Biobank - Investigating the Gut Microbiota, Genetics, Epigenetics and Metabolites
Investigating the Intestinal Microbiota, Epigenetic Markers and Body Fluid Metabolites to Identify Biomarkers for Inflammatory Bowel Diseases
研究概览
地位
条件
详细说明
Inflammatory bowel disease (IBD) affects 1 in 500 to 1,000 people in the West. Previously a disease predominantly of the West, there is now a marked increase in the incidence of ulcerative colitis (UC) and Crohn's disease (CD) in Asia, with an estimated prevalence of 1 in 3,000 and 1 in 10,000 respectively [1]. IBD is thought to result from an aberrant immune response to intestinal bacteria in genetically susceptible individuals [2]. Genetic variants have been shown to contribute to an increased IBD risk. Although genetic traits predispose to the development of IBD in Asia, the change in epidemiology that has occurred over only a few decades suggests that other, presumably environmental factors play the major role in the development of disease [10].
IBD patients often rely on medical therapy to achieve remission. Due to the diverse features of severity, phenotypes, clinical courses and responses, personalizing IBD therapy is important to maximize management efficacy, minimize adverse events and decrease cost. Thiopurines is a key component of medications in the treatment of Inflammatory Bowel Disease (IBD). However, achieving an optimal efficacious thiopurine dosing can be difficult, as up to 10% of patients have dose-dependent toxicities and up to 9% of patients are resistant to thiopurine therapy [16, 17]. Such clinical toxicity could be due to inherited genetic variation of certain enzyme, leading to an unusual metabolic pathway, which generates toxic metabolites. On the other hand, few studies have studied the longitudinal changes in the gut microbiome with drug treatment in IBD. Shaw et al. characterized 19 children with CD and 4 with ulcerative colitis (UC), showing that dysbiosis at baseline correlated with the degree of inflammatory burden of luminal disease.Therefore, identification of comprehensive targets for drug monitoring will improve our understanding of the basis for inter-patient variability in drug toxicity and efficacy, and enable more individualized therapy.
Metabolism has an essential role in biological systems; and metabolites represent the end products of this important process from a cell of a certain physiological status. Blood and urine are integrative fluids that incorporates the metabolic outputs at different of the body, and thus providing a metabolic footprint as an end product [4].
Metagenomics which is a study of microbes as communities is also an important approach to study microbiota in human.The interplay between microbiota and genetics gives unique transcription profiles in the gut, and gene expression analyses provide insights into the transcriptional activity and functional molecular pathways underlying disease progression. Therefore, deep sequencing analysis of the colon suggests hypotheses about the pathophysiological processes in IBD patients. Further transcriptomics study and in combination with other meta'omics studies will provide the basis for in-depth understanding of IBD pathogenesis.
Due to the bio-clinical complexity of diseases and microbiota, a long term, large-scale prospective biobank is necessary to carry out meaningful research. This biobank will provide a powerful platform for studying a range of complex factors associated with IBD that are of great relevance to public health. Such biobank may be extended to other diseases including GI diseases and autoimmune disorder, which may possibly provide insight to the role of microbiota in human health.
In conclusion, a comprehensive understanding of the intestinal ecosystem, epigenetic, metabolic and transcription profiles, as well as their mechanisms in the disease pathogenesis in patients with IBD and other diseases may help us identify potential biomarkers. However, our current knowledge about them is still very limited, particularly in Asian patients, who have not been extensively researched. Further investigation in this field is needed. To serve these purposes, we aim to setup a large scale biobank with comprehensive clinical data.
研究类型
注册 (预期的)
联系人和位置
学习地点
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Hong Kong、香港
- 招聘中
- Prince of Wales Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
通过内窥镜检查、放射学和组织学诊断为克罗恩病或溃疡性结肠炎的患者
对照组将包括接受结肠镜检查以进行息肉或结直肠癌筛查或胃肠道症状调查的个人,以及威尔斯亲王医院或爱丽丝何妙龄那打素医院患者的朋友和配偶或伴侣,或任何有兴趣参与此活动的个人学习。
将招募患有 IBD 或其他疾病和对照的患者的亲属或家庭成员。
描述
Inclusion Criteria:
- Patient ≥18 with a diagnosis of Crohn's disease or ulcerative colitis
- Informed Consent obtained
Exclusion Criteria:
- Known current infection with an enteric pathogen
- Previously been diagnosed with IBD (Control)
- Have a first of second degree relative with IBD (Control)
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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Inflammatory Bowel Disease Patient
Patient with confirmed diagnosis of Inflammatory Bowel Disease
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Healthy control
Controls (non-IBD) will comprise individuals undergoing colonoscopy for polyp or colorectal cancer screening, or investigations of gastrointestinal symptoms, and friends and spouses or partners of patients at Prince of Wales Hospital or Alice Ho Miu Ling Nethersole Hospital, or any individuals who are interested to participate in this study.
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Healthy relatives of Inflammatory Bowel Disease patient
Relatives or household members of both patients with IBD or other diseases and controls will be recruited.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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建立一个大规模的生物样本库
大体时间:20年
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建立大规模的生物样本库以收集综合临床数据等数据,例如患者的人口统计和临床信息(例如
年龄、体重、性别、IBD 家族史、阑尾切除史、药物使用情况等)
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20年
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Intestinal microbiota of IBD patient
大体时间:20 years
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Study samples will be collected to characterize which microbiota affect severity of IBD by performing metagenomics of gut microbiome in stool and biospy samples
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20 years
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Genetics and epigenetic markers in IBD
大体时间:20 years
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Study samples will be collected from patients with IBD and other diseases for genetic material isolation and gene expression checking by performing PCR.
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20 years
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Therapeutic drug monitoring
大体时间:20 years
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To understand the metabolic pathway leading to the target metabolites and therapeutic drug monitoring during following up by filling in questionniare
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20 years
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Biomarker of IBD
大体时间:20 years
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Study samples will be collected to characterize which microbiota affect severity of IBD by performing metagenomics of gut microbiome in stool and biospy samples
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20 years
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IBD 致病菌
大体时间:20年
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将收集研究样本以通过分析实验室结果(例如
细胞特定毒素的细胞组织培养分析等)
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20年
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Microbiota-induced molecular mechanisms
大体时间:20年
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将收集研究样本,以通过对粪便和活检样本中的肠道微生物组进行宏基因组学来表征哪些微生物群诱导的分子机制
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20年
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Disease pathogenesis
大体时间:20 years
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Study samples will be collected to characterize which microbiota induces disease by performing metagenomics of gut microbiome in stool and biospy samples
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20 years
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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