Inflammatory Bowel Diseases最新文献

{"title":"Winnie Mice: A Chronic and Progressive Model of Ulcerative Colitis.","authors":"Marcello Chieppa, Stefania De Santis, Giulio Verna","doi":"10.1093/ibd/izaf006","DOIUrl":"https://doi.org/10.1093/ibd/izaf006","url":null,"abstract":"<p><p>Recent trends show a continuous worldwide rise in the incidence of ulcerative colitis (UC), leading to increased interest in its etiology and pathogenesis, which is currently unknown. To gain a better mechanistic understanding of this disease, many mouse models have been developed over the last several years, with variations of dextran sodium sulfate administration representing the most widely employed. The Winnie mouse strain was created through elicited random mutations in Muc2, resulting in a progressive, chronic intestinal inflammation localized to the colon that worsens over time. Moreover, Winnie mice display immunologic and microbiota features that are similar to those that can be found in UC patients. Phenotypically, the presence, albeit rare, of rectal prolapse and other complications impacting quality of life can be observed in Winnie mice, as well as extraintestinal manifestations that are often associated with UC. While Winnie mice are currently less studied compared to other more established models of colitis, much has been discovered in the initial years of its use as a UC-like model. In summary, the use of Winnie mice adds to the growing armamentarium that is required to develop precision-based medicine for its future application in treating complex multifactorial diseases, such as UC.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255544","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":"Intestinal Ultrasound Identified Crohn's Disease In Previously Undiagnosed Siblings.","authors":"Noa Krugliak Cleveland, Khushi S Bhondwe, Charlotte M Duty, David T Rubin","doi":"10.1093/ibd/izaf019","DOIUrl":"https://doi.org/10.1093/ibd/izaf019","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189152","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 Consequences of Preterm Birth in the Children of Mothers with Inflammatory Bowel Disease: A Nationwide Cohort Study.","authors":"Sonia Friedman, Olav Sivertsen Garvik, Jan Nielsen, Line Riis Jølving, Mette Louise Andersen, Bente Mertz Nørgård","doi":"10.1093/ibd/izaf010","DOIUrl":"https://doi.org/10.1093/ibd/izaf010","url":null,"abstract":"<p><strong>Introduction: </strong>Mothers with inflammatory bowel disease (IBD) are at increased risk of delivering their infants preterm. In the general population, chronic diseases in adulthood as well as increased morbidity and mortality are associated with being born preterm. We aimed to examine whether this was true for preterm versus full-term infants born to mothers with IBD.</p><p><strong>Methods: </strong>This is an observational cohort study based on the Danish Health Registries. The study population comprised all live-born singleton children, born to mothers with IBD, during the study period of 1995 through 2016. We estimated the risk of selected chronic diseases in offspring born preterm to mothers with IBD. These included epilepsy, chronic lung disease and asthma, depression and bipolar affective disorder, autism spectrum disorders, schizophrenia/psychosis, attention-deficit hyperactivity disorder, and mental retardation/intellectual disabilities. We adjusted for relevant confounders.</p><p><strong>Results: </strong>In all, 736 children were born preterm, and 9655 were born full-term to mothers with IBD. The median, 25th, and 75th percentiles of the follow-up time of the children were 11.1 (6.4, 16.3) years and 11.4 (7.3, 16.3) years for the full-term and preterm cohorts, respectively. There was a statistically significant increased risk of mental retardation/intellectual disabilities in preterm versus full-term children (aHR 2.15; 95% CI 1.07-4.36). We also found a non-significantly increased risk of epilepsy (1.11; 0.51-2.42), chronic lung disease and asthma (1.10; 0.76-1.60), schizophrenia/psychosis (1.17; 0.50-2.73), and attention-deficit/hyperactivity disorder 1.15 (0.83-1.60).</p><p><strong>Conclusion: </strong>Our study indicates the possibility of chronic health consequences in children born preterm to mothers with IBD.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122872","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":"Resting-State Functional Connectivity of the Cerebellum Differs Between Persons With Inflammatory Bowel Disease and Healthy Controls in Relation to Executive Function.","authors":"Jennifer Kornelsen, Theresa A McIver, Ruth Ann Marrie, Ronak Patel, Charles N Bernstein","doi":"10.1093/ibd/izaf020","DOIUrl":"https://doi.org/10.1093/ibd/izaf020","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065390","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":"Generalizability of Randomized Controlled Trials to Routine Clinical Care in Ulcerative Colitis.","authors":"Tarun Chhibba, Alexandra Frolkis, Levi R Stein, Sangmin Lee, Kaela Schill, Elena Mitevska, Allap K Judge, Marie-Louise Martin, Meaghan Martin, Kerri L Novak, Cathy Lu, Richard J M Ingram, Melissa M Chan, Tushar Shukla, Cynthia H Seow, Gilaad G Kaplan, Ashwin N Ananthakrishnan, Remo Panaccione, Christopher Ma","doi":"10.1093/ibd/izaf012","DOIUrl":"https://doi.org/10.1093/ibd/izaf012","url":null,"abstract":"<p><strong>Background: </strong>Historically, randomized controlled trials (RCTs) have been criticized for being poorly generalizable to patients with ulcerative colitis (UC) evaluated in routine care. We aimed to evaluate the proportion of patients with UC starting an advanced therapy who would be eligible to participate in phase 3 registrational UC RCTs.</p><p><strong>Methods: </strong>We conducted a retrospective cohort analysis of UC patients starting vedolizumab, ustekinumab, or tofacitinib at 2 IBD clinics at the University of Calgary. Patient charts, endoscopy reports, and laboratory results were reviewed, and compared against the inclusion and exclusion criteria from 5 RCTs (GEMINI-I, UNIFI, OCTAVE, ELEVATE, and LUCENT). The proportion of patients who would have been deemed eligible versus ineligible for trial participation at the time of starting a new advanced therapy was determined.</p><p><strong>Results: </strong>A total of 125 patients with UC were included: 78 (62.4%) would have been eligible for at least one of the considered RCTs. Trial-eligible patients were younger, less likely to be exposed to prior immunosuppressants, and had higher C-reactive protein and fecal calprotectin. The most common reason for trial ineligibility was having inadequate disease activity at baseline (Mayo endoscopy subscore <2 or absence of rectal bleeding). A significantly greater proportion of patients would have been eligible for LUCENT (45.6%) compared to GEMINI-I (24.8%), OCTAVE (35.2%), or ELEVATE (35.2%) (P < .01 for all comparisons).</p><p><strong>Conclusions: </strong>Half of patients with UC starting advanced therapy in routine care may be eligible for participation in phase 3 RCTs. Disease activity is the primary reason for trial exclusion.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065387","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":"Bridging the Gap Between Explanatory and Pragmatic Trials in Inflammatory Bowel Disease.","authors":"Joana Roseira, Vipul Jairath","doi":"10.1093/ibd/izae314","DOIUrl":"https://doi.org/10.1093/ibd/izae314","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059037","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":"Serum Periostin is Able to Stratify Type 2-Dominant Ulcerative Colitis.","authors":"Hironobu Takedomi, Satoshi Nunomura, Yasuhiro Nanri, Yuko Honda, Kanako Yokomizo, Takashi Akutagawa, Nanae Tsuruoka, Yasuhisa Sakata, Simon Conway, Atsushi Kawaguchi, Shinichi Aishima, Motohiro Esaki, Kenji Izuhara","doi":"10.1093/ibd/izaf009","DOIUrl":"https://doi.org/10.1093/ibd/izaf009","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a heterogeneous disease composed of different endotypes. It is important to develop useful biomarkers for endotyping UC; however, available biomarkers are insufficient. We have already established that periostin is a surrogate biomarker of type 2 inflammation. In this study, we examined the usefulness of periostin as a biomarker of UC and the role of periostin in its pathogenesis.</p><p><strong>Methods: </strong>We examined periostin expression in the colons of UC patients. We next investigated serum periostin in UC patients and its correlation with eosinophilic infiltration in their colons. We then examined whether serum periostin could predict the efficacy of oral prednisolone. Finally, we investigated the role of periostin in UC pathogenesis by creating its genetic deficiency using dextran sulfate sodium (DSS)-treated mice.</p><p><strong>Results: </strong>Periostin expression and serum periostin were significantly high in UC patients compared to healthy controls; however, both were diverse, showing heterogeneity of the underlying mechanism of UC. Both serum periostin and tissue periostin expression, but not blood eosinophils, were significantly associated with eosinophil infiltration. Type 2-dominant UC patients as defined by serum periostin showed significantly higher clinical remission rates for the treatment with oral prednisolone. Genetic deficiency in periostin improved colonic inflammation in a DSS-treated mouse model.</p><p><strong>Conclusions: </strong>Periostin can be a useful biomarker to stratify type 2-dominant UC patients, thereby predicting the efficacy of oral prednisolone. Moreover, periostin plays an important role in the setting of type 2-dominant UC.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046493","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":"Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), for the Prevention of Recurrent Clostridioides difficile Infection in Participants With Inflammatory Bowel Disease in PUNCH CD3-OLS.","authors":"Jessica R Allegretti, Paul Feuerstadt, Whitfield L Knapple, Robert Orenstein, Philippe Pinton, Alexander Sheh, Sahil Khanna","doi":"10.1093/ibd/izae291","DOIUrl":"https://doi.org/10.1093/ibd/izae291","url":null,"abstract":"<p><strong>Background: </strong>Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD.</p><p><strong>Methods: </strong>Participants with IBD (ulcerative colitis [UC], Crohn's disease [CD], or unspecified) who had rCDI were included. Treatment-emergent adverse event (TEAE) data were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months.</p><p><strong>Results: </strong>Overall, 793 participants were enrolled, and 697 received RBL; 74 had IBD (UC: n = 45; CD: n = 25; unspecified IBD: n = 4). TEAEs within 8 weeks of administration were reported by 45.9% and 47.5% of participants with and without IBD, respectively; most were mild or moderate gastrointestinal symptoms. Serious TEAEs within 8 weeks of administration were reported by 1.4% and 4.2% of participants with and without IBD, respectively. The treatment success rate at 8 weeks was 78.9%, and the sustained clinical response rate at 6 months was 91.1% in participants with IBD, similar to rates in participants without IBD (73.2% and 91.0%, respectively).</p><p><strong>Conclusions: </strong>The results of this subgroup analysis of PUNCH CD3-OLS suggest RBL is safe and efficacious in patients with IBD.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038281","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":"Circulating and Magnetic Resonance Imaging Biomarkers of Intestinal Fibrosis in Small Bowel Crohn's Disease.","authors":"Jonathan R Dillman, Jean A Tkach, Joel G Fletcher, David H Bruining, Aiming Lu, Subra Kugathasan, Adina L Alazraki, Jack Knight-Scott, Ryan W Stidham, Jeremy Adler, Phillip Minar, Bruce C Trapnell, Erin L Bonkowski, Holden Jurrell, Oscar Lopez-Nunez, Margaret H Collins, Scott D Swanson, Lin Fei, Lucia Qian, Alexander J Towbin, Murat Kocaoglu, Christopher G Anton, Rebecca A Imbus, Jonathan A Dudley, Lee A Denson","doi":"10.1093/ibd/izae319","DOIUrl":"https://doi.org/10.1093/ibd/izae319","url":null,"abstract":"<p><strong>Background: </strong>We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn's disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content.</p><p><strong>Methods: </strong>Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers. Circulating CD64, extracellular matrix protein 1 (ECM1), GM-CSF autoantibodies (GM-CSF Ab), and fecal calprotectin were measured by ELISA. Ileal 3-dimensional magnetization transfer ratio (3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, diffusion-weighted intravoxel incoherent motion (IVIM), and the simplified magnetic resonance index of activity (sMaRIA) were measured by MRI. Ileal resection specimen acute inflammation was graded, and collagen content was measured quantitatively using second harmonic imaging microscopy. Associations between biomarkers and ileal collagen content were tested.</p><p><strong>Results: </strong>Median (interquartile range [IQR]) age was 19.5 (16-33) years. We observed an inverse relationship between ileal acute inflammation and collagen content (r = -0.39 [95% confidence interval {CI}: -0.61, -0.10], P = .008). Most patients (33 [66%]) received biologics, with no variation in collagen content with treatment exposures. In the univariate analysis, CD64, GM-CSF Ab, fecal calprotectin, and sMaRIA were positively associated with acute inflammation and negatively associated with collagen content (P < .1). The multivariable model for ileal collagen content (R2 = 0.31 [95% CI: 0.11, 0.52]) included log CD64 (β = -.27; P = .19), log ECM1 (β = .47; P = .06), log GM-CSF Ab (β = -.15; P = .01), IVIM f (β = .29, P = .10), and IVIM D* (β = 1.69, P = .13).</p><p><strong>Conclusions: </strong>Clinically available and exploratory circulating and MRI biomarkers are associated with the degree of inflammation versus fibrosis in CD ileal resections. With further validation, these biomarkers may be used to guide medical and surgical decision-making for refractory CD.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033090","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":"Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury.","authors":"Jonathan L Golob, Guoqing Hou, Benjamin J Swanson, Jeffrey A Berinstein, Shreenath Bishu, Helmut Grasberger, Mohamed El Zataari, Allen Lee, John Y Kao, Nobuhiko Kamada, Shrinivas Bishu","doi":"10.1093/ibd/izae293","DOIUrl":"https://doi.org/10.1093/ibd/izae293","url":null,"abstract":"<p><strong>Background and aims: </strong>Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10-/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells.</p><p><strong>Methods: </strong>We subjected C57BL6, RAG1-/-, or JH-/- mice to systemic or gastrointestinal (GI) Citrobacter rodentium (Cr). Mice were then subjected to 2.5% dextran sodium sulfate (DSS) to cause epithelial injury. Fecal microbiota transfer was performed by bedding transfer and co-housing. Flow cytometry, qPCR, and histology were used to assess mucosal and systemic immune responses, cytokines, and tissue inflammation. 16s sequencing was used to assess gut bacterial taxonomy.</p><p><strong>Results: </strong>Transient inflammation with GI but not systemic Cr was protective against subsequent intestinal injury. This was replicated with sequential DSS collectively indicating that transient inflammation provides tissue-specific protection. Inflammatory Th17 cells that have a tissue-resident memory (TRM) signature expanded in the intestine. Experiments with reconstituted RAG1-/-, JH-/- mice, and cell trafficking inhibitors showed that inflammation-induced Th17 cells were required for protection. Fecal microbiota transfer showed that the inflammation-trained microbiota was necessary for protection, likely by maintaining protective Th17 cells in situ.</p><p><strong>Conclusion: </strong>Inflammation can generate protective Th17 cells that synergize with the inflammation-trained microbiota to provide host resiliency against subsequent injury, indicating that inflammation-induced Th17 TRM T cells are heterogenous and contain protective subsets.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033092","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}