Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.
Redox Biol. 2023 Apr;60:102603. doi: 10.1016/j.redox.2023.102603. Epub 2023 Jan 6.
Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are intimately associated with inflammation and overproduction of reactive oxygen species (ROS). Temporal and inter-individual variabilities in disease activity and response to therapy pose significant challenges to diagnosis and patient care. Discovery and validation of truly integrative biomarkers would benefit from embracing redox metabolomics approaches with prioritization of central regulatory hubs. We here make a case for applying a personalized redox medicine approach that aims to selectively inhibit pathological overproduction and/or altered expression of specific enzymatic sources of ROS without compromising physiological function. To this end, improved 'clinical-omics integration' may help to better understand which particular redox signaling pathways are disrupted in what patient. Pharmacological interventions capable of activating endogenous antioxidant defense systems may represent viable therapeutic options to restore local/systemic redox status, with HIF-1α and NRF2 holding particular promise in this context. Achieving the implementation of clinically meaningful mechanism-based biomarkers requires development of easy-to-use, robust and cost-effective tools for secure diagnosis and monitoring of treatment efficacy. Ultimately, matching redox-directed pharmacological interventions to individual patient phenotypes using predictive biomarkers may offer new opportunities to break the therapeutic ceiling in IBD.
炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），与炎症和活性氧物质（ROS）的过度产生密切相关。疾病活动的时间和个体间变异性以及对治疗的反应给诊断和患者护理带来了重大挑战。发现和验证真正的综合生物标志物将受益于采用氧化还原代谢组学方法，并优先考虑中央调节枢纽。在这里，我们提出了应用个性化氧化还原医学方法的理由，该方法旨在选择性地抑制病理性过量产生和/或特定 ROS 酶源的异常表达，而不影响生理功能。为此，提高“临床组学整合”可能有助于更好地了解哪些特定的氧化还原信号通路在哪些患者中受到了破坏。能够激活内源性抗氧化防御系统的药物干预可能代表有前途的治疗选择，以恢复局部/系统氧化还原状态，在这方面 HIF-1α 和 NRF2 具有特殊的前景。实现具有临床意义的基于机制的生物标志物的实施需要开发易于使用、稳健且具有成本效益的工具，以安全诊断和监测治疗效果。最终，使用预测生物标志物将针对个体患者表型的氧化还原靶向药物干预相匹配，可能为 IBD 中的治疗突破提供新的机会。
