One Health at the Microbial Frontier: Early-Life Exposures, Environment and the Origins of Antimicrobial Resistance

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Abstract
Antimicrobial resistance (AMR) is one of the most pressing threats to global public health. Its origins, however, go far beyond the walls of hospitals and clinics. Under the One Health paradigm, the health of humans, animals, and the environment is deeply interconnected. Microbial communities move freely across these domains, forming a vast ecological network. This chapter explores a striking and underappreciated phenomenon: newborns and infants, even those who have never received antibiotics, carry diverse repertoires of antibiotic resistance genes (ARGs). These genes arrive through prenatal, perinatal, and postnatal pathways. Water systems, agricultural soils, livestock, food chains, and built environments like hospitals and homes all act as conduits, funneling resistant bacteria and mobile genetic elements into vulnerable infant microbiomes. Horizontal gene transfer, sub-inhibitory antibiotic selection, co-selection by heavy metals and biocides, and disruption of the early-life microbiome all drive these processes. Drawing on recent meta-analyzes, longitudinal cohort studies, outbreak investigations, and One Health reviews, we bring together current evidence on the sources, mechanisms, and consequences of early-life AMR colonization. We outline integrated policy responses, from surveillance and environmental regulation to antibiotic stewardship and agricultural reform. Finally, we identify critical research gaps and chart a path forward for protecting newborns from the expanding microbial frontier of antimicrobial resistance.

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