MUCOBIOME-MEDIATED IMMUNE PATHWAYS IN INFLAMMATORY BOWEL DISEASES

Inflammatory Bowel Diseases (IBD) are chronic disorders characterized by persistent ulcerations in the gastrointestinal tract, drastically affecting the patient’s quality of life. Initially regarded as “Western diseases”, they have now become a global problem. Despite IBD being a set of inflammatory diseases, the underlying host immune pathways remain unclear, making it difficult to reliably treat and cure patients. The low-fiber Western diet, and the microbial communities that live in our intestines (the gut “microbiome”), have been proposed as major environmental contributors of the disease - but the mechanisms of their contribution are poorly understood.
Among the gut microbiome, the mucobiomes are defined as the microbial communities enzymatically geared to digest the host intestinal mucus layer – our first line of defense against invading pathogens. Their mucolytic activities are regulated by dietary fibers. Thus, we hypothesize that, under a low-fiber diet, the mucobiomes catalyze important disease-promoting immune pathways of IBD. Using an original animal model combining genetic susceptibility, dietary fiber deficiency and different microbiota compositions, we aim at highlighting (1) the role of the mucobiome in IBD pathogenesis, and (2) key immune-pathways regulated by the mucobiome. These objectives are ambitious, yet highly feasible given the expertise of the actors. The proposed work provides a unique dimension to understand the underlying pathogenic mechanisms of a key physiological trait of gut bacteria: host-secreted mucus degradation. The success of this project relies on a close interdisciplinary collaboration that will benefit to develop the researcher's career, the hosting group’s projects, the hosting institute's visibility, and establish innovative diet-based therapies for IBD patients.