Association of childhood and perinatal blood metals with children gut microbiome in a Canadian gestation cohort

Abstract

BACKGROUND AND AIM: 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 metals with childhood gut microbiome diversity, structure, species, and pathway alterations. METHODS: We assessed the gut microbiome using 16S rRNA amplicon sequencing and shotgun metagenomic sequencing in 6-7 year-old children participating in the GESTation and Environment (GESTE) cohort study. We assessed blood metal concentrations (cadmium, manganese, mercury, lead, selenium) at two time points, i.e., perinatal exposures at delivery (N=70) and childhood exposures at the 6-7 year follow up (N=68). We used covariate-adjusted models to determine microbiome associations with continuous blood metal levels, including linear regression (Shannon and Pielou diversity indexes), permutational multivariate analysis of variance (adonis) (weighted UniFrac, Bray-Curtis, unweighted UniFrac, and Jaccard distance matrices), and multivariable association model (MaAsLin2) (phylum, family, species, and pathway). RESULTS:Children's manganese and selenium exposure had significant associations with microbiome phylum (i.e., Verrucomicrobiota [coef=-0.305, q value =0.03]) and family (i.e., Eggerthellaceae [coef=-0.228, q value =0.05]) level differences. Individual species, including potential pathogens (i.e., Bacteriodes vulgatus, Eubacterium rectale) and beneficial species (i.e., Bifidobacterium longum, Faecalibacterium prausnitzii), had significantly higher relative abundance in relation to low level children or perinatal blood cadmium, mercury, and lead (q value 0.1). We found significant negative associations between childhood blood lead and acetylene degradation pathway abundance (q value 0.1). Finally, neither perinatal or childhood metal concentrations were associated with children's gut microbial inter- and intra-subject diversity. CONCLUSIONS:Our findings suggest both long-term 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. KEYWORDS: microbiome, heavy metals