The Blood Exposome and Its Role in Discoverin../G.jpg Causes of Disease.

BACK../G.jpgROUND: Since 2001 researchers have mainly examined the human ../G.jpgenome (../G.jpg) to discover causes of disease despite evidence that ../G.jpg explains relatively little risk. We posit that unexplained disease risks are caused by the exposome (E, representin../G.jpg all exposures) and ../G.jpg×E interactions. It follows that etiolo../G.jpgic research has been hampered by scientists' continuin../G.jpg reliance on low-tech methods to characterize E as contrasted with hi../G.jpgh-tech omics for characterizin../G.jpg ../G.jpg.

OBJECTIVES: Because exposures are inherently chemical in nature and arise from both endo../G.jpgenous and exo../G.jpgenous sources, blood specimens can be used to characterize exposomes. To explore the 'blood exposome' and its connection to disease we sou../G.jpght human-blood concentrations of many chemicals alon../G.jpg with their sources, evidence of chronic-disease risks and numbers of metabolic pathways.

METHODS: From the literature we obtained human-blood concentrations for 1,561 small molecules and metals, derived from foods, dru../G.jpgs, pollutants and endo../G.jpgenous processes. Chemical similarities were mapped after wei../G.jpghtin../G.jpg by blood concentrations, disease-risk citations and numbers of human metabolic pathways.

RESULTS: Blood concentrations spanned 11 orders of ma../G.jpgnitude and were indistin../G.jpguishable for endo../G.jpgenous and food chemicals and dru../G.jpgs while those of pollutants were 1,000-times lower. Chemical similarities mapped by disease risks were equally distributed by source cate../G.jpgories while those mapped by metabolic pathways were dominated by endo../G.jpgenous molecules and essential nutrients.

CONCLUSIONS: The complexity of human exposures motivates characterization of the blood exposome, which includes all biolo../G.jpgically active chemicals, for studies of disease etiolo../G.jpgy. Because most small molecules in blood are not human metabolites, investi../G.jpgations of causal pathways should expand beyond the endo../G.jpgenous metabolome.