Intestinal Research最新文献

Children diagnosed with inflammatory bowel disease (IBD) before the age of 6 years are considered to have "very early-onset IBD (VEO-IBD)," which is challenging to diagnose and treat. Notably, many children with VEO-IBD have monogenic forms of the disease, meaning that early genetic testing is useful. However, because the prevalence of genetic variants causing VEO-IBD differs globally, the diagnosis and treatment of this disease should be tailored to each region. In the present review paper, the IBD Subcommittee of the Scientific Committee of the Asia-Pacific Society of Pediatric Gastroenterology, Hepatology and Nutrition (APSPGHAN) has summarized the epidemiology, presenting features, diagnosis, and treatment of VEO-IBD in the Asia- Pacific region, with an aim to guide clinicians and researchers who work with VEO-IBD in this area. Our 3 main messages are as follows: endoscopy is essential for VEO-IBD diagnosis; all children diagnosed with VEO-IBD should be suspected of having a monogenic form; and children with suspected monogenic IBD should undergo early genetic testing. Our messages aim to improve the early diagnosis and treatment of VEO-IBD in the Asia-Pacific region, including the early detection of monogenic IBD in this area.

The gut microbiota, a complex community of trillions of microorganisms inhabiting the human gastrointestinal tract, has emerged as a critical regulator of immune homeostasis and gastrointestinal health. In the context of inflammatory bowel disease (IBD), comprising primarily Crohn's disease and ulcerative colitis, disruptions to this microbial ecosystem-collectively termed dysbiosis-have been increasingly recognized as central to disease pathogenesis. Recent research has established that alterations in gut microbiota not only reflect disease states but may actively drive immune dysregulation, barrier dysfunction, and mucosal inflammation. This review synthesizes current knowledge on the role of the gut microbiota in IBD and evaluates the therapeutic landscape of microbiota-modulating strategies using selected examples. Fecal microbiota transplantation, while offering proof-of-concept validation, is hindered by standardization challenges and variable clinical outcomes. As a response, microbiome-based therapeutics have evolved toward defined live biotherapeutic products including bacterial consortia and single-strain products, postbiotics, and metabolite-centered approaches targeting specific pathways. Groundbreaking research into rationally designed synthetic microbiomes and next-generation probiotics is driving a paradigm shift in microbiota-based treatment for IBD from empirical to precision-guided interventions.

Background/aims: Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract, and encompasses both ulcerative colitis (UC) and Crohn's disease (CD). Refractory disease is common, a combination of advanced drug therapies may be required to obtain maximal efficacy. We describe the use of upadacitinib therapy in combination with vedolizumab therapy for the management of refractory UC and CD.

Methods: In this retrospective observational study, patients who received upadacitinib in combination with vedolizumab were identified at a tertiary IBD center between November 2022 and March 2024. Patients were followed for 6 months with clinical, biochemical, endoscopic and intestinal ultrasound outcomes.

Results: Sixteen patients (7 with UC, 9 with CD) were identified. Median age was 44 years (range, 25-58 years), 11 (69%) were male, and median number of prior biologic exposures was 3 (range, 2-5). Twelve patients (75%) achieved clinical response, clinical remission, biochemical remission, corticosteroid-free clinical remission, and transmural remission by intestinal ultrasound. Eleven patients (69%) achieved endoscopic remission, with 4 (25%) achieving histological remission. Adverse events were seen in 8 patients (50%), but the majority were mild and did not require interruption of therapy.

Conclusions: Upadacitinib in combination with vedolizumab may have a role in refractory UC and CD patients who have previously failed to respond to standard therapy, with a favorable safety profile. Prospective studies are required to determine the safety and efficacy of this combination in larger cohorts before routine use can be recommended.

Background/aims: Despite international guidelines recommending against the use of 5-aminosalicylic acid (5-ASA) for Crohn's disease (CD), it remains widely prescribed. This study aimed to investigate current patterns of 5-ASA use and physicians' perceptions of its efficacy among Korean specialists.

Methods: A nationwide online survey was conducted in August 2025 targeting Korean gastroenterologists and colorectal surgeons managing inflammatory bowel disease. The questionnaire included 19 items addressing prescribing behaviors, perceived efficacy, and clinical decision-making regarding 5-ASA in CD.

Results: A total of 118 out of 124 physicians (95.2%) responded to the survey. The majority (67.8%) reported prescribing 5-ASA to more than half of their patients with CD. Standard to high doses ( > 2 g/day) were commonly used (94.9%), and timedependent formulations were preferred (92.4%). Although 55.1% used 5-ASA irrespective of disease location, it was frequently prescribed for colonic/ileocolonic disease (57.7%). Physicians primarily used 5-ASA in cases of non-active or mildly active CD. Notably, over 70% of respondents perceived 5-ASA to have a marginal yet beneficial effect on clinical remission, biomarker improvement, and mucosal healing. Approximately one-third of physicians reported continuing 5-ASA even after initiating biologics or small molecules.

Conclusions: This survey reveals a substantial gap between clinical guidelines and current practice in Korea regarding 5-ASA use for CD. Many physicians continue to view 5-ASA as a relevant option, particularly for patients with low inflammatory burden. These discrepancies likely reflect practical factors such as clinical experience and drug characteristics, which should be carefully considered before excluding 5-ASA from CD management.

Background/aims: Inflammatory bowel disease can be triggered by disturbances in intestinal mucosal integrity, leading to bacterial transmigration. The treatment of inflammatory bowel diseases must not only aim to reduce inflammation, but also to reverse the damage to mucosal barrier function. Janus kinase (JAK) inhibitors have been used to treat inflammatory diseases, including ulcerative colitis. However, little is known about the ability of this class of drugs to reverse the loss of mucosal integrity. This study evaluated the effects of tofacitinib, a JAK pathway inhibitor, on inflammation and colonic mucosal integrity in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis.

Methods: Colitis was induced in Wistar rats via rectal administration of TNBS (20 mg+50% ethanol). The control group received only saline. The animals were pretreated with tofacitinib (15 mg/kg) or saline 30 minutes before induction and twice daily thereafter. Seven days after induction, the animals were euthanized, the colon was removed, and myeloperoxidase activity, baseline transepithelial electrical resistance (TER), TER after 1 hour, and fluorescein permeability were assessed. Tight junction proteins in the colon (claudin-2, claudin-15, and tricellulin) were detected using Western blotting.

Results: Tofacitinib treatment significantly reduced (P< 0.05) the inflammatory parameters and preserved the integrity of the intestinal epithelial barrier compared with the colitis group (P< 0.05), increased baseline TER, reduced the drop in TER after 1 hour, and decreased paracellular permeability to fluorescein by reducing claudin-2 and claudin-15 expression.

Conclusions: JAK inhibition by tofacitinib restored colonic barrier function through antiinflammatory effects and decreased claudin-2 and claudin-15 expressions.

Background/aims: We compared intravenous and subcutaneous infliximab (IFX) as treatment for inflammatory bowel disease (IBD).

Methods: This retrospective, multicenter, observational study enrolled patients treated with either intravenous or subcutaneous IFX. Sequential parameters were compared at baseline, 6 months, and 12 months following the initiation of treatment with either type of IFX. The primary outcome was the comparison of the IFX trough levels after 12 months of treatment.

Results: In total, 183 participants were included in this study. After 6 months, the subcutaneous group exhibited significant differences compared to the intravenous group; in terms of clinical disease activity (0% vs. 15%, P= 0.007) and IFX trough level (21.72 ± 8.71 μg/mL vs. 7.70 ± 16.65 μg/mL, P= 0.002). After 12 months, subcutaneous, as compared to intravenous, achieved improved clinical disease activity (0% vs. 15%, P= 0.044) and IFX trough level (20.41 ± 12.91 μg/mL vs. 7.06 ± 6.81 μg/mL, P< 0.001). Analyzing the sequential changes compared with baseline data within each group, we observed significant alterations in subcutaneous; 6 months fecal calprotectin (676.3 ± 976.6 μg/g vs. 253.9 ± 483.9 μg/g, P= 0.014), 6 months IFX trough level (7.00 ± 5.67 μg/mL vs. 18.44 ± 6.34 μg/mL, P= 0.026), and 12 months IFX trough level (7.00 ± 5.67 μg/mL vs. 21.33 ± 4.50 μg/mL, P= 0.034).

Conclusions: This study indicates the potential suitability of subcutaneous IFX as an alternative treatment option for IBD.

Background/aims: Real-world data on the use of filgotinib (FILGO) in patients with ulcerative colitis (UC) are limited. This study aims to provide consistent results on the effectiveness and safety of FILGO in treating UC.

Methods: A retrospective assessment of clinical and endoscopic activity was conducted in a cohort of patients with UC according to the full Mayo score. The primary co-endpoints of the study were the evaluation of the effectiveness and safety of FILGO.

Results: We enrolled 102 patients with a median follow-up of 24 weeks (interquartile range, 8-24 weeks). At 8 weeks and the end of follow-up, clinical remission was achieved by 38 (37.2%) and 47 (46.1%) patients, respectively. Clinical remission was achieved in 13 of 18 patients (72.2%) receiving first-line therapy, 7 of 19 patients (36.8%) receiving second-line therapy, and 27 of 65 patients (41.5%) receiving third-line therapy (P= 0.002). Clinical remission at 8 weeks predicted clinical remission at the end of follow-up (P= 0.021). Age > 40 years (P= 0.046) and being on second- or third-line of treatment (P= 0.005) were negative predictors for clinical remission. Seventy-one patients (69.6%) achieved a clinical response. At endoscopic evaluation, mucosal healing was observed in 18 out of 30 patients (60.0%). Steroid-free remission was present in 38 out of 46 patients (82.6%). Five patients (4.9%) needed colectomy. Adverse events were recorded in 6 patients (5.8%): 2 cases (2%) were severe, requiring discontinuation of FILGO.

Conclusions: Our real-world data confirms that FILGO is safe and effective for patients with UC. Its efficacy is significantly improved when used as a first-line treatment.

Background/aims: Carotegrast methyl is a novel small-molecule drug that inhibits α4 integrin. It is prescribed for up to 6 months in patients with moderate ulcerative colitis who have demonstrated an inadequate response to or intolerance of 5-aminosalicylic acid. However, only a few clinical trials have been conducted to assess its effectiveness. This study aimed to evaluate the efficacy and safety of carotegrast methyl in patients with ulcerative colitis.

Methods: This multicenter retrospective study included patients with active ulcerative colitis treated with carotegrast methyl between March 2022 and October 2024. The primary outcome was the clinical remission rate following treatment with carotegrast methyl. Secondary outcomes included the clinical response rate, predictors of clinical remission, ulcerative colitis relapse rate after discontinuing carotegrast methyl, and incidence of adverse events.

Results: This study included 62 patients who received carotegrast methyl treatment. The median duration of administration was 84 days, with 48.4% of patients achieving clinical remission at the time of carotegrast methyl discontinuation. In 42 patients with corticosteroid/advanced therapies-naive disease, the clinical remission rate was 54.8%. Multivariate analysis identified the baseline partial Mayo score as an independent predictor of clinical remission. Among those who achieved clinical remission, 34.8% experienced a relapse with a median time to relapse of 152 days. Adverse events occurred in 8 patients, but none were serious.

Conclusions: Carotegrast methyl demonstrated good efficacy and safety, potentially benefiting patients with low baseline disease activity. This drug may be a useful treatment option to consider before systemic corticosteroid therapy for ulcerative colitis.