Search Results (16)

Physiological and metabolic adaptations during pregnancy may increase susceptibility to harmful environmental chemicals. High maternal BMI that perturbs the metabolic, inflammatory, and hormonal milieus could modulate toxicant effects on pregnancy outcomes. First-trimester targeted urinary exposomes of 119 women (BMI ≥ 25 = 55; BMI < 25 = 64) from the Michigan Mother–Infant Pair cohort were profiled to assess how BMI influences urinary exposomes and related biological responses. A validated approach measured 96 chemicals and biomarkers of oxidative stress and glucocorticoids. Women in both groups reported similar lifestyles and consumer product use. Women with high BMI had lower urinary concentrations of several chemicals than women with low BMI. Phytoestrogens, polycyclic aromatic hydrocarbons, and insect repellants showed a higher magnitude of positive associations with other markers of exposure, oxidative and glucocorticoid stress in the high-BMI group, while UV filters, flame retardants, and phthalates showed a higher magnitude of positive associations with oxidative stress markers in the low-BMI group. The patterns of associations of exposure markers with stress markers and pregnancy outcomes (gestational age and birthweight) differed by maternal BMI. This highlights the importance of incorporating maternal BMI into the evaluation of exposure burden and its effects, as a factor that may actively shape biological responses. Full article

Maternal stress during lifetime and pregnancy may influence offspring epigenetic age, impacting long-term health. We conducted a systematic review and meta-analysis of associations between maternal stress and epigenetic aging markers: telomere length (TL) and DNA methylation (DNAm) age acceleration. The systematic search was performed according to PRISMA guidelines and registered on PROSPERO (ref. CRD42023474640). Fixed and random effect meta-analyses were carried out, stratified by stress type and marker type (TL, DNAm). Sixteen studies met inclusion criteria; 12 were meta-analyzed (10 TL, 2 DNAm). Due to high heterogeneity, restricted maximum likelihood meta-analysis suggested significant inverse associations between maternal stress and offspring TL. Perceived stress was associated with shorter TL (p-value = 7 × 10⁻⁴, β = −0.085, 95%CI [−0.135, −0.036]), as was lifetime stress/trauma (p-value = 0.01, β = −0.209, 95%CI [−0.370, −0.049]). In contrast, maternal stress showed no significant associations with DNAm age acceleration (p-value = 0.32). Both perceived maternal stress and maternal stress were associated with shorter offspring TL, suggesting that stress exposure across the maternal lifespan influences offspring biological aging markers. No significant association was observed with DNAm-based aging clocks. Further studies with larger sample sizes and more homogeneous settings are needed to confirm and expand upon our observations. Full article

Dibutyl phthalate (DBP) is used as a plasticizer to enhance flexibility in several household products, cosmetics, and food-contact materials. Due to its harmful effects, DBP is restricted or banned in children’s products and food items, particularly in Europe. Due to its endocrine disruptor properties and considering its ability to cross the placental barrier, it is imperative to study DBP’s vascular effects in pregnancy, given the vulnerability of this period. Thus, this study investigated the potential effects of DBP on the cardiovascular system using umbilical arteries from healthy pregnant women. Specifically, the impact of DBP on the vascular reactivity after both rapid and 24 h DBP exposure was analyzed, as well as the contractility and the cell viability of vascular smooth muscle cells (VSMC). DBP did not exhibit overt cytotoxic effects on VSMCs, possibly due to its adsorption onto polystyrene surfaces, potentially limiting bioavailability. Interestingly, DBP induced vasorelaxation in a concentration-dependent manner. Although mechanistic insights remain to be fully elucidated, the results suggest the involvement of pathways associated with nitric oxide signaling and calcium handling. Overall, DBP exposure appears to modulate arterial tone regulation, which may have implications for vascular function during pregnancy. Full article

Background/Objectives: Endocrine disruptors (EDs) are xenobiotic chemicals that disrupt hormone signaling and homeostasis within the human body. Accumulative evidence proposes that EDs could affect systemic hormone balance and local microbial communities, including the female genital tract (FGT) microbiome. The FGT microbiome, and especially the vaginal microbiota, contributes significantly to reproductive health maintenance, defense against infection, and favorable pregnancy outcomes. Disruption of the delicate microbial environment is associated with conditions like bacterial vaginosis, infertility, and preterm birth. Methods: The present narrative review summarizes the existing literature on EDs’ potential for changing the FGT microbiome. We discuss EDs like bisphenol A (BPA), phthalates, and parabens and their potential for disrupting the FGT microbiome through ED-induced hormone perturbations, immune modulation, and epithelial barrier breach, which could lead to microbial dysbiosis. Results: Preliminary evidence suggests that ED exposure–microbial composition changes relationships; however, robust human evidence for EDs’ changes on the FGT microbiome remains scarce. Conclusions: Our review addresses major research gaps and suggests future directions for investigation, such as the necessity for longitudinal and mechanistic studies that combine microbiome, exposome, and endocrine parameters. The relationship between EDs and the FGT microbiome could be critical for enhancing women’s reproductive health and for steering regulatory policies on exposure to environmental chemicals. Full article

The “Exposome” is a concept that indicates the set of exposures to which a human is subjected during their lifetime. These factors influence the health state of individuals and can drive the development of Noncommunicable Diseases (NCDs). Artificial Intelligence (AI) allows one to analyze large amounts of data in a short time. As such, several authors have used AI to study the relationship between exposome and chronic diseases. Under such premises, this study reviews the use of AI in analyzing the exposome to understand its role in the development of chronic diseases, focusing on how AI can identify patterns in exposure-related data and support prevention strategies. To achieve this, we carried out a search on multiple databases, including PubMed, ScienceDirect, and SCOPUS, from 1 January 2019 to 31 May 2023, using the MeSH terms (exposome) and (‘Artificial Intelligence’ OR ‘Machine Learning’ OR ‘Deep Learning’) to identify relevant studies on this topic. After completing the identification, screening, and eligibility assessment, a total of 18 studies were included in this literature review. According to the search, most authors used supervised or unsupervised machine learning models to study multiple exposure factors’ role in the risk of developing cardiovascular, metabolic, and chronic respiratory diseases. In some more recent studies, authors also used deep learning. Furthermore, the exposome analysis is useful to study the risk of developing neuropsychiatric disorders or evaluating pregnancy outcomes and child growth. Understanding the role of the exposome is pivotal to overcome the classic concept of a single exposure/disease. The application of AI allows one to analyze multiple environmental risks and their combined effects on health conditions. In the future, AI could be helpful in the prevention of chronic diseases, providing new diagnostic, therapeutic, and follow-up strategies. Full article

Fortified balanced energy–protein (BEP) supplementation is a promising intervention for improving maternal health, birth outcomes and infant growth in low- and middle-income countries. This nested biospecimen sub-study aimed to evaluate the physiological effect of multi-micronutrient-fortified BEP supplementation on pregnant and lactating women and their infants. Pregnant women (15–40 years) received either fortified BEP and iron–folic acid (IFA) (intervention) or IFA only (control) throughout pregnancy. The same women were concurrently randomized to receive either a fortified BEP supplement during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention) or the postnatal standard of care, which comprised IFA alone for 6 weeks postpartum (i.e., control). Biological specimens were collected at different timepoints. Multi-omics profiles will be characterized to assess the mediating effect of BEP supplementation on the different trial arms and its effect on maternal health, as well as birth and infant growth outcomes. The mediating effect of the exposome in the relationship between BEP supplementation and maternal health, birth outcomes and infant growth were characterized via biomonitoring markers of air pollution, mycotoxins and environmental contaminants. The results will provide holistic insight into the granular physiological effects of prenatal and postnatal BEP supplementation. Full article

Atopic dermatitis (AD) or atopic eczema is an increasingly manifested inflammatory skin disorder of complex etiology which is modulated by both extrinsic and intrinsic factors. The exposome includes a person’s lifetime exposures and their effects. We recently reviewed the extrinsic exposome’s environmental risk factors that contribute to AD. The periods of pregnancy, infancy, and teenage years are recognized as crucial stages in the formation of AD, where the exposome leads to enduring impacts on the immune system. However, research is now focusing on the interactions between intrinsic pathways that are modulated by the extrinsic exposome, including genetic variation, epigenetic modifications, and signals, such as diet, stress, and microbiome interactions. As a result, immune dysregulation, barrier dysfunction, hormonal fluctuations, and skin microbiome dysbiosis are important factors contributing to AD development, and their in-depth understanding is crucial not only for AD treatment but also for similar inflammatory disorders. Full article

Autism spectrum disorder (ASD) is a heterogeneous collection of neurodevelopmental disorders, difficult to diagnose and currently lacking treatment options. The possibility of finding reliable biomarkers useful for early identification would offer the opportunity to intervene with treatment strategies to improve the life quality of ASD patients. To date, there are many recognized risk factors for the development of ASD, both genetic and non-genetic. Although genetic and epigenetic factors may play a critical role, the extent of their contribution to ASD risk is still under study. On the other hand, non-genetic risk factors include pollution, nutrition, infection, psychological states, and lifestyle, all together known as the exposome, which impacts the mother’s and fetus’s life, especially during pregnancy. Pathogenic and non-pathogenic maternal immune activation (MIA) and autoimmune diseases can cause various alterations in the fetal environment, also contributing to the etiology of ASD in offspring. Activation of monocytes, macrophages, mast cells and microglia and high production of pro-inflammatory cytokines are indeed the cause of neuroinflammation, and the latter is involved in ASD’s onset and development. In this review, we focused on non-genetic risk factors, especially on the connection between inflammation, macrophage polarization and ASD syndrome, MIA, and the involvement of microglia. Full article

Intra-amniotic infection (IAI) is one major driver for preterm birth and has been demonstrated by clinical studies to exert both beneficial and injurious effects on the premature lung, possibly due to heterogeneity in the microbial type, timing, and severity of IAI. Due to the inaccessibility of the intra-amniotic cavity during pregnancies, preclinical animal models investigating pulmonary consequences of IAI are indispensable to elucidate the pathogenesis of bronchopulmonary dysplasia (BPD). It is postulated that on one hand imbalanced inflammation, orchestrated by lung immune cells such as macrophages, may impact on airway epithelium, vascular endothelium, and interstitial mesenchyme, resulting in abnormal lung development. On the other hand, excessive suppression of inflammation may as well cause pulmonary injury and a certain degree of inflammation is beneficial. So far, effective strategies to prevent and treat BPD are scarce. Therapeutic options targeting single mediators in signaling cascades and mesenchymal stromal cells (MSCs)-based therapies with global regulatory capacities have demonstrated efficacy in preclinical animal models and warrant further validation in patient populations. Ante-, peri- and postnatal exposome analysis and therapeutic investigations using multiple omics will fundamentally dissect the black box of IAI and its effect on the premature lung, contributing to precisely tailored and individualized therapies. Full article

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn’s disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated. Full article

Background—The exposome concept refers to the totality of exposures from internal and external sources, including chemical and biological agents from conception throughout the lifetime. Exposome is also made up of psychosocial components such as socio-economic status (SES), which will focus on in this review. Despite exposures to the same environmental nuisances, individuals and groups are impacted differently. According to the literature, health inequalities exist among different socioeconomic groups, and SES may influence the association between environmental nuisances and health outcomes. However, the variation of this interaction across ages has rarely been studied. There is a need to adopt a life course approach to understand the history of diseases better. Objective—The main objective of this review is to document how SES could modify the association between environmental nuisances and health outcomes, across different ages, as a first crucial step introducing the emerged concept of social exposome. Methods—The PubMed database was searched from January 2010 to August 2021 for systematic reviews published in English addressing the interaction between SES, environmental nuisances, and health outcomes. Socio-economic indicators considered include education, level of income, neighborhood environment. Environmental nuisances considered many environment nuisances, mainly air pollution and noise. Results—Among 242 literature reviews identified, 11 of them address the question of the effect modification. Overall, our work reveals that environmental nuisances were mostly associated with poorer health outcomes and that SES modified this association, increasing the health risk among the poorest. Very interestingly, our work reports the existence of this interaction across different ages, including pregnancy, childhood, and adulthood, and for various environmental nuisances. Conclusion—In conclusion, our work confirms that we are not all equal to face environmental nuisances. The poorest are more vulnerable to the health effect of environmental nuisances. Policy decisions and interventions should target this high-risk population as a priority. Further investigations are needed to formalize the concept of social exposome more precisely and then communicate about it. Full article

Holistic and life-long medical surveillance is the core of personalised medicine and supports an optimal implementation of both preventive and curative healthcare. Personal medical records are only partially unified by hospital or general practitioner informatics systems, but only for citizens with long-term permanent residence. Otherwise, insight into the medical history of patients greatly depends on their medical archive and memory. Additionally, occupational exposure records are not combined with clinical or general practitioner records. Environmental exposure starts preconceptionally and continues during pregnancy by transplacental exposure. Antenatal exposure is partially dependent on parental lifestyle, residence and occupation. Newborn screening (NBS) is currently being performed in developed countries and includes testing for rare genetic, hormone-related, and metabolic conditions. Transplacental exposure to substances such as endocrine disruptors, air pollutants and drugs may have life-long health consequences. However, despite the recognised impact of transplacental exposure on the increased risk of metabolic syndrome, neurobehavioral disorders as well as immunodisturbances including allergy and infertility, not a single test within NBS is geared toward detecting biomarkers of exposure (xenobiotics or their metabolites, nutrients) or effect such as oestradiol, testosterone and cytokines, known for being associated with various health risks and disturbed by transplacental xenobiotic exposures. The outcomes of ongoing exposome projects might be exploited to this purpose. Developing and using a OneHealth Medical Record (OneHealth^MR) may allow the incorporated chip to harvest information from different sources, with high integration added value for health prevention and care: environmental exposures, occupational health records as well as diagnostics of chronic diseases, allergies and medication usages, from birth and throughout life. Such a concept may present legal and ethical issues pertaining to personal data protection, requiring no significant investments and exploits available technologies and algorithms, putting emphasis on the prevention and integration of environmental exposure and health data. Full article

In humans, studies based on Developmental Origins of Health and Disease (DOHaD) concept and targeting short half-lived chemicals, including many endocrine disruptors, generally assessed exposures from spot biospecimens. Effects of early-life exposure to atmospheric pollutants were reported, based on outdoor air pollution levels. For both exposure families, exposure misclassification is expected from these designs: for non-persistent chemicals, because a spot biospecimen is unlikely to capture exposure over windows longer than a few days; for air pollutants, because indoor levels are ignored. We developed a couple-child cohort relying on deep phenotyping and extended personal exposure assessment aiming to better characterize the effects of components of the exposome, including air pollutants and non-persistent endocrine disruptors, on child health and development. Pregnant women were included in SEPAGES couple-child cohort (Grenoble area) from 2014 to 2017. Maternal and children exposure to air pollutants was repeatedly assessed by personal monitors. DNA, RNA, serum, plasma, placenta, cord blood, meconium, child and mother stools, living cells, milk, hair and repeated urine samples were collected. A total of 484 pregnant women were recruited, with excellent compliance to the repeated urine sampling protocol (median, 43 urine samples per woman during pregnancy). The main health outcomes are child respiratory health using early objective measures, growth and neurodevelopment. Compared to former studies, the accuracy of assessment of non-persistent exposures is expected to be strongly improved in this new type of birth cohort tailored for the exposome concept, with deep phenotyping and extended exposure characterization. By targeting weaknesses in exposure assessment of the current approaches of cohorts on effects of early life environmental exposures with strong temporal variations, and relying on a rich biobank to provide insight on the underlying biological pathways whereby exposures affect health, this design is expected to provide deeper understanding of the interplay between the Exposome and child development and health. Full article

Metabolomics studies of the early-life exposome often use maternal urine specimens to investigate critical developmental windows, including the periconceptional period and early pregnancy. During these windows changes in kidney function can impact urine concentration. This makes accounting for differential urinary dilution across samples challenging. Because there is no consensus on the ideal normalization approach for urinary metabolomics data, this study’s objective was to determine the optimal post-analytical normalization approach for untargeted metabolomics analysis from a periconceptional cohort of 45 women. Urine samples consisted of 90 paired pre- and post-implantation samples. After untargeted mass spectrometry-based metabolomics analysis, we systematically compared the performance of three common approaches to adjust for urinary dilution—creatinine adjustment, specific gravity adjustment, and probabilistic quotient normalization (PQN)—using unsupervised principal components analysis, relative standard deviation (RSD) of pooled quality control samples, and orthogonal partial least-squares discriminant analysis (OPLS-DA). Results showed that creatinine adjustment is not a reliable approach to normalize urinary periconceptional metabolomics data. Either specific gravity or PQN are more reliable methods to adjust for urinary concentration, with tighter quality control sample clustering, lower RSD, and better OPLS-DA performance compared to creatinine adjustment. These findings have implications for metabolomics analyses on urine samples taken around the time of conception and in contexts where kidney function may be altered. Full article

Objective: We have conducted a study to assess the role of environment on the burden of maternal morbidities and mortalities among women using an external exposome approach for the purpose of developing targeted public health interventions to decrease disparities. Methods: We identified counties in the 48 contiguous USA where observed low birthweight (LBW) rates were higher than expected during a five-year study period. The identification was conducted using a retrospective space-time analysis scan for statistically significant clusters with high or low rates by a Discrete Poisson Model. Results: We observed statistically significant associations of LBW rate with a set of predictive variables. However, in one of the two spatiotemporal models we discovered LBW to be associated with five predictive variables (teen birth rate, adult obesity, uninsured adults, physically unhealthy days, and percent of adults who smoke) in two counties situated in Alabama after adjusting for location changes. Counties with higher than expected LBW rates were similarly associated with two environmental variables (ozone and fine particulate matter). Conclusions: The county-level predictive measures of LBW offer new insights into spatiotemporal patterns relative to key contributory factors. An external framework provides a promising place-based approach for identifying “hotspots” with implications for designing targeted interventions and control measures to reduce and eliminate health disparities. Full article