SummaryIn this proposed pilot project we will harness our newly developed IPHOMED pipeline (Valdes-Mas et al, Cell 2025) to functionally decode the trilateral dietary-microbiome-host interactome driving human colorectal cancer (CRC). In short, we will utilize pre-collected fecal samples from the population-based NAKO cohort, of newly diagnosed CRC patients as well as age and gender matched healthy controls, and perform metagenome-informed metaproteomics. Thus, we are able to reach a species level functional microbiome resolution, and assess the host protein response to the microbiome, while objectively characterizing the dietary exposome using food frequency questionnaires and dietary recalls. Using deep learning analyses, we will decode potential trans-kingdom CRC biomarkers, discrete dysbiotic microbiome functions associated with human CRC and the protein level host response to these commensal changes, while linking them to nutrient-specific dietary intake patterns. This pilot will be the first to assess the groundbreaking potential of IPHOMED in cancer, while forming the framework for a global, function-focused causal exploration of host, microbiome and dietary orchestration of human CRC. E. Elinav is a leading authority on host–microbiome interactions, using multi-omics and mechanistic models to uncover microbiome driven disease pathways. His lab recently developed IPHOMED, the first metagenomic informed metaproteomic platform for noninvasive functional profiling of the host–microbiome–diet axis (Valdes Mas et al., Cell 2025). V. Katzke and R. Fortner bring extensive experience in cancer epidemiology, registry linkage, and nutrition research, while K. H. Greiser has led the design and implementation of NAKO questionnaires and examinations from the outset.

Keywords Fecal-microbiome colorectal-cancer metagenome-informed-metaproteomics

InstitutionsThe German Cancer Research Center (DKFZ), DKFZ Heidelberg, Deutsches Krebsforschungszentrum, DKFZ, Deutsches Krebsforschungszentrum (DKFZ)