Mucobiomes in the pathogenesis of inflammatory bowel disease

Project Details


Inflammatory Bowel Disease (IBD) is a chronic disorder that includes ulcerative colitis and Crohn’s disease. The prevalence of IBD is consistently increasing in the worldwide population, which is compounded by the in efficiencyof the available treatment options. Several genetic and environmental factors are linked to the disease, yet the pathogenesis mechanisms are poorly understood. Since the genetics alone cannot explain the entire disease risk,it is critical to identify the environmental “triggers” of IBD.
Using a gnotobiotic mouse model containing a characterized synthetic human gut microbiota, we recently showed that a dietary fiber-deprived gut microbiome erodes the colonic mucus barrier, which is the host’s first line of defense against the commensal and pathogenic microbes. Our follow-up unpublished work using the synthetic microbiota in IL10-/- mice, a mutant line that mimics inflammation in human IBD, suggests that deficiency of dietary fiber is an environmental “trigger” of IBD, which in our model potentially acts via the increased activities of mucus-degrading bacteria.
Based on our preliminary work, the central hypothesis for the proposed research project is that the communities of colonic mucus-degrading bacteria (“mucobiomes”) play vital roles in the pathogenesis of IBD and their activities are regulated by dietary fibers. Using patient cohorts and gnotobiotic models, we will test our hypothesis by addressing these three research objectives: 1) Establish personalized culture collections of mucobiomes from patients,followed by mechanistic studies in gnotobiotic mice; 2) Identify the underlying immune pathways related to mucobiome-mediated mucus deterioration; and 3) Examine the alterations in the mucobiomes during anti-tumor necrosis factor (TNF) therapy of IBD patients, which leads to mucosal healing. Our proposed research will shed important light on understanding the role of commensal mucobiomes in the pathogenesis of IBD, and might help to design dietary therapeutic strategies.
Effective start/end date1/05/1930/04/23


  • FNR - Fonds National de la Recherche: €678,000.00


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