Exposome contribution to the brain metabolome: importance of body brain connection.
Karu, N.; Zhao, H. N.; Batra, R.; Arnold, M.; Krumsiek, J.; David, L. C.; Barupal, D.; Schimmel, L.; Kueider-Paisley, A.; Blach, C.; Borkowski, K.; Dorrestein, P.; Bennett, D. A.; Kaddurah-Daouk, R.; Alzheimer's Disease Metabolomics Consortium,
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INTRODUCTIONMounting evidence support exposome influences on brain function and health, complementing genome influences. Understanding the molecular imprint of exposome on brain metabolism and the biochemical communication between the body and brain can impact our fundamental understanding and treatment of neuropsychiatric diseases. METHODSLeveraging two complementary metabolomics platforms, we classified 1400 features in 514 brains from the ROSMAP collection. We evaluated the origin of these compounds using literature and databases. We correlated those metabolites with cognitive function using linear models. RESULTSWe identified over 230 non-endogenous compounds in the brain, including 103 drugs and metabolites, 120 dietary and microbial products and possibly 15 compounds from environmental exposures. Over 20 dietary and gut microbial compounds showed associations with cognition. DISCUSSIONComprehensive profiling of chemicals in the brain and the link to cognitive function provides foundational work to connect body and brain in the study of AD and related dementias.
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