Studying the effects of anti-inflammatory dietary compounds using novel in vitro 3D co-culture models of colon chronic inflammation

使用结肠慢性炎症的新型体外 3D 共培养模型研究抗炎膳食化合物的作用

• 批准号: 2433261
• 金额: --
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2433261
• 关键词: Studying; effects; anti; inflammatory; dietary

"Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are non- communicable diseases (NCDs) characterised by chronic inflammation. The current standard of care of IBD and CRC includes anti-inflammatory drugs, which act on the symptoms while poorly addressing the causative factors [1]. Therefore, treatments result merely palliative, addressing the need to find the most appropriate preventive and/or therapeutic protocol.Since the inflammation manifested with IBD and CRC tends to be persistent, unresolved and age-related, recent studies have investigated how lifestyle habits could influence and prevent inflammation's onset, progression and comorbidities [3]. In this regard, it has been recognized the primary role of the meta-exposome, a combination of environmental factors, such as diet, physical activity, exposure to xenobiotics, and microbiome, among others [2, 4]. Dietary choices play a pivotal role in regulating homeostasis and physical wellbeing since food-derived bioactive compounds can actively balance effector (pro-inflammatory) and regulatory (anti-inflammatory) functions [5-7]. This modulation is determined by nutrients' ability to shape genome and epigenome, rearranging their expression profiles. These observations warrant further investigation into food-derived bioactive compounds and their ability to regulate inflammation.We hypothesize that approaching different dietary regimens (Western diet VS Mediterranean diet) leads to a specific modulation of the inflammatory response, both directly, through the immune and adipose systems, and indirectly, through the signals mediated by the microbiome. Since the inflamed phenotype is typical of IBD and CRC, the current project aims to:1. Developa3Dco-culturemodelthatmimicstheintestinalepithelium;2. Dissect the crosstalk between inflammatory cytokines and nutritionalregimens;3. Assess and compare transcriptome and epigenome profiles followingtreatment."

炎症性肠病（IBD）和结直肠癌（CRC）是以慢性炎症为特征的非传染性疾病（NCDs）。目前IBD和CRC的治疗标准包括抗炎药物，这些药物对症状起作用，但对致病因素的处理却很差。因此，治疗的结果仅仅是姑息性的，需要找到最合适的预防和/或治疗方案。由于IBD和CRC表现出的炎症往往是持续性的、未解决的和与年龄相关的，最近的研究调查了生活习惯如何影响和预防炎症的发生、进展和合并症。在这方面，人们已经认识到元暴露体的主要作用，它是环境因素的组合，如饮食、身体活动、接触外源性药物和微生物群等[2,4]。饮食选择在调节体内平衡和身体健康方面起着关键作用，因为食物来源的生物活性化合物可以积极平衡效应（促炎）和调节（抗炎）功能[5-7]。这种调节是由营养物质塑造基因组和表观基因组，重新排列其表达谱的能力决定的。这些观察结果为进一步研究食物来源的生物活性化合物及其调节炎症的能力提供了依据。我们假设，接近不同的饮食方案（西方饮食VS地中海饮食）会导致炎症反应的特定调节，直接通过免疫和脂肪系统，间接通过微生物组介导的信号。由于炎症表型是IBD和CRC的典型表型，因此目前的项目旨在：1。Developa3Dco-culturemodelthatmimicstheintestinalepithelium; 2。2 .分析炎症细胞因子与营养方案之间的相互作用；评估和比较治疗后的转录组和表观基因组谱。”