Associations of Childhood and Perinatal Blood Metals with Children's Gut Microbiomes in a Canadian Gestation Cohort

• Published in: Environmental health perspectives Vol. 130; no. 1; p. 17007
• Main Authors: Shen, Yike, Laue, Hannah E, Shrubsole, Martha J, Wu, Haotian, Bloomquist, Tessa R, Larouche, Annie, Zhao, Kankan, Gao, Feng, Boivin, Amélie, Prada, Diddier, Hunting, Darel J, Gillet, Virginie, Takser, Larissa, Baccarelli, Andrea A
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences 01.01.2022; Environmental Health Perspectives
• Subjects: Abundance; Acetylene; Biodegradation; Blood; Blood levels; Body mass index; Cadmium; Canada - epidemiology; Child; Children; Children & youth; Cohort Studies; Diabetes; Epidemiology; Exposure; Families & family life; Family income; Feces; Female; Gastrointestinal Microbiome; Gene families; Gene sequencing; Genetic testing; Genomes; Gestation; Gestational age; Heavy metals; Humans; Intestinal microflora; Lead; Manganese; Mathematical models; Mercury; Mercury (metal); Metagenomics; Metal concentrations; Metals; Microbiomes; Microorganisms; Mothers; Multivariate analysis; Pregnancy; Prenatal care; Public health; Relative abundance; RNA, Ribosomal, 16S - genetics; rRNA 16S; Selenium; Species; Species diversity; Standard deviation; Statistical analysis; Statistical models; Variance analysis; Canada; New York; United States > US; Quebec Canada
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp9674

The gut microbiome is important in modulating health in childhood. Metal exposures affect multiple health outcomes, but their ability to modify bacterial communities in children is poorly understood. We assessed the associations of childhood and perinatal blood metal levels with childhood gut microbiome diversity, structure, species, gene family-inferred species, and potential pathway alterations. We assessed the gut microbiome using 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing in stools collected from 6- to 7-year-old children participating in the GESTation and Environment (GESTE) cohort study. We assessed blood metal concentrations [cadmium (Cd), manganese (Mn), mercury (Hg), lead (Pb), selenium (Se)] at two time points, namely, perinatal exposures at delivery ( ) and childhood exposures at the 6- to 7-y follow-up ( ). We used multiple covariate-adjusted statistical models to determine microbiome associations with continuous blood metal levels, including linear regression (Shannon and Pielou alpha diversity indexes), permutational multivariate analysis of variance (adonis; beta diversity distance matrices), and multivariable association model (MaAsLin2; phylum, family, species, gene family-inferred species, and pathways). Children's blood Mn and Se significantly associated with microbiome phylum [e.g., Verrucomicrobiota ( , ; , , respectively)] and children's blood Mn significantly associated with family [e.g., ( , )]-level differences. Higher relative abundance of potential pathogens (e.g., ), beneficial species (e.g., , ), and both potentially pathogenic and beneficial species (e.g., , ) inferred from gene families were associated with higher childhood or perinatal blood Cd, Hg, and Pb ( ). We found significant negative associations between childhood blood Pb and acetylene degradation pathway abundance ( ). Finally, neither perinatal nor childhood metal concentrations were associated with children's gut microbial inter- and intrasubject diversity. Our findings suggest both long- and short-term associations between metal exposure and the childhood gut microbiome, with stronger associations observed with more recent exposure. Future epidemiologic analyses may elucidate whether the observed changes in the microbiome relate to children's health. https://doi.org/10.1289/EHP9674.