Background: Metabolomics helps to identify links between environmental exposures and intermediate biomarkers of disturbed pathways. We previously reported variations in phosphatidylcholines in male smokers compared with non-smokers in a cross-sectional pilot study with a small sample size, but knowledge of the reversibility of smoking effects on metabolite profiles is limited. Here, we extend our metabolomics study with a large prospective study including female smokers and quitters.Methods: Using targeted metabolomics approach, we quantified 140 metabolite concentrations for 1,241 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) human cohort at two time points: baseline survey conducted between 1999 and 2001 and follow-up after seven years. Metabolite profiles were compared among groups of current smokers, former smokers and never smokers, and were further assessed for their reversibility after smoking cessation. Changes in metabolite concentrations from baseline to the follow-up were investigated in a longitudinal analysis comparing current smokers, never smokers and smoking quitters, who were current smokers at baseline but former smokers by the time of follow-up. In addition, we constructed protein-metabolite networks with smoking-related genes and metabolites.Results: We identified 21 smoking-related metabolites in the baseline investigation (18 in men and six in women, with three overlaps) enriched in amino acid and lipid pathways, which were significantly different between current smokers and never smokers. Moreover, 19 out of the 21 metabolites were found to be reversible in former smokers. In the follow-up study, 13 reversible metabolites in men were measured, of which 10 were confirmed to be reversible in male quitters. Protein-metabolite networks are proposed to explain the consistent reversibility of smoking effects on metabolites.Conclusions: We showed that smoking-related changes in human serum metabolites are reversible after smoking cessation, consistent with the known cardiovascular risk reduction. The metabolites identified may serve as potential biomarkers to evaluate the status of smoking cessation and characterize smoking-related diseases.
Bibliographical noteFunding Information:
We express our appreciation to all KORA study participants for donating their blood and time. We thank the field staff in Augsburg who conducted the KORA studies. The KORA research platform and the KORA Augsburg studies were initiated and financed by the Helmholtz Zentrum München, which is funded by the German Federal Ministry of Education, Science, Research and Technology and by the State of Bavaria. The KORA study group consists of A. Peters (speaker), J. Heinrich, R. Holle, R. Leidl, C. Meisinger, K. Strauch and their co-workers, who are responsible for the design and conduct of the KORA studies. We thank Julia Scarpa, Katharina Sckell and Arsin Sabunchi for metabolomics measurements performed at the Helmholtz Zentrum München, Genome Analysis Centre, Metabolomics Core Facility. This study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Centre for Diabetes Research (DZD e.V.) and this work was partly supported by the BMBF project ‘Metabolomics of ageing’ (FKZ: 01DO12030) and EU FP7 grant HEALTH-2009-2.2.1-3/242114 (Project OPTiMiSE).
- Metabolic network
- Molecular epidemiology
- Smoking cessation