Characterization of molecular mechanisms of metabolic bariatric surgery on microbiome, bile acid, and lipid metabolism for targeted therapeutic intervention in patients with fatty liver disease.

• Applicants: Professor Dr. Stefan Tenzer; Professor Andreas Teufel, Ph.D.
• Subject Area: Gastroenterology ; Medical Informatics and Medical Bioinformatics ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560059170

Our project investigates the molecular mechanisms of metabolic-bariatric surgery (MBS) in relation to the microbiome, bile acid, and lipid metabolism in patients with fatty liver diseases. The aim is to develop targeted therapeutic interventions for this patient group. The project is structured around four main objectives: First, pathophysiological changes after MBS are examined in a mouse model, analyzing the microbiome, gene expression, and liver metabolism, and determining the optimal loop length for metabolic effects. Subsequently, these results are validated in a human cohort, with the goal of integrative consideration of hepatic and serological changes and the development of surrogate markers for fatty liver diseases. Another focus is on the analysis of metabolic changes through the pre- and post-operative microbiome. For this purpose, fecal transplantations are performed in a fatty liver mouse model, and long-term changes in the microbiome after bariatric surgery are evaluated. Finally, OMICS-based drug repositioning is pursued to optimize drug therapy for fatty liver disease and to investigate the possibility of simulating bariatric surgery influences through medication. Methodologically, the project combines animal models, human cohorts, and bioinformatic analyses. Various techniques are employed, including RNA sequencing, proteome analysis, bile acid profile analysis, 16S DNA sequencing of the microbiome, fecal microbiome transfer, in vitro experiments with steatotic hepatocytes, and drug repositioning using transcriptome data. This project is expected to provide important insights into the pathophysiology of fatty liver disease and the mechanisms of action of MBS. The results could lead to an improved understanding of metabolic changes after MBS, identification of new biomarkers for fatty liver diseases, development of potential drug therapy approaches, and optimization of surgical techniques in MBS. Ultimately, this project promises to develop improved treatment strategies for patients with fatty liver diseases and potentially open up new drug therapy options.

• DFG Programme: Research Grants
• Co-Investigators: Privatdozentin Dr. Claudia Läßle; Professor Dr. Mirko Otto