Clinical trial NCT03589183: Gut Microbiome in Inflammatory Bowel Disease
Official title: Discovery of Gut Microbial Signatures in Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Inflammatory Bowel Diseases
Ulcerative Colitis
Crohn Disease
Keywords: Gut Microbiome
Ulcerative colitis
Crohn disease
Multi-omics
Psychometrics
anxiety
depression
Lead sponsor: Kyunghee University Medical Center
Sponsor class: OTHER
First posted: 2018-07-17
Enrollment: 1500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We are planned to study all patients with established diagnosis of IBD (Crohn disease or ulcerative colitis) registered in single tertiary referral IBD center (KyungHee University Medical Center).

Brief summary: Inflammatory bowel disease (IBD) is a chronic inflammatory condition for gastrointestinal tract. There have been numerous studies to reveal dysbiosis of fecal/mucosal microbiome composition in IBD patients but actual trend of dysbiosis is strikingly different among patient's ethnicity.

In this background, the investigators have composed a prospective cohort of Korean IBD patients in a large academic referral IBD center. Using an integrated multi-omics bioinformatic analysis, the investigators aim to explore gut microbial signatures along with distinct clinical/genetic features, and their potential interplay in patients with IBD.

Detailed description: This prospective cohort study aims to build a gut microbiome library for Korean IBD patients, and also aims to explore gut microbial signatures along with distinct clinical/genetic features and their potential interplay using the investigator's multi-omics analysis platform.

After signing the informed consent, various biological samples (fecal, mucosal and blood samples) as well as comprehensive clinical data (including psychometric evaluations using patient survey) will be obtained from patients periodically.

The multi-omics investigations will comprise: metagenomics (16s RNA sequencing and whole metagenomic sequecing), metabolomics, human genomics (genome-wide SNP data, whole exome and genome sequencing), transcriptomics, proteomics, epigenetics and single-cell multi-omics analysis. In vitro and in vivo study using fecal samples will be conducted.

In brief, after extracting the DNA from blood samples, whole genome sequencing will be performed and data will be compared with the previously reported variances. Novel variances or incidence of specific variances will be measured. Fecal sample will be collected and microbiome composition of each study subjects will be analyzed. Fecal microbial diversity will be measured from sequencing data of 16S ribosomal RNA which is highly preserved area of genetic information amongst microorganisms. Colonic mucosal sample will be collected when routine endoscopic surveillance is planned. Sample will be collected from diseased and normal mucosal altogether for analysis. Microbial diversity will be measured from 16S RNA sequencing data of the samples.

The multi-omics data will be analyzed with comprehensive clinical metadata using an integrated bioinformatics analysis platform. Clinical data include demographics, disease characteristics and variouis patient-reported outomes data (including health-related quality of life, anxiety, depression and others). Patient-reported outcomes data will be collected using validated questionnaires periodically.

Data from basic analysis will be re-explore in terms of inter-individual difference, difference between disease characteristics (such as disease phenotype, type of medical treatment and serologic markers), difference between psychosocial characteristics (such as the presence of anxiety or depression and quality of life) and etc. In addition, data from basic analysis will be used as the reference for the Korean IBD patient and it will be compared with other data obtained from the "different ethnicity" or "healthy" Korean population.

In conclusion, this long term, large-scale prospective study will provide a platform for studying a field of translational medicine to reveal hidden signatures of gut microbiome underlying IBD and to identify potential biological markers in IBD.

Eligibility criteria: Inclusion Criteria:

* Patients with established diagnosis of inflammatory bowel disease, including ulcerative colitis and Crohn disease

Exclusion Criteria:

* Person with history of using antibiotics or probiotics within previous 2 weeks.

Primary outcomes:
measure: Composition and diversity of gut microbiome
timeFrame: Up to 10 years
Secondary outcomes:
measure: Taxonomic profiling of gut microbiome
timeFrame: Up to 10 years
measure: Finding of single nucleotide polymorphisms (SNPs)
timeFrame: Up to 10 years
measure: Finding of serologic biomarkers
timeFrame: Up to 10 years
measure: Correlation between host genotyping and gut microbiome
timeFrame: Up to 10 years
measure: Liquid biopsy biosignatures assessed by single cell RNA-Seq
timeFrame: Up to 10 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
Study officials:
affiliation: KyungHee University Hospital
name: Hyo-Jong Kim, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: KyungHee University Hospital
name: Chang Kyun Lee, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007 Jun 7;447(7145):661-78. doi: 10.1038/nature05911.
citation: Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol. 2008 Dec;103(12):3167-82. doi: 10.1111/j.1572-0241.2008.02158.x.
citation: Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, Andoh A. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol. 2018 Feb;11(1):1-10. doi: 10.1007/s12328-017-0813-5. Epub 2017 Dec 29.
citation: Huang H, Vangay P, McKinlay CE, Knights D. Multi-omics analysis of inflammatory bowel disease. Immunol Lett. 2014 Dec;162(2 Pt A):62-8. doi: 10.1016/j.imlet.2014.07.014. Epub 2014 Aug 15.