SPP 1656:  Intestinal Microbiota - A Microbial Ecosystem at the Edge between Immune Homeostasis and Inflammation

• Subject Area: Medicine
• Term: from 2013 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 220134278

The Priority Programme aims at developing an interdisciplinary research programme that determines fundamental principles of microbe-host interactions in health and disease. The gut provides an explicitly large and dynamic interface towards the luminal microbiota and tissue homeostasis is achieved by a compartimentalised immune system. The goal is to achieve a functional understanding of the complex microbial ecosystem in the gut, reaching far beyond compositional analysis and metagenomic sequence acquisition. Fundamental research will help to identify factors that shape the bi-directional interaction between microbiota and host under physiologic and pathologic conditions, specifically aiming to understand the transition of immune homeostasis towards inflammatory pathologies. In the first funding phase, 22 research groups from 17 different German institutions contribute to this rapidly emerging field. This programme addresses the following research themes along with the aim to build and interconnect important scientific infrastructure and facilities. (1) Developing novel scientific concepts: a. Understanding the physiology of a bi-directional interaction between the intestinal microbiota and the mucosal immune system at early life stages and in response to diet and host genotypes; b. Understanding the role of microbe-host interactions in the pathophysiological transition from immune homeostasis to infectious and chronic inflammatory disorders; c. Establishing mechanistic concepts for pre-clinical efficacy and risk evaluation of probiotic intervention and fecal transplantation in infectious and chronic inflammatory disorders. (2) Developing infrastructure networks: Building the infrastructure to facilitate a gnotobiotic facility network with one-core centres for the generation of novel germ-free models and three outposts for specific experimental applications. In addition, we strengthen two core centres for metagenomic and metabolite analysis with a strong emphasis on the transfer of standardised methodologies and protocols for sample processing and data analysis. (3) Training and educating the next generation: Providing platforms for scientific project guidance and scientific education, establishing local and network training courses in both scientific education and career development.

• DFG Programme: Priority Programmes
• International Connection: Austria, USA

Projects

• Aging-associated modification of intestinal homeostasis and barrier function: Role of microbiota, iNOS and innate immunity (Applicants Bergheim, Ina ;  Camarinha Silva, Amelia )
• Characterization of mononuclear phagocyte populations that mediate microbiota-ILC3 interactions (Applicant Diefenbach, Andreas )
• Characterizing the interaction between blood group-related glycosyltransferases and the intestinal microbiota using multi-omic approaches (Applicants Baines, John F. ;  Graßl, Guntram Alexander )
• Control of intestinal inflammation through CD101 expression (Applicant Mattner, Jochen )
• Coordination Funds (Applicant Haller, Dirk )
• Functional consequences of intestinal microbiota altered by ingestion of gluten and wheat alpha-amylase-trypsin inhibitors (Applicants Pickert, Geethanjali ;  Schuppan, Detlef )
• Functional dynamics of dysbiosis in a gnotobiotic transfer model of Crohn`s disease-like ileitis: Impact of diet and inflammation (Applicant Haller, Dirk )
• Generation of gnotobiotic mice to investigate the role of the intestinal microbiota in Salmonella enterica spp. I serovar Typhimurium colitis in AGR2-deficient mice (Applicant Stecher, Barbara )
• Genetic circuits underlying fungal-bacterial interactions in the mammalian intestine (Applicant Perez, Ph.D., Christian )
• Gnotobiology unit within the SPP 1656 (Applicant Bleich, André )
• Healing Mucosa, interaction of microbial ecology and the immune system (Applicant von Bergen, Martin )
• Host control of the enteric microbiota during the postnatal period (Applicant Hornef, Mathias Walter )
• Immune modulation by metagenomic DNA from the gastrointestinal microbiota of newborn infants (Applicant Fricke, Wolfgang Florian )
• Impact of microbiota on the intestinal macrophage compartment (Applicants Blaut, Michael ;  Siegmund, Britta )
• Impact of Prevotellaceae on the interplay between host and microbiota during health and disease (Applicant Strowig, Till )
• Impact of the intestinal microbiota and microbiota mediated immune responses on the host cell death machinery in the intestinal epithelium (Applicant Günther, Claudia )
• In depth characterization of Gut microbial Sulfometabolome in a mouse model of Crohn´s Disease (Applicant Schmitt-Kopplin, Philippe )
• Interaction between microbiota, antimicrobial defense and differentiation factors in Inflammatory Bowel Disease (Applicant Wehkamp, Jan )
• Interaction between Yersinia enterocolitica, the intestinal microbiota, and the host: from molecular analysis to therapeutic intervention (Applicants Autenrieth, Ingo Birger ;  Huson, Daniel H. )
• Mechanisms of microbiota induced IL-23/Th17 immune responses in chronic colitis (Applicants Neurath, Markus F. ;  Wirtz, Stefan )
• - MIMIC - Culture-based and molecular study of the mouse gut microbiome towards Minimal Microbial Consortia (Applicants Clavel, Thomas ;  Overmann, Jörg )
• Modulation of the intestinal barrier by the intestinal microbiota - Role of dietetic factors and the mucosal immune system (Applicant Bischoff, Stephan )
• Molecular analysis of the immune-modulatory properties of colitogenic intestinal microbiota (Applicant Hildner, Kai )
• Mutual interactions between the pathobiont Helicobacter hepaticus and the mouse intestinal microbiota: Ecology, mechanisms and relevance to the induction of IBD (Applicant Suerbaum, Sebastian )
• Neonatal imprinting of tolerogenic properties in stromal cells from gut-draining lymph nodes by commensal microbiota (Applicant Hühn, Jochen )
• Reciprocal interactions between the intestinal microbiota and immunoglobulin A (Applicant Pabst, Oliver )
• Role of bactericidal permeability increasing protein (BPI) in bidirectional hostmicrobiota communication in the gut (Applicant Gessner, Ph.D., André )
• Role of dietary sulfonates in the stimulation of intestinal bacteria promoting gut inflammation (Applicant Braune, Annett )
• Spatial Organization of the Microbiota - Impact of Direct Bacterial Interaction with the Colonic Crypt Epithelium and Long-lived Stem Cells (Applicants Meyer, Thomas F. ;  Sigal, Michael )
• The impact of dietary proteins for mucosal homeostasis and inflammation (Applicants Siegmund, Britta ;  Steinhoff, Ulrich )
• The influence of gut microbiota composition and diversity on the resorption and de novo synthesis of fatty acids in the small intestine (Applicants Ecker, Josef ;  Liebisch, Gerhard )
• Therapy of IBD: Identification of bacteria, bacterial components and the host intestinal immune mechanisms (Applicant Frick, Julia-Stefanie )
• TLR-mediated microbiota-host interaction in the regulation of intestinal homeostasis and nflammation (Applicant Pasparakis, Manolis )
• X-linked inhibitor of apoptosis protein in intestinal homeostasis and the pathogenesis of inflammatory bowel disease (Applicant Zeissig, Sebastian )

• Spokesperson: Professor Dr. Dirk Haller