A prevalent huge phage clade in human and animal gut microbiomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A prevalent huge phage clade in human and animal gut microbiomes Lin-xing Chen, Antonio Pedro Camargo, Yiting Qin, Haoyu Wang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7356405/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (Jumbo gut) phages with genomes of 360-402 kilobase pairs that comprise ~1.1% of the reads in human gut metagenomes, and are predicted to infect Bacteroides and/or Phocaeicola. Although three of the four major groups of Jug phages shared >90% genome-wide sequence identity, their large terminase subunits exhibited only 38–57% identity, suggesting horizontal acquisition from other phages. Over 1,500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug phages as potential major players in gut microbiome ecology. Biological sciences/Ecology/Microbial ecology Biological sciences/Microbiology/Bacteriophages Viruses Huge phages Jumbo phages Metagenomics Gut microbiomes Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTables.xlsx Supplementary Table SupplementaryFigure.pdf Supplementary Figure Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7356405","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":502091337,"identity":"66f9819e-4bf7-4ed7-aad7-f48931f60e3a","order_by":0,"name":"Lin-xing Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYBACPmYgkQDEBgwMjA+gggZ4tbAhaWE2gKomoAXGACpjkyBOCzvvMYmHO2rlzdl7j1Xz/Pkjz8DevE2CoeYOHofxJRsknjluuLPnXNpt3jYDwwaeY2USDMee4dHCY/ggse1YgsGNHLPbvA0GCQwSOWYSjA2H8WkxOADWcv+NWTHPH6AW+TcEtYBsqQHawmPGzMMGsoWHoBZjg8S2A4YbzuQYS85tMzZs40krtkg4hlsLP/8ZM8mfbXXyBsfPGH5480dOnp/98MYbH2pwa4ECJAXgmEogpIGBoY6wklEwCkbBKBi5AAAk8EnTYfmX5AAAAABJRU5ErkJggg==","orcid":"","institution":"State Key Laboratory of Advanced Environmental Technology, the Department of Environmental Science and Engineering, University of Science and Technology of China, Hefei, China, 230026","correspondingAuthor":true,"prefix":"","firstName":"Lin-xing","middleName":"","lastName":"Chen","suffix":""},{"id":502091338,"identity":"acb3a2c1-3300-4549-aa0e-d4988d9f9168","order_by":1,"name":"Antonio Pedro Camargo","email":"","orcid":"https://orcid.org/0000-0003-3913-2484","institution":"Lawrence Berkeley National Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"Pedro","lastName":"Camargo","suffix":""},{"id":502091339,"identity":"14e1bc11-4711-4d0e-b271-225b0bfd12b4","order_by":2,"name":"Yiting Qin","email":"","orcid":"","institution":"University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Yiting","middleName":"","lastName":"Qin","suffix":""},{"id":502091340,"identity":"2636d907-04e4-4df9-9985-3ee7351448a5","order_by":3,"name":"Haoyu Wang","email":"","orcid":"","institution":"BGI Research","correspondingAuthor":false,"prefix":"","firstName":"Haoyu","middleName":"","lastName":"Wang","suffix":""},{"id":502091341,"identity":"02610601-2b2d-45c3-8a11-547c6fd70d87","order_by":4,"name":"Yuangqiang Zou","email":"","orcid":"https://orcid.org/0000-0003-2380-264X","institution":"BGI Institute of Applied Agriculture","correspondingAuthor":false,"prefix":"","firstName":"Yuangqiang","middleName":"","lastName":"Zou","suffix":""},{"id":502091342,"identity":"804d4df5-8991-4b64-9edc-d8f1fdf528a0","order_by":5,"name":"Yi Duan","email":"","orcid":"","institution":"University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Duan","suffix":""},{"id":502091343,"identity":"d706c299-c46d-4a99-84ab-4768d9b23d80","order_by":6,"name":"Hao Li","email":"","orcid":"","institution":"University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Li","suffix":""},{"id":502091344,"identity":"e61f5590-9226-43f0-9e5b-d94131dae748","order_by":7,"name":"Eugene Koonin","email":"","orcid":"https://orcid.org/0000-0003-3943-8299","institution":"National Institutes of Health","correspondingAuthor":false,"prefix":"","firstName":"Eugene","middleName":"","lastName":"Koonin","suffix":""}],"badges":[],"createdAt":"2025-08-12 13:42:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7356405/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7356405/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89373112,"identity":"1009e0a8-e025-478e-be81-259014190f8e","added_by":"auto","created_at":"2025-08-19 10:36:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2671795,"visible":true,"origin":"","legend":"Article File","description":"","filename":"maintext.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7356405/v1_covered_019b5a49-e23b-46c8-8bb3-776ead2f8bb4.pdf"},{"id":89371579,"identity":"3f387333-003f-4866-83bb-19704e443dae","added_by":"auto","created_at":"2025-08-19 10:12:21","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":8184763,"visible":true,"origin":"","legend":"Supplementary Table","description":"","filename":"SupplementaryTables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7356405/v1/6af608901145f7b75244d01c.xlsx"},{"id":89371580,"identity":"4032504d-8c41-4aa7-9d71-cfcea09e9dd3","added_by":"auto","created_at":"2025-08-19 10:12:21","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":19452235,"visible":true,"origin":"","legend":"Supplementary Figure","description":"","filename":"SupplementaryFigure.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7356405/v1/7ccff0ce32daf9d506fa10f6.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"A prevalent huge phage clade in human and animal gut microbiomes","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Viruses, Huge phages, Jumbo\tphages, Metagenomics, Gut microbiomes","lastPublishedDoi":"10.21203/rs.3.rs-7356405/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7356405/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (Jumbo gut) phages with genomes of 360-402 kilobase pairs that comprise ~1.1% of the reads in human gut metagenomes, and are predicted to infect Bacteroides and/or Phocaeicola. Although three of the four major groups of Jug phages shared \u003e90% genome-wide sequence identity, their large terminase subunits exhibited only 38–57% identity, suggesting horizontal acquisition from other phages. Over 1,500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug phages as potential major players in gut microbiome ecology.","manuscriptTitle":"A prevalent huge phage clade in human and animal gut microbiomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-19 10:12:16","doi":"10.21203/rs.3.rs-7356405/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2f6051b0-0f9f-472e-8483-e6950abe7e18","owner":[],"postedDate":"August 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53329716,"name":"Biological sciences/Ecology/Microbial ecology"},{"id":53329717,"name":"Biological sciences/Microbiology/Bacteriophages"}],"tags":[],"updatedAt":"2025-08-19T10:12:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-19 10:12:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7356405","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7356405","identity":"rs-7356405","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.