FLORINASH

FLORINASH: The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD)

 

Coordinator: Rémy BURCELIN
Project Number: 241913
EC contribution: € 5,729,810.00

Project website: http://www.florinash.org/

Background and aims

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. This project entitled “The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD)” brings together 6 leading institutions from 4 countries.

Cases of fatty liver disease with inflammation that resembled alcoholic steatohepatitis but occurring in non drinkers were described 30 years ago, first in the Japanese literature and then in the United States. Ludwig coined the term non alcoholic steatohepatitis (NASH) in 1980. The more embracing term non alcoholic fatty liver disease (NAFLD) has been adopted to cover the full spectrum of metabolic fatty liver disorders. This progressive chronic disease is characterized by a graded severity which could lead to hepatic failure and premature death.

The FLORINASH project is a collaborative project funded by the European Union as part of the 7th framework programme. FLORINASH – contract N° HEALTH-F2-2009-241913 – started on January 1st 2010 and will last 5 years.

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:

  • 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.
  • The application of coupled bioinformatic and chemometric modelling of phenotypes via advanced system level omics metrics (utilizing metabolomic, proteomic, transcriptomic, and metagenomic platforms).
  • The mechanistic refinement and validation of human markers and target-HITS in complementary animal models and innovative humanized mice.
  • To validate currently available therapeutic candidates for the target-HITS and synthesize new chemical entities to interfere with these target-HITS.
  • 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.