Influence of the human microbiome on disease risks in a population-based setting (SHIP) and in disease cohorts

• Applicant: Professor Dr. Lars Kaderali
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Medical Informatics and Medical Bioinformatics
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458957273

The human host and its site-specific microbiomes display complex interactions. Distinctive microbiomes occur at different sites of the body and each microbiome is quite stable in healthy individuals, albeit microbial translocation can occur between different niches. If microbial dysbiosis occurs, this can trigger local and systemic host responses. This is the central topic of this proposal, which aims to understand how the microbiome and its host interact and how microbial dysbiosis impacts the host. Our central hypothesis is that dysbiosis can drive chronic, low-grade, systemic inflammation and triggers increased reactivity of immune cells, ultimately leading or at least contributing to many diseases. To shed light on these processes we will use a unique resource available in Greifswald: the population-based Study of Health in Pomerania (SHIP). The large collection of biomaterials readily available from the SHIP-biobank allows us to analyze the microbiomes at different body sites, how they vary over time and communicate with each other and with their host, and to link this with already available extensive clinical and molecular data for the SHIP participants. This allows us and other researchers who can request access to SHIP data to analyze risk factors, subclinical disorders and their complex associations with the microbiome. In addition, we will include a chronic pancreatitis cohort to elucidate pathogenic properties of the microbiome, by comparing microbiomes and clinical phenotypes of the general population and patients.By integrative analysis of the metagenome data in these cohorts with functional, phenotypic and clinical parameters we want to improve our understanding of how the human bacterial microbiome influences the risk of endogenous infections and the degree of systemic inflammation. We will focus on three overarching aims: i) To profile individual microbiomes in different niches of the body (anterior nares, tongue, periodontal pockets, skin and stool), determine their stability and screen for indications of a transfer of species between niches. ii) To elucidate the functional consequences of microbiome composition and its alterations by integrative analysis of these data with functional data such as the stool metabolome and metaproteome. iii) To analyze the immune response by profiling specific antibodies, plasma proteome and cytokine patterns and relate these to the microbiome. To achieve these aims, we have formulated research hypotheses which will guide our scientific program, but will also use advanced machine learning and pattern recognition algorithms to exploit the power of the extensive data and break new ground using data-driven approaches.

• DFG Programme: Research Grants
• Co-Investigators: Professorin Dr. Barbara Bröker; Privatdozentin Dr. Birte Holtfreter; Professor Dr. Thomas Kocher; Professor Dr. Markus M. Lerch; Professor Dr. Stefan Simm; Professor Dr. Uwe Völker