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
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (予想される)
連絡先と場所
研究場所
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Hong Kong、香港
- 募集
- Prince of Wales Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
-内視鏡検査、放射線学、および組織学によって定義されたクローン病または潰瘍性大腸炎の診断を受けた患者
コントロールには、ポリープまたは結腸直腸がんのスクリーニングのための大腸内視鏡検査を受ける個人、または胃腸症状の調査を受ける個人、プリンス オブ ウェールズ病院またはアリス ホー ミュウ リン ネザーソール病院の患者の友人、配偶者またはパートナー、またはこの参加に関心のある個人が含まれます。勉強。
IBDまたは他の疾患および対照を有する患者の両方の親戚または家族が募集されます。
説明
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)
研究計画
研究はどのように設計されていますか?
デザインの詳細
コホートと介入
グループ/コホート |
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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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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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大規模なバイオバンクのセットアップ
時間枠:20年
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患者の人口統計や臨床情報などの包括的な臨床データなどのデータを収集するために、大規模なバイオバンクを設定します (例:
年齢、体重、性別、IBDの家族歴、虫垂切除歴、薬物使用状況など)
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20年
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Intestinal microbiota of IBD patient
時間枠: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
時間枠: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
時間枠: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
時間枠: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 の病原体
時間枠:20年
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研究サンプルは、検査結果の分析によって自然免疫応答を誘発する特定の病原体を特定するために収集されます (例:
細胞組織培養による細胞特異的毒素の解析など)
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20年
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Microbiota-induced molecular mechanisms
時間枠:20年
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研究サンプルを収集して、糞便および生検サンプルの腸内マイクロバイオームのメタゲノミクスを実行することにより、微生物叢が誘導する分子メカニズムを特徴付けます
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20年
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Disease pathogenesis
時間枠: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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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予期された)
研究の完了 (予期された)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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