Inflammatory Bowel Diseases最新文献

{"title":"Sustained Increase in Pediatric Inflammatory Bowel Disease Incidence Across the South West United Kingdom Over the Last 10 Years.","authors":"Zachary Green, James J Ashton, Astor Rodrigues, Christine Spray, Lucy Howarth, Akshatha Mallikarjuna, Neil Chanchlani, James Hart, Christopher Bakewell, Kwang Yang Lee, Amar Wahid, R Mark Beattie","doi":"10.1093/ibd/izad302","DOIUrl":"10.1093/ibd/izad302","url":null,"abstract":"<p><strong>Background: </strong>Pediatric inflammatory bowel disease (pIBD) incidence has increased over the last 25 years. We aim to report contemporaneous trends across the South West United Kingdom.</p><p><strong>Methods: </strong>Data were provided from centers covering the South West United Kingdom (Bristol, Oxford, Cardiff, Exeter, and Southampton), with a total area at-risk population (<18 years of age) of 2 947 534. Cases were retrieved from 2013 to 2022. Incident rates were reported per 100 000 at-risk population, with temporal trends analyzed through correlation. Subgroup analysis was undertaken for age groups (0-6, 6-11, and 12-17 years of age), sex, and disease subtype. Choropleth maps were created for local districts.</p><p><strong>Results: </strong>In total, 2497 pIBD cases were diagnosed between 2013 and 2022, with a mean age of 12.6 years (38.7% female). Diagnosis numbers increased from 187 to 376, with corresponding incidence rates of 6.0 per 100 000 population per year (2013) to 12.4 per 100 000 population per year (2022) (b = 0.918, P < .01). Female rates increased from 5.1 per 100 000 population per year in 2013 to 11.0 per 100 000 population per year in 2022 (b = 0.865, P = .01). Male rates increased from 5.7 per 100 000 population per year to 14.4 per 100 000 population per year (b = 0.832, P = .03). Crohn's disease incidence increased from 3.1 per 100 000 population per year to 6.3 per 100 000 population per year (b = 0.897, P < .01). Ulcerative colitis increased from 2.3 per 100 000 population per year to 4.3 per 100 000 population per year (b = 0.813, P = .04). Inflammatory bowel disease unclassified also increased, from 0.6 per 100 000 population per year to 1.8 per 100 000 population per year (b = 0.851, P = .02). Statistically significant increases were seen in those ≥12 to 17 years of age, from 11.2 per 100 000 population per year to 24.6 per 100 000 population per year (b = 0.912, P < .01), and the 7- to 11-year-old age group, with incidence rising from 4.4 per 100 000 population per year to 7.6 per 100 000 population per year (b = 0.878, P = .01). There was no statistically significant increase in very early onset inflammatory bowel disease (≤6 years of age) (b = 0.417, P = .231).</p><p><strong>Conclusions: </strong>We demonstrate significant increases in pIBD incidence across a large geographical area including multiple referral centers. Increasing incidence has implications for service provision for services managing pIBD.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2271-2279"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899805","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":"Older Adults With Inflammatory Bowel Disease Are at Higher Risk of Developing Antibodies to Infliximab.","authors":"Adam S Faye, Kate E Lee, David Hudesman, Thierry Dervieux","doi":"10.1093/ibd/izad305","DOIUrl":"10.1093/ibd/izad305","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2509-2511"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086717","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":"Unique Metabolomic and Lipidomic Profile in Serum From Patients With Crohn's Disease and Ulcerative Colitis Compared With Healthy Control Individuals.","authors":"Hauke Christian Tews, Franziska Schmelter, Arne Kandulski, Christa Büchler, Stephan Schmid, Sophie Schlosser, Tanja Elger, Johanna Loibl, Stefanie Sommersberger, Tanja Fererberger, Stefan Gunawan, Claudia Kunst, Karsten Gülow, Dominik Bettenworth, Bandik Föh, Carlos Maaß, Philipp Solbach, Ulrich L Günther, Stefanie Derer, Jens U Marquardt, Christian Sina, Martina Müller","doi":"10.1093/ibd/izad298","DOIUrl":"10.1093/ibd/izad298","url":null,"abstract":"<p><strong>Background: </strong>Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease.</p><p><strong>Methods: </strong>Serum samples were obtained from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale.</p><p><strong>Results: </strong>Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2.</p><p><strong>Conclusions: </strong>Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2405-2417"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Services Utilization and Specialist Care in Pediatric Inflammatory Bowel Disease: A Multiprovince Population-Based Cohort Study.","authors":"M Ellen Kuenzig, Alain Bitton, Matthew W Carroll, Anthony R Otley, Harminder Singh, Gilaad G Kaplan, Therese A Stukel, David R Mack, Kevan Jacobson, Anne M Griffiths, Wael El-Matary, Laura E Targownik, Geoffrey C Nguyen, Jennifer L Jones, Sanjay K Murthy, Charles N Bernstein, Lisa M Lix, Juan Nicolás Peña-Sánchez, Trevor J B Dummer, Sarah Spruin, Stephen G Fung, Zoann Nugent, Stephanie Coward, Yunsong Cui, Janie Coulombe, Christopher Filliter, Eric I Benchimol","doi":"10.1093/ibd/izae010","DOIUrl":"10.1093/ibd/izae010","url":null,"abstract":"<p><strong>Background: </strong>Patterns of health services utilization among children with inflammatory bowel disease (IBD) are important to understand as the number of children with IBD continues to increase. We compared health services utilization and surgery among children diagnosed <10 years of age (Paris classification: A1a) and between 10 and <16 years of age (A1b).</p><p><strong>Methods: </strong>Incident cases of IBD diagnosed <16 years of age were identified using validated algorithms from deterministically linked health administrative data in 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec) to conduct a retrospective cohort study. We compared the frequency of IBD-specific outpatient visits, emergency department visits, and hospitalizations across age groups (A1a vs A1b [reference]) using negative binomial regression. The risk of surgery was compared across age groups using Cox proportional hazards models. Models were adjusted for sex, rural/urban residence location, and mean neighborhood income quintile. Province-specific estimates were pooled using random-effects meta-analysis.</p><p><strong>Results: </strong>Among the 1165 (65.7% Crohn's) children with IBD included in our study, there were no age differences in the frequency of hospitalizations (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.06) or outpatient visits (RR, 0.95; 95% CI, 0.78-1.16). A1a children had fewer emergency department visits (RR, 0.70; 95% CI, 0.50-0.97) and were less likely to require a Crohn's-related surgery (hazard ratio, 0.49; 95% CI, 0.26-0.92). The risk of colectomy was similar among children with ulcerative colitis in both age groups (hazard ratio, 0.71; 95% CI, 0.49-1.01).</p><p><strong>Conclusions: </strong>Patterns of health services utilization are generally similar when comparing children diagnosed across age groups.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2356-2369"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring-Based Model for Personalizing Fecal Incontinence in Patients With Crohn's Disease: A Multicenter Inception Cohort Study.","authors":"Can Wang, Fan Yang, Lichao Qiao, Xiaoxiao Wang, Qi Chen, Hongjin Chen, Yi Li, Xiaoqi Zhang, Xiujun Liao, Lei Cao, Haixia Xu, Yu Xiang, Bolin Yang","doi":"10.1093/ibd/izae006","DOIUrl":"10.1093/ibd/izae006","url":null,"abstract":"<p><strong>Background and aims: </strong>Fecal incontinence (FI) is a common complaint that greatly affects the quality of life of patients with Crohn's disease (CD) and is associated with the clinical characteristics of CD. We aimed to identify risk factors related to FI and construct a risk prediction model for FI in patients with CD.</p><p><strong>Methods: </strong>This retrospective study included 600 Chinese patients with CD from 4 IBD centers between June 2016 and October 2021. The patients were assigned to the training (n = 480) and testing cohorts (n = 120). Two nomograms were developed based on the logistic regression and Cox regression models to predict the risk factors for FI in patients with CD. The discriminatory ability and accuracy of the nomograms were evaluated using the receiver operating characteristic (ROC) curves and the area under the ROC curves (AUCs). Additionally, the Kaplan-Meier survival curve was also used further to validate the clinical efficacy of the Cox regression model.</p><p><strong>Results: </strong>The overall prevalence of FI was 22.3% (n = 134 of 600). In the logistic regression model, age at diagnosis (odds ratio [OR], 1.032; P = .033), penetrating behavior of disease (OR, 3.529; P = .008) and Perianal Disease Activity Index score >4 (OR, 3.068; P < .001) were independent risk factors for FI. In the Cox regression model, age at diagnosis (hazard ratio [HR], 1.027; P = .018), Montreal P classification (HR, 2.608; P = .011), and Perianal Disease Activity Index score >4 (HR, 2.190; P = .001) were independent predictors of the prevalence of FI over time. Two nomograms were developed to facilitate risk score calculation, and they showed good discrimination ability according to AUCs.</p><p><strong>Conclusions: </strong>In this study, we identified 4 risk factors related to the prevalence of FI and developed 2 models to effectively predict the risk scores of FI in CD patients, helping to delay the course of FI and improve the prognosis with timely intervention.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2314-2322"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681071","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":"Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.","authors":"Bruce E Sands, Geert D'Haens, David B Clemow, Peter M Irving, Jordan T Johns, Theresa Hunter Gibble, Maria T Abreu, Scott Lee, Tadakazu Hisamatsu, Taku Kobayashi, Marla C Dubinsky, Severine Vermeire, Corey A Siegel, Laurent Peyrin-Biroulet, Richard E Moses, Joe Milata, Vipin Arora, Remo Panaccione, Axel Dignass","doi":"10.1093/ibd/izae024","DOIUrl":"10.1093/ibd/izae024","url":null,"abstract":"<p><strong>Background: </strong>Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at week 12 (W12) and maintaining clinical remission at W52 in patients with moderately to severely active ulcerative colitis. Results are presented from the open-label extension study through W104.</p><p><strong>Methods: </strong>Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders and extended induction responders, including biologic-failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC).</p><p><strong>Results: </strong>Among W52 mirikizumab responders, clinical response at W104 was 74.5%, 87.2%, and 96.7% and clinical remission was 54.0%, 62.8%, and 70.1% for NRI, mNRI, and OC, respectively. Among W52 mirikizumab remitters, clinical response at W104 was 76.6%, 89.0%, and 98.3% and clinical remission was 65.6%, 76.1%, and 84.2%. Using mNRI, remission rates at W104 for W52 clinical remitters were 74.7% corticosteroid-free, 79.5% endoscopic, 63.9% histologic-endoscopic mucosal remission, 85.9% symptomatic, 59.8% bowel urgency, 80.5% Inflammatory Bowel Disease Questionnaire (using NRI), 71.2% histologic-endoscopic mucosal improvement, and 77.5% bowel urgency improvement. Previous biologic-failed vs not-biologic-failed patient data were generally similar. Extended induction mNRI clinical response was 81.9%. Serious adverse events were reported in 5.2% of patients; 2.8% discontinued treatment due to adverse events.</p><p><strong>Conclusions: </strong>Endoscopic, histologic, symptomatic, and quality-of-life outcomes support the long-term benefit of mirikizumab treatment up to 104 weeks in patients with ulcerative colitis, including biologic-failed patients, with no new safety concerns.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2245-2258"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Active Crohn's Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products.","authors":"Caroline Kerbiriou, Caitlin Dickson, Ben Nichols, Michael Logan, Anna Mascellani, Jaroslav Havlik, Richard K Russell, Richard Hansen, Simon Milling, Konstantinos Gerasimidis","doi":"10.1093/ibd/izae124","DOIUrl":"10.1093/ibd/izae124","url":null,"abstract":"<p><strong>Background: </strong>Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN.</p><p><strong>Methods: </strong>Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing.</p><p><strong>Results: </strong>Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi.</p><p><strong>Conclusions: </strong>This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2457-2466"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Assessment of Serum Cytokines Predicts Clinical and Endoscopic Response to Ustekinumab in Patients With Crohn's Disease: A Prospective Pilot Study.","authors":"Lorenzo Bertani, Luca Antonioli, Marco Fornili, Vanessa D'Antongiovanni, Linda Ceccarelli, Luca Carmisciano, Laura Benvenuti, Maria Gloria Mumolo, Andrea Bottari, Veronica Pardi, Giovanni Baiano Svizzero, Laura Baglietto, Nicola De Bortoli, Massimo Bellini, Matteo Fornai, Francesco Costa","doi":"10.1093/ibd/izae133","DOIUrl":"10.1093/ibd/izae133","url":null,"abstract":"<p><strong>Background: </strong>No biomarkers are currently available to predict therapeutic response to ustekinumab (UST) in Crohn's disease (CD). The aim of this prospective study was to identify 1 or more cytokines able to predict mucosal healing in patients with CD treated with UST.</p><p><strong>Methods: </strong>We prospectively enrolled consecutive CD patients treated with UST. At weeks 0 (baseline), 24, and 48, a panel of serum cytokines was measured by a fluorescence assay. At the same time points, fecal calprotectin (FC) was assessed. A colonoscopy was performed at baseline and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing.</p><p><strong>Results: </strong>Out of 44 patients enrolled, 22 (50%) achieved mucosal healing at the end of follow-up. Response was associated with higher interleukin (IL)-23 levels (P < .01). Fecal calprotectin levels decreased over time in responders but did not change in nonresponders (test for the interaction between time and mucosal healing, P < .001).</p><p><strong>Conclusions: </strong>This pilot study showed that IL-23 and FC could be reliable biomarkers in predicting therapeutic outcome to UST therapy in CD. In particular, the correlation between baseline serum levels of IL-23 and mucosal healing at 48 weeks is particularly strong, paving the way for its use to drive therapeutic decisions.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2449-2456"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305885","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":"Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis.","authors":"Takeo Naito, Ryuya Osaka, Yoichi Kakuta, Yosuke Kawai, Seik-Soon Khor, Junji Umeno, Katsushi Tokunaga, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune","doi":"10.1093/ibd/izae143","DOIUrl":"10.1093/ibd/izae143","url":null,"abstract":"<p><strong>Background: </strong>It is crucial to pinpoint the metabolites that cause Crohn's disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese patients with CD and UC.</p><p><strong>Methods: </strong>As exposure datasets, genetic instruments with blood-circulating metabolites were obtained from the Tohoku Medical Megabank Organization, which includes 204 metabolites from the genome-wide association study data of 7843 Japanese individuals. As outcome datasets, we enrolled Japanese patients with CD (n = 1803), Japanese patients with UC (n = 1992), and healthy controls (n = 2022). The main analysis utilized the inverse variance-weighted method, while stability of the findings was evaluated through sensitivity analyses.</p><p><strong>Results: </strong>After single nucleotide polymorphism (SNP) filtering, 169 SNPs for 45 metabolites were available for MR. Genetically predicted elevated circulating trans-glutaconic acid and tryptophan were associated with a lower CD risk (odds ratio [OR], 0.68; P = 5.95 × 10-3; and OR, 0.64; P = 1.90 × 10-2, respectively). Genetically predicted elevated caffeic acid was associated with a lower UC risk (OR, 0.67; P = 4.2 × 10-4), which remained significant after multiple testing correction. We identified a causal link between UC and 3-hydroxybutyrate (OR, 2.21; P = 1.41 × 10-2), trans-glutaconic acid (OR, 0.72; P = 1.77 × 10-2), and 2-hydroxyvaleric acid (OR, 1.31; P = 4.23 × 10-2). There was no evidence of pleiotropy or reverse causal effects for these candidate metabolites.</p><p><strong>Conclusions: </strong>In our metabolome-wide MR study, we discovered a notable protective effect of caffeic acid against UC.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2440-2448"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467764","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":"Predicting Adverse Events to Thiopurines in IBD: Are We a Step Closer?","authors":"Mohmmed Tauseef Sharip, Miles Parkes, Sreedhar Subramanian","doi":"10.1093/ibd/izae125","DOIUrl":"10.1093/ibd/izae125","url":null,"abstract":"<p><p>Thiopurines remain an important option in the treatment of IBD. However, the unpredictable and sometimes serious side effects and intolerance remain a major challenge. Pretreatment of extended genetic panel analysis, identification of novel variants, and monitoring of intermediate metabolites will help improve the overall outcome and reduce the toxicity.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2521-2522"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619813","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}