Blood metabolomics in the DAG3 samples to understand gut microbiome-host metabolism cross-talks

During the last 5 years we have performed an extensive multi-omics phenotyping in the Lifelines-DEEP cohort (N~1500 samples), including omics measurements of the gut microbiome. Research studies deriving from the integration of these data with phenotypic information of the volunteers have lead to the discovery of a central role of the gut microbiome in regulating the host immune system, host metabolism, and other host biological processes. For example, we identified that the combination of gut microbiome and host genetics can explain the level of circulating proteins relevant to cardiovascular diseases (Zhernakova et al, Nature Genetics, 2018), that gut microbiome variation is associated with cardiovascular disease-related plasma metabolites (Kurilshikov et al, Circulation Research, 2019), and that the gut microbiome has a causal role on modulating risk to Type 2 diabetes and glucose/insulin related phenotypes (Sanna et al, Nature Genetics, 2019). All these results were achieved thanks to a strict collaboration between the Department of Genetics (groups led by Prof. Zhernakova and Prof. Wijmenga), the Department of Gastroenterology (Prof. Weersma) and the Department of Pediatrics (Prof. Fu, Prof. Kuipers), joining our expertise on genetics, microbiome and metabolic system.

Now the characterization of the genome and of the gut microbiome of DAG3 samples has been performed; measurements of other omics layer will allow us to continue and extend to a much larger sample size the studies that were carried out in LifelinesDEEP. In this study we propose to investigate the variation of blood metabolism in relation to each person gut microbiome profile as well as genetic and phenotypic profiles, by analyzing blood speciments from DAG3 samples. Furthermore, in depth analyses of volunteers enrolled in both LifelinesDEEP and DAG3 will allow us to corroborate dynamic changes of host metabolism in relation to changes in the gut microbiome. We will focus on a broad range of metabolites, including several circulating short-chain fatty acids (SCFA) that have no been measured before in Lifelines volunteers