Multi-Omics Gut Microbiome Species Communities and Functional Modules Linking Metal Exposures to Children’s Neurodevelopmental Health in a Canadian Birth Cohort

Abstract

Early life metal exposure has been associated with adverse neurodevelopment, with gut microbiome disruption proposed as a potential pathway. However, most studies have focused on individual taxa or pathways, despite microbes functioning within ecological communities and coordinated functional networks. Here, we integrated stool metal measurements, shotgun metagenomics, metatranscriptomics, and neurodevelopmental assessments in 116 children aged 8–12 years from the GESTE birth cohort in Sherbrooke, Canada. Nineteen metals were quantified in stool samples, and neurodevelopment was assessed using parent-reported behavioral scales, attention performance testing, and resting-state fMRI. Using network-based community detection, we identified 10 co-occurring species communities (SCs) from metagenomic data and 16 coexpressed functional modules (FMs) from metatranscriptomic data and evaluated their associations with metal exposures and neurodevelopmental outcomes. Higher levels of lead, cadmium, aluminum, zinc, copper, and magnesium were associated with lower abundance of Streptococcus- and Veillonella-dominated SCs, while multiple metals were associated with lower abundance of amino acid metabolism and carbohydrate degradation FMs. Exploratory mediation analyses suggested potential indirect associations between stool metals and parent-reported ADHD-related traits througha methionine cycle-related FM or sequentially through a Clostridium spp. SC and a Factor 420 biosynthesis FM. These findings suggest that stool metal concentrations are associated with community-level variations in gut microbial composition and function, some of which were further associated with parent-reported ADHD-related traits.