期刊文献

Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms 收藏

IBD研究的挑战2024：临床前人IBD机制

原文求助发布源

作者

Matthew A Ciorba [1];Liza Konnikova [2];Simon A Hirota [3];Elena M Lucchetta [4];Jerrold R Turner [5];Anthony Slavin [6];Kristen Johnson [7];Cass D Condray [8];Sungmo Hong [9];Brandon K Cressall [10];Theresa T Pizarro [11];Andrés Hurtado-Lorenzo (0000-0003-4660-8604) [12];Caren A Heller [13];Alan C Moss [14];Jennifer L Swantek (0000-0002-9823-5048) [15];Wendy S Garrett [16];

作者单位

[1]Inflammatory Bowel Diseases Center, Division of Gastroenterology, Washington University in St. Louis , Saint Louis, MO , USA; [2]Departments of Pediatrics, Immunobiology, and Obstetric, Gynecology and Reproductive Sciences, Yale School of Medicine , New Haven, CT , USA; [3]Snyder Institute for Chronic Diseases, Dept. of Physiology and Pharmacology, University of Calgary , Calgary, Alberta , Canada; [4]The Leona M. and Harry B. Helmsley Charitable Trust , New York, NY , USA; [5]Departments of Pathology and Medicine, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA , USA; [6]Kymera Therapeutics , Watertown, MA , USA; [7]Generate Biomedicines , Somerville, MA , USA; [8]Patient Representative for the Crohn’s & Colitis Foundation , New York, NY , USA; [9]Patient Representative for the Crohn’s & Colitis Foundation , New York, NY , USA; [10]Patient Representative for the Crohn’s & Colitis Foundation , New York, NY , USA; [11]Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH , USA; [12]Research Department, Crohn’s & Colitis Foundation , New York, NY , USA; [13]Research Department, Crohn’s & Colitis Foundation , New York, NY , USA; [14]Research Department, Crohn’s & Colitis Foundation , New York, NY , USA; [15]Research Department, Crohn’s & Colitis Foundation , New York, NY , USA; [16]Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health , Boston, MA , USA;

发布日期

2024-5-23

页码

S5–S18

DOI

10.1093/ibd/izae081

来源信息

Inflammatory Bowel Diseases ISSN：1078-0998, 2024年, 30卷, Supplement_2期, S5–S18页

摘要

【Abstract】 Preclinical human inflammatory bowel disease (IBD) mechanisms is one of 5 focus areas of the Challenges in IBD Research 2024 document, which also includes environmental triggers, novel technologies, precision medicine, and pragmatic clinical research. Herein, we provide a comprehensive overview of current gaps in inflammatory bowel diseases research that relate to preclinical research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in IBD interception, remission, and restoration. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. This preclinical human IBD mechanisms section identifies major research gaps whose investigation will elucidate pathways and mechanisms that can be targeted to address unmet medical needs in IBD. Research gaps were identified in the following areas: genetics, risk alleles, and epigenetics; the microbiome; cell states and interactions; barrier function; IBD complications (specifically fibrosis and stricturing); and extraintestinal manifestations. To address these gaps, we share specific opportunities for investigation for basic and translational scientists and identify priority actions.

摘要译文

【摘要】临床前人类炎症性肠病（IBD）机制是IBD Research 2024文档中挑战的5个重点领域之一，其中还包括环境触发器，新型技术，精密医学和实用临床研究。本文中，我们提供了与临床前研究有关的炎症性肠道疾病研究中当前差距的全面概述，该研究与临床前研究有关，并提供可行的方法来解决它们，重点关注这些差距如何导致IBD拦截，缓解，缓解和恢复方面的进步。该文件是科学家，临床医生，患者和资助者的多学科投入的结果，代表了以患者为中心的研究优先级的宝贵资源。这个临床前的人类IBD机制部分确定了主要的研究差距，其研究将阐明可以针对IBD中未满足的医疗需求的途径和机制。在以下领域确定了研究差距：遗传学，风险等位基因和表观遗传学；微生物组；细胞状态和相互作用；屏障功能；IBD并发症（特别是纤维化和狭窄）；和肠外表现。为了解决这些差距，我们为基本和转化科学家的调查提供了具体的调查机会，并确定了优先行动。