Trending Topics in Gastroenterology | GastroAGI

Upadacitinib in Perianal Crohn’s Disease: CGH | May 2026

Introduction Perianal Crohn’s disease (pCD) remains one of the most challenging manifestations of inflammatory bowel disease, often associated with fistulas, recurrent infections, impaired quality of life, and repeated surgeries. Although anti-TNF agents have been the cornerstone of therapy, many patients experience incomplete response or treatment failure. Upadacitinib (UPA), a selective JAK1 inhibitor, has shown promise in clinical trials, but real-world evidence in perianal disease has been limited. Problem Statement Management of perianal Crohn’s disease remains difficult because: Complex fistulas frequently persist despite biologic therapy Radiologic healing is difficult to achieve Long-standing disease often becomes refractory Real-world effectiveness data for newer agents like UPA are scarce The key question was: Can upadacitinib improve both clinical and radiologic outcomes in real-world perianal Crohn’s disease? Summary This multicenter North American study evaluated 125 patients with active perianal Crohn’s disease treated with upadacitinib. Most patients had severe disease, with nearly half having complex fistulas and over 75% previously exposed to anti-TNF therapy. The study demonstrated meaningful clinical improvement: Nearly 46% achieved clinical response Around 39% achieved clinical remission MRI improvement was seen in over half of patients Complete radiologic healing occurred in approximately 11% Hospitalization and surgery rates were relatively low during follow-up. Importantly, outcomes were significantly better in: Anti-TNF–naïve patients Patients with shorter disease duration Prior anti-TNF exposure predicted lower response rates, suggesting earlier introduction of UPA may yield better outcomes. Overall, this real-world study supports upadacitinib as a promising therapeutic option for perianal Crohn’s disease, particularly when used earlier in the disease course before multiple biologic failures occur.

Vaccination Uptake Remains Poor in Immunosuppressed IBD Patients : Frontline Gastroenterol | May 2026

Introduction Inflammatory bowel disease patients receiving immunosuppressive therapy are at increased risk of vaccine-preventable infections, including influenza, pneumococcal disease and COVID-19. International guidelines strongly recommend routine immunization in this vulnerable population, yet real-world vaccine adherence remains inconsistent. Problem Statement The COVID-19 pandemic has intensified vaccine hesitancy and misinformation, potentially worsening already suboptimal vaccination uptake in patients with IBD. Limited data exist regarding post-pandemic adherence patterns and barriers to immunization among immunosuppressed IBD populations. Summary This cross-sectional observational study demonstrated persistently low vaccination adherence among immunosuppressed patients with IBD in the post-pandemic era. Fewer than one-quarter of patients were fully vaccinated according to recommended schedules for pneumococcal, influenza and SARS-CoV-2 vaccines. Uptake was particularly poor for pneumococcal vaccination and COVID-19 booster doses, despite the heightened infection risk associated with immunosuppressive therapy. Importantly, healthcare professional–led counselling emerged as one of the strongest predictors of vaccine adherence, with patients receiving direct vaccine recommendations significantly more likely to complete immunization schedules. Older age was also associated with better vaccine uptake, suggesting younger patients may represent a particularly vulnerable group for vaccine hesitancy and misinformation. Commonly reported barriers included uncertainty regarding vaccine necessity, concerns about safety and lack of awareness regarding vaccine recommendations. Alarmingly, more than 40% of patients reported inadequate counselling before initiation of immunosuppressive therapy, highlighting major deficiencies in preventive care pathways. The study also demonstrated inconsistent delivery of vaccine recommendations across different vaccines, particularly for shingles vaccination. These findings reinforce the critical role of gastroenterologists, IBD nurses, pharmacists and primary care providers in proactively addressing vaccine education and preventive healthcare during routine IBD management. Overall, the study highlights an urgent need for structured vaccination pathways, standardized counselling protocols and multidisciplinary preventive care strategies to improve immunization adherence in immunosuppressed IBD populations.

A Pragmatic Prevention Framework for IBD in the Global South : Gut | 2026

Introduction Inflammatory bowel disease is rapidly emerging as a global disease, with rising incidence across low-income and middle-income countries. Although biologics and small-molecule therapies have transformed disease outcomes, long-term treatment remains costly, infrastructure-intensive and difficult to sustain in resource-constrained healthcare systems. Problem Statement Conventional IBD prevention and interception models—including biomarker screening, precision medicine and large-scale prevention trials—may be impractical in much of the Global South because of economic limitations, inadequate healthcare infrastructure and shortages of trained specialists. A scalable and economically feasible preventive strategy is urgently needed. Summary This conceptual review proposes a pragmatic prevention framework for IBD modeled on successful public health approaches used in non-communicable diseases such as metabolic syndrome and cardiovascular disease. The authors argue that rather than relying exclusively on expensive precision medicine strategies, IBD prevention in resource-limited regions should focus on modifiable environmental and lifestyle risk factors already linked to broader NCD prevention initiatives. The proposed “sieving strategy” prioritizes interventions that satisfy three key criteria: evidence supporting IBD prevention, overlap with established NCD prevention measures and economic feasibility for widespread implementation. Potential preventive targets include dietary modification, smoking reduction, physical activity promotion, obesity prevention, antibiotic stewardship and improvement in early-life environmental exposures. By integrating IBD prevention into existing NCD public health infrastructure, the framework aims to maximize scalability and cost-effectiveness while avoiding creation of parallel healthcare systems. The review also highlights major barriers to conventional prevention models, including limited access to advanced diagnostics, biologic therapies and population-level risk stratification tools in developing countries. Importantly, the authors emphasize that prevention-focused strategies may ultimately provide greater long-term population benefit than relying solely on escalating therapeutic complexity after disease onset. Overall, the article presents a highly relevant public health-oriented roadmap for addressing the growing burden of IBD in the Global South and advocates for prevention strategies grounded in equity, feasibility and population-level impact rather than resource-intensive precision approaches alone.

Jejunal Feeding Challenges in DGBI and GI Dysmotility : Frontline Gastroenterol | May 2026

Introduction Patients with disorders of gut–brain interaction (DGBI) and gastrointestinal dysmotility (GID) frequently experience severe nutritional compromise requiring enteral support. Jejunal feeding is often considered in patients unable to maintain adequate oral intake, particularly when gastric feeding intolerance or severe dysmotility exists. However, clinical practice in this area remains highly variable and evidence guiding management is limited. Problem Statement The experiences, confidence levels and perceptions of healthcare professionals managing jejunal feeding in DGBI and GID are poorly understood. Limited specialist neurogastroenterology access and uncertainty regarding feeding tolerance may contribute to inconsistent care pathways and suboptimal nutritional management. Summary This survey-based study evaluated healthcare professionals’ perceptions regarding jejunal feeding in patients with DGBI and gastrointestinal dysmotility. Most respondents were dietitians and physicians actively involved in nutritional support, although a striking majority reported limited access to specialist neurogastroenterology services. Clinicians perceived jejunal feeding to be more commonly required in severe gastrointestinal dysmotility disorders than in DGBI, reflecting the greater burden of objective motility impairment in GID. Interestingly, despite DGBI generally being considered less structurally severe conditions, respondents reported lower confidence managing these patients compared with those with GID. This likely reflects the complex overlap of visceral hypersensitivity, symptom amplification, psychosocial comorbidity and uncertainty surrounding pathophysiology in DGBI populations. Tolerance to jejunal feeding was also perceived to be poorer in DGBI compared with GID, with most clinicians reporting inability of patients to tolerate infusion rates above 50 mL/hour. Another important finding was the extremely high prevalence of opioid exposure across both groups, highlighting the growing concern regarding opioid-associated gut dysfunction and worsening dysmotility in these patients. The study emphasizes substantial gaps in specialist service provision and underscores the need for multidisciplinary neurogastroenterology-led nutritional pathways. It also highlights the importance of individualized feeding strategies, cautious opioid stewardship and further prospective research to optimize jejunal feeding protocols in complex DGBI and dysmotility populations.

Personalized Infliximab Dosing in ASUC: JCC | March 2026

Introduction Acute severe ulcerative colitis (ASUC) is a life-threatening condition requiring urgent treatment. In patients who fail steroids, Infliximab is widely used as rescue therapy. However, response is highly variable, and a significant proportion of patients still require colectomy despite treatment. One major limitation is the lack of individualized dosing strategies, as drug pharmacokinetics in ASUC are highly unpredictable due to inflammation, protein loss, and altered clearance. Problem Statement Standard infliximab dosing does not account for patient-specific pharmacokinetics, leading to suboptimal exposure and increased risk of colectomy in ASUC. Summary This multicenter study developed a pharmacokinetic-based model to personalize infliximab therapy in ASUC. The key finding was that infliximab exposure between weeks 2–4, adjusted for drug clearance (AUCw2–4/CL), strongly predicted colectomy risk within 90 days. Patients with low exposure (log AUC/CL < 5.79) were identified as high risk for colectomy, with good predictive accuracy (≈85%). The model incorporated simple clinical parameters such as body weight, CRP, and drug levels to estimate individualized drug exposure. This approach allows early identification of patients who may benefit from intensified dosing strategies, moving beyond fixed regimens toward precision therapy. Clinically, this represents a paradigm shift—from “one-size-fits-all” rescue therapy to personalized infliximab optimization—aimed at maximizing colectomy-free survival in ASUC.

Statins Reduce Stricture Risk in Crohn’s Disease: JCC | March 2026

Introduction Stricture formation is a major complication of Crohn’s disease, affecting more than half of patients and often leading to obstruction, repeated hospitalizations, and need for surgery. Current therapies primarily target inflammation, but effective strategies to prevent fibrosis and stricturing remain limited. Statins, widely used for cardiovascular disease, have demonstrated anti-inflammatory and anti-fibrotic properties, raising interest in their potential role in modifying disease progression in Crohn’s disease. Problem Statement Despite advances in biologic therapies, there are no proven pharmacological interventions that effectively prevent fibrotic complications like strictures in Crohn’s disease. Summary This large, real-world study evaluated the impact of statin use on stricture development in Crohn’s disease using two independent US population databases. In both cohorts, statin use was consistently associated with a significant reduction in the risk of new-onset intestinal strictures—approximately 28–29% risk reduction over a follow-up of around 3.5–4 years. The findings were robust across two large datasets and after propensity score matching, suggesting that the observed benefit is independent of confounding clinical variables and background IBD therapies. Mechanistically, statins may exert beneficial effects by reducing chronic inflammation and inhibiting fibrogenesis, which are central drivers of stricture formation in Crohn’s disease. Clinically, this study introduces the possibility of drug repurposing—using statins as a disease-modifying adjunct in Crohn’s disease to prevent long-term structural complications. However, given the observational design, prospective randomized trials are needed before routine clinical adoption. Overall, this study highlights a promising, low-cost, and widely available strategy to potentially alter the natural history of Crohn’s disease by targeting fibrosis rather than inflammation alone.

Colitis-Associated CRC: Nature Reviews Gastroent & Hepatol | April 2026

Introduction Colitis-associated colorectal cancer (caCRC) represents a distinct subtype of colorectal cancer that develops in patients with long-standing Inflammatory Bowel Disease, particularly Ulcerative Colitis and Crohn’s Disease. With the rising global burden of IBD, the population at risk for caCRC is steadily increasing. Unlike sporadic colorectal cancer, caCRC arises in a background of chronic inflammation, leading to unique molecular, cellular, and microenvironmental changes that influence tumor initiation and progression. Problem Statement Despite improved control of inflammation in IBD, caCRC remains a major clinical challenge because its pathogenesis is complex, heterogeneous, and fundamentally different from sporadic colorectal cancer, making early detection, risk stratification, and targeted therapy difficult. Summary This review highlights that caCRC is driven primarily by chronic inflammation-induced epithelial damage and regeneration. Persistent barrier disruption accelerates epithelial aging and promotes early genetic alterations—particularly early loss of p53, unlike the adenoma–carcinoma sequence seen in sporadic colorectal cancer. Inflammatory pathways such as IL-17 and NF-κB play a central role in early tumorigenesis. The tumor microenvironment is equally critical, involving dynamic interactions between epithelial cells, immune cells, cancer-associated fibroblasts, and the gut microbiome. Dysbiosis further amplifies inflammatory signaling and tumor promotion. caCRC is also characterized by rapid progression and a tendency toward mesenchymal tumor phenotypes, contributing to aggressive behavior. Importantly, the review emphasizes that future management will likely shift toward personalized strategies targeting inflammation, microbiome modulation, immune pathways, and stromal interactions to prevent and treat caCRC more effectively.

Multiomic Insights into Guselkumab Response in UC: BMJ Open Gastroenterology | March 2026

Introduction Ulcerative colitis is a chronic inflammatory disorder driven by dysregulated immune pathways, with the interleukin-23 (IL-23)/Th17 axis playing a central pathogenic role. Modern treatment strategies have shifted toward achieving deep remission, including histological and endoscopic healing, rather than symptom control alone. Guselkumab, a selective IL-23p19 inhibitor, has demonstrated clinical efficacy in moderate-to-severe disease. However, the molecular and cellular mechanisms underlying its therapeutic benefit remain incompletely understood, particularly in relation to mucosal healing and tissue-level remission. Problem Statement While clinical trials have confirmed the efficacy of IL-23 inhibition, there is a critical gap in understanding how these therapies translate into molecular remission. Specifically, the absence of integrated multiomic data limits the ability to define biomarkers of response, predict outcomes, and refine precision medicine approaches in ulcerative colitis. Summary This Phase IIb QUASAR multiomic analysis demonstrates that guselkumab induces early and sustained suppression of systemic and mucosal inflammatory pathways. Treatment reduced pro-inflammatory cytokine signatures and downregulated IL-23/Th17-driven transcriptional activity, while simultaneously promoting epithelial repair mechanisms. Single-cell and transcriptomic analyses revealed a decrease in inflammatory monocytes, fibroblasts, and plasma cells, alongside an increase in epithelial and reparative cell populations in responders achieving histo-endoscopic mucosal improvement at 12 weeks. These findings establish a biological basis for deep remission, linking IL-23 blockade to both immune suppression and mucosal restoration. Importantly, this study lays the groundwork for molecular definitions of remission and predictive biomarkers, advancing precision therapy in ulcerative colitis.

Colorectal Surveillance in IBD: Updated BSG Guidance: Gut | 2026

Introduction The updated British Society of Gastroenterology guideline reflects an important change in the way we think about colorectal cancer surveillance in inflammatory bowel disease. The modern message is not that every patient with colonic IBD should automatically undergo the same surveillance forever, but that surveillance should be more precise, more individualised, and more closely linked to actual cancer risk. Although the risk of colorectal cancer in IBD is lower than older literature suggested, it still remains meaningfully higher than in the general population, especially in those with longstanding colitis, persistent inflammation, primary sclerosing cholangitis, dysplasia, strictures, or extensive disease. The guideline, therefore, shifts the field from a rigid surveillance model to a risk-adapted, quality-driven, patient-centred approach. Key Points Patients with colonic IBD still have a higher risk of colorectal cancer and colorectal cancer-related death than the general population, even in the modern treatment era. The risk is no longer as high as older historical studies suggested, which means surveillance should now be more personalised rather than automatically intensive for everyone. Surveillance colonoscopy should begin 8 years after symptom onset in patients with colonic IBD. In patients with primary sclerosing cholangitis, surveillance should begin immediately at diagnosis because this remains one of the highest-risk groups. Patients with ulcerative proctitis alone or Crohn’s disease without colonic involvement generally do not need IBD-specific surveillance and should instead follow population screening pathways. Persistent inflammation is the single most important modifiable driver of colorectal neoplasia in IBD, so mucosal healing is also a cancer prevention strategy. Surveillance intervals should be based on risk, with annual surveillance for high-risk patients, 3-yearly surveillance for intermediate-risk patients, and much less frequent reassessment for very low-risk patients. Some patients with very low inflammatory burden and no additional risk factors may have a colorectal cancer risk close to the general population and may not need lifelong intensive surveillance. The guideline strongly supports use of multivariable risk assessment rather than relying only on the single highest risk factor. A major practical advance is the use of the web-based IBD dysplasia risk calculator, which helps clinicians individualize surveillance intervals more accurately. Post-colonoscopy colorectal cancer is substantially more common in IBD than in sporadic colorectal cancer, showing that surveillance quality matters as much as surveillance frequency. Many failures in surveillance are caused by delayed colonoscopy, missed appointments, poor systems, and inadequate follow-up rather than by biology alone. High-definition colonoscopy should now be considered the standard for IBD surveillance, and standard-definition colonoscopy is no longer adequate. Dye-based chromoendoscopy offers an additional benefit for dysplasia detection and remains the preferred enhanced imaging technique when expertise is available. Current artificial intelligence systems are not yet ready for routine IBD dysplasia surveillance because they have not been adequately trained for IBD-specific lesions. Targeted biopsies are preferred in most surveillance procedures, but random or segmental biopsies still have a role in selected high-risk settings such as PSC, previous dysplasia, retained rectum, or pouch surveillance. Most visible dysplastic lesions in colitis-affected segments can now be managed endoscopically, ideally with complete en bloc resection, rather than proceeding directly to surgery. Invisible dysplasia remains a serious finding and should always trigger repeat expert colonoscopy with chromoendoscopy and careful mapping biopsies within a short interval. Multifocal invisible low-grade dysplasia or invisible high-grade dysplasia usually shifts management toward colectomy because the future cancer risk is high. Every case of dysplasia in a colitis-affected segment should be discussed in a multidisciplinary team because management decisions now depend on lesion visibility, grade, resectability, patient risk factors, and patient preference. Conclusion This updated BSG guideline brings colorectal surveillance in IBD firmly into the era of precision medicine. Its most important message is that surveillance should no longer be viewed as a uniform lifelong protocol, but as a carefully tailored strategy based on inflammatory burden, dysplasia risk, colonoscopy quality, and patient-specific factors. For the practicing clinician, the real advances are the move toward dynamic risk stratification, the emphasis on high-quality high-definition colonoscopy, the selective use of chromoendoscopy and biopsies, and the recognition that many patients can be managed more intelligently rather than simply more intensively.

JAK Inhibitors in ASUC: A Systematic Review: AJG March 2026

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.