Environmental chemical exposures have been linked to gut microbiome dysregulation and adverse health outcomes in children. Halogenated flame retardants (HFRs) are persistent chemicals with substantial early-life exposure, yet evidence on their effects on the pediatric gut microbiome remains limited. We examined associations between HFR exposures and the gut microbiome among 8–12-y-old children from the GESTation and Environment (GESTE) cohort in Sherbrooke, Canada. In a multi-matrix, multi-omics design, 10 HFRs were quantified in plasma (n = 140) and stool (n = 182), with shotgun metagenomic and metatranscriptomic sequencing characterized microbial species and functional pathways. After false discovery rate correction, plasma BDE-47 and BDE-99 were inversely associated with Clostridium sp. CAG:221 and Bacteroides dorei, respectively (q < 0.2). Stool BDE-153 was negatively associated with short-chain fatty acid–producing taxa, including Eubacterium spp. and Roseburia intestinalis, and positively associated with Alistipes putredinis and Faecalibacterium spp. Stool BDE-153 and anti-DP were associated with higher activity of pathways involved in phospholipid homeostasis and 4-aminobutanoate degradation. Mediation analysis suggested that Faecalibacterium spp. partly mediated the association between stool BDE-153 and cytidine diphosphate-diacylglycerol biosynthesis. Our findings suggest that childhood HFR exposure is associated with alterations in gut microbiome composition and function, with potential implications for pediatric health.
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