Metabolome informs about the chemical exposome and links to brain health

The Alzheimer Gut Microbiome Project

doi:10.1016/j.envint.2025.109741

Metabolome informs about the chemical exposome and links to brain health

The Alzheimer Gut Microbiome Project

Turku Bioscience Centre

Research output: Contribution to journal › Review Article or Literature Review › peer-review

3 Citations (Scopus)

Abstract

The metabolome is an intermediate phenotype, summarizing the profile of all small molecules (<1.5 kDa) in biospecimens. The metabolome provides a readout for the net influence of the chemical exposome, diet, gut microbiome, and genome on human health. Metabolic changes observed in exposome studies may thus provide clues about adverse outcome pathways related to cancer, diabetes, heart disease, cognitive impairment and other neurological conditions such as Alzheimer's disease (AD). Whilst the number of human cohort studies including both metabolomic and exposomic profiles is increasing, they are particularly limited in the domain of neurological conditions. Environmental exposures and chemical toxicants are known to have significant effects on the brain, gut microbiome, and gut-brain axis. Environmental chemicals of greatest interest include bisphenols, phthalates, persistent organic pollutants such as polychlorinated biphenyls (PCBs) and per- and poly-fluoroalkyl substances (PFAS), heavy metals, chemicals from household products and pesticides/herbicides; all of which may increase the risk of AD as they impact relevant biochemical mechanisms, especially with chronic exposure. In this review we describe how the chemical exposome can be assessed, including the approach our consortium is taking in the context of AD. Further, we review the current evidence about the impact of the chemical exposome on cognition as well as its influence on the risk and pathogenesis of AD. Finally, we highlight our approach to study the exposome in AD as part of large national and international collaborative efforts on the topic.

Original language	English
Article number	109741
Journal	Environment International
Volume	203
DOIs	https://doi.org/10.1016/j.envint.2025.109741
Publication status	Published - Sept 2025
MoE publication type	A2 Review article in a scientific journal

Funding

This project was enabled in part by the Alzheimer's Gut Microbiome Project (AGMP) and the Alzheimer's Disease Metabolomics Consortium (ADMC) funded wholly or in part by the following grants thereto: U01AG088562, U01AG061359, U19AG063744, and 3U19AG063744-04S1 awarded to Dr. Kaddurah-Daouk at Duke University in partnership with multiple academic institutions. As such, the investigators within the AGMP and the ADMC, not listed specifically in this publication's author's list, provided data along with its pre-processing and prepared it for analysis, but did not participate in analysis or writing of this manuscript. A listing of AGMP Investigators can be found at https://alzheimergut.org/meet-the-team/. A complete listing of ADMC investigators can be found at: https://sites.duke.edu/adnimetab/team/. Declaration of conflicts of interest. Dr. Kaddurah-Daouk in an inventor on a series of patents on use of metabolomics for the diagnosis and treatment of CNS diseases and holds equity in Metabolon Inc. Chymia LLC and PsyProtix. PCD is an advisor and holds equity in Cybele and Sirenas and a Scientific co-founder, advisor and holds equity to Ometa, Enveda, and Arome with prior approval by UC-San Diego. PCD also consulted for DSM animal health in 2023. This project was enabled in part by the Alzheimer’s Gut Microbiome Project (AGMP) and the Alzheimer’s Disease Metabolomics Consortium (ADMC) funded wholly or in part by the following grants thereto: U01AG088562, U01AG061359, U19AG063744, and 3U19AG063744-04S1 awarded to Dr. Kaddurah-Daouk at Duke University in partnership with multiple academic institutions. As such, the investigators within the AGMP and the ADMC, not listed specifically in this publication’s author’s list, provided data along with its pre-processing and prepared it for analysis, but did not participate in analysis or writing of this manuscript.

Keywords

Alzheimer's disease
Brain health
Chemical exposure
Environmental exposure
Exposome
Metabolomics

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10.1016/j.envint.2025.109741Licence: CC BY-NC-ND

1-s2.0-S0160412025004921-mainFinal published version, 3.34 MBLicence: CC BY-NC-ND

https://urn.fi/URN:NBN:fi-fe2026020310886

Cite this

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title = "Metabolome informs about the chemical exposome and links to brain health",

abstract = "The metabolome is an intermediate phenotype, summarizing the profile of all small molecules (<1.5 kDa) in biospecimens. The metabolome provides a readout for the net influence of the chemical exposome, diet, gut microbiome, and genome on human health. Metabolic changes observed in exposome studies may thus provide clues about adverse outcome pathways related to cancer, diabetes, heart disease, cognitive impairment and other neurological conditions such as Alzheimer's disease (AD). Whilst the number of human cohort studies including both metabolomic and exposomic profiles is increasing, they are particularly limited in the domain of neurological conditions. Environmental exposures and chemical toxicants are known to have significant effects on the brain, gut microbiome, and gut-brain axis. Environmental chemicals of greatest interest include bisphenols, phthalates, persistent organic pollutants such as polychlorinated biphenyls (PCBs) and per- and poly-fluoroalkyl substances (PFAS), heavy metals, chemicals from household products and pesticides/herbicides; all of which may increase the risk of AD as they impact relevant biochemical mechanisms, especially with chronic exposure. In this review we describe how the chemical exposome can be assessed, including the approach our consortium is taking in the context of AD. Further, we review the current evidence about the impact of the chemical exposome on cognition as well as its influence on the risk and pathogenesis of AD. Finally, we highlight our approach to study the exposome in AD as part of large national and international collaborative efforts on the topic.",

keywords = "Alzheimer's disease, Brain health, Chemical exposure, Environmental exposure, Exposome, Metabolomics, Metabolomics, Environmental exposure, Chemical exposure, Brain health, Alzheimer{\textquoteright}s disease, Exposome",

author = "Matej Ore{\v s}i{\v c} and Naama Karu and Zhao, \{Haoqi Nina\} and Arthur Moseley and Thomas Hankemeier and Wishart, \{David S.\} and Dorrestein, \{Pieter C.\} and Oliver Fiehn and Tuulia Hy{\"o}tyl{\"a}inen and Daouk, \{Rima Kaddurah\} and \{The Alzheimer Gut Microbiome Project\}",

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year = "2025",

month = sep,

doi = "10.1016/j.envint.2025.109741",

language = "English",

volume = "203",

journal = "Environment International",

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T1 - Metabolome informs about the chemical exposome and links to brain health

AU - Orešič, Matej

AU - Karu, Naama

AU - Zhao, Haoqi Nina

AU - Moseley, Arthur

AU - Hankemeier, Thomas

AU - Wishart, David S.

AU - Dorrestein, Pieter C.

AU - Fiehn, Oliver

AU - Hyötyläinen, Tuulia

AU - Daouk, Rima Kaddurah

AU - The Alzheimer Gut Microbiome Project

PY - 2025/9

Y1 - 2025/9

N2 - The metabolome is an intermediate phenotype, summarizing the profile of all small molecules (<1.5 kDa) in biospecimens. The metabolome provides a readout for the net influence of the chemical exposome, diet, gut microbiome, and genome on human health. Metabolic changes observed in exposome studies may thus provide clues about adverse outcome pathways related to cancer, diabetes, heart disease, cognitive impairment and other neurological conditions such as Alzheimer's disease (AD). Whilst the number of human cohort studies including both metabolomic and exposomic profiles is increasing, they are particularly limited in the domain of neurological conditions. Environmental exposures and chemical toxicants are known to have significant effects on the brain, gut microbiome, and gut-brain axis. Environmental chemicals of greatest interest include bisphenols, phthalates, persistent organic pollutants such as polychlorinated biphenyls (PCBs) and per- and poly-fluoroalkyl substances (PFAS), heavy metals, chemicals from household products and pesticides/herbicides; all of which may increase the risk of AD as they impact relevant biochemical mechanisms, especially with chronic exposure. In this review we describe how the chemical exposome can be assessed, including the approach our consortium is taking in the context of AD. Further, we review the current evidence about the impact of the chemical exposome on cognition as well as its influence on the risk and pathogenesis of AD. Finally, we highlight our approach to study the exposome in AD as part of large national and international collaborative efforts on the topic.

AB - The metabolome is an intermediate phenotype, summarizing the profile of all small molecules (<1.5 kDa) in biospecimens. The metabolome provides a readout for the net influence of the chemical exposome, diet, gut microbiome, and genome on human health. Metabolic changes observed in exposome studies may thus provide clues about adverse outcome pathways related to cancer, diabetes, heart disease, cognitive impairment and other neurological conditions such as Alzheimer's disease (AD). Whilst the number of human cohort studies including both metabolomic and exposomic profiles is increasing, they are particularly limited in the domain of neurological conditions. Environmental exposures and chemical toxicants are known to have significant effects on the brain, gut microbiome, and gut-brain axis. Environmental chemicals of greatest interest include bisphenols, phthalates, persistent organic pollutants such as polychlorinated biphenyls (PCBs) and per- and poly-fluoroalkyl substances (PFAS), heavy metals, chemicals from household products and pesticides/herbicides; all of which may increase the risk of AD as they impact relevant biochemical mechanisms, especially with chronic exposure. In this review we describe how the chemical exposome can be assessed, including the approach our consortium is taking in the context of AD. Further, we review the current evidence about the impact of the chemical exposome on cognition as well as its influence on the risk and pathogenesis of AD. Finally, we highlight our approach to study the exposome in AD as part of large national and international collaborative efforts on the topic.

KW - Alzheimer's disease

KW - Brain health

KW - Chemical exposure

KW - Environmental exposure

KW - Exposome

KW - Metabolomics

KW - Environmental exposure

KW - Chemical exposure

KW - Brain health

KW - Alzheimer’s disease

KW - Exposome

UR - https://www.scopus.com/pages/publications/105015151006

U2 - 10.1016/j.envint.2025.109741

DO - 10.1016/j.envint.2025.109741

M3 - Review Article or Literature Review

C2 - 40889412

AN - SCOPUS:105015151006

SN - 0160-4120

VL - 203

JO - Environment International

JF - Environment International

M1 - 109741

ER -

Metabolome informs about the chemical exposome and links to brain health

Abstract

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