Inflammatory Bowel Diseases最新文献

{"title":"Rediversion of the Failing Ileoanal Pouch: First Step in Pouch Salvage?","authors":"Tairin Uchino, Eddy P Lincango, Oscar Hernandez Dominguez, Anuradha Bhama, Emre Gorgun, Arielle Kanters, Hermann Kessler, Jeremy Lipman, David Liska, Joshua Sommovilla, Michael Valente, Scott R Steele, Tracy Hull, Stefan D Holubar","doi":"10.1093/ibd/izae061","DOIUrl":"10.1093/ibd/izae061","url":null,"abstract":"<p><strong>Background: </strong>Ileal pouch-anal anastomosis is a technically demanding procedure with many potential complications. Rediversion with an ileostomy is often the first step in pouch salvage; however, it may not be clear if an individual patient will undergo subsequent pouch salvage surgery. We aimed to describe the indications and short- and long-term outcomes of rediversion in our pouch registry.</p><p><strong>Methods: </strong>We queried our institutional pouch registry for patients who underwent index 2- or 3-stage IPAA and subsequent rediversion at our institution between 1985 and 2022. Pouches constructed elsewhere, rediverted elsewhere, or those patients who underwent pouch salvage/excision without prior rediversion were excluded. Patients were selected for pouch salvage according to the surgeon's discretion.</p><p><strong>Results: </strong>Overall, 177 patients (3.4% of 5207 index pouches) were rediverted. At index pouch, median patient age was 32 years and 50.8% were women. Diagnoses included ulcerative colitis (86.4%), indeterminate colitis (6.2%), familial adenomatous polyposis (4.0%), and others (3.4%). Median time from prior ileostomy closure to rediversion was 7.2 years. Indications for rediversion were inflammatory in 98 (55.4%) and noninflammatory in 79 (44.6%) patients. After rediversion, 52% underwent pouch salvage, 30% had no further surgery, and 18.1% underwent pouch excision. The 5-year pouch survival rates for inflammatory and noninflammatory indications were 71.5% and 94.5%, respectively (P = .02).</p><p><strong>Conclusion: </strong>Rediversion of ileoanal pouches is a safe initial strategy to manage failing pouches and is a useful first step in pouch salvage in many patients. Subsequent salvage surgery for noninflammatory indications had a significantly higher pouch salvage rate than those rediverted for inflammatory complications.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"105-112"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.","authors":"Myvizhi Esai Selvan, Daniel I Nathan, Daniela Guisado, Giulia Collatuzzo, Sushruta Iruvanti, Paolo Boffetta, John Mascarenhas, Ronald Hoffman, Louis J Cohen, Bridget K Marcellino, Zeynep H Gümüş","doi":"10.1093/ibd/izae312","DOIUrl":"https://doi.org/10.1093/ibd/izae312","url":null,"abstract":"<p><strong>Background: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD).</p><p><strong>Methods: </strong>We analyzed whole-exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes.</p><p><strong>Results: </strong>Older UC patients (age > 45) harbored increased myeloid-CHIP mutations compared to younger patients (age ≤ 45) (P = .01). Lymphoid-CHIP was more prevalent in older IBD patients (P = .007). Young CD patients were found to have myeloid-CHIP with high-risk features. Inflammatory bowel disease patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP (P = .05), while anti-TNF therapy was associated with decreased myeloid-CHIP (P = .03). Pathway enrichment analyses indicated an overlap between CHIP genes, IBD phenotypes, and inflammatory pathways.</p><p><strong>Conclusions: </strong>Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles, especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease, and acceleration of their inflammatory disease.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness of Ustekinumab in Ulcerative Colitis in a United States Multicenter Cohort Consortium.","authors":"Andres J Yarur, Ryan Ungaro, Katherine Huang, Wenfei Wang, Priya Sasankan, Mir Zulqarnain, Amanda M Johnson, Geoffrey Bader, Carl Kay, Nicholas Costable, David Dulaney, Marc Fenster, Poonam Beniwal-Patel, Gaurav Syal, Anish Patel, Edward Loftus, Joel Pekow, Benjamin Cohen, Parakkal Deepak","doi":"10.1093/ibd/izae058","DOIUrl":"10.1093/ibd/izae058","url":null,"abstract":"<p><strong>Background: </strong>Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC.</p><p><strong>Methods: </strong>We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin.</p><p><strong>Results: </strong>A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission.</p><p><strong>Conclusions: </strong>In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"131-139"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic Normalization and Transition of J-Pouch Phenotypes Over Time in Patients With Inflammatory Bowel Disease.","authors":"Shintaro Akiyama, Jacob E Ollech, Nathaniel A Cohen, Cindy Traboulsi, Victoria Rai, Laura R Glick, Yangtian Yi, Joseph Runde, Russell D Cohen, Kinga B Skowron Olortegui, Roger D Hurst, Konstantin Umanskiy, Benjamin D Shogan, Neil H Hyman, Michele A Rubin, Sushila R Dalal, Atsushi Sakuraba, Joel Pekow, Eugene B Chang, David T Rubin","doi":"10.1093/ibd/izae106","DOIUrl":"10.1093/ibd/izae106","url":null,"abstract":"<p><strong>Background: </strong>Patients with inflammatory bowel disease (IBD) who undergo proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. We previously proposed a novel endoscopic classification of pouchitis describing 7 phenotypes with differing outcomes. This study assessed phenotype transitions over time.</p><p><strong>Methods: </strong>We classified pouch findings into 7 main phenotypes: (1) normal, (2) afferent limb (AL) involvement, (3) inlet (IL) involvement, (4) diffuse, (5) focal inflammation of the pouch body, (6) cuffitis, and (7) pouch-related fistulas noted more than 6 months after ileostomy takedown. Among 2 endoscopic phenotypes, the phenotype that was first identified was defined as the primary phenotype, and the phenotype observed later was defined as the subsequent phenotype.</p><p><strong>Results: </strong>We retrospectively reviewed 1359 pouchoscopies from 426 patients (90% preoperative diagnosis of ulcerative colitis). The frequency of primary phenotype was 31% for AL involvement, 42% for IL involvement, 28% for diffuse inflammation, 72% for focal inflammation, 45% for cuffitis, 18% for pouch-related fistulas, and 28% for normal pouch. The most common subsequent phenotype was focal inflammation (64.8%), followed by IL involvement (38.6%), cuffitis (37.8%), AL involvement (25.6%), diffuse inflammation (23.8%), normal pouch (22.8%), and pouch-related fistulas (11.9%). Subsequent diffuse inflammation, pouch-related fistulas, and AL or IL stenoses significantly increased the pouch excision risk. Patients who achieved subsequent normal pouch were less likely to have pouch excision than those who did not (8.1% vs 15.7%; P = .15).</p><p><strong>Conclusions: </strong>Pouch phenotype and the risk of pouch loss can change over time. In patients with pouch inflammation, subsequent pouch normalization is feasible and associated with favorable outcome.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"63-71"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Utility of Intestinal Ultrasound in a Case of Microscopic Colitis.","authors":"Haley N Gamboa, Heather Abellana, Rishika Chugh","doi":"10.1093/ibd/izae172","DOIUrl":"10.1093/ibd/izae172","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"302-303"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis.","authors":"Konstantinos Ouranos, Hira Saleem, Stephanos Vassilopoulos, Athanasios Vassilopoulos, Evangelia K Mylona, Fadi Shehadeh, Markos Kalligeros, Bincy P Abraham, Eleftherios Mylonakis","doi":"10.1093/ibd/izae031","DOIUrl":"10.1093/ibd/izae031","url":null,"abstract":"<p><strong>Background: </strong>Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents.</p><p><strong>Methods: </strong>We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase.</p><p><strong>Results: </strong>There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group.</p><p><strong>Conclusions: </strong>There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"37-51"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Bowel Disease and Breastfeeding: A Narrative Review.","authors":"Tedi Hoxha, Michael Youssef, Vivian Huang, Parul Tandon","doi":"10.1093/ibd/izae033","DOIUrl":"10.1093/ibd/izae033","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) frequently affects women of childbearing age who may consider breastfeeding. Although breastfeeding has numerous benefits, there remain concerns regarding the safety of breastfeeding among women with IBD. Breastfeeding is important in developing the immune system of infants and has been shown to protect against the development of IBD. The risk of developing an increase in disease activity postpartum is the same regardless of breastfeeding status. Most IBD medications are also considered safe in breastfeeding and have no major risks to infants. Despite this, breastfeeding rates remain low among women with IBD, mostly due to concerns about the safety of IBD therapy with breastfeeding. Many women self-discontinue their IBD medications to breastfeed, and there is often uncertainty among health professionals to make recommendations about therapy. Dedicated IBD clinics can greatly support mothers during pregnancy and breastfeeding periods to enhance their knowledge, optimize their medication adherence, and improve their postpartum outcomes. This review aims to provide the most recent evidence-based literature regarding the safety of breastfeeding in women with IBD and the current recommendations about medical therapies with breastfeeding.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"210-219"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Fecal Calprotectin and Myeloperoxidase in Predicting Outcomes in Inflammatory Bowel Disease.","authors":"A Swaminathan, G M Borichevsky, C M Frampton, A S Day, M B Hampton, A J Kettle, R B Gearry","doi":"10.1093/ibd/izae032","DOIUrl":"10.1093/ibd/izae032","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers have been proposed as surrogate treatment targets for the management of inflammatory bowel disease (IBD); however, their relationship with IBD-related complications remains unclear. This study investigated the utility of neutrophil biomarkers fecal calprotectin (fCal) and fecal myeloperoxidase (fMPO) in predicting a complicated IBD course.</p><p><strong>Methods: </strong>Participants with IBD were followed for 24 months to assess for a complicated IBD course (incident corticosteroid use, medication escalation for clinical disease relapse, IBD-related hospitalizations/surgeries). Clinically active IBD was defined as Harvey-Bradshaw index >4 for Crohn's disease (CD) and simple clinical colitis activity index >5 for ulcerative colitis (UC). Area under the receiver-operating-characteristics curves (AUROC) and multivariable logistic regression assessed the performance of baseline symptom indices, fCal, and fMPO in predicting a complicated disease IBD course at 24 months.</p><p><strong>Results: </strong>One hundred and seventy-one participants were included (CD, n = 99; female, n = 90; median disease duration 13 years [interquartile range, 5-22]). Baseline fCal (250 μg/g; AUROC = 0.77; 95% confidence interval [CI], 0.69-0.84) and fMPO (12 μg/g; AUROC = 0.77; 95% CI, 0.70-0.84) predicted a complicated IBD course. Fecal calprotectin (adjusted OR = 7.85; 95% CI, 3.38-18.26) and fMPO (adjusted OR = 4.43; 95% CI, 2.03-9.64) were associated with this end point after adjustment for other baseline variables including clinical disease activity. C-reactive protein (CRP) was inferior to fecal biomarkers and clinical symptoms (pdifference < .05) at predicting a complicated IBD course. A combination of baseline CRP, fCal/fMPO, and clinical symptoms provided the greatest precision at identifying a complicated IBD course.</p><p><strong>Conclusions: </strong>Fecal biomarkers are independent predictors of IBD-related outcomes and are useful adjuncts to routine clinical care.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"28-36"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healthy Lifestyle Is a Protective Factor from Moderate and Severe Relapses and Steroid Use in Inflammatory Bowel Disease: A Prospective Cohort Study.","authors":"Sandra García-Mateo, Samuel Jesús Martínez-Domínguez, Carla Jerusalén Gargallo-Puyuelo, Beatriz Gallego, Erika Alfambra, María Escuin, Sergio García-Mateo, Julia López, Fernando Gomollón","doi":"10.1093/ibd/izae062","DOIUrl":"10.1093/ibd/izae062","url":null,"abstract":"<p><strong>Background: </strong>A healthy lifestyle, including good adherence to a Mediterranean diet (MD) and regular physical exercise, may be an important factor during the course of inflammatory bowel disease (IBD). Our aim is to determine whether adherence to MD, physical activity, and the combination of both can impact on IBD course.</p><p><strong>Methods: </strong>This prospective cohort study includes 693 IBD outpatients who were in remission with a median follow-up time of 27 months (interquartile range 22-29 months). Each patient completed a survey to assess their adherence to the MD and physical activity. Healthy lifestyle was considered to be a proper adherence to both MD and an active lifestyle. Relapse during follow-up, severity of relapses, need for systemic steroids, and therapy changes were recorded.</p><p><strong>Results: </strong>During the follow-up period, 188 patients (27.1%) experienced relapse, of which 56.1% were moderate or severe. Among patients with relapse, 85 (45%) required treatment with corticosteroids, and 15 (7.9%) were hospitalized. Patients with ulcerative colitis (CU) were more adherent to healthy lifestyle than patients with Crohn's disease (P = .011). Healthy lifestyle was associated with lower risk of moderate and severe relapses (adjusted Hazard ratio [aHR], 0.250; 95% confidence interval [CI], 0.093-0.670) and steroids use (aHR 0.292; 95% CI, 0.103-0.828) in IBD patients and with lower risk of moderate and severe relapses (aHR 0.270; 95% CI, 0.093-0.789) in UC patients.</p><p><strong>Conclusions: </strong>Healthy lifestyle has a favorable influence on promoting a milder disease course, and thus should be a crucial part of clinical management of patients with IBD.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"95-104"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting NCAPD2 as a Therapeutic Strategy for Crohn's Disease: Implications for Autophagy and Inflammation.","authors":"Hao Ge, Can Wang, Haoran Zhao, Hao Chen, Yuxia Gong, Lichao Qiao, Yi Zhang, Ping Liu, Bolin Yang","doi":"10.1093/ibd/izae211","DOIUrl":"10.1093/ibd/izae211","url":null,"abstract":"<p><strong>Background: </strong>Our earlier studies identified that non-SMC condensin I complex subunit D2 (NCAPD2) induces inflammation through the IKK/NF-κB pathway in ulcerative colitis. However, its role in the development of Crohn's disease (CD) and the specific molecular mechanism still need to be further studied.</p><p><strong>Methods: </strong>NCAPD2 expression in clinical ileal CD mucosa vs normal mucosa was examined, alongside its correlation with CD patients' clinical characteristics via their medical records. The biological function and molecular mechanism of NCAPD2 in CD were explored using a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD mouse model, along with immunofluorescence, western blot, quantitative real-time PCR, immunohistochemistry, hematoxylin and eosin staining, and cell functional analysis.</p><p><strong>Results: </strong>NCAPD2 was overexpressed in CD tissues and significantly correlated with disease activity in CD patients (P = .016). In a TNBS-induced CD mouse model, NCAPD2 knockdown inhibited the development of TNBS-induced intestinal inflammation in mice. In addition, we found that NCAPD2 inhibited autophagy. Mechanistically, NCAPD2 promoted the phosphorylation of mammalian target of the rapamycin (mTOR) and its direct effector S6K and downregulated the expression of autophagy-related proteins Beclin1, LC3II, and Atg5. In addition, NCAPD2 activates the NF-κB signaling pathway, and the downstream inflammatory factors are continuously released, leading to the persistence of inflammation.</p><p><strong>Conclusions: </strong>Our results show that NCAPD2 suppresses autophagy and worsens intestinal inflammation by modulating mTOR signaling and impacting the NF-κB pathway, suggesting a critical role in CD progression. Targeting NCAPD2 could be a promising therapeutic approach to stop CD advancement.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"178-188"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}