Data_Sheet_1_Influence of perinatal and childhood exposure to tobacco and mercury in children’s gut microbiota.pdf

BackgroundEarly 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.ObjectiveIn 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.MethodsGut microbiome was studied by 16S rRNA amplicon sequencing in 151 children at the genus level. Exposure to tobacco was quantified during pregnancy through questionnaire (active tobacco consumption, second-hand smoking -SHS) and biomonitoring (urinary cotinine) at 4 years (urinary cotinine, SHS) and 7 years (SHS). Exposure to mercury was quantified during pregnancy (cord blood) and at 4 years (hair). Forty nine other potential environmental determinants (12 at pregnancy/birth/infancy, 15 at 4 years and 22 at 7 years, such as diet, demographics, quality of living/social environment, and clinical records) were registered. We used multiple models to determine microbiome associations with pollutants including multi-determinant multivariate analysis of variance and linear correlations (wUnifrac, Bray-Curtis and Aitchison ß-diversity distances), single-pollutant permutational multivariate analysis of variance adjusting for co-variates (Aitchison), and multivariable association model with single taxa (MaAsLin2; genus). Sensitivity analysis was performed including genetic data in a subset of 107 children.ResultsActive smoking in pregnancy was systematically associated with microbiome composition and ß-diversity (R2 2–4%, p DiscussionOur findings suggest a long-term sustainable effect of prenatal tobacco exposure on the children’s gut microbiota. This effect was not found for mercury exposure or tobacco exposure during childhood. Assessing the role of these exposures on the children’s microbiota, considering multiple environmental factors, should be further investigated.</p

Epigenome–wide Meta–Analysis Reveals Associations between Dietary Glycemic Index and Glycemic Load and DNA methylation in Children and Adolescents with Different Body Size

Objective: Dietary glycemic index (GI) and glycemic load (GL) are associated with cardio–metabolic health in children and adolescents, with potential distinct effects in people with increased body mass index (BMI). DNA methylation (DNAm) may mediate these effects. Thus, we conducted meta–analyses of epigenome–wide association studies (EWASs) between dietary GI and GL and blood DNAm of children and adolescents.Research Design and Methods: We calculated dietary GI and GL and performed EWASs in children and adolescents (age range: 4.5–17 years) from six cohorts (ntotal = 1,187). We performed stratified analyses of participants with normal–weight (ntotal = 801) or overweight/obesity (ntotal = 386). We performed look–ups for the identified cytosine–phosphate–guanine (CpG) sites (false discovery rate (FDR) Results: Dietary GL was positively associated with DNAm of cg20274553 (FDR Conclusions: We identified 537 associations between dietary GI and GL and blood DNAm, mainly in children and adolescents with overweight/obesity. High GI and/or GL diets may influence epigenetic gene regulation and thereby, promote metabolic derangements in young persons with increased BMI.</p