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

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]. The rapid increase of IBD in Asian raising concern of investigators. Therefore setting up a large scale biobank with comprehensive clinical data is require.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 6000

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of Crohn's disease or ulcerative colitis defined by endoscopy, radiology and histology

Control 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.

Relatives or household members of both patients with IBD or other diseases and controls will be recruited.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Inflammatory Bowel Disease Patient; Patient with confirmed diagnosis of Inflammatory Bowel Disease
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.
Healthy relatives of Inflammatory Bowel Disease patient; Relatives or household members of both patients with IBD or other diseases and controls will be recruited.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Setup a large scale biobank	Set up a large scale biobank to collect data such as comprehensive clinical data, such as patient's demographic and clinical information (e.g. age, weight, gender, family history of IBD, appendectomy history, drug usage etc.)	20 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal microbiota of IBD patient	Study samples will be collected to characterize which microbiota affect severity of IBD by performing metagenomics of gut microbiome in stool and biospy samples	20 years
Genetics and epigenetic markers in IBD	Study samples will be collected from patients with IBD and other diseases for genetic material isolation and gene expression checking by performing PCR.	20 years
Therapeutic drug monitoring	To understand the metabolic pathway leading to the target metabolites and therapeutic drug monitoring during following up by filling in questionniare	20 years
Biomarker of IBD	Study samples will be collected to characterize which microbiota affect severity of IBD by performing metagenomics of gut microbiome in stool and biospy samples	20 years
Pathobionts of IBD	Study samples will be collected to identify specific pathobionts that induce innate immune response by analysis of laboratory result (e.g. cell tissue culturing analysis of specific toxin to cells etc.)	20 years
Microbiota-induced molecular mechanisms	Study samples will be collected to characterize which Microbiota-induced molecular mechanisms by performing metagenomics of gut microbiome in stool and biospy samples	20 years
Disease pathogenesis	Study samples will be collected to characterize which microbiota induces disease by performing metagenomics of gut microbiome in stool and biospy samples	20 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2014
• Primary Completion (ANTICIPATED): February 1, 2034
• Study Completion (ANTICIPATED): July 1, 2034

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: February 24, 2019
• First Posted (ACTUAL): February 27, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Biobank
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: IBD Biobank Study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No