The Metabolome as a Readout for Adverse Social Exposome Influences on Human Health - A Roadmap for Modifiable Factors and Proactive Health

The exposome factors, such as diet, lifestyle, microbiome, chemical exposures and social exposome, shapes human health beyond genetic influences, but the mechanisms remain only partially understood. Leveraging the Area Deprivation Index (ADI) of Neighborhood Atlas, a validated measure of the US social exposome, we derive molecular insights on how adverse social exposome (ASE) may impact cardiometabolic and brain health. Using complementary metabolomics platforms, we measured blood metabolome as readouts on net influences of exposome factors. Participants from six Alzheimer's disease research centers (n=449) were studied with generalizability confirmed in the UK Biobank using its harmonizable metric for ASE (n=380,943). Our results suggest that participants living in ASE have metabolic features often shown to predispose individuals to higher risks for cardiovascular diseases and cognitive decline, with impaired mitochondrial energetics, amino acid and lipid metabolism. Diet, microbiome and chemical exposures may contribute to these metabolic features. Molecular insights from metabolic signatures for ASE allows us to map potential modifiable risk factors that can impact and sustain health including brain health.