Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide.
Alterations of intestinal microbiota composition and associated impairments of intestinal
barrier function are critical in the onset and progression of NAFLD. Recent data suggest a
pivotal role of bile acids and microbial bile acid metabolism as mediators of gut-liver-crosstalk
subsequently affecting NAFLD initiation and progression. Soluble fibers like oat β-glucans
bind bile acids and modulate intestinal microbiota composition thereby affecting metabolic
parameters and liver health. Furthermore, intervention trails suggest that manipulating
intestinal microbiota composition through prebiotics may improve disease progression of
NAFLD. However, the molecular mechanisms involved remain incompletely understood and
established therapeutic strategies are still missing. The proposed project combines the
complementary expertise of 5 groups with a strong background in various aspects of diet,
liver disease, bile acids and intestinal microbiota. Through combining this expertise and
combining clinical interventions with mouse models, the project aims to determine in the
following 3 work packages (WP): Is the interaction of bile acids and intestinal microbiota
critical for the initiating (WP1 and 2) and progressing stages (WP3) of NAFLD? Can these
stages be targeted through diet and more specifically with prebiotics like oat β-glucans
thereby improving disease progression and overall health?