RTF V: Clinical and Nutritional Metabolomics

Coordinators: M. Laudes (CAU), K. Schwarz (CAU), A. Tholey (CAU), S. Waschina (CAU)

RTF V studies the metabolic exchange (co-metabolism) between host and microbiome, i.e. all the micro-organisms in the body, in inflammatory diseases. It considers the questions of what contribution the microbiome makes to the metabolism and how metabolic products, what is known as the metabolome, and the microbiome can be changed by one another. The aim here is to identify biomarkers for successful treatments and individual responses to pharmaceutical and dietary interventions.

For this purpose, RTF V is developing new methods of analyzing the metabolome and the proteome and is making advances in models for co-metabolism and miniaturization of analytical systems for the metabolome and proteome including immunogenic peptides. It is using biosamples to generate organoids and perform fermentations as “clinical trials in a dish”. It is also developing bioinformatic prediction models for metabolic performance and the co-metabolism of host and microbiome as well as routines for knowledge-based evaluation.

Interactions between metabolites and the microbiome are ubiquitous in the human body. The microbiome has a profound influence on the human metabolome and proteome and, in turn, the metabolome and the proteome influence the microbiome. This crosstalk between microbiome and metabolome/proteome influences many human diseases through a large number of mechanisms.

High and ultra-high resolution mass spectrometry platforms have been established to study the metabolome and proteome. These platforms provide the basis for studies on metabolomics ranging from data acquisition to bioinformatic and statistical evaluation. They are supported by many years of experience in the analysis of metabolites and miniaturization of analytical systems for peptides, peptidomes, proteins and proteomes.

With the aid of explorative metabolome-wide association studies, multivariate machine learning models as well as targeted and detailed analysis of the metabolome and proteome in experimental studies, the objective is to identify mechanisms of inflammatory diseases, develop new treatment strategies and predict the success of treatments for individual patients.

The existing infrastructure for metabolome and proteome research is to be further expanded to create a strong, central, science and technology-based unit. Innovative analytical and experimental approaches are to be introduced and existing analytical platforms supplemented by other platforms. Among other measures, a core unit for nuclear magnetic resonance spectroscopy-based metabolomics is to be established to supplement the existing mass spectrometry platforms. New prediction models for the metabolic function of microbiota are to be created and metabolome and proteome data verified.

Research on the interaction between metabolome, microbiome and host is a relatively young field of research in which new methods and technologies are being developed that are expected to produce far-reaching findings for health and the prevention and treatment of diseases.

The field of metabolome and proteome research is founded on many disciplines of natural sciences and is a highly interdisciplinary science that combines methods from chemistry, physics, biology and bioinformatics through to materials science.

Knowledge of molecular processes, especially at the level of the active molecule (peptides/proteins/metabolites), is a prerequisite for the diagnosis and understanding of these diseases and is a key to the development of treatments. In order to achieve holistic understanding in terms of systems medicine and systems biology, the data generated is combined with data from other areas of the cluster, e.g. on the metagenome of microbiota. The foundation for this will be advanced through the development of comprehensive metabolite databases and prediction models of the metabolism for future integrative analyses. The availability of new, more rapid and more sensitive analytical methods is essential, especially in the field of precision medicine.

CD II: Investigation of the metabolome in intervention studies with nicotinamide on Tryptophan metabolism
RTF III: Development and implementation of low cell number/single cell proteomics and multi-omics for the analysis of in vitro models collected from patient material (“clinical trial in a dish”)
RTF VII: Expansion and validation of theoretical models of co-metabolism between microbiome and human.
TI-II: Identification and molecular characterization of immunogenic peptides