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炎症性肠病研究的挑战:环境触发因素。

Challenges in IBD Research: Environmental Triggers.

机构信息

University of Cincinnati, Cincinnati, Ohio.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

出版信息

Inflamm Bowel Dis. 2019 May 16;25(Suppl 2):S13-S23. doi: 10.1093/ibd/izz076.

Abstract

Environmental triggers is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, novel technologies, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the environmental triggers section is focused on the main research gaps in elucidating causality of environmental factors in IBD. Research gaps were identified in: 1) epidemiology of exposures; 2) identification of signatures of biological response to exposures; and 3) mechanisms of how environmental exposures drive IBD. To address these gaps, the implementation of longitudinal prospective studies to determine disease evolution and identify sub-clinical changes in response to exposures is proposed. This can help define critical windows of vulnerability and risk prediction. In addition, systems biology analysis and in silico modeling were proposed as approaches to integrate the IBD exposome for the identification of biological signatures of response to exposures, and to develop prediction models of the effects of environmental factors in driving disease activity and response to therapy. This research could lead to identification of biomarkers of exposures and new modalities for therapeutic intervention. Finally, hypothesis-driven mechanistic studies to understand gene-environment interactions and to validate causality of priority factors should be performed to determine how environment influences clinical outcomes.

摘要

环境触发因素是《炎症性肠病研究挑战》文件五个重点关注领域之一,其他四个领域分别为临床前人类 IBD 发病机制、新技术、精准医学和实用临床研究。《炎症性肠病研究挑战》文件全面概述了当前炎症性肠病研究中的空白,并提出了切实可行的解决方案。该文件由来自科学家、临床医生、患者和资助者的多学科人员共同参与完成,是患者为中心的研究重点确定的宝贵资源。特别是,环境触发因素部分重点关注阐明环境因素在 IBD 中因果关系的主要研究空白。研究空白包括:1)暴露的流行病学;2)识别暴露生物反应的特征;3)环境暴露驱动 IBD 的机制。为了解决这些空白,建议实施纵向前瞻性研究以确定疾病演变并识别暴露反应的亚临床变化。这有助于确定脆弱和风险预测的关键窗口期。此外,还提出了系统生物学分析和计算机建模作为方法,用于整合 IBD 外显子组以识别对暴露的生物反应特征,并开发环境因素对疾病活动和治疗反应影响的预测模型。这一研究可能会发现暴露的生物标志物,并为治疗干预提供新方法。最后,应进行假设驱动的机制研究以了解基因-环境相互作用并验证优先因素的因果关系,以确定环境如何影响临床结果。

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