An exposome perspective: Early-life events and immune development in a changing world
Open accessAbstract
Advances in metagenomics, proteomics, metabolomics, and systems biology are providing a new emphasis in research; interdisciplinary work suggests that personalized medicine is on the horizon. These advances are illuminating sophisticated interactions between human-associated microbes and the immune system. The result is a transformed view of future prevention and treatment of chronic noncommunicable diseases, including allergy. Paradigm-shifting gains in scientific knowledge are occurring at a time of rapid global environmental change, urbanization, and biodiversity losses. Multifactorial and multigenerational implications of total environmental exposures, the exposome, require coordinated interdisciplinary efforts. It is clear that the genome alone cannot provide answers to urgent questions. Here we review the historical origins of exposome research and define a new concept, the metaexposome, which considers the bidirectional effect of the environment on human subjects and the human influence on all living systems and their genomes. The latter is essential for human health. We place the metaexposome in the context of early-life immune functioning and describe how various aspects of a changing environment, especially through microbiota exposures, can influence health and disease over the life course.
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The risk of developing chronic inflammation can be traced to early development, and its effects persist across the life span to influence adult health and mortality risk.
“Evidence is emerging that the risk of developing chronic inflammation can be traced back to early development, and its effects are now known to persist throughout the life span to affect adulthood health and risk of mortality6–8.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
Systemic chronic inflammation during pregnancy and childhood can elevate the risk of non-communicable diseases across the life span.
“SCI during pregnancy and childhood can have serious developmental consequences that include elevating the risk of non-communicable diseases over the life span7,8,26,27.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
Dietary and lifestyle habits and exposure to pollutants can increase oxidative stress, upregulate mitogenic signaling pathways, and cause genomic and epigenomic perturbations that induce the senescence-associated secretory phenotype.
“dietary and lifestyle habits, as well as exposure to a variety of different pollutants, can increase oxidative stress, upregulate mitogenic signaling pathways and cause genomic and epigenomic perturbations8,60,62,63 that can induce the SASP.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
The rapid rise in urbanization over the past 200 years brought an unprecedented increase in human exposure to xenobiotics, such as air pollutants, hazardous waste and industrial chemicals that drive SCI.
“The rapid rise in urbanization over the past 200 years8 brought with it an unprecedented increase in humans’ exposure to various xenobiotics, including air pollutants, hazardous waste products and industrial chemicals that promote SCI8,161”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
These compounds promote inflammatory activity through multiple mechanisms, including cytotoxicity, oxidative stress, and endocrine disruption beginning in utero.
“These compounds and others promote inflammatory activity via multiple mechanisms. For example, they can be cytotoxic8,162, cause oxidative stress or act as endocrine disruptors, starting in utero8”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
More microbial exposure during infancy is linked to a lower chance of chronic inflammation later in adulthood, as the hygiene or 'old friends' hypothesis predicts.
“greater microbial exposure in infancy is associated with reduced risk of chronic inflammation in adulthood8,168, as predicted by the hygiene, or ‘old friends’, hypothesis82”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
These chemicals are thought to contribute causally to hormone-dependent cancers, metabolic syndrome, type 2 diabetes, hypertension, cardiovascular disease, allergy and asthma, and autoimmune and neurodegenerative diseases.
“These chemicals are thus suspected of playing a causal role in hormone-dependent cancers, metabolic syndrome, type 2 diabetes, hypertension, CVD, allergy and asthma, and autoimmune and neurodegenerative diseases8,162,166”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
Childhood conditions have a major influence on later metabolic and immune responses, which then drive SCI in adulthood.
“childhood circumstances significantly impact metabolic and immune responses later in life, which in turn promote SCI in adulthood8,26,27,168,169”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [8]
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Self-citation
- Authors
- Renz, H., Holt, P. G., Inouye, M., Logan, A. C., Prescott, S. L., & Sly, P. D.
- Affiliations
- Philipps University of Marburg (DE)
- The Kids Research Institute Australia (AU)
- The University of Melbourne (AU)
- Worldwide Universities Network (GB)
- The University of Western Australia (AU)
- The University of Queensland (AU)
- Corresponding author
- Renz, Harald
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 140
- Issue
- 1
- Pages
- 24-40
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2732858253
- Cited by
- 226
- References
- 238
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 28 · 2023: 25 · 2022: 31 · 2021: 27 · 2020: 23 · 2019: 26 · 2018: 20 · 2017: 4
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Danone
- Deutsche Forschungsgemeinschaft (SFB 1021)
- National Health and Medical Research Council (1061435)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- exposome, early life immune development, environmental exposure, microbiota, human-microbe interactions, allergy, non-communicable diseases, global change, urbanization, biodiversity loss, life course, personalized medicine
- MeSH terms
- Animals, Diet, Environmental Exposure, Humans, Immune System, Gastrointestinal Tract, Microbiota
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