The bottleneck in translating the successful prevention of MASLD by microbial manipulation to the clinic may lie in the prevalence of “forward” translation of preclinical models into clinical trials, while the “reverse” translation, in which real-time clinical data from humans are tested in preclinical studies, is rarely used. Thus, the specific “reverse” approach, in which potentially MASLD-preventing microbial metabolites are identified in high-risk patients prior to evaluating their anti-inflammatory and anti-fibrotic effects in preclinical in vitro and in vivo models, may represent a significant added value of the STRIMHealth project.

Work package 3 comprises two research tasks. The first task (MetaMark) will apply a reverse translational approach focussing on the role of bacterial metabolites in the prevention of MASLD and provide clues to potential new therapeutics. Potentially useful bacterial metabolites identified in Work package 2 will be analyzed for their effects on cell function, metabolic profiles and cell survival using lipid-loaded in vitro systems. Selected metabolites from the first task will then be added to the diet-induced MASLD animal model in the second task to investigate their effects on liver histology, lipid metabolism, inflammation and fibrosis. This could overcome the risk of failure in early drug development and provide potential metabolites that can be further tested in the clinical trials in collaboration with the healthcare centers.