{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:35:42Z","timestamp":1776861342402,"version":"3.51.2"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Key Research and Development Program of China"},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["Project32098"],"award-info":[{"award-number":["Project32098"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Plasmids are key vectors for disseminating antibiotic resistance genes, yet their diversity and dynamics in the healthy human gut microbiome remain largely unexplored. Using fecal metagenomes from two cohorts (n\u2009=\u2009498 samples), we constructed a comprehensive atlas of the healthy human gut plasmidome. We observed a polarization: while 97.4% of 19\u2009151 plasmid clusters exhibited low prevalence (&amp;lt;5%), we identified 17 plasmid clusters that were detected in &amp;gt;30% of individuals. Among these, the plasmid pGut1 emerged as a paradigm of a stealth vector. Prevalent globally (&amp;gt;50% in independent cohorts), pGut1 possesses a minimal 4-kb conserved backbone ensuring stability and a hypervariable region acting as a \u201cplug-and-play\u201d module. We documented 40 distinct cargo inserts, including multiple antibiotic resistance genes such as cfr(C), erm(B), and aphA, across individuals, within individuals over time, and even within single fecal samples- validated by single-cell and long-read Nanopore sequencing. Screening of 2.3 million bacterial genomes revealed pGut1 in 93 strains across 49 genera and 2 phyla, including pathogenic Clostridioides difficile and three distinct Salmonella enterica strains. This pattern suggests potential repeated cross-species transmission events, equipping diverse pathogens with new antibiotic resistance genes. Our study exposes a hidden reservoir of highly adaptable, multi-host plasmids like pGut1 silently propagating antibiotic resistance genes in healthy populations. These plasmids, pre-adapted for cross-boundary dissemination, may pose a threat by fueling the emergence of multidrug-resistant pathogens.<\/jats:p>","DOI":"10.1093\/ismejo\/wrag004","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:17:50Z","timestamp":1768825070000},"source":"Crossref","is-referenced-by-count":0,"title":["Hidden reservoir of highly adaptable multi-host plasmids that propagate antibiotic genes in healthy human populations"],"prefix":"10.1093","volume":"20","author":[{"given":"Na","family":"Han","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianhui","family":"Peng","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujun","family":"Qiang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuwen","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0109-2085","authenticated-orcid":false,"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"2026042207365767000_ref1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41579-023-00926-x","article-title":"Plasmids, a molecular cornerstone of antimicrobial resistance in the one health era","volume":"22","author":"Casta\u00f1eda-Barba","year":"2024","journal-title":"Nat Rev Microbiol"},{"key":"2026042207365767000_ref2","doi-asserted-by":"crossref","first-page":"6574751","DOI":"10.1155\/agm3\/6574751","article-title":"Antibiotics and antimicrobial resistance genes in a gut microbiota as a reservoir\u2014a review","volume":"2025","author":"Dabuo","year":"2025","journal-title":"Adv Microbiome Res"},{"key":"2026042207365767000_ref3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s40168-025-02062-5","article-title":"Global analysis of the metaplasmidome: ecological drivers and spread of antibiotic resistance genes across ecosystems","volume":"13","author":"Debroas","year":"2025","journal-title":"Microbiome"},{"key":"2026042207365767000_ref4","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1128\/MMBR.00020-10","article-title":"Mobility of plasmids","volume":"74","author":"Smillie","year":"2010","journal-title":"Microbiol Mol Biol Rev"},{"key":"2026042207365767000_ref5","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.cell.2024.01.039","article-title":"A cryptic plasmid is among the most numerous genetic elements in the human gut","volume":"187","author":"Fogarty","year":"2024","journal-title":"Cell"},{"key":"2026042207365767000_ref6","doi-asserted-by":"publisher","DOI":"10.1101\/2020.03.31.997171","article-title":"Metagenome-assembled genome binning methods with short reads disproportionately fail for plasmids and genomic islands","volume":"6","author":"Maguire","year":"2020","journal-title":"Microbial Genomics"},{"key":"2026042207365767000_ref7","doi-asserted-by":"publisher","first-page":"e56998","DOI":"10.7554\/elife.56998.sa1","article-title":"Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes","volume":"9","author":"Watterson","year":"2020","journal-title":"Elife"},{"key":"2026042207365767000_ref8","doi-asserted-by":"publisher","first-page":"D189","DOI":"10.1093\/nar\/gkae1095","article-title":"The PLSDB 2025 update: enhanced annotations and improved functionality for comprehensive plasmid research","volume":"53","author":"Molano","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"2026042207365767000_ref9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature23889","article-title":"Strains, functions and dynamics in the expanded human microbiome project","volume":"550","author":"Lloyd-Price","year":"2017","journal-title":"Nature"}],"container-title":["The ISME Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ismej\/advance-article-pdf\/doi\/10.1093\/ismejo\/wrag004\/66557796\/wrag004.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ismej\/article-pdf\/20\/1\/wrag004\/68134768\/wrag004.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ismej\/article-pdf\/20\/1\/wrag004\/68134768\/wrag004.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:37:03Z","timestamp":1776857823000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ismej\/article\/doi\/10.1093\/ismejo\/wrag004\/8439645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":9,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,14]]}},"URL":"https:\/\/doi.org\/10.1093\/ismejo\/wrag004","relation":{},"ISSN":["1751-7362","1751-7370"],"issn-type":[{"value":"1751-7362","type":"print"},{"value":"1751-7370","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2026,1]]},"article-number":"wrag004"}}