Intestinal Research最新文献

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis, is a chronic condition marked by immune dysregulation, genetic predisposition, and metabolic disturbances. Emerging evidence highlights the role of lipid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling in modulating immune responses in IBD. PPAR-γ and PPAR-α regulate macrophage polarization, T-cell differentiation, and epithelial barrier integrity, influencing disease severity and progression. Alterations in PPAR activity contribute to metabolic stress and inflammation, linking IBD pathophysiology to immunometabolism. Studies suggest that targeting PPARs may mitigate inflammation through modulation of cytokine production, immune cell function, and gut microbiota interactions. In this review, we focus specifically on CD and explore how PPAR signaling intersects with mesenteric adipose tissue dysfunction and microbial dysbiosis, 2 hallmark features of CD. PPAR agonists, already used in metabolic-inflammatory diseases such as metabolic-associated liver disease, have demonstrated antiinflammatory effects in experimental colitis models. Translating these findings into clinical applications could offer novel treatment strategies for CD. Future research should focus on clinical trials, genetic studies, and microbiota-targeted approaches to elucidate PPAR-driven mechanisms in CD pathogenesis. Understanding the interplay between PPARs, lipid metabolism, and immune responses may lead to innovative therapeutic strategies, improving disease management and patient outcomes.

Background/aims: Inflammatory bowel disease (IBD) has become a global health concern. With the growing evidence of the gut microbiota's role in IBD, studying microbial compositions across ethnic cohorts is essential to identify unique, populationspecific microbial signatures.

Methods: We analyzed stool samples and clinical data from 254 IBD patients (226 ulcerative colitis, 28 Crohn's disease) and 66 controls in northern India using metagenomic shotgun sequencing to assess microbiota diversity, composition, and function. Results were replicated in 436 IBD patients and 903 controls from the Netherlands using identical workflows. Using machine learning, we evaluated the generalizability of Indian IBD signals to the Dutch cohort, and vice versa.

Results: Indian IBD patients exhibited reduced bacterial diversity and an abundance of opportunistic pathogens, including Clostridium, Streptococcus, and oral bacteria like Streptococcus oralis and Bifidobacterium dentium. There was a significant loss of energy metabolic pathways and distinct co-occurrence patterns among microbial species. Notably, 39% of these signals replicated in the Dutch cohort. Unique to the Indian cohort were oral pathobionts such as Scardovia, Oribacterium, Actinomyces dentalis, and Klebsiella pneumoniae. Both Indian and Dutch IBD patients shared reduced butyrate producers. Machine-learning diagnostic models trained on the Indian cohort achieved high predictive accuracy (sensitivity 0.84, specificity 0.95) and moderately generalized to the Dutch cohort (sensitivity 0.77, specificity 0.69).

Conclusions: IBD patients across populations exhibit shared and unique microbial signatures, suggesting a role for the oral-gut microbiome axis in IBD. Crossethnic diagnostic models show promise for broader applications in identifying IBD.

Background/aims: Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy.

Methods: This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression).

Results: Overall, 332 patients with UC (176 biologic-naïve and 156 biologic-non-naïve) were included. Significantly more biologic-naïve than biologic-non-naïve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05-1.94; P= 0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P< 0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30-4.48; P= 0.0052; biologic-naïve patients: OR, 2.40; 95% CI, 1.10-5.24; P= 0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use.

Conclusions: Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363).

Background/aims: Carotegrast methyl, an oral α4-integrin inhibitor, was recently approved for the treatment of active ulcerative colitis (UC). However, real-world data regarding its efficacy and safety remain scarce. This study aimed to assess the clinical effectiveness and safety profile of carotegrast methyl in patients with active UC.

Methods: Patients with active UC received carotegrast methyl at a dosage of 960 mg three times daily. Treatment was discontinued at 8 weeks for patients who achieved endoscopic remission. For those not achieving endoscopic remission, treatment was continued for up to 24 weeks. Clinical and endoscopic assessments were performed at 8 and 24 weeks to evaluate treatment progress.

Results: Among 50 UC patients, 45% achieved clinical remission, and 22% achieved endoscopic remission by week 8. Of those who discontinued treatment after reaching endoscopic remission, 55% experienced relapse during a median follow-up period of 30 weeks. For patients who continued treatment through 24 weeks, 52% achieved clinical remission, with a cumulative remission maintenance rate of 74.2%. Mild adverse events were reported in 6% of patients, including hyperamylasemia, hepatic dysfunction, and elevated biliary enzymes, all of which resolved after discontinuation of treatment. In 8 patients who relapsed and were re-administered carotegrast methyl, 62.5% achieved clinical remission, demonstrating the drug's effectiveness and safety in re-treatment.

Conclusions: Carotegrast methyl effectively induces both clinical and endoscopic remission in patients with active UC and has a favorable safety profile. Re-administration is safe and effective for patients experiencing relapse.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions affecting the gastrointestinal tract that can lead to multiple systemic complications. Among these, osteosarcopenia has emerged as a significant concern, characterized by the concurrent deterioration of bone density and muscle mass, strength, and function. This dual deterioration significantly elevates the risk of falls and fractures, thereby exacerbating morbidity and diminishing quality of life. The pathogenesis of IBD-associated osteosarcopenia is multifactorial, with chronic intestinal inflammation serving as a central driver. Pro-inflammatory cytokines simultaneously disrupt bone homeostasis and muscle metabolism, creating a catabolic environment that impacts both tissues. Nutritional deficiencies, common in IBD due to malabsorption and decreased dietary intake, further compromise both bone mineralization and muscle protein synthesis. Management requires a comprehensive approach combining nutritional optimization, structured physical therapy, and lifestyle modifications. Pharmacological interventions integrate diseasespecific treatments with targeted therapies including vitamin D supplementation, hormonal treatments, and bisphosphonates when indicated. This review synthesizes current evidence regarding the prevalence, pathogenesis, and clinical impact of osteosarcopenia in IBD, highlighting areas requiring further investigation.

Inflammatory bowel disease (IBD) was once considered rare in Korea, with the first reported case documented in 1961. Since then, its incidence and prevalence have increased markedly, accompanied by significant progress in clinical care and research. This narrative review traces the historical evolution of IBD in Korea, dividing the timeline into 4 periods: 1960-1979, 1980-1999, 2000-2019, and 2020-2039. For each period, major developments in the research environment and trends, diagnostic process, patient population and characteristics, and treatment are outlined. Over the past 6 decades, diagnostic and therapeutic approaches in Korea have advanced markedly, transitioning from limited diagnostic capacity and symptom-based management to practices that align with global standards. Notably, Korean patients with IBD exhibit distinctive clinical features compared with Western counterparts, including a markedly higher proportion of proctitis and a lower long-term risk of colectomy in ulcerative colitis, and a substantially higher prevalence of perianal fistulas in Crohn's disease, highlighting the need for population- specific strategies to advance personalized medicine. In parallel, the research landscape has evolved through multicenter collaborations, expanded research capacity, and growing international engagement, positioning Korea as an increasingly active contributor to the global IBD research community. Looking ahead, the future of IBD research in Korea is expected to be shaped by innovation-driven research, including advances in artificial intelligence, large-scale data integration, and deeper international collaboration. By tracing the clinical and research trajectory of IBD in Korea, this review offers insight into how the country has adapted to global trends and is preparing to meet future challenges.

Background/aims: Radial incision and cutting (RIC) is an alternative dilation method for stenosis of the lower gastrointestinal tract. However, its safety and efficacy for the small intestine requiring balloon-assisted enteroscopy (BAE) remain limited. Therefore, this pilot study aimed to evaluate the safety and efficacy of RIC using BAE.

Methods: We included 10 patients with Crohn's disease and performed 12 sessions of RIC for 10 lesions. The rate of adverse events 1 month after RIC was the primary outcome, whereas short- and long-term prognoses and improvements in subjective symptoms that were evaluated using a visual analog scale were the secondary outcomes.

Results: The technical success rate for RIC, defined as scope passage immediately following the procedure, was 100% (12/12). The rates of delayed bleeding and perforation were 0% (0/12). One patient developed restenosis because of the worsening of Crohn's disease and underwent surgery 2 months after RIC. The cumulative restenosis-, reintervention-, and surgery-free rates at 1 year after RIC were 67.5%, 78.7%, and 90.0%, respectively. Abdominal pain, abdominal bloating, nausea, and difficulties in defecation significantly improved 4 weeks after RIC.

Conclusions: RIC for small intestine using BAE has the potential to be safe and effective for relieving symptoms (jRCT identifier jRCTs022200040).