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

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are immune-related disorders characterized by

inappropriate gut inflammation. Their incidence has increased dramatically in Western countries in recent decades, supporting a role

for environmental factors. Despite the development of new treatments, IBD are insufficiently controlled in a large proportion of

patients, inducing an alteration in quality of life and a socioeconomic burden. A better understanding of the pathogenesis and

identification of new therapeutic targets are therefore urgently needed. In this context, the gut microbiota has been recognized as a

strong actor in IBD. Additionally, an alteration in intestinal and immune cell energy metabolism has been suggested in the

pathogenesis. Classical host-microbe interaction concepts rely on the recognition of conserved microbial motifs by innate immunity

sensors or on the action of microbial molecules on a host cell receptor. However, energy metabolism plays a crucial role in mounting

the appropriate cellular response, and emerging data indicate that the gut microbiota may directly affect it. I hypothesize that the

altered gut microbiota in IBD contributes to the impairment of host cell energy metabolism and pathogenesis. The aims of

ENERGISED are to (i) identify the microorganisms and microbiota-derived metabolites impacting host cell energy metabolism and the

mechanisms involved and (ii) decipher the consequences of gut microbiota alterations on host cell energy metabolism in IBD and

design 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 of

multiple cutting-edge technologies; and translational analysis from mice to humans. In addition to its scientific importance, it will

have societal impacts due to the identification of new therapeutic strategies.