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.

Cases (Crohn's disease or Ulcerative colitis)Inclusion Criteria:Aged ≥18 years oldConfirmed diagnosis of Crohn's disease or Ulcerative colitis defined by endoscopy, radiology, and histologyCompetent to provide informed consentExclusion Criteria:Use of antibiotics in the last 1 monthKnown 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 / stomaCurrent pregnancyControls Inclusion CriteriaAged ≥18 years oldNo known medical history including inflammatory bowel disease, irritable bowel syndrome or GI malignancyCompetent to provide informed consentExclusion CriteriaUse of antibiotics in the last 1 monthKnown 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