS offers real-time insights into bowel wall inflammation, making it a game-changer for tight disease monitoring. #### Treatment Comparison: The trial compares two treatment strategies: 1. **Corticosteroid-free TMH Remission Group**: - TMH assessed via serial IUS. - Combined with clinical and biomarker remission. 2. **Corticosteroid-free Clinical and Biomarker Remission Group**: - Focuses only on clinical and biomarker remission without TMH as a target. #### Endpoints: - **Primary Endpoint**: Corticosteroid-free endoscopic remission at week 48. - **Key Secondary Endpoint**: CD-related complications through week 96, such as strictures, fistulae, and surgeries. ### Why the VECTORS Trial Matters: 1. **Pushes the Boundaries of Treatment**: By moving beyond mucosal healing to target the entire bowel wall, the trial addresses the full scope of Crohn’s disease pathology. 2. **Validates IUS**: Demonstrates the utility of intestinal ultrasound as a safe, accessible, and radiation-free tool for real-time disease monitoring. 3. **Potential to Reduce Complications**: TMH could help prevent long-term complications like strictures, fistulae, and surgeries, which are common in Crohn's disease. 4. **Influences Clinical Guidelines**: If successful, the trial could lead to updated clinical guidelines emphasising TMH as a formal treatment target. 5. **Builds on Previous Successes**: Builds on the "treat-to-target" approach established by prior trials like CALM, but takes it a step further by targeting deeper disease control. ### Summary of Implications: 1. Current treatment targets, such as mucosal healing, may be insufficient to address the transmural nature of Crohn’s disease. 2. TMH could offer a more comprehensive approach to disease management, potentially improving long-term outcomes for patients. 3. The use of IUS as a monitoring tool is a significant advancement, offering a fast, cost-effective, and non-invasive alternative to traditional imaging methods. 4. The VECTORS trial is the first RCT to rigorously test TMH as a treatment target, and its findings could have substantial real-world implications for both patients and clinicians. In conclusion, the VECTORS trial is a groundbreaking study that could redefine treatment strategies for Crohn’s disease, emphasizing the importance of transmural healing and the role of innovative tools like intestinal ultrasound in achieving better patient outcomes.

Caffeine and IBD - JGH Feb 26

This is the first comprehensive meta-analysis examining the relationship between caffeine intake and inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), synthesising data from 21 studies (13,209 participants). Overall, caffeine intake was not significantly associated with total IBD risk. However, important differences emerged in subgroup analyses. For ulcerative colitis, caffeine—particularly from coffee and tea—was associated with a reduced risk, especially in Asia and Europe. Coffee reduced UC risk by 57%, and tea by 46%. In contrast, in the Americas, caffeine intake was associated with an increased UC risk. For Crohn’s disease, no overall association was observed. However, in smokers, caffeine intake increased CD risk by 80%, whereas in non-smokers, the association was neutral or potentially protective. Education level also influenced findings, suggesting lifestyle and socioeconomic confounding. Age was a critical modifier: in individuals ≤18 years, caffeine was associated with markedly increased IBD risk, whereas in adults, the association was neutral to slightly protective. Clinical implications: The relationship between caffeine and IBD appears context-dependent—varying by age, geography, smoking status, and caffeine source. Blanket recommendations are inappropriate. Instead, clinicians should individualise advice, particularly for adolescents and smokers. Further dose-response and mechanistic studies are needed to clarify causality.

Subcutaneous Guselkumab for Crohn’s: Interpreting GRAVITI Carefully- Gastroenterology Feb.26

Introduction Fully subcutaneous biologic regimens are attractive in Crohn’s disease because they can reduce infusion burden and improve convenience. The GRAVITI trial evaluated a fully subcutaneous induction and maintenance strategy with guselkumab (IL-23p19) and reported improvements in clinical remission and endoscopic response through 48 weeks. The key questions raised for GRAVITI 1) Does the endoscopic endpoint reliably reflect inflammation (vs fibrosis)? The coprimary endoscopic endpoint relied on improvement in SES-CD. The critique highlights a real-world limitation: SES-CD can over-score fibrostenotic segments as “active” disease, potentially inflating perceived response. This concern is most relevant in ileal-predominant Crohn’s, where fibrostenotic disease is common. Clinical implication: If fibrotic strictures are misclassified as inflammatory activity, “endoscopic response” may not always mean the drug is reversing active inflammation. What would strengthen confidence: histologic correlation (where feasible), imaging stratification (e.g., MRE features of fibrosis vs inflammation), or predefined exclusion of fixed fibrotic strictures. 2) Does crossover/rescue design distort placebo vs drug comparisons? A major critique is that a substantial proportion of placebo patients crossed over to active therapy early and were then counted as “nonresponders” for placebo in longer-term analyses. Why clinicians should care: This can make: placebos look artificially low long-term, and Active therapy looks stronger by comparison. What would help: reporting outcomes for rescued participants as a separate analytic group, sensitivity analyses that show how rescue impacts the effect size. 3) Is the SC induction dose “validated,” especially in higher-clearance subgroups? The SC induction regimen appears to have been extrapolated from IV data using assumed bioavailability, rather than derived from dedicated SC dose-ranging. The critique emphasises that: Some patients (e.g., higher BMI) may have altered clearance, and without pharmacokinetic (PK) and exposure–response analyses, it’s hard to know whether the SC dose is optimised. Clinical implication: In real practice, heterogeneous PK could mean variable efficacy—especially in patients who need rapid disease control. What would help: through levels and exposure–response relationships, subgroup analyses by BMI, and explicit discussion of underdosing risk vs safety margin. 4) How does SC guselkumab compare with IV induction (the established route)? Even if SC regimens are convenient, clinicians want to know: Is SC truly noninferior to IV for induction? Are there differences in early control, durability, or safety? The critique argues that cross-trial comparisons are not enough, and head-to-head or noninferiority designs would provide the clarity needed to guide route choice. Additional pragmatic points raised Prior IL-23 exposure: With increasing real-world use of IL-23 agents, the key question is whether guselkumab works after prior IL-23p19 therapy (class effect vs meaningful differences). Durability beyond 48 weeks and “deep remission” outcomes: endoscopic healing, sustained steroid-free remission, and persistence/adherence matter for practice. Health system implications: SC induction reduces infusion-centre burden but shifts monitoring and adherence responsibility—raising the need for cost-effectiveness and implementation studies. Bottom-line takeaway: GRAVITI supports the feasibility of fully subcutaneous guselkumab in Crohn’s disease, but important uncertainties remain about endpoint interpretation (fibrosis vs inflammation), rescue-related bias, PK validation across patient subgroups, and how SC compares directly with IV induction. Clinicians should view the results as promising, not definitive, and await more granular analyses and head-to-head data before changing protocols broadly. One-line GastroAGI takeaway SC guselkumab in Crohn’s looks promising—but GRAVITI’s design leaves key unanswered questions about “true” endoscopic benefit and real-world dosing.