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

BMC Medicine

Research Article

Markus M. Lerch¹  Gabi Kastenmüller²  Ann-Kristin Henning³  Anne Kaul³  Maik Pietzner⁴  Nele Friedrich⁴  Matthias Nauck⁴  Anna Artati⁵  Jerzy Adamski⁶ 

[1] Department of Medicine A, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. NK, 17475, Greifswald, Germany;Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764, Neuherberg, Germany;Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. NK, 17475, Greifswald, Germany;Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. NK, 17475, Greifswald, Germany;DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany;Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764, Neuherberg, Germany;Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764, Neuherberg, Germany;Lehrstuhl für Experimentelle Genetik, Technische Universität München, 85350, Freising-Weihenstephan, Germany;

关键词: Inflammation;    White blood cell count;    C-reactive protein;    Fibrinogen;    Metabolomics;    Mass spectrometry;    Nuclear magnetic resonance spectroscopy;   

DOI  :  10.1186/s12916-017-0974-6

 received in 2017-07-12, accepted in 2017-11-08,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017