Mécanismes de régulation du microbiote intestinal par les peptides/protéines antimicrobiens et conséquences pour l'hôte

par Nicolas Geoffre

Projet de thèse en Microbiologie

Sous la direction de Jamila Faivre.

Thèses en préparation à Paris Saclay , dans le cadre de Innovation thérapeutique : du fondamental à l'appliqué , en partenariat avec Physiopathogenèse et Traitement des Maladies du Foie (laboratoire) et de Université Paris-Sud (établissement de préparation de la thèse) depuis le 01-10-2016 .

  • Titre traduit

    Regulatory mechanisms of gut microbiota by antimicrobial peptides/proteins and consequences for the host

  • Résumé

    Abnormal gut microbiota composition (dysbiosis) and defective antimicrobial mucosal barrier are often pointed out as important pathogenic factors of chronic intestinal inflammation and metabolic disorders. A deficiency in antimicrobial peptides/proteins (AMPs) secretion resulting, in particular, from Paneth cell dysfunction might be a key contributor to dysbiosis and mucosal barrier alteration. The enteric AMP arsenal, which includes defensins, cathelicidins and C-type lectins, is part of the innate immunity, contributing to balance clearance of pathogens and tolerance of commensal microbes in the gut. AMPs may also exert other activities ranging from immunomodulation to cell proliferation. Thus AMPs are major regulators of gut microbiota composition, but the underlying mechanisms are not well understood. The PhD proposal is based on data showing that AMPs were capable of modulating gut microbiota composition and function, in such a way that the immuno-inflammatory components in the gut and extra-gut were reduced and health was improved. The specific objectives are twofold: (i) elucidate the mechanisms by which AMPs shape the gut microbiota composition and determine whether they could correct dysbiotic microbiota and thereby alleviate a pathological state; (ii) characterize the biological properties of AMPs-shaped gut microbiota, and study their anti-inflammatory and metabolic potential in experimental models of diseases.