IMIB - Institute for Molecular Infection Biology

The functional relevance of the intestinal mycobiome in the pathogenesis of non-alcoholic fatty liver disease

The emerging non-alcoholic fatty liver disease (NAFLD) gained a prevalence of about 25-35% in European population and is closely linked to obesity. Main indicators of the disease are hepatic steatosis and inflammation, which could ultimately lead to severe cirrhosis of liver tissue. As the liver is closely connected to the human intestine via portal vein blood supply, it is exposed to high fat diet-related implications like compositional microbiome shifts. It has been shown before, that the composition of the intestinal bacteriome in NAFLD patients significantly changes in comparison to healthy controls. Additionally, some bacterial metabolites like e.g. short chain fatty acids can influence fungal growth and may modulate the fungal part of the intestinal microbiome. Therefore, the human intestinal mycobiome composition in NAFLD pathogenesis will be defined within this project and additionally possible bacterial influences on the mycobiome will be studied.

Changes in intestinal mycobiome composition may cause an imbalance between immune tolerance and antifungal immune responses, contributing to the inflammatory aspect of NAFLD. An impaired antifungal immunity could be caused by possible genetic modifications like single nucleotide polymorphisms in the antifungal immunity pathway genes, which may predispose patients for NAFLD. The combined investigation of possible genetic predispositions and the imbalance between mycobiome composition and immune system responses should ultimately elucidate the functional relevance of the intestinal mycobiome in NAFLD development and progression.