SFB 1382:  Gut-liver axis – Functional circuits and therapeutic targets

• Subject Area: Medicine ; Biology ; Chemistry
• Term: since 2019
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403224013

The gut-liver axis refers to the cooperative function and mutual interaction between gut and liver, including their exchange of cellular and molecular components such as microbial metabolites, nutritional substrates, immune cells, and mediators such as cytokines. The gut-liver axis is not only important for health but it also contributes to the pathogenesis and progression of many important human diseases. However, molecular and cellular circuits underlying the gut-liver axis are still poorly described. The mission of this CRC is to elucidate these functional circuits and, on this basis, to define new molecular and immunological strategies for prevention, diagnostics and treatment. In the second funding period, a particular scientific focus is placed on understanding the multi-layered functional and structural barriers of the gut-liver axis. CRC1382 projects investigate cellular, dietary, immunological, and microbial mechanisms that modulate them. This includes the analysis of barrier function by experimental approaches and clinical imaging as well as investigation of early life events that shape the establishment of barriers. A second focus is placed on investigating dynamic changes within the gut-liver axis. CRC 1382 projects will delineate the underlying events triggering and precipitating dynamic processes along the gut-liver axis. Specifically, we will build on our established expertise in bile acid analytics and employ human sample collections to describe dynamic changes in the bile acids pool by computational models and study their role during liver regeneration. Processes of immune adaptation will be studied by high-resolution approaches such as single-cell sequencing complemented by higher throughput methods to analyse larger numbers of samples. With respect to the gut microbiome as a key component of the gut-liver axis, CRC 1382 will obtain unique clinical insights and samples from a faecal microbiota transfer study in patients with decompensated cirrhosis. New technical developments within the CRC 1382 core projects will enable the implementation of individualised collections of cultured gut microbes and integrate artificial intelligence for the analysis and interpretation of imaging data. Considering the ever-increasing clinical relevance of the gut-liver axis, CRC 1382 is ideally positioned to spur further developments in this field.

• DFG Programme: Collaborative Research Centres

Current projects

• A02 - Tissue regeneration as a critical component of gut‐liver homeostasis (Project Head Liedtke, Christian )
• A03 - The role of proteotoxic stress in the gut-liver axis (Project Heads Güldiken, Nurdan ;  Strnad, Pavel )
• A04 - Molecular signatures underlying pathological gut-liver crosstalk and liver regeneration (Project Heads Barzakova, Emona ;  Jankowski, Joachim ;  Noels, Ph.D., Heidi )
• A05 - Functional analysis of lipid metabolism by the microbiome in gut-liver interactions (Project Heads von Bergen, Martin ;  Clavel, Thomas )
• A07 - Consequences of bile-salt signalling for liver regeneration and pathophysiology (Project Heads Olde Damink, Ph.D., Steven ;  Schaap, Ph.D., Frank G. )
• A08 - Functional impact of risk factors for disease progression within the gut-liver axis (Project Heads Candels, Lena ;  Trautwein, Christian )
• A09 - Role of the gut microbiome in the decompensation of chronic liver disease with portal hypertension (Project Head Trebicka, Ph.D., Jonel )
• A10 - Navigation abilities of gut commensals and their modulation in the gut-liver axis (Project Head Grognot, Marianne )
• A11 - A population-based approach to diet-microbiota interactions that drive liver diseases (Project Head Schneider, Carolin Victoria )
• B01 - Enterohepatic cooperation in the postnatal establishment of immune homeostasis (Project Head Hornef, Mathias Walter )
• B02 - Coordination of gut-liver communication through directed immune cell migration (Project Heads Schippers, Angela ;  Wagner, Norbert )
• B04 - Dendritic cells as cellular targets of gut-liver communication regulating therapy induced HCC as well as CRC liver metastasis regression (Project Head Berres, Marie-Luise )
• B05 - Impact of gut-liver communication on hepatic macrophage composition and function (Project Heads Guillot, Adrien ;  Tacke, Ph.D., Frank )
• B06 - Topology and function of secretory antibodies in gut-liver communication (Project Head Pabst, Oliver )
• B07 - Peritoneal immune states link gut and liver pathology in cirrhosis (Project Heads Bruns, Tony ;  Vehreschild, Maria J G T )
• B08 - Effects of the gut microenvironment on liver during cancer (Project Heads Izcue, Ph.D., Ana ;  Neumann, Ulf P. )
• B09 - Elucidating microbiota-dependent and independent functions of inflammasome-mediated innate immunity during hepatocellular carcinoma development (Project Head Schneider, Kai Markus )
• Q01 - Non-invasive imaging of gut, liver and their communication (Project Heads Kiessling, Fabian ;  Lederle, Wiltrud )
• Q02 - Functional microbiome analysis (Project Heads Blank, Ph.D., Lars ;  Clavel, Thomas )
• Q03 - Integrated Research Training Group ‘Gut-Liver Axis’ (Project Heads Hornef, Mathias Walter ;  Liedtke, Christian )
• Q04 - Central Tasks of the Collaborative Research Centre (Project Head Pabst, Oliver )

Completed projects

• A01 - Microbiota and TLR-Signalling in the Development and Recurrence of intrahepatic Cholangiocarcinoma (Project Heads Lüdde, Ph.D., Tom ;  Neumann, Ulf P. )
• A06 - A physiologically-based model of bile acid metabolism (Project Heads Blank, Ph.D., Lars ;  Neumann, Ulf P. ;  Trautwein, Christian )
• B03 - Tolerogenic function of dendritic cells in the gut-liver axis (Project Head Cerovic, Ph.D., Vuk )

• Applicant Institution: Rheinisch-Westfälische Technische Hochschule Aachen
• Participating Institution: Charité - Universitätsmedizin Berlin; Helmholtz-Zentrum für Umweltforschung (UFZ)
• Participating University: Goethe-Universität Frankfurt am Main; Universität Münster
• Spokesperson: Professor Dr. Oliver Pabst