Temporal Metabolic Response Yields a Dynamic Biosignature of Inflammation

Abstract

Chronic low-grade inflammation is a subclinical condition directly and indirectly linked to the development of a wide range of highly prevalent diseases responsible for the vast majority of morbidity. To examine mechanisms coupled to chronic disease, a group of overweight and obese human subjects without known inflammatory diseases were selected. Study participants underwent a high-fat meal challenge as an inflammation stimulus. Fasting and post-prandial serum samples were analyzed for pro-inflammatory cytokines and metabolites. Analysis of serum metabolites grouped by baseline cytokine levels revealed that single samples had little power in differentiating the groups. However, an analysis that incorporated temporal response separated high and low inflammatory response phenotypes and allowed us to create a metabolic signature of inflammation. The use of temporal response rather than absolute concentrations dramatically improved clinical diagnostics in this study and suggests that dynamic biosignatures may be a powerful tool for stratifying risk to a wide range of diseases.