FLORINASH
The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD)
| Coordinatore | INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Organization address
address: 101 Rue de Tolbiac contact info |
| Nazionalità Coordinatore | France [FR] |
| Sito del progetto | http://florinash.org/ |
| Totale costo | 7˙494˙793 € |
| EC contributo | 5˙729˙810 € |
| Programma | FP7-HEALTH
Specific Programme "Cooperation": Health |
| Code Call | FP7-HEALTH-2009-single-stage |
| Funding Scheme | CP-FP |
| Anno di inizio | 2010 |
| Periodo (anno-mese-giorno) | 2010-01-01 - 2014-12-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
Organization address
address: 101 Rue de Tolbiac contact info |
FR (PARIS) | coordinator | 2˙557˙564.80 |
| 2 |
IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD contact info |
UK (LONDON) | participant | 925˙934.40 |
| 3 |
UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA
Organization address
address: VIA ORAZIO RAIMONDO 18 contact info |
IT (ROMA) | participant | 718˙445.20 |
| 4 |
Colosseum Combinatorial Chemistry Centre for Technology SCRL
Organization address
address: VIA DEL MARE 87 contact info |
IT (Pomezia) | participant | 587˙285.00 |
| 5 |
INSTITUT D'INVESTIGACIO BIOMEDICA DE GIRONA DOCTOR JOSEP TRUETA
Organization address
address: AVENIDA DE FRANCA S/N contact info |
ES (GIRONA) | participant | 519˙716.00 |
| 6 |
INSERM - TRANSFERT SA
Organization address
address: Rue Watt 7 contact info |
FR (PARIS) | participant | 420˙864.60 |
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Obiettivo del progetto (Objective)
'As worldwide metabolic disease pandemics rise relentlessly with their concomitant clinical complications such as non alcoholic fatty liver disease, FLORINASH proposes an innovative research concept to address the role of intestinal microfloral activity in the pathogenesis of NAFLD. Firstly, to discover novel metabolic markers for the differential diagnosis and prediction of patient risk. Secondly, to identify HITS as targets for new therapeutic or interventional approaches. The strength of the FLORINASH proposal lies in: i) The construction a large bank of tissues and biofluids (liver biopsies, urine, faeces, plasma) from NAFLD patients that have been phenotyped for obesity and for insulin resistance by hyperinsulinemic clamping. ii) The application of coupled bioinformatic and chemometric modelling of phenotypes via advanced system level omics metrics (utilizing metabolomic, proteomic, transcriptomic, and metagenomic platforms). iii) The mechanistic refinement and validation of human markers and target-HITS in complementary animal models and innovative humanized mice. iv) To validate currently available therapeutic candidates for the target-HITS and synthesize new chemical entities to interfere with these target-HITS. v) To elucidate and widely disseminate the systemic and long range metabolic impacts of intestinal microflora modulation on molecular pathways such as ER stress, lipogenic transcription factors and inflammatory agents. Hence, in addition to fundamental scientific advances that can be tranlated to individual healthcare scenarios, the European community will benefit more widely from numerous social, economical, clinical, scientific impacts resulting from the FLORINASH project.'
Introduzione (Teaser)
The prevalence of metabolic disorders and their co-morbidities is increasing at an alarming rate. To improve diagnosis and therapy, new biomarkers are urgently needed.
Descrizione progetto (Article)
Non-alcoholic fatty liver disease (NAFLD) is a disorder that resembles alcoholic liver disease but is caused by excess fat deposition in the liver. This can lead to inflammation, liver injury and in extreme cases to liver cirrhosis.
The EU-funded project 'The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD)' (http://www.florinash.org/ (FLORINASH)) addresses the role of intestinal microflora activity in the pathogenesis of NAFLD. Among the study objectives is to improve diagnosis and prediction through novel metabolic markers and to identify new therapeutic targets. For this purpose, researchers are investigating the biological processes and mechanisms implicated in the interaction of intestinal microbiota with the host.
In this context, the team obtained biological samples from a cohort of patients with various degrees of NAFLD, obesity and insulin resistance. Analysis of these samples using metabolomics, metagenomics and proteomics technologies is anticipated to provide fundamental insight into the molecular aetiology of NAFLD. Particular emphasis is given to endoplasmic reticulum stress, TNFa-related inflammation, and the lipogenic pathway.
The information from the omics studies is being fed into new animal models to validate the identified molecules. To evaluate the role of microbiota in NAFLD development, mice have been colonised with human microbiota from patients with different NAFLD states and are currently being analysed.
From a therapeutic perspective, the consortium is using bioinformatics modelling to design innovative drugs against molecular targets involved in inflammation and lipogenesis. The therapeutic efficacy of these drugs will be tested in NAFLD animal models.
Taken together, the activities and deliverables of the FLORINASH study should shed light onto a previously unexplored association of intestinal microbiota and NAFLD. From a clinical point of view, the biomarkers should improve the sensitivity and accuracy of NAFLD diagnosis and the novel interventions should contribute to disease prevention or therapy.