Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications.

Childhood exposure to non-persistent endocrine disruptors, glucocorticosteroids, and attentional function: A cross-sectional study based on the parametric g-formula.

Background: Evidence suggests that endocrine disrupting chemicals (EDCs) may perturb the hypothalamic-pituitary-adrenocortical (HPA) axis, which has a major role in brain development. We aimed to evaluate the effects of childhood exposure to organophosphate pesticides, phenols, and phthalate metabolites, on urinary glucocorticosteroids and inattention in childhood.

Methods: We used data from the Human Early-Life Exposome (HELIX) cohort (2013-2016) and the parametric g-formula to estimate associations between EDCs, glucocorticosteroids, and hit reaction time standard error (HRT-SE), a measure of inattention, and tested for possible effect modification by sex.

Integrating Multi-Omics with environmental data for precision health: A novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease.

Background: Precision Health aims to revolutionize disease prevention by leveraging information across multiple omic datasets (multi-omics). However, existing methods generally do not consider personalized environmental risk factors (e.g.

Machine learning-based health environmental-clinical risk scores in European children.

Background: Early life environmental stressors play an important role in the development of multiple chronic disorders. Previous studies that used environmental risk scores (ERS) to assess the cumulative impact of environmental exposures on health are limited by the diversity of exposures included, especially for early life determinants. We used machine learning methods to build early life exposome risk scores for three health outcomes using environmental, molecular, and clinical data.

Prenatal Exposure to Chemical Mixtures and Metabolic Syndrome Risk in Children.

Importance: Prenatal exposure to ubiquitous endocrine-disrupting chemicals (EDCs) may increase the risk of metabolic syndrome (MetS) in children, but few studies have studied chemical mixtures or explored underlying protein and metabolic signatures.

Objective: To investigate associations of prenatal exposure to EDC mixtures with MetS risk score in children and identify associated proteins and metabolites.

Design, Setting, And Participants: This population-based, birth cohort study used data collected between April 1, 2003, and February 26, 2016, from the Human Early Life Exposome cohort based in France, Greece, Lithuania, Norway, Spain, and the UK.

Social inequalities in pregnancy metabolic profile: findings from the multi-ethnic Born in Bradford cohort study.

Background: Lower socioeconomic position (SEP) associates with adverse pregnancy and perinatal outcomes and with less favourable metabolic profile in nonpregnant adults. Socioeconomic differences in pregnancy metabolic profile are unknown. We investigated association between a composite measure of SEP and pregnancy metabolic profile in White European (WE) and South Asian (SA) women.

Association of exposure to mixture of chemicals during pregnancy with cognitive abilities and fine motor function of children.

Chemical exposures often occur in mixtures and exposures during pregnancy may lead to adverse effects on the fetal brain, potentially reducing lower cognitive abilities and fine motor function of the child. We investigated the association of motheŕs exposure to a mixture of chemicals during pregnancy (i.e.

Influence of perinatal and childhood exposure to tobacco and mercury in children's gut microbiota.

Background: Early life determinants of the development of gut microbiome composition in infants have been widely investigated; however, if early life pollutant exposures, such as tobacco or mercury, have a persistent influence on the gut microbial community, its stabilization at later childhood remains largely unknown.

Objective: In this exposome-wide study, we aimed at identifying the contribution of exposure to tobacco and mercury from the prenatal period to childhood, to individual differences in the fecal microbiome composition of 7-year-old children, considering co-exposure to a width of established lifestyle and clinical determinants.

Methods: Gut microbiome was studied by 16S rRNA amplicon sequencing in 151 children at the genus level.

Blurred lines: Crossing the boundaries between the chemical exposome and the metabolome.

The aetiology of every human disease lies in a combination of genetic and environmental factors, each contributing in varying proportions. While genomics investigates the former, a comparable holistic paradigm was proposed for environmental exposures in 2005, marking the onset of exposome research. Since then, the exposome definition has broadened to include a wide array of physical, chemical, and psychosocial factors that interact with the human body and potentially alter the epigenome, the transcriptome, the proteome, and the metabolome.

Associations between combined urban and lifestyle factors and respiratory health in European children.

Introduction: Previous studies identified some environmental and lifestyle factors independently associated with children respiratory health, but few focused on exposure mixture effects. This study aimed at identifying, in pregnancy and in childhood, combined urban and lifestyle environment profiles associated with respiratory health in children.

Methods: This study is based on the European Human Early-Life Exposome (HELIX) project, combining six birth cohorts.

Metabolomic Signatures of Exposure to Nitrate and Trihalomethanes in Drinking Water and Colorectal Cancer Risk in a Spanish Multicentric Study (MCC-Spain).

We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation.

Blood miRNA levels associated with ADHD traits in children across six European birth cohorts.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance.

Firefighters and the liver: Exposure to PFAS and PAHs in relation to liver function and serum lipids (CELSPAC-FIREexpo study).

Introduction: Firefighting is one of the most hazardous occupations due to exposure to per- and polyfluoroalkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAHs). Such exposure is suspected to affect the cardiometabolic profile, e.g.

Associations of four biological age markers with child development: A multi-omic analysis in the European HELIX cohort.

Background: While biological age in adults is often understood as representing general health and resilience, the conceptual interpretation of accelerated biological age in children and its relationship to development remains unclear. We aimed to clarify the relationship of accelerated biological age, assessed through two established biological age indicators, telomere length and DNA methylation age, and two novel candidate biological age indicators, to child developmental outcomes, including growth and adiposity, cognition, behavior, lung function and the onset of puberty, among European school-age children participating in the HELIX exposome cohort.

Methods: The study population included up to 1173 children, aged between 5 and 12 years, from study centres in the UK, France, Spain, Norway, Lithuania, and Greece.

Prenatal environmental exposures associated with sex differences in childhood obesity and neurodevelopment.

Background: Obesity and neurodevelopmental delay are complex traits that often co-occur and differ between boys and girls. Prenatal exposures are believed to influence children's obesity, but it is unknown whether exposures of pregnant mothers can confer a different risk of obesity between sexes, and whether they can affect neurodevelopment.

Methods: We analyzed data from 1044 children from the HELIX project, comprising 93 exposures during pregnancy, and clinical, neuropsychological, and methylation data during childhood (5-11 years).

Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: A scoping review.

Health effects of endocrine disrupting chemicals (EDCs) are challenging to detect in the general population. Omics technologies become increasingly common to identify early biological changes before the apparition of clinical symptoms, to explore toxic mechanisms and to increase biological plausibility of epidemiological associations. This scoping review systematically summarises the application of omics in epidemiological studies assessing EDCs-associated biological effects to identify potential gaps and priorities for future research.

Childhood exposure to non-persistent endocrine disrupting chemicals and multi-omic profiles: A panel study.

Background: Individuals are exposed to environmental pollutants with endocrine disrupting activity (endocrine disruptors, EDCs) and the early stages of life are particularly susceptible to these exposures. Previous studies have focused on identifying molecular signatures associated with EDCs, but none have used repeated sampling strategy and integrated multiple omics. We aimed to identify multi-omic signatures associated with childhood exposure to non-persistent EDCs.