Population-level impacts of antibiotic usage on the human gut microbiome

Lee, Kihyun, Raguideau, Sebastien, Sirén, Kimmo, Asnicar, Francesco, Cumbo, Fabio, Hildebrand, Falk, Segata, Nicola, Cha, Chang Jun and Quince, Christopher (2023) Population-level impacts of antibiotic usage on the human gut microbiome. Nature Communications, 14. ISSN 2041-1723

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Abstract

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.

Item Type:	Article
Additional Information:	Data availability statement: We downloaded metagenome assemblies generated in a previous study26 fasta files accessed at: http://segatalab.cibio.unitn.it/data/Pasolli_et_al.htmlRaw Illumina sequencing reads of these metagenome samples were downloaded from the read archive at the NCBI or the EMBL using kingfisher: https://github.com/wwood/kingfisher-downloadwhen the run accession number was available. The list of sample identifiers analyzed using raw reads can be found along with the matched run accession numbers in the Supplementary Data 1. The ARG catalogue and abundance profiles generated in this study and the sample metadata table can be accessed at: https://doi.org/10.5281/zenodo.7188053 Source data are provided with this paper. Code availability statement: The analysis scripts used in this study are available from: https://github.com/kihyunee/gut_resistotype and the exact version used for this analysis archived at: https://doi.org/10.5281/zenodo.7465315. Funding Information: This work was supported by the Korea Center for Disease Control and Prevention (2017ER540701). CQ was supported by the BBSRC Core Strategic Programme Grant (BB/CSP1720/1, BBS/E/T/000PR9818, and BBS/E/T/000PR9817). S.R is funded through NERC grant ResPharm (NE/T013230/1). F.H. was supported by European Research Council H2020 StG (erc-stg-948219, EPYC), the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Gut Microbes and Health BB/r012490/1 and its constituent project BBS/e/F/000Pr10355. This work was also partially supported by the European Research Council (ERC-STG project MetaPG-716575 and ERC-CoG microTOUCH-101045015) to NS.
Uncontrolled Keywords:	chemistry(all),biochemistry, genetics and molecular biology(all),physics and astronomy(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	23 Oct 2024 11:30
Last Modified:	19 Nov 2024 01:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/97143
DOI:	10.1038/s41467-023-36633-7

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