Temporal dynamics and microbial interactions shaping the gut resistome in early infancy

Despite the critical role of the gut resistome in spreading of antimicrobial resistance (AMR), strategies to reduce the abundance of antibiotic resistance genes (ARGs) during microbiota development in infancy remain underexplored. Using longitudinal quantitative metagenomic data, we here show that ARGs are present in the gut microbiota from the first week of life, with a peak in absolute ARG abundance and richness at 6 months. Delivery mode significantly affects early ARG dynamics, and vaginally delivered infants exhibit higher ARG abundance due to maternal transmission of Escherichia coli strains harbouring extensive resistance repertoires. The abundance of E. coli and other ARG-rich taxa inversely correlates with aromatic lactic acid-producing bifidobacteria, and aromatic lactic acids strongly inhibit the in vitro growth of E. coli and other opportunistic ARG-rich taxa. Our results highlight temporal and critical microbial interactions shaping the gut resistome in early infancy, pointing to potential interventions to curb AMR during this vulnerable developmental window by promoting colonization of aromatic lactic acid-producing bifidobacteria.