Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Environmental Interventions for Preventing Atopic Diseases.

PURPOSE OF REVIEW: In this review, we detail the exposome (consisting of environmental factors such as diet, microbial colonization, allergens, pollutants, and stressors), mechanistic and clinical research supporting its influence on atopic disease, and potentiation from climate change. We highlight contemporary environmental interventions and available evidence substantiating their roles in atopic disease prevention, from observational cohorts to randomized controlled trials, when available. RECENT FINDINGS: Early introduction to allergenic foods is an effective primary prevention strategy to reduce food allergy. Diverse dietary intake also appears to be a promising strategy for allergic disease prevention, but additional study is necessary. Air pollution and tobacco smoke are highly associated with allergic disease, among other medical comorbidities, paving the way for campaigns and legislation to reduce these exposures. There is no clear evidence that oral vitamin D supplementation, prebiotic or probiotic supplementation, daily emollient application, and antiviral prophylaxis are effective in preventing atopic disease, but these interventions require further study. While some environmental interventions have a well-defined role in the prevention of atopic disease, additional study of many remaining interventions is necessary to enhance our understanding of their role in disease prevention. Alignment of research findings from randomized controlled trials with public policy is essential to develop meaningful public health outcomes and prevent allergic disease on the population level.

The indispensable whole of work and population health: How the working life exposome can advance empirical research, policy, and action.

OBJECTIVES: The thesis of this paper is that health and safety challenges of working people can only be fully understood by examining them as wholes with interacting parts. This paper unravels this indispensable whole by introducing the working life exposome and elucidating how associated epistemologies and methodologies can enhance empirical research. METHODS: Network and population health scientists have initiated an ongoing discourse on the state of empirical work-health-safety-well-being research. RESULTS: Empirical research has not fully captured the totality and complexity of multiple and interacting work and nonwork factors defining the health of working people over their life course. We challenge the prevailing paradigm by proposing to expand it from narrow work-related exposures and associated monocausal frameworks to the holistic study of work and population health grounded in complexity and exposome sciences. Health challenges of working people are determined by, embedded in, and/or operate as complex systems comprised of multilayered and interdependent components. One can identify many potentially causal factors as sufficient and component causes where removal of one or more of these can impact disease progression. We, therefore, cannot effectively study them by an a priori determination of a set of components and/or properties to be examined separately and then recombine partial approaches, attempting to form a picture of the whole. Instead, we must examine these challenges as wholes from the start, with an emphasis on interactions among their multifactorial components and their emergent properties. Despite various challenges, working-life-exposome-grounded frameworks and associated innovations have the potential to accomplish that. CONCLUSIONS: This emerging paradigm shift can move empirical work-health-safety-well-being research to cutting-edge science and enable more impactful policies and actions.

A cross-sectional epidemiological study conducted in Argentina to evaluate the impact of the exposome on skin aging.

BACKGROUND: Skin aging is a gradual cumulative process that may be accelerated by various exposome factors. AIMS: To investigate associations between exposome factors and facial skin aging in 11 locations in Argentina. PATIENTS/METHODS: An observational, cross-sectional study with assessments by exposome questionnaire, Glogau photoaging classification from I to IV, AI-based algorithm analysis of 7 skin aging signs, and SCINEXA score. RESULTS: Of 1346 participants, most were women (82%), aged 31-50 years (62%), of skin phototype III (52%), and living in urban areas (94%). The Glogau skin age was higher than the chronological age for 28% of overall participants, 36% of men, and 45% of participants from Ciudad de Buenos Aires versus 12% from Jujuy (p < 0.001). Being male (OR = 1.59; 95% CI 1.18-2.13), exposed to agrochemicals (OR = 1.59: 95% CI 1.01-2.51), of lower socioeconomic levels (OR = 2.06; 95% CI 1.32-3.21) and doing outdoor physical activity (OR = 1.33; 95% CI 1.00-1.76) increased the risk for premature aging. Odds decreased with high daily intake of water (OR = 0.76; 95% CI 0.59-0.97), daily dermocosmetic use (moisturizers [OR = 0.72; 95% CI 0.55-0.94], cleansers [OR = 0.53; CI 95% 0.42-0.67], retinoids [OR = 0.61; 95% CI 0.39-0.95]), and antiaging treatments (OR = 0.74; 95% CI 0.57-0.97). CONCLUSIONS: Some exposome factors increased the risk for premature skin aging (physical outdoor activity, exposure to agrochemicals), while others were protective factors (high water intake, antiaging treatments, use of dermocosmetics). Locations with higher pollution levels had more premature skin aging.

A methodological study of exposome based on an open database: Association analysis between exposure to metal mixtures and hyperuricemia.

BACKGROUND: Exposome recognizes that humans are constantly exposed to multiple environmental factors, and elucidating the health effects of complex exposure mixtures places greater demands on analytical methods. OBJECTS: We aimed to explore the association between mixed exposure to metals and hyperuricemia (HUA), and highlight the potential of explainable machine learning (EML) and causal mediation analysis (CMA) for application in the analysis of exposome data. METHODS: Pre-pandemic data from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 and a total of 13780 individuals were included. We first used traditional statistical models (multiple logistic regression (MLR) and restricted cubic spline regression (RCS)) and EML to explore associations between mixed metals exposures and HUA, followed by the CMA using the 4-way decomposition method to analyze the interaction and mediation effects among BMI or estimated glomerular filtration rate (eGFR), metals and HUA. RESULTS: The prevalence of HUA was 18.91% (2606/13780). The MLR showed that mercury (Q4 vs Q1: OR = 1.08, 95% CI:1.02-1.14) and lead (Q4 vs Q1: OR = 1.23, 95% CI:1.13-1.34) were generally positively associated with HUA. Higher concentrations of lead, mercury, selenium and manganese were associated with the increased odds of HUA, and BMI and eGFR were the top two variables attributable to the risk of developing HUA in the EML. Subgroup analyses from the MLR and EML consistently demonstrated the positive relationship between exposure to lead, mercury and selenium in participants with BMI <25 kg/m2 and BMI ≥30 kg/m2. BMI mediated 32.12% of the association between lead exposure and HUA, and the interaction between BMI and lead accounted for 3.88% of the association in the CMA. CONCLUSIONS: Heavy metals can increase the HUA risk and BMI or eGFR can mediate and interact with metals to cause HUA. Future studies based on exposome can attempt to utilize the EML and CMA.

Integrating the social environment with an equity perspective into the exposome paradigm: A new conceptual framework of the Social Exposome.

The importance of the social environment and social inequalities in disease etiology is well-known due to the profound research and conceptual framework on social determinants of health. For a long period, in exposome research with its classical orientation towards detrimental health effects of biological, chemical, and physical exposures, this knowledge remained underrepresented. But currently it gains great awareness and calls for innovations in rethinking the role of social environmental health determinants. To fill this gap that exists in terms of the social domain within exposome research, we propose a novel conceptual framework of the Social Exposome, to integrate the social environment in conjunction with the physical environment into the exposome concept. The iterative development process of the Social Exposome was based on a systematic compilation of social exposures in order to achieve a holistic portrayal of the human social environment - including social, psychosocial, socioeconomic, sociodemographic, local, regional, and cultural aspects, at individual and contextual levels. In order to move the Social Exposome beyond a mere compilation of exposures, three core principles are emphasized that underly the interplay of the multitude of exposures: Multidimensionality, Reciprocity, and Timing and continuity. The key focus of the conceptual framework of the Social Exposome is on understanding the underlying mechanisms that translate social exposures into health outcomes. In particular, insights from research on health equity and environmental justice have been incorporated to uncover how social inequalities in health emerge, are maintained, and systematically drive health outcomes. Three transmission pathways are presented: Embodiment, Resilience and Susceptibility or Vulnerability, and Empowerment. The Social Exposome conceptual framework may serve as a strategic map for, both, research and intervention planning, aiming to further explore the impact of the complex social environment and to alter transmission pathways to minimize health risks and health inequalities and to foster equity in health.

Gut distress and intervention via communications of SARS-CoV-2 with mucosal exposome.

Acute coronavirus disease 2019 (COVID-19) has been associated with prevalent gastrointestinal distress, characterized by fecal shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA or persistent antigen presence in the gut. Using a meta-analysis, the present review addressed gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and diarrhea. Despite limited data on the gut-lung axis, viral transmission to the gut and its influence on gut mucosa and microbial community were found to be associated by means of various biochemical mechanisms. Notably, the prolonged presence of viral antigens and disrupted mucosal immunity may increase gut microbial and inflammatory risks, leading to acute pathological outcomes or post-acute COVID-19 symptoms. Patients with COVID-19 exhibit lower bacterial diversity and a higher relative abundance of opportunistic pathogens in their gut microbiota than healthy controls. Considering the dysbiotic changes during infection, remodeling or supplementation with beneficial microbial communities may counteract adverse outcomes in the gut and other organs in patients with COVID-19. Moreover, nutritional status, such as vitamin D deficiency, has been associated with disease severity in patients with COVID-19 via the regulation of the gut microbial community and host immunity. The nutritional and microbiological interventions improve the gut exposome including the host immunity, gut microbiota, and nutritional status, contributing to defense against acute or post-acute COVID-19 in the gut-lung axis.

Characterizing the marine mammal exposome by iceberg modeling, linking chemical analysis and in vitro bioassays.

The present study complements work on mixture effects measured with in vitro bioassays of passive equilibrium sampling extracts using the silicone polydimethylsiloxane (PDMS) in organs from marine mammals with chemical profiling. Blubber, liver, kidney and brain tissues of harbor porpoise (Phocoena phocoena), harbor seal (Phoca vitulina), ringed seal (Phoca hispida) and orca (Orcinus orca) from the North and Baltic Seas were investigated. We analyzed 117 chemicals including legacy and emerging contaminants using gas chromatography-high resolution mass spectrometry and quantified 70 of those chemicals in at least one sample. No systematic differences between the organs were found. Only for single compounds a clear distribution pattern was observed. For example, 4,4'-dichlorodiphenyltrichloroethane, enzacamene and etofenprox were mainly detected in blubber, whereas tonalide and the hexachlorocyclohexanes were more often found in liver. Furthermore, we compared the chemical profiling with the bioanalytical results using an iceberg mixture model, evaluating how much of the biological effect could be explained by the analyzed chemicals. The mixture effect predicted from the quantified chemical concentrations explained 0.014-83% of the aryl hydrocarbon receptor activating effect (AhR-CALUX), but less than 0.13% for the activation of the oxidative stress response (AREc32) and peroxisome-proliferator activated receptor (PPARγ). The quantified chemicals also explained between 0.044-45% of the cytotoxic effect measured with the AhR-CALUX. The largest fraction of the observed effect was explained for the orca, which was the individuum with the highest chemical burden. This study underlines that chemical analysis and bioassays are complementary to comprehensively characterize the mixture exposome of marine mammals.

[Exposome: from definition to future challenges.] / Esposoma: dalla definizione alle sfide future.

The exposome concept arises from the need to integrate different disciplines of public health and environmental sciences, mainly including environmental epidemiology, exposure science, and toxicology. The role of the exposome is to understand how the totality of an individual's exposures throughout the lifetime can impact human health. The etiology of a health condition is rarely explained by a single exposure. Therefore, examining the human exposome as a whole becomes relevant to simultaneously consider multiple risk factors and more accurately estimate concurrent causes of different health outcomes. Generally, the exposome is explained through three domains: general external exposome, specific external exposome, and internal exposome. The general external exposome includes measurable population-level exposures such as air pollution or meteorological factors. The specific external exposome includes information on individual exposures, such as lifestyle factors, typically obtained from questionnaires. Meanwhile, the internal exposome encompasses multiple biological responses to external factors, detected through molecular and omics analyses. Additionally, in recent decades, the socio-exposome theory has emerged, where all exposures are studied as a phenomenon dependent on the interaction between socioeconomic factors that vary depending on the context, allowing the identification of mechanisms that lead to health inequalities. The considerable production of data in exposome studies has led researchers to face new methodological and statistical challenges, introducing various approaches to estimate the effect of the exposome on health. Among the most common are regression models (Exposome-Wide Association Study - ExWAS), dimensionality reduction and exposure grouping techniques, and machine learning methods. The significant conceptual and methodological innovation of the exposome for a more holistic evaluation of the risks associated with human health is continuously expanding and will require further investigations related to the application of information obtained from studies into prevention and public health policies.

A molecular sensitization map of European children reveals exposome- and climate-dependent sensitization profiles.

BACKGROUND: Understanding differences in sensitization profiles at the molecular allergen level is important for diagnosis, personalized treatment and prevention strategies in allergy. METHODS: Immunoglobulin E (IgE) sensitization profiles were determined in more than 2800 sera from children in nine population-based cohorts in different geographical regions of Europe; north [BAMSE (Sweden), ECA (Norway)], west/central [PIAMA (the Netherlands), BiB (the United Kingdom), GINIplus (Germany)], and south [INMA Sabadell and Gipuzkoa (Spain) and ROBBIC Rome and Bologna (Italy)] using the MeDALL-allergen chip. RESULTS: Sensitization to grass pollen allergen, Phl p 1, and to major cat allergen, Fel d 1, dominated in most European regions whereas sensitization to house dust mite allergens Der p 1, 2 and 23 varied considerably between regions and were lowest in the north. Less than half of children from Sabadell which has a hot and dry climate were sensitized to respiratory allergens, in particular house dust mite allergens as compared to Gipuzkoa nearby with a more humid climate. Peanut allergen Ara h 1 was the most frequently recognized class 1 food allergen in Northern/Western Europe, while the fruit allergens Pru p 3, Act d 1 and 2 were prominent in Southern and Western/Central Europe. Ves v 5-sensitization dominated in North and West/Central Europe. CONCLUSION: We show regional, exposome- and climate-dependent differences in molecular IgE-reactivity profiles in Northern, Western/Central and Southern Europe which may form a molecular basis for precision medicine-based approaches for treatment and prevention of allergy.

Understanding the Chemical Exposome During Fetal Development and Early Childhood: A Review.

Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possiblemodels for studying maternal-fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed.

Population-wide measures due to the COVID-19 pandemic and exposome changes in the general population of Cyprus in March-May 2020.

Non-pharmacological interventions (e.g., stay-at-home orders, school closures, physical distancing) implemented during the COVID-19 pandemic are expected to have modified routines and lifestyles, eventually impacting key exposome parameters, including, among others, physical activity, diet and cleaning habits. The objectives were to describe the exposomic profile of the general Cypriot population and compliance to the population-wide measures implemented during March-May 2020 to lower the risk of SARS-CoV-2 transmission, and to simulate the population-wide measures' effect on social contacts and SARS-CoV-2 spread. A survey was conducted in March-May 2020 capturing different exposome parameters, e.g., individual characteristics, lifestyle/habits, time spent and contacts at home/work/elsewhere. We described the exposome parameters and their correlations. In an exposome-wide association analysis, we used the number of hours spent at home as an indicator of compliance to the measures. We generated synthetic human proximity networks, before and during the measures using the dynamic-[Formula: see text]1 model and simulated SARS-CoV-2 transmission (i.e., to identify possible places where higher transmission/number of cases could originate from) on the networks with a dynamic Susceptible-Exposed-Infectious-Recovered model. Overall, 594 respondents were included in the analysis (mean age 45.7 years, > 50% in very good health and communicating daily with friends/family via phone/online). The median number of contacts at home and at work decreased during the measures (from 3 to 2 and from 12 to 0, respectively) and the hours spent at home increased, indicating compliance with the measures. Increased time spent at home during the measures was associated with time spent at work before the measures (ß= -0.87, 95% CI [-1.21,-0.53]) as well as with being retired vs employed (ß= 2.32, 95% CI [1.70, 2.93]). The temporal network analysis indicated that most cases originated at work, while the synthetic human proximity networks adequately reproduced the observed SARS-CoV-2 spread. Exposome approaches (i.e., holistic characterization of the spatiotemporal variation of multiple exposures) would aid the comprehensive description of population-wide measures' impact and explore how behaviors and networks may shape SARS-CoV-2 transmission.

A review on the application of the exposome paradigm to unveil the environmental determinants of age-related diseases.

Age-related diseases account for almost half of all diseases among adults worldwide, and their incidence is substantially affected by the exposome, which is the sum of all exogenous and endogenous environmental exposures and the human body's response to these exposures throughout the entire lifespan. Herein, we perform a comprehensive review of the epidemiological literature to determine the key elements of the exposome that affect the development of age-related diseases and the roles of aging hallmarks in this process. We find that most exposure assessments in previous aging studies have used a reductionist approach, whereby the effect of only a single environmental factor or a specific class of environmental factors on the development of age-related diseases has been examined. As such, there is a lack of a holistic and unbiased understanding of the effect of multiple environmental factors on the development of age-related diseases. To address this, we propose several research strategies based on an exposomic framework that could advance our understanding-in particular, from a mechanistic perspective-of how environmental factors affect the development of age-related diseases. We discuss the statistical methods and other methods that have been used in exposome-wide association studies, with a particular focus on multiomics technologies. We also address future challenges and opportunities in the realm of multidisciplinary approaches and genome-exposome epidemiology. Furthermore, we provide perspectives on precise public health services for vulnerable populations, public communications, the integration of risk exposure information, and the bench-to-bedside translation of research on age-related diseases.

State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event.

The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P > 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother-child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field.

SUPPLEMENT ARTICLE: Scientific and Clinical Insights into the Facial Application of Mineralizing Volcanic Water.

BACKGROUND: The term "exposome" describes the totality of exposures an individual is subjected to from conception to death. Both internal and external exposome factors affect skin health. External exposures that contribute to facial skin aging include solar radiation, air pollution, tobacco smoke, and unbalanced nutrition. The review explores scientific and clinical insights into the exposome impact on facial skin aging and topical mineralizing volcanic water use potential benefits. METHODS: An expert panel of seven dermatologists and two clinical researchers specializing in aesthetic and dermatological indications reviewed and discussed the literature on the exposome and mineralizing volcanic water's role in relation to the exposome. Two virtual advisory boards were conducted between February and May 2021. Following the meetings, an additional systematic literature review explored publications relevant to the exposome, topical essential minerals, and skin health. The results of the two advisory boards, coupled with expert opinion and the outcome of the updated systematic literature review, informed the statements on which the advisors reached a consensus. CONCLUSIONS: A combination of in vivo, in vitro, and clinical data on topical mineralizing volcanic water application indicates that the serum supports the skin's antioxidant defenses and reduces skin inflammation. Additionally, the serum may have benefits as an adjunct for facial dermatoses and post-procedural skincare. J Drugs Dermatol. 2022;21:4(Suppl 1):s3-10.

Exposome-wide ranking of modifiable risk factors for cardiometabolic disease traits.

The present study assessed the temporal associations of ~ 300 lifestyle exposures with nine cardiometabolic traits  to identify exposures/exposure groups that might inform lifestyle interventions for the reduction of cardiometabolic disease risk. The analyses were undertaken in a longitudinal sample comprising > 31,000 adults living in northern Sweden. Linear mixed models were used to assess the average associations of lifestyle exposures and linear regression models were used to test associations with 10-year change in the cardiometabolic traits. 'Physical activity' and 'General Health' were the exposure categories containing the highest number of 'tentative signals' in analyses assessing the average association of lifestyle variables, while 'Tobacco use' was the top category for the 10-year change association analyses. Eleven modifiable variables showed a consistent average association among the majority of cardiometabolic traits. These variables belonged to the domains: (i) Smoking, (ii) Beverage (filtered coffee), (iii) physical activity, (iv) alcohol intake, and (v) specific variables related to Nordic lifestyle (hunting/fishing during leisure time and boiled coffee consumption). We used an agnostic, data-driven approach to assess a wide range of established and novel risk factors for cardiometabolic disease. Our findings highlight key variables, along with their respective effect estimates, that might be prioritised for subsequent prediction models and lifestyle interventions.

The exposome in practice: an exploratory panel study of biomarkers of air pollutant exposure in Chinese people aged 60-69 years (China BAPE Study).

The exposome overhauls conventional environmental health impact research paradigms and provides a novel methodological framework that comprehensively addresses the complex, highly dynamic interplays of exogenous exposures, endogenous exposures, and modifiable factors in humans. Holistic assessments of the adverse health effects and systematic elucidation of the mechanisms underlying environmental exposures are major scientific challenges with widespread societal implications. However, to date, few studies have comprehensively and simultaneously measured airborne pollutant exposures and explored the associated biomarkers in susceptible healthy elderly subjects, potentially resulting in the suboptimal assessment and management of health risks. To demonstrate the exposome paradigm, we describe the rationale and design of a comprehensive biomarker and biomonitoring panel study to systematically explore the association between individual airborne exposure and adverse health outcomes. We used a combination of personal monitoring for airborne pollutants, extensive human biomonitoring, advanced omics analysis, confounding information, and statistical methods. We established an exploratory panel study of Biomarkers of Air Pollutant Exposure in Chinese people aged 60-69 years (China BAPE), which included 76 healthy residents from a representative community in Jinan City, Shandong Province. During the period between September 2018 and January 2019, we conducted prospective longitudinal monitoring with a 3-day assessment every month. This project: (1) leveraged advanced tools for personal airborne exposure monitoring (external exposures); (2) comprehensively characterized biological samples for exogenous and endogenous compounds (e.g., targeted and untargeted monitoring) and multi-omics scale measurements to explore potential biomarkers and putative toxicity pathways; and (3) systematically evaluated the relationships between personal exposure to air pollutants, and novel biomarkers of exposures and effects using exposome-wide association study approaches. These findings will contribute to our understanding of the mechanisms underlying the adverse health impacts of air pollution exposures and identify potential adverse clinical outcomes that can facilitate the development of effective prevention and targeted intervention techniques.

The Exposome in the Era of One Health.

Current studies on environmental chemistry mainly focus on a single stressor or single group of stressors, which does not reflect the multiple stressors in the dynamic exposome we are facing. Similarly, current studies on environmental toxicology mostly target humans, animals, or the environment separately, which are inadequate to solve the grand challenge of multiple receptors in One Health. Though chemical, biological, and physical stressors all pose health threats, the susceptibilities of different organisms are different. As such, significant relationships and interactions of the chemical, biological, and physical stressors in the environment and their holistic environmental and biological consequences remain unclear. Fortunately, the rapid developments in various techniques, as well as the concepts of multistressors in the exposome and multireceptor in One Health provide the possibilities to understand our environment better. Since the combined stressor is location-specific and mixture toxicity is species-specific, more comprehensive frameworks to guide risk assessment and environmental treatment are urgently needed. Here, three conceptual frameworks to categorize unknown stressors, spatially visualize the riskiest stressors, and investigate the combined effects of multiple stressors across multiple species within the concepts of the exposome and One Health are proposed for the first time.

Environmental factors associated with biological use and surgery in inflammatory bowel disease.

BACKGROUND AND AIM: While major efforts were made studying the complex etiology of inflammatory bowel disease (IBD) including environmental factors, less is known about underlying causes leading to the heterogeneous and highly variable course of disease. As cigarette smoking cessation is the best-known environmental factor with beneficial effect in Crohn's disease (CD), more exposome factors are likely involved. Further insights into the role of the exposome in heterogeneity of disease might not only further knowledge of underlying pathways, but also allow for better risk stratification. METHODS: Seven hundred twenty-eight IBD patients completed the validated Groningen IBD Environmental Questionnaire, collecting exposome data for 93 exposome factors. Associations with disease course, that is, for need for surgery or biological therapy, were evaluated using univariate and multivariate-adjusted logistic regression modeling. RESULTS: No significant associations were seen after Bonferroni correction. However, 11 novel exposome factors were identified with P < 0.05. Two factors were associated with course of CD and ulcerative colitis (UC): beer (CD OR0.3/UC OR0.3) and cannabis (0.5/2.2). While in CD, carpet flooring (0.5) was associated with biological use, and four factors were associated with surgery: working shifts (1.8), appendectomy (2.4), frequent tooth brushing (2.8), and large household size (0.1). For UC, migrants more often required biologicals (10.2). Childhood underweight (3.4), amphetamine use (6.2), and cocaine use (4.8) were associated with surgery. Five factors were replicated. CONCLUSIONS: We identified 16 environmental factors nominally associated with biological use and surgery in established IBD. These new insights form an important stepping stone to guide research on biological pathways involved, risk stratification, tailor-made interventions, and preventive strategies in IBD.

Blood donor exposome and impact of common drugs on red blood cell metabolism.

Computational models based on recent maps of the RBC proteome suggest that mature erythrocytes may harbor targets for common drugs. This prediction is relevant to RBC storage in the blood bank, in which the impact of small molecule drugs or other xenometabolites deriving from dietary, iatrogenic, or environmental exposures ("exposome") may alter erythrocyte energy and redox metabolism and, in so doing, affect red cell storage quality and posttransfusion efficacy. To test this prediction, here we provide a comprehensive characterization of the blood donor exposome, including the detection of common prescription and over-the-counter drugs in blood units donated by 250 healthy volunteers in the Recipient Epidemiology and Donor Evaluation Study III Red Blood Cell-Omics (REDS-III RBC-Omics) Study. Based on high-throughput drug screenings of 1366 FDA-approved drugs, we report that approximately 65% of the tested drugs had an impact on erythrocyte metabolism. Machine learning models built using metabolites as predictors were able to accurately predict drugs for several drug classes/targets (bisphosphonates, anticholinergics, calcium channel blockers, adrenergics, proton pump inhibitors, antimetabolites, selective serotonin reuptake inhibitors, and mTOR), suggesting that these drugs have a direct, conserved, and substantial impact on erythrocyte metabolism. As a proof of principle, here we show that the antacid ranitidine - though rarely detected in the blood donor population - has a strong effect on RBC markers of storage quality in vitro. We thus show that supplementation of blood units stored in bags with ranitidine could - through mechanisms involving sphingosine 1-phosphate-dependent modulation of erythrocyte glycolysis and/or direct binding to hemoglobin - improve erythrocyte metabolism and storage quality.