The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition.

Summary Antimicrobial resistance (AMR) is an accelerating global threat, yet the nature of AMR in the gut microbiome and how AMR is acquired during early life remain largely unknown. In a cohort of 662 Danish children, we characterized the antibiotic resistance genes (ARGs) acquired during the first year of life and assessed the impacts of diverse environmental exposures on ARG load. Our study reveals a clear bimodal distribution of ARG richness that is driven by the composition of the gut microbiome, especially E. coli. ARG profiles were significantly affected by various environmental factors. Among these factors, the importance of antibiotics diminished with time since treatment. Finally, ARG load and ARG clusters were also associated with the maturity of the gut microbiome and a bacterial composition associated with increased risk of asthma. These findings broaden our understanding of AMR in early life and have critical implications for efforts to mitigate its spread.