Gut microbes link with 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 liver cirrhosis. The EU-funded project FLORINASH (The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD)) addressed the role of intestinal microflora activity in the pathogenesis of NAFLD. Researchers investigated the biological processes and mechanisms implicated in the interaction of intestinal microbiota with the host. Research success could mean improved diagnosis and prediction through novel metabolic markers and identification of new therapeutic targets. The team obtained biological samples from several hundred patients with various degrees of NAFLD, obesity and insulin resistance. The resulting database has been populated with 'omics data and clinical parameters. Analysis has provided fundamental insight into the molecular aetiology of NAFLD. Particular emphasis was given to endoplasmic reticulum stress, TNFa-related inflammation, and the lipogenic pathway. Information from the 'omics studies fed into new animal models validated the identified molecules. To evaluate the role of microbiota in NAFLD development, mice were colonised with human microbiota from patients with different NAFLD states and then 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 between intestinal microbiota and NAFLD. Diagnosis of complications of NAFLD such as steatosis, fibrosis, cirrhosis and hepatocarcinoma normally requires liver biopsy, a risk for the patient. From a clinical perspective, biomarkers should improve the sensitivity and accuracy of liver disease diagnosis and the novel interventions should contribute to disease prevention or therapy. No final biomarkers could be validated at the close of the project but future research efforts could identify biomarkers using data collected during this project.
Keywords
Gut microbes, non-alcoholic fatty liver disease, biomarkers, obesity, insulin resistance
