Projets soutenus

Inflammatory bowel diseases (IBD) are increasingly affecting developed and developing countries. In addition of being highly debilitating, these diseases can promote the development of colon cancer as well as extra-intestinal manifestations. The intestinal microbiota plays a central role in the development of IBD, which previously led to the emergence of the ecological Koch’s postulates stating that a given dysbiotic microbiota can be both necessary and sufficient to drive chronic intestinal inflammation, bringing an infectious component to the IBD pathogenesis. Select microbiota members are playing central roles in driving chronic intestinal inflammation, with for example the identification of the pathovar of Escherichia coli called Adherent- Invasive E. coli (AIEC) at play in a subset of IBD patients. However, the observation that most IBD patients are not colonized by AIEC indicates that IBD pathogenesis is complex and that other actors, such as diet, are involved. Partner 1’s laboratory previously demonstrated that dietary emulsifiers highly used by the food industry in order to improve texture and extent shelf-life are sufficient to induce colitis in genetically susceptible mice. Mechanistic investigations demonstrated that the intestinal microbiota is the direct target of dietary emulsifier and is both necessary and sufficient for the promotion of chronic intestinal inflammation when exposed to emulsifier. Importantly, only select dietary emulsifiers seems to hold these detrimental properties toward the intestinal microbiota. Moreover, in both pre-clinical studies as well as in a recently released randomized controlled-feeding study of dietary emulsifier in healthy human volunteers, Partner 1’s laboratory identified a high level of inter-individual susceptibility to emulsifier exposure. Altogether, these data suggest that additive microbiota interactions are complex and need in depth screening and mechanistic characterization to better understand environment/pathobiome relationship in IBD. The central objective of the ADIBIOTE project is to define additive/pathobiome interaction in the etiology of chronic intestinal inflammation in order to advance microbiota-based personalized nutrition.