Improving diagnosis of non-alcoholic fatty liver disease

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)' (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.