Description du projet
Importance du microbiote intestinal dans les maladies inflammatoires de l’intestin
Les maladies inflammatoires chroniques de l’intestin (MICI) liées au système immunitaire incluent la maladie de Crohn et la colite ulcéreuse, des troubles caractérisés par une inflammation de l’intestin. L’incidence des MICI a augmenté dans les pays occidentaux au cours des dernières décennies, mettant en évidence le rôle des facteurs environnementaux. L’état du microbiote intestinal et une altération du métabolisme énergétique des cellules intestinales et immunitaires ont été liés à la pathogenèse des MICI. Le projet ENERGISED, financé par l’UE, entend identifier les micro-organismes et leurs métabolites qui ont un impact sur le métabolisme énergétique des cellules hôtes et comprendre l’importance des altérations du microbiote intestinal et du métabolisme dans la pathogenèse des MICI. L’objectif du projet est de concevoir de nouvelles stratégies thérapeutiques basées sur le microbiote afin de réguler l’état énergétique des cellules hôtes dans les cas de MICI.
Objectif
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.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
75006 Paris
France