Linked projectsNAKO-385NAKO-423NAKO-372
SummaryWhile there is strong evidence for an association between the human microbiome and health/disease in the human host, the causal mechanisms behind this association are only partially understood. Dependent on the disease or health status under study, similar patterns of microbiome dysbiosis have been described for various body sites associated with different organ systems. This led to the hypothesis that there exist body-wide microbiome-induced pathways linked by microbial organ cross talk. We will use data and biosamples of 2,000 NAKO participants to investigate the microbial organ cross talk between the human gut (stool samples), oral cavity (saliva samples) and upper respiratory system (nasal swabs) by whole metagenome shotgun sequencing. Based on standardized platforms for biosample collection and storage, DNA extraction and whole metagenome shotgun sequencing, this project will be able to derive the site-specific as well as the joint composition and functional capacity of the microbiome in the human host. Microbial translocations will be studied between the three body sites to gain a comprehensive insight into the microbial dynamics based on bacterial and non-bacterial reads, and to identify microbial signatures down to rare species of the human microbiota that might shape health or disease. Compositional and functional microbiome clusters (defined as archetypes with distinct metacommunities) will be derived within and across body sites together with their respective compositional and functional patterns. Determinants of these archetypes (and the associated metacommunities) will be investigated based on phenotype data including age, nutrition, dentition functionality, sociodemographic factors, infection history, host metabolism, environmental exposure, medication (including antibiotic treatment), as well as disease status and disease pathways. Finally, we will establish procedures to take advantage of the longitudinal design of NAKO for health implications. As an initial use case we will study conditions where gradual loss of homeostasis of host-microbiome interaction results in substantial and relevant subclinical variation, focusing on the role of microbiota 1) in early cardio-metabolic diseases and 2) through the gut-brain axis, in the continuum of mood disorders.
Keywords
Besiedlung
Darmflora
Determinanten
Infektion
Mikrobiom
Nasenabstrich
OMICS
Speichelprobe
Stuhlmikrobiom
Stuhlprobe
InstitutionsUniversität Münster, Lehrstuhl für Klinische Bioinformatik, Universität des Saarlandes, University Hospital Schleswig-Holstein (UKSH), Westfälische Wilhelms-Universität Münster, Helmholtz Zentrum München, HZI, Helmholtz Zentrum für Infektionsforschung, Christian-Albrechts-Universität Kiel, Helmholtz München, Medizinische Hochschule Hannover, MDC Berlin-Buch Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Robert-Rössle-Straße 10 13125 Berlin, Universitätsklinikum des Saarlandes, Helmholtz-Zentrum für Infektionsforschung, Max Delbrück Center