SFB 1371:  Microbiome Signatures -- Functional Relevance in the Digestive Tract

• Subject Area: Medicine ; Biology ; Chemistry
• Term: since 2019
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 395357507

Research of the past decade identified a fundamental role of the intestinal microbiome in the regulation of human health and disease. Microbiome signatures are suggested to be unique configurations of microbial communities and their function capable of stratifying disease risk and progression. The Collaborative Research Centre (CRC) 1371 established an interdisciplinary network of basic and clinical scientists to build a mechanistic and functional understanding of clinically relevant microbiome risk profiles, and ultimately, to translate this information into clinical strategies for targeted intervention. Infections, immune-mediated diseases (IBD, GvHD) and colorectal cancer are important clinical endpoints in the digestive tract reflecting a continuum of acute and chronic pathologies with microbiome changes as a common link. In the first funding phase, we generated a unique combination of highly standardized analytical tools and novel pre-clinical models to characterize the role of microbes and their metabolites in inflammatory, metabolic and tumorigenic processes of these pathologies. In the second funding phase, we will validate the functional and clinical relevance of microbiome-related therapy in the newly established pre-clinical models (e.g., gnotobiotic mice and pigs) and defined patient cohorts. A hallmark of this research consortium is the development of synthetic bacterial consortia and the identification of clinically relevant metabolites based on complementary in silico, ex vivo and in vivo approaches. The specification of evidence-based applications for therapeutic microbiome interventions, using diet, phages and fecal microbiota transplantation will be the key objective in the next funding period. The scientific excellence (110 publications with mean impact factor of 15.9), the collaborative strategy (51% shared publications) and outreach activities ensure the visibility of CRC 1371. The appointment of female colleagues to four microbiome-related professorships and the implementation of early career scientists highlights the strategic commitment to foster gender equality (61% female contribution in projects) and young academic careers in the area of microbiome research. In summary, CRC 1371 established a vital and comprehensive environment for microbiome research in Munich, and the 2nd funding phase will help to further stratify and specify the functional relevance of microbiome risk profiles in inflammatory and tumorigenic pathologies of the digestive tract, pursuing the 12-year vision of this consortium to implement evidence-based microbiome therapy in patient care.

• DFG Programme: Collaborative Research Centres
• International Connection: Netherlands

Current projects

• INF01 - Integration and analysis of clinical and multi-omics data (Project Heads Baumbach, Jan ;  Boeker, Martin ;  Kuhn, Klaus A. ;  Lagkouvardos, Ilias ;  List, Markus ;  Prasser, Fabian ;  Schirmer, Melanie ;  Sharma, Ph.D., Sapna )
• NP18 - Impact of Desulfovibrio spp. and sulfur metabolism on the pathogenesis of chronic intestinal inflammation and colitis-associated cancer (Project Heads Haller, Dirk ;  Schirmer, Melanie )
• NP19 - Microbiome-based strategies for biocontrol of preterm necrotising enterocolitis (Project Heads Deng, Li ;  Ebner, Friederike ;  Hall, Ph.D., Lindsay )
• P01 - Impact of exclusive enteral nutrition on microbiome signatures and function in pediatric Crohn’s disease (Project Heads Haller, Dirk ;  Schwerd, Tobias )
• P02 - Microbial triggers of intestinal inflammation in hosts deficient in X-linked inhibitor of apoptosis protein (Project Heads Jost, Philipp ;  Yabal, Monica ;  Zeissig, Sebastian )
• P04 - T cell skewing in relation to intestinal dysbiosis and GvHD in allogeneic stem cell transplantation (Project Heads Busch, Dirk ;  Holler, Ernst ;  Meedt, Elisabeth )
• P05 - Impact of microbiome-derived metabolites on innate immunity, immune function and tissue homeostasis in graft-versus-host disease (Project Heads Poeck, Hendrik ;  Ruland, Jürgen )
• P06 - Defining intestinal microbiota orchestrating immune tolerance to intervene with allergic reactions to food and beyond (Project Heads Biedermann, Tilo ;  Fischer, Konrad ;  Schnieke, Angelika )
• P07 - Microbiota-mediated modulation of protective immunity and immunopathology (Project Heads Ohnmacht, Ph.D., Caspar ;  Zehn, Dietmar )
• P08 - The role of primary metabolites in the intestinal ecosystem under normal and inflamed conditions (Project Heads Jung, Kirsten ;  Stecher-Letsch, Barbara )
• P11 - Deciphering the role of the gut microbiota in the success of radiation therapy for colorectal cancer (Project Heads Fischer, Julius ;  Tschurtschenthaler, Ph.D., Markus )
• P12 - Identifying microbiome-related mechanisms of polyp progression and regression in a porcine model for colorectal cancer (Project Heads Flisikowska, Ph.D., Tatiana ;  Saur, Dieter ;  Schnieke, Angelika )
• P13 - Impact of gut microbiota on colorectal cancer lipid metabolism (Project Heads Ecker, Josef ;  Janssen, Klaus-Peter ;  Klingenspor, Martin )
• P14 - Targeted design and manipulation of minimal bacterial consortia for strain replacement within microbiomes (Project Heads Clavel, Thomas ;  Stecher-Letsch, Barbara )
• P16 - Functional characterization of carcinogenic and inflammatory secondary metabolites from the intestinal microbiota (Project Heads Gulder, Tobias A. M. ;  Sieber, Stephan A. ;  Zeller, Georg )
• Z01 - Gnotobiotic mouse models and minimal bacterial consortia (Project Heads Basic, Marijana ;  Bleich, André ;  Clavel, Thomas ;  Haller, Dirk )
• Z02 - Clinical integration of microbiome research (Project Heads Gessner, Ph.D., André ;  Middelhoff, Moritz ;  Quante, Michael ;  Steiger, Katja )
• Z03 - Integrated Research Training Group (Project Heads Hall, Ph.D., Lindsay ;  Tschurtschenthaler, Ph.D., Markus )
• Z04 - Central tasks of the Collaborative Research Centre (Project Head Haller, Dirk )

Completed projects

• MGKZ03 - Integrated Research Training Group (Project Head Klingenspor, Martin )
• P03 - Circadian control of microbial function in chronic intestinal inflammation (Project Head Kiessling, Silke )
• P09 - Helicobacter infection and microbiota-dependent colonic pathologies (Project Heads Deng, Li ;  Gerhard, Markus )
• P10 - Microbiota- and TLR-dependent regulation of intestinal tumor development (Project Heads Janssen, Klaus-Peter ;  Zeissig, Sebastian )
• P18 - Impact of Desulfovibrio spp. and sulfur metabolism on the pathogenesis of chronic intestinal inflammation and colitis-associated cancer (Project Heads Haller, Dirk ;  Schirmer, Melanie )

• Applicant Institution: Technische Universität München (TUM)
• Participating Institution: European Molecular Biology Laboratory (EMBL); Structural and Computational Biology Unit
• Participating University: Ludwig-Maximilians-Universität München; Medizinische Hochschule Hannover; Technische Universität Dresden; Universitätsklinikum Aachen; Medizinische Fakultät der RWTH; Universitätsklinikum Regensburg
• Spokesperson: Professor Dr. Dirk Haller