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The Role of Exposome in Brain Health: A Comprehensive Overview

The exposome refers to the cumulative environmental exposure that an individual encounters throughout their lifetime.

In our previousarticle, we gave a brief overview of the exposome and advocated incorporating multi-omics studies to get an in-depth understanding. Every day an American is potentially exposed to more than 80,000 toxic chemicals, yet their impact on neuro-diseases is not well understood.

Studies have shown that exposure to toxic chemicals in the early stages of life could have permanent consequences for neurodevelopment and neurodegeneration in later life. With advanced research in neurodevelopmental and neurodegenerative disorders, it is now clear that genetic risk factors cannot fully explain them. 

Understanding the role of individual environmental chemical exposures is critical. In this article, we will explore the role of exposome in brain health, including the impact of toxic chemicals on neurodevelopment, neurodegeneration, and mental health.

Agricultural Pesticides in Neurodevelopment

Agricultural pesticides are commonly available to humans via dietary means, and their impact on neurodevelopment has been studied extensively. According to a study published in Environmental Neuroscience: Advancing the Understanding of How Chemical Exposures Impact Brain Health and Disease: Proceedings of a Workshop by the National Academies of Sciences and Medicine, exposure to three toxic chemicals, lead, organophosphate pesticides (OP), and methyl mercury, are responsible for greater IQ loss than medical conditions such as preterm birth, neurodevelopmental disorders, and socioeconomic and nutrition-related factors [1]. Further studies in animals have found that exposure to pesticide (glyphosate) is linked to oxidative stress, neurotransmitter alterations, and depressive-like behaviors, signifying that agricultural pesticides are also strong neurotoxicants for humans [2].

Air Pollutants in Neurodevelopment

Recent studies have shown that even air pollutants are neurotoxicants [3–5]. Air pollution causes biological reactions such as increased oxidative stress and inflammation in the brain and peripheral areas, which may help to accelerate the development of cerebrovascular disease and the buildup of neuropathology in the brain [4–6].

EWAS for Neurodevelopment

Recently, many exposome-wide association studies (EWAS) have been undertaken to understand the overall impact of environmental exposure, socio-economical parameters, and dietary habits on neurodevelopment in pregnant mothers and their children. In these EWAS studies, the pregnant mother's biological samples (blood, urine, hair, breast milk, cord blood, and urine) are collected each trimester. The questionnaires are used to note the dietary habits during pregnancy. Children’s biological samples (urine and blood) are collected for postnatal studies, and Bayley-III modules analyze cognitive development.

Recent examples of these approaches include a large-scale EWAS study that evaluated prenatal and postnatal exposure to heavy metals and sociodemographic parameters [7]. The study found that heavy metal exposure was correlated with impaired mitochondrial respiration, which leads to oxidative stress and cellular damage response [7]. Another study from Poland found that cognitive development during the first year of children was positively correlated with exposure to copper in the first week of pregnancy [8,9]. The study also found that alcohol consumption during pregnancy negatively affected the motor development of children. The metabolomic analysis revealed that cognitive and language ability is affected by alterations in mitochondrial respiration which result in the production and accumulation of reactive oxygen species (ROS), causing cellular damage response. The study also found that language development in the second year of child growth was positively associated with daycare attendance. The impact on children's neurodevelopment was also associated with the mother's gestational age [8].

Exposome in Neurological Diseases

Autism Spectrum Disorder (ASD)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired glutamatergic synapse formation, development, and maintenance. ASD is classified after assessing children's behavior and developmental delays by physicians. Currently, there are no available diagnostic tests for ASD where any biological fluid could be analyzed. Attempts have been made to predict or test early ASD in children using the exposome approach. One of the exposome studies found 191 features after metabolomic analysis that were associated with ASD [11]. Glutathione metabolism malfunctioning was linked with ASD [11].

Additionally, prioritizing potential diagnostic traits can be helped by the family-based correlation of ASD-associated features [11]. Baby teeth provide evidence that the cycles involved in the metabolism of zinc and copper are dysregulated in ASD, which could be used to predict who will eventually acquire the condition [12]. The researchers utilized the teeth to recreate healthy and autistic children's prenatal and early life exposures to nutrients and harmful substances [12].

Neurodegenerative Disorders

It is believed that a complex interplay between genetic (genome) and environmental variables (exposome) plays a role in the etiology of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). According to a study by Baranger et al., prenatal cannabis exposure is associated with a mental health burden in children from childhood to early adolescence [26]. Neurodegenerative diseases have been linked to a number of neurotoxicant exposure-related processes, including impacts on synaptic function and endo-lysosomal pathways, oxidative stress, epigenetic alterations, and cellular mosaicism.

Alzheimer's Disease (AD)

A study published in the Proceedings of the National Academy of Sciences found that air pollution was a risk factor for AD [14]. Air pollution triggers oxidative stress and inflammation that leads to the accumulation of hallmark neuropathologies associated with AD. The study showed that higher PM2.5 concentrations and brain amyloid beta (Aβ) plaques could be correlated [14]. It is hence important to take airborne hazardous contaminants related to Aβ pathology. Similar studies have found a linkage between air pollutants and AD [15]; gray matter atrophy in women exposed to higher PM2.5 concentration increases the risk of AD [16]. Recently, “AD Exposome” was constituted to fill up significant knowledge gaps about how environmental factors affect AD's hereditary and non-genetic risk and associated dementias [17].

Parkinson's Disease (PD)

There is growing evidence linking air pollution and PD. A study by Nagata et al. found that sexual orientation disparities in early adolescent sleep are linked to PD [32]. A study on more than 200,000 individuals from six European nations found that prolonged exposure to air PM2.5, nitric oxide, and black carbon increases the chance of death from PD [18]. PM2.5 was found to be the most relevant pollutant for this risk. Another study with more than 75,000 participants found a significant risk of PD with longer exposure to higher concentrations of nitric oxide [19]. One of the most commonly used pesticides in the world, paraquat, has been linked in studies to a significant risk of PD [20]. An exposome study to understand the role of metabolites and exposure was performed on plasma and fecal samples [21]. The authors observed higher relevant features like alanine betaine or nicotinamide in the fecal samples showing the role of gut microbiota in the development of PD.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a progressive, incurable degenerative disease of the motor neurons in the brain, brainstem, and spinal cord. Environmental toxins have been associated with ALS. A study published in the Journal of the American Medical Association - Neurology found that exposure to environmental toxins is associated with ALS [23]. Early life metal dysregulation is also linked to ALS [24]. Dysregulated biodynamics in metabolic attractor systems precede the emergence of ALS [25].

Sleep and Exposome

Sleep is an essential component of brain health, and its quality and duration can be impacted by the exposome. A study by Cheng et al. found that sleep duration is linked to brain structure and psychiatric and cognitive problems in children [31]. Another study by Jessel et al. found that sleep quality and duration in children that consume caffeine are impacted by dose and genetic variation [30]. Letzen et al. found that racial disparities in sleep-related cardiac function in young, healthy adults can impact cardiovascular-related health [33]. Separation of circadian and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism [28]. Habitual sleep and human plasma metabolomics are also linked [29].


The role of exposome in brain health is significant. Agricultural pesticides, air pollutants, and environmental toxins can impact neurodevelopment and neurodegeneration, leading to neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Understanding the impact of the exposome on brain health is critical to prevent and manage these conditions. Additionally, sleep quality and duration can also be impacted by the exposome, leading to psychiatric and cognitive problems in children and cardiovascular-related health issues in young, healthy adults. Further research is needed to understand the full impact of the exposome on brain health and to develop effective prevention and management strategies.

Written by Anurag Srivastava, PhD

Edited by Scott Sherr, MD 


  1. Bellinger, D. C. A strategy for comparing the contributions of environmental chemicals and other risk factors to children's neurodevelopment.Environ Health Perspect 120, 501–507 (2012).
  2. Cattani, al. Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress.Toxicology 387, 67–80 (2017).
  3. Genc, S., Zadeoglulari, Z., Fuss, S. H. & Genc, K. The Adverse Effects of Air Pollution on the Nervous System.J Toxicol 2012, 782462 (2012).
  4. Milani, al. Systemic exposure to air pollution induces oxidative stress and inflammation in mouse brain, contributing to neurodegeneration onset.Int J Mol Sci 21, 3699 (2020).
  5. Wang, al. The impact of air pollution on neurodegenerative diseases.Ther Drug Monit 43, 69–78 (2021).
  6. Song, al. Microglial Activation and Oxidative Stress in PM2. 5-Induced Neurodegenerative Disorders.Antioxidants 11, 1482 (2022).
  7. Anesti, al. An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment.Front Public Health 10, (2022).
  8. Sarigiannis, D. al. The neurodevelopmental exposome: The effect of in utero co-exposure to heavy metals and phthalates on child neurodevelopment.Environ Res 197, 110949 (2021).
  9. Garí, al. Prenatal exposure to neurotoxic metals and micronutrients and neurodevelopmental outcomes in early school age children from Poland.Environ Res 204, 112049 (2022).
  10. Randall, al. Diagnostic tests for autism spectrum disorder (ASD) in preschool children.Cochrane Database of Systematic Reviews (2018).
  11. Chung, M. al. Plasma metabolomics of autism spectrum disorder and influence of shared components in proband families.Exposome 1, osab004 (2021).
  12. Curtin, al. Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder.Sci Adv 4, eaat1293 (2018).
  13. Laura. FDA cites hair-based autism diagnostic aid as ‘breakthrough’.Spectrum (2022).
  14. Iaccarino, al. Association between ambient air pollution and amyloid positron emission tomography positivity in older adults with cognitive impairment.JAMA Neurol 78, 197–207 (2021).
  15. Younan, al. Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer’s disease.Brain 143, 289–302 (2020).
  16. Younan, al. PM2. 5 associated with gray matter atrophy reflecting increased Alzheimer risk in older women.Neurology 96, e1190–e1201 (2021).
  17. Finch, C. E. & Kulminski, A. M. The Alzheimer’s disease exposome.Alzheimer’s & Dementia 15, 1123–1132 (2019).
  18. Cole-Hunter, al. Long-term air pollution exposure and Parkinson’s disease mortality in a large pooled European cohort: An ELAPSE study.Environ Int 171, 107667 (2023).
  19. Jo, al. Association of NO2 and other air pollution exposures with the risk of Parkinson disease.JAMA Neurol 78, 800–808 (2021).
  20. Goldman, S. M., Musgrove, R. E., Jewell, S. A. & Di Monte, D. A. Pesticides and Parkinson’s disease: current experimental and epidemiological evidence. inAdvances in Neurotoxicology vol. 1 83–117 (Elsevier, 2017).
  21. Talavera Andújar, al. Studying the Parkinson’s disease metabolome and exposome in biological samples through different analytical and cheminformatics approaches: a pilot study.Anal Bioanal Chem 414, 7399–7419 (2022).
  22. National Academies of Sciences and Medicine, E.Environmental Neuroscience: Advancing the Understanding of How Chemical Exposures Impact Brain Health and Disease: Proceedings of a Workshop. (National Academies Press, 2020).
  23. Su, al. Association of environmental toxins with amyotrophic lateral sclerosis.JAMA Neurol 73, 803–811 (2016).
  24. Figueroa‐Romero, al. Early life metal dysregulation in amyotrophic lateral sclerosis.Ann Clin Transl Neurol 7, 872–882 (2020).
  25. Curtin, al. Dysregulated biodynamics in metabolic attractor systems precede the emergence of amyotrophic lateral sclerosis.PLoS Comput Biol 16, e1007773 (2020).
  26. Baranger, D. A. al. Association of mental health burden with prenatal cannabis exposure from childhood to early adolescence: longitudinal findings from the adolescent brain cognitive development (ABCD) study.JAMA Pediatr 176, 1261–1265 (2022).
  27. Choi, K. al. Integrative analysis of genomic and exposomic influences on youth mental health.Journal of Child Psychology and Psychiatry 63, 1196–1205 (2022).
  28. Skene, D. al. Separation of circadian-and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.Proceedings of the National Academy of Sciences 115, 7825–7830 (2018).
  29. Xiao, al. Habitual sleep and human plasma metabolomics.Metabolomics 13, 1–13 (2017).
  30. Jessel, C. D., Narang, A., Zuberi, R. & Bousman, C. A. Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in ADORA2A and CYP1A.Genes (Basel) 14, 289 (2023).
  31. Cheng, al. Sleep duration, brain structure, and psychiatric and cognitive problems in children.Mol Psychiatry 26, 3992–4003 (2021).
  32. Nagata, J. al. Sexual Orientation Disparities in Early Adolescent Sleep: Findings from the Adolescent Brain Cognitive Development Study.LGBT Health (2023).
  33. 33. Letzen, J. al. Racial disparities in sleep-related cardiac function in young, healthy adults: implications for cardiovascular-related health.Sleep 44, zsab164 (2021)

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