Impact Of The Gut Microbiota On Host Cells Energy Metabolism: Role In Health And In Inflammatory bowel disease

Inflammatory bowel diseases (IBD), including Crohns disease and ulcerative colitis, are immune-related disorders characterized byinappropriate gut inflammation. Their incidence has increased dramatically in Western countries in recent decades, supporting a rolefor environmental factors. Despite the development of new treatments, IBD are insufficiently controlled in a large proportion ofpatients, inducing an alteration in quality of life and a socioeconomic burden. A better understanding of the pathogenesis andidentification of new therapeutic targets are therefore urgently needed. In this context, the gut microbiota has been recognized as astrong actor in IBD. Additionally, an alteration in intestinal and immune cell energy metabolism has been suggested in thepathogenesis. Classical host-microbe interaction concepts rely on the recognition of conserved microbial motifs by innate immunitysensors or on the action of microbial molecules on a host cell receptor. However, energy metabolism plays a crucial role in mountingthe appropriate cellular response, and emerging data indicate that the gut microbiota may directly affect it. I hypothesize that thealtered gut microbiota in IBD contributes to the impairment of host cell energy metabolism and pathogenesis. The aims ofENERGISED are to (i) identify the microorganisms and microbiota-derived metabolites impacting host cell energy metabolism and themechanisms involved and (ii) decipher the consequences of gut microbiota alterations on host cell energy metabolism in IBD anddesign new microbiota-based therapeutic strategies to manipulate the host cell energy state in IBD.This challenging project involves multidisciplinary aspects from microbiology to immunology, metabolism, and medicine; the use ofmultiple cutting-edge technologies; and translational analysis from mice to humans. In addition to its scientific importance, it willhave societal impacts due to the identification of new therapeutic strategies.