-Nutriperso: Tailoring food and dietary recommendations to prevent chronic diseases: health, social and economic issue
Funding: Lidex Paris Saclay 2017-2020
Partners: INRA UR 1303 Aliss, INRA UR Micalis, INSERM CESP, UMR INRA‐APT PNCA, UMR INRA‐APT GMPA, UMR INRA‐APT Genial, CEA‐List, CNRS‐INRIA‐LRI‐Université Paris‐Sud Research group TAO, UMR CNRS I3 et Telecom ParisTech SHS.
Coordinator: L.G. Soler (INRA)
-Modelling gut microbiota
Funding: INRA MEM
The gut microbial community is a highly complex ecosystem, harboring a high taxonomic diversity. The gut microbiota plays an important role in the health and well-being of its host. Our aim is to develop mathematical, data analysis and modelling approaches to help integrate knowledge and data. We work on knowledge based dynamic models but also design new models, hypothesis driven, to analyze metagenomic datasets. Our team and Béatrice Laroche (MAIAGE) have been collaborating since 2007 and we co-supervise Sébastien Raguideau's PhD.
-CorioFunc "Functions and metabolic adaptation of Coriobacteriaceae, a dominant microbial family of the intestine, in the context of lipid metabolism"
Partners: T. Clavel (TUM, Freising, Co-PI), S. Rohn (Institute of Food Chemistry, University Hamburg), P. Gérard (INRA-MICALIS)
Funding: ANR Blanc International 2014
The main objective of the CorioFunc project is to study the impact of bacterial conversion of cholesterol-derived compounds on the lipid metabolism of the host and the development of non-alcoholic fatty liver disease by bacteria of Coriobacteriaceae family.
Recent work on experimental models has shown that the prevalence of 16S rDNA sequences assigned to Coriobacteriaceae family is a function of the genotype of the host and positively correlated with hepatic triglyceride levels and non-HDL cholesterol plasma levels. Although still poorly studied, the metabolism of bile acids by intestinal microorganisms is considered a factor that strongly influences the lipid metabolism of the host. We have recently demonstrated, using microbiota transfer experiments in a murine model, the key role played by the gut microbiota in the development of liver pathologies (non-alcoholic fatty liver disease). However, the molecular mechanisms associated with this effect are still poorly described. In addition, the metabolism of endogenous corticosteroids by intestinal bacteria is also poorly known.
The combination of expertise specific to the French and German teams involved in the CorioFunc project will allow us to characterize the ecological and patho-physiological importance of Coriobacteriaceae within the intestinal ecosystem and more generally on a systemic scale.
-NeoMAIT: MAIT cells and microbiota colonization in preterms
Funding ANR PRTS 2014 http://www.agence-nationale-recherche.fr/?Project=ANR-14-CE15-0005
Given the potential importance of MAIT cells in protection from microbial infections at epithelial surfaces, we investigate the maturation dynamics of MAIT cells in relation with gut microbiota diversity and function during the neonatal period. Our study combine multiparametric phenotypic and functional characterization of MAIT cells with microbiota analysis (high throughput sequencing, metagenomics, Rib microbiology) to determine how the presence or functionality of MAIT cells is influenced by the gut microbiota, and vice versa.
Partners: INRA PNCA (D. Tomé), GMPA (I. Souchon), GENIAL (C. Michon)
-Epiflore "Intestinal ecosystem of large and very premature babies: microbiota analysis, short and long term clinical implications"
Partners: MJ Butel (Univ Paris V, Coord.), PY Ancel (INSERM U953)
Funding: ANR Blanc 2013
The purpose of the EPIFLORE project is to conduct a large-scale analysis of microbiota establishment in the preterm infant. This project takes advantage of the opportunity of 2 French cohorts that started in 2011: (1) EPIPAGE 2 which included all premature infants born in France and (2) ELFE which included all term newborns and preterm infants of high gestational age. All children included will be followed up to 12 years old. The EPIFLORE project has three objectives: (1) to study on a large scale the specific intestinal microbiota of very premature newborns with a multicentric approach taking into account the interindividual variability and the variability linked to the center, (2) to link the great prematurity with development of short and longer-term pathologies; and (3) to look for relationships between the microbiota profile and the development of sepsis or NEC. Six hundred and sixty children from 19 level III intensive care centers and belonging to the EPIPAGE 2 cohort were included. The comparison of the children belonging to these 2 cohorts will make it possible to determine the risk for a very premature baby to develop pathologies in the short and long term.
- ClosNEC "Clostridium and pathophysiology of ulcerative necrotizing enterocolitis of the newborn baby: clinical and molecular approaches"
Partners: J. Aires (Univ Paris V, Coord.), JC. Rozé (CHU de Nantes), S. Rabot (INRA-ANAXEM-Micalis)
Funding: ANR PRTS 2013
Ulceronecrotizing enterocolitis (NEC) is a digestive pathology affecting premature babies with high morbidity and mortality. If its pathophysiology remains poorly known, bacterial intestinal colonization of prematurity is a risk factor. The bacterial involvement in NEC is based on the fermentation of undigested lactose in the small intestine by colonic bacteria leading to hyper-production of metabolites involved in the genesis of lesions. The clinical signs of NEC are consistent with a Clostridian etiology. These bacteria, often isolated from samples from NEC cases, cause in NEC animal model digestive lesions related to hyperproduction of butyric acid, lactose fermentation product.
Our goal is to demonstrate the biological involvement of clostridia in the etiology of NEC by comparing the microbiota of premature infants with or without NEC and to search for biomarkers of pathogenicity. This project will bring new clinical and mechanistic data in order to improve the care and prevention of this dramatic digestive disease of the premature baby.