Identification of metabotypes in critically ill patients with sepsis - a translational systems medicine approach ("SEPSYS")

Sepsis, a syndrome caused by a dysregulated host response to infection, remains a major public health concern with increasing incidence and mortality. Survivors of sepsis frequently progress to a persistent inflammation, immunosuppression, and catabolism syndrome and develop long-term sequelae with decreased quality of life.
Apart from global metabolic changes including hyperglycaemia, insulin resistance and catabolism, specific underlying mechanisms are yet not fully unravelled and individual treatment options not available. The emerging concept of “personalized” nutrition, implying stratification of the patient based on a better assessment of the complex disease process and inherent metabolic changes holds promise for improving (long-term) clinical outcomes. The aim of this translational project is to disentangle distinct mechanisms of intra- and
inter-individual inflammatory and metabolic changes in sepsis and gain more mechanistic insights into their aetiology and the relation to artificial nutrition. In a prospective cohort study of 50 septic patients, we will evaluate acute inflammatory phenotypes and derive core metabolomic, autophagic and microbiome-related signatures in order to derive hypotheses about key regulators in response to artificial nutrition. These regulators may be aligned into a composite metabolic network model used to guide personalized diagnosis and therapy of different "metabotypes" in sepsis.

Funded by Universitätsklinikum Schleswig-Holstein (UKSH) with € 69,625 (ca. 522,187 DKK).