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.
Authors
- David S. Wishart (ORCID: https://orcid.org/0000-0002-3207-2434)
- Matthew Taylor (ORCID: https://orcid.org/0000-0001-9480-4832)
- Margo B. Heston (ORCID: https://orcid.org/0000-0002-0980-2275)
- Kamil Borkowski (ORCID: https://orcid.org/0000-0003-3637-3450)
- Naama Karu (ORCID: https://orcid.org/0000-0001-8005-0726)
- K. Huynh
- Nuanyi Liang (ORCID: https://orcid.org/0000-0002-6802-5015)
- Christopher R. Brydges (ORCID: https://orcid.org/0000-0001-5901-638X)
- Leyla Schimmel
- Desarae A. Dempsey (ORCID: https://orcid.org/0000-0003-4681-0108)
- Pallavi Kaushik (ORCID: https://orcid.org/0000-0003-3566-1418)
- Siamak MahmoudianDehkordi (ORCID: https://orcid.org/0000-0002-6843-1718)
- Rupasri Mandal
- Michelle Quirke
- James B. Brewer
- Najaf Amin
- Kelley M. Faber
- Victor W Henderson
- Colette Blach
- Peter J. Meikle
- Doris Chen
- Tatiana M. Foroud
- Andrew J. Saykin
- Amy J. Kind
- W. Ryan Powell
- Jared R. Brosch
- Russell H. Swerdlow
- Rima F. Kaddurah-Daouk
- Suzanne Craft
- Jennifer S. Labus
- Barbara B. Bendlin
- Justin B. Miller
- Thomas Wisniewski
- Alzheimer Gut Microbiome Project (AGMP)
- Alexandra Kueider-Paisley
Institutions
- Rutgers, The State University of New Jersey (US)
- University of Wisconsin–Madison (US)
- Baker Heart and Diabetes Institute (AU)
- University of Kansas (US)
- University of Alberta (CA)
- University of California, Los Angeles (US)
- Duke University (US)
- La Trobe University (AU)
- University of Washington (US)
- University of Alabama at Birmingham (US)
- University of California San Diego (US)
- University of Oxford (GB)
- University Memory and Aging Center (US)
- Alzheimer’s Disease Neuroimaging Initiative (US)
- University of Kansas Medical Center (US)
- Tasmanian Abalone Council (Australia) (AU)
- Stanford Medicine (US)
- Wisconsin Division of Public Health (US)
- Cognitive Research (United States) (US)
- Indiana University School of Medicine
- Wake Forest University (US)
- Indiana University – Purdue University Indianapolis (US)
- New York University (US)
- University of California, Davis (US)
- Stanford University (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-02-03
- DOI
- https://doi.org/10.64898/2026.02.02.26344798
- Primary Topic
- Health, Environment, Cognitive Aging
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute on Aging