Shangzhi Gao1, Corbin Quick2, Marta Guasch-Ferre3, Zhu Zhuo2, John M Hutchinson2, Li Su1, Frank Hu3, Xihong Lin2, David Christiani1,4. 1. Environmental Health, Harvard University T H Chan School of Public Health, Boston, MA, USA. 2. Biostatistics, Harvard University T H Chan School of Public Health, Boston, MA, USA. 3. Nutrition, Harvard University T H Chan School of Public Health, Boston, MA, USA. 4. Pulmonary and Critical Care Division, Department of Medicine, MA General Hospital, Boston, Massachusetts, USA.
Abstract
INTRODUCTION: Human metabolism and inflammation are closely related modulators of homeostasis and immunity. Metabolic profiling is a useful tool to understand the association between metabolism and inflammation at a systemic level. OBJECTIVE: To investigate the longitudinal associations between the concentration of plasma metabolites and biomarkers related to inflammation and oxidative stress. METHODS: We conducted a repeated cross-sectional analysis consisting of 8 short-term panels that included 88 healthy adult male welders in Massachusetts, USA. In each panel, we collected 1-6 repeated measurements of blood and urine. We used a human vascular injury panel assay and custom cytokine/chemokine assay to quantify inflammatory biomarker plasma levels, liquid chromatography-mass spectrometry to quantify the concentrations of 665 plasma metabolites, and a competitive enzyme-linked immunoassay to quantify urinary 8-OHdG and 8-isoprostane levels. We used linear mixed effects models to estimate the longitudinal association between each inflammatory and oxidative stress biomarker and each metabolite. RESULTS: At a 5% FDR threshold, we detected ≥1metabolite association for 8 unique inflammatory and oxidative stress biomarkers: urinary 8-isoprostane, plasma C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1, circulating vascular cell adhesion molecule-1, interleukin 8 (IL-8), interleukin 10 (IL-10) and vascular endothelial growth factor. Specifically, 3 metabolites in the androgenic steroids pathway were negatively associated with SAA; 3 dihydrosphingomyelins metabolites were positively associated with 1 or more of CRP, SAA, IL-8 and IL-10; 4 metabolites in acyl choline metabolism pathways were negatively associated with IL-8; 7 lysophospholipid metabolites were negatively associated with 1 or more of CRP, SAA and IL-8; 4 sphingomyelins were positively associated with CRP and/or SAA; and 10 metabolites in the xanthine pathway were positively associated with urinary 8-isoprostane. CONCLUSION: We found that metabolites in phospholipid groups had strong associations with multiple inflammatory biomarkers, especially CRP, SAA and IL-8. The mechanism of these associations warrants further investigation.
INTRODUCTION: Human metabolism and inflammation are closely related modulators of homeostasis and immunity. Metabolic profiling is a useful tool to understand the association between metabolism and inflammation at a systemic level. OBJECTIVE: To investigate the longitudinal associations between the concentration of plasma metabolites and biomarkers related to inflammation and oxidative stress. METHODS: We conducted a repeated cross-sectional analysis consisting of 8 short-term panels that included 88 healthy adult male welders in Massachusetts, USA. In each panel, we collected 1-6 repeated measurements of blood and urine. We used a human vascular injury panel assay and custom cytokine/chemokine assay to quantify inflammatory biomarker plasma levels, liquid chromatography-mass spectrometry to quantify the concentrations of 665 plasma metabolites, and a competitive enzyme-linked immunoassay to quantify urinary 8-OHdG and 8-isoprostane levels. We used linear mixed effects models to estimate the longitudinal association between each inflammatory and oxidative stress biomarker and each metabolite. RESULTS: At a 5% FDR threshold, we detected ≥1metabolite association for 8 unique inflammatory and oxidative stress biomarkers: urinary 8-isoprostane, plasma C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1, circulating vascular cell adhesion molecule-1, interleukin 8 (IL-8), interleukin 10 (IL-10) and vascular endothelial growth factor. Specifically, 3 metabolites in the androgenic steroids pathway were negatively associated with SAA; 3 dihydrosphingomyelins metabolites were positively associated with 1 or more of CRP, SAA, IL-8 and IL-10; 4 metabolites in acyl choline metabolism pathways were negatively associated with IL-8; 7 lysophospholipid metabolites were negatively associated with 1 or more of CRP, SAA and IL-8; 4 sphingomyelins were positively associated with CRP and/or SAA; and 10 metabolites in the xanthine pathway were positively associated with urinary 8-isoprostane. CONCLUSION: We found that metabolites in phospholipid groups had strong associations with multiple inflammatory biomarkers, especially CRP, SAA and IL-8. The mechanism of these associations warrants further investigation.
Authors: Thomas A Pearson; George A Mensah; R Wayne Alexander; Jeffrey L Anderson; Richard O Cannon; Michael Criqui; Yazid Y Fadl; Stephen P Fortmann; Yuling Hong; Gary L Myers; Nader Rifai; Sidney C Smith; Kathryn Taubert; Russell P Tracy; Frank Vinicor Journal: Circulation Date: 2003-01-28 Impact factor: 29.690
Authors: Bartholomeus C M Benno Haarman; Rixt F Riemersma-Van der Lek; Willem A Nolen; R Mendes; Hemmo A Drexhage; Huibert Burger Journal: J Biomed Inform Date: 2014-10-14 Impact factor: 6.317
Authors: David Furman; Judith Campisi; Eric Verdin; Pedro Carrera-Bastos; Sasha Targ; Claudio Franceschi; Luigi Ferrucci; Derek W Gilroy; Alessio Fasano; Gary W Miller; Andrew H Miller; Alberto Mantovani; Cornelia M Weyand; Nir Barzilai; Jorg J Goronzy; Thomas A Rando; Rita B Effros; Alejandro Lucia; Nicole Kleinstreuer; George M Slavich Journal: Nat Med Date: 2019-12-05 Impact factor: 53.440