Kihyun Lee^1,2, Sebastien Raguideau³, Kimmo Sirén⁴, Francesco Asnicar⁵, Fabio Cumbo⁵, Falk Hildebrand^3,6, Nicola Segata⁵, Chang-Jun Cha^1,8 & Christopher Quince^3,6,7,8

¹Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong 17546, Republic of Korea. 
²CJ Bioscience, Seoul 04527, Republic of Korea. 
³Organisms and Ecosystems, Earlham Institute, Norwich NR4 7UZ, UK. 
⁴Section for Evolutionary Genomics, The GLOBE Institute, University of Copenhagen, Copenhagen, Denmark. 
⁵Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy. 
⁶Gut Microbes and Health, Quadram Institute, Norwich NR4 7UQ, UK. 
⁷Warwick Medical School, University of Warwick, Coventry CV4 7HL, UK. 
⁸These authors jointly supervised this work: Chang-Jun Cha, Christopher Quince.

Corresponding authors: Correspondence to Chang-Jun Cha or Christopher Quince.

The widespread usage of antimicrobials has driven the evolution of resistance in pathogenic microbes, both increased prevalence of antimicrobial resistance genes (ARGs) and their spread across species by horizontal gene transfer (HGT). However, the impact on the wider community of commensal microbes associated with the human body, the microbiome, is less well understood. Small-scale studies have determined the transient impacts of antibiotic consumption but we conduct an extensive survey of ARGs in 8972 metagenomes to determine the population-level impacts. Focusing on 3096 gut microbiomes from healthy individuals not taking antibiotics we demonstrate highly significant correlations between both the total ARG abundance and diversity and per capita antibiotic usage rates across ten countries spanning three continents. Samples from China were notable outliers. We use a collection of 154,723 human-associated metagenome assembled genomes (MAGs) to link these ARGs to taxa and detect HGT. This reveals that the correlations in ARG abundance are driven by multi-species mobile ARGs shared between pathogens and commensals, within a highly connected central component of the network of MAGs and ARGs. We also observe that individual human gut ARG profiles cluster into two types or resistotypes. The less frequent resistotype has higher overall ARG abundance, is associated with certain classes of resistance, and is linked to species-specific genes in the Proteobacteria on the periphery of the ARG network.