Development of Novel Fecal Microbial Biomarkers for Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative colitis (UC), is a chronic idiopathic inflammatory condition of the intestine. Endoscopy has been used to monitor the disease, but it is time-consuming, costly, invasive, and associated with certain risks of morbidity. Many patients are reluctant to undergo repeated endoscopic examinations, particularly when their disease is quiescent. Acute phase reactants have been used to monitor disease including C-reactive protein and stool leucocyte markers including fecal calprotectin, but their sensitivity and specificity in correlating to intestinal inflammation activity are low. Clinical challenge of patient heterogeneity in disease phenotype and response to therapy has compounded discovery of disease-related biomarkers. In IBD, altered fecal microbiota signatures have been consistently reported which included a reduction in biodiversity with lower proportions of Firmicutes and increases in Proteobacteria and Bacteroidetes phylum members. Moreover, overall bacterial diversity is consistently decreased in IBD patients compared to controls. Even though a number of fecal biomarkers have been evaluated for their utility for disease diagnosis in IBD, to date none has been accurate enough for clinical application. Therefore, identification and validation of a non-invasive biomarker which can be easily applied in disease diagnosis and prognosis is warranted to provide an earlier opportunity to intervene. In this study, it aims to develop a metagenomics-based model using fecal microbial biomarkers for differentiating IBD patients from healthy controls, and then validate these fecal microbial biomarkers in different populations.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis; Microbiome

Detailed Description

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative colitis (UC), is a chronic idiopathic inflammatory condition of the intestine, which results in diarrhea, rectal bleeding, urgency, weight loss and abdominal pain. The natural course of IBD is characterized by activity outbreaks and periods of remission.

Endoscopy has been used to monitor the disease, but it is time-consuming, costly, invasive, and associated with certain risks of morbidity. Many patients are reluctant to undergo repeated endoscopic examinations, particularly when their disease is quiescent. Acute phase reactants have been used to monitor disease including C-reactive protein and stool leucocyte markers including fecal calprotectin, but their sensitivity and specificity in correlating to intestinal inflammation activity are low. Clinical challenge of patient heterogeneity in disease phenotype and response to therapy has compounded discovery of disease-related biomarkers. In IBD, altered fecal microbiota signatures have been consistently reported which included a reduction in biodiversity with lower proportions of Firmicutes and increases in Proteobacteria and Bacteroidetes phylum members. Moreover, overall bacterial diversity is consistently decreased in IBD patients compared to controls. Even though a number of fecal biomarkers have been evaluated for their utility for disease diagnosis in IBD, to date none has been accurate enough for clinical application. Therefore, identification and validation of a non-invasive biomarker which can be easily applied in disease diagnosis and prognosis is warranted to provide an earlier opportunity to intervene.

In this study, it aims to develop a metagenomics-based model using fecal microbial biomarkers for differentiating IBD patients from healthy controls, and then validate these fecal microbial biomarkers in different populations.

This is a cross-sectional multi-centre study. Two groups of subjects, IBD patients (cases) and healthy subjects (controls), will be recruited from each centre. Each center will provide fecal samples from 80-100 Crohn's disease, 80-100 ulcerative colitis, and 80-100 controls. We will collect clinical data and stool sample from each subject. Fecal microbiota composition will be compared between cases and controls. The abundance of bacterial biomarkers will be assessed, and the efficacy of a diagnostic model will be validated.

• Study Type: Observational
• Enrollment (Estimated): 3300

Contacts and Locations

• Study Contact: Name: Jingwan Zhang, PhD; Phone Number: 852-39798632; Email: wendyjwzhang@cuhk.edu.hk
• Study Contact Backup: Name: Siew Chien Ng, PhD; Phone Number: 852-35053996; Email: siewchienng@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital
    • Contact: Siew Chien Ng, PhD; Phone Number: 852-35053996; Email: siewchienng@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Cases (Crohn's disease or Ulcerative colitis) and healthy controls

Description

Cases (Crohn's disease or Ulcerative colitis)

Inclusion Criteria:

• Aged ≥18 years old
• Confirmed diagnosis of Crohn's disease or Ulcerative colitis defined by endoscopy, radiology, and histology
• Competent to provide informed consent

Exclusion Criteria:

• Use of antibiotics in the last 1 month
• Known current sepsis (excluding uncomplicated infections such as influenza)
• Known history of severe organ failure (including decompensated cirrhosis, malignant disease, kidney failure, epilepsy, active serious infection, acquired immunodeficiency syndrome)
• Major bowel surgery in the last 6 months (excluding colonoscopy/ procedure related to perianal disease)
• Presence of an ileostomy / stoma
• Current pregnancy

Controls Inclusion Criteria

• Aged ≥18 years old
• No known medical history including inflammatory bowel disease, irritable bowel syndrome or GI malignancy
• Competent to provide informed consent

Exclusion Criteria

• Use of antibiotics in the last 1 month
• Known current sepsis (excluding uncomplicated infections such as influenza)
• Known history of severe organ failure (including decompensated cirrhosis, malignant disease, kidney failure, epilepsy, active serious infection, acquired immunodeficiency syndrome)
• Bowel surgery in the last 6 months (excluding colonoscopy/ procedure related to perianal disease)
• Presence of an ileos

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal microbial biomarkers for IBD	To identify and develop fecal microbial biomarkers for IBD, and validate fecal microbial biomarkers in different populations	1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: National University Hospital, Singapore; University of Chicago; Heidelberg University; Mahidol University; Ruijin Hospital; Indonesia University; Hanoi Medical University; Duke-NUS Graduate Medical School; National Taiwan University; National University of Malaysia; National Academy of Medical Sciences, Nepal; Kiang Wu Hospital
• Investigators: Principal Investigator: Siew Chien Ng, PhD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2022
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: October 25, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases
• Other Study ID Numbers: IBDFMB

Drug and device information, study documents

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