Comprehensive metabolic profiling of chronic low-grade inflammation among generally healthy individuals

Abstract

BackgroundInflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers.MethodsBased on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis.ResultsHsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3’-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83).ConclusionsComprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0974-6) contains supplementary material, which is available to authorized users.

Metabolic signature associated with parameters of the complete blood count in apparently healthy individuals

“…Despite some different exclusion criteria, WBC associations replicated those from our previous publication 12 and were in part mirrored by PLT or MPV. Notably, this study clearly distinguishes from our previous work on inflammatory parameters, including WBC.…”

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…LPCs activate signaling pathways promoting the release of second messengers, related to G protein-coupled receptors [186]. In obesity, significantly lower concentrations of most of the LPCs are detected [68], whereas LPCs concentrations were inversely correlated with the increased CRP levels [184]. Therefore, LPC could be useful early biomarkers to detect inflammatory states associated with MetS and related disorders.…”

“…and external exposures (smoking, toxins, ionizing radiation, etc.). In order to regulate the reactive species, organism has endogenous antioxidant systems, or it obtains exogenous antioxidants from diet, that neutralizes these species and keeps the homeostasis of the body [68]. Production of free radicals and the resulting oxidative stress are part of the energy metabolism, emphasizing mitochondrial dysfunction in the development of disease.…”

The association between metabolic syndrome components, low-grade systemic inflammation and insulin resistance in non-diabetic Indonesian adolescent male

“…Development of IR has been postulated to be linked with inflammation as additional pathogenic factors. Several inflammatory markers are showing clinical importance including C-reactive protein (hsCRP), white blood cell, fibrinogen and albumin [27,30]. However, previous studies found that C-reactive protein (CRP), a nonspecific marker of the inflammatory response, is most consistently associated with the development of IR and type 2 diabetes [10,11].…”