Characterization of the gut virome in patients with non-alcoholic fatty liver disease

Characterization of the gut virome in patients with non-alcoholic fatty liver disease | 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 Research Article Characterization of the gut virome in patients with non-alcoholic fatty liver disease Lvyue Wang, Leyi Wang, Min Liu, Qi Yuan, Lin Cheng, Huixiang Chen, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7377965/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Nov, 2025 Read the published version in Journal of Translational Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with complex gut microbiome involvement. While bacterial dysbiosis in NAFLD has been widely studied, the role of the gut virome remains largely unexplored. Methods: We conducted a comprehensive analysis of gut viral communities in 90 NAFLD patients and 90 non-NAFLD controls using whole-metagenome shotgun sequencing. Viral taxonomic composition, host associations, and functional gene profiles were characterized. Serum metabolomic data were integrated to explore virus–metabolite interactions, and a random forest model was developed to assess the diagnostic potential of virome signatures. Results: No significant differences were observed in overall viral diversity. However, compositional shifts at the vOTU level revealed 105 viruses enriched in NAFLD and 185 in non-NAFLD individuals. NAFLD-enriched viruses were mainly associated with Bacteroides, while non-NAFLD phages targeted beneficial genera such as Faecalibacterium and Oscillibacter. Functional analysis identified 65 differentially abundant KEGG orthologs, with metabolism-related viral genes notably depleted in NAFLD. Serum metabolomic analysis revealed nine differential metabolites, some of which were significantly correlated with vOTU abundances. A random forest classifier based on viral features achieved an AUC of 75.79% for distinguishing NAFLD status. Conclusion: Our findings demonstrate that the gut virome exhibits compositional and functional alterations in NAFLD, with potential implications for host metabolism. These viral signatures show promise as noninvasive biomarkers and highlight the virome as an overlooked contributor to NAFLD pathogenesis. Non-alcoholic fatty liver disease Gut virome Metagenomics Serum metabolomics Full Text Cite Share Download PDF Status: Published Journal Publication published 28 Nov, 2025 Read the published version in Journal of Translational Medicine → Version 1 posted Reviewers agreed at journal 29 Aug, 2025 Reviewers invited by journal 29 Aug, 2025 Editor assigned by journal 20 Aug, 2025 First submitted to journal 14 Aug, 2025 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. 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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-7377965","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":507498753,"identity":"5d7d7478-ff5e-4340-b2f6-1d6269e6deb9","order_by":0,"name":"Lvyue Wang","email":"","orcid":"","institution":"The Second Hospital of Nanjing","correspondingAuthor":false,"prefix":"","firstName":"Lvyue","middleName":"","lastName":"Wang","suffix":""},{"id":507498754,"identity":"7ff51131-a2e1-4eb7-b3a0-818bea309cb6","order_by":1,"name":"Leyi Wang","email":"","orcid":"","institution":"Loudi Central 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Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Non-alcoholic fatty liver disease, Gut virome, Metagenomics, Serum metabolomics","lastPublishedDoi":"10.21203/rs.3.rs-7377965/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7377965/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with complex gut microbiome involvement. While bacterial dysbiosis in NAFLD has been widely studied, the role of the gut virome remains largely unexplored.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods: We conducted a comprehensive analysis of gut viral communities in 90 NAFLD patients and 90 non-NAFLD controls using whole-metagenome shotgun sequencing. Viral taxonomic composition, host associations, and functional gene profiles were characterized. Serum metabolomic data were integrated to explore virus–metabolite interactions, and a random forest model was developed to assess the diagnostic potential of virome signatures.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults: No significant differences were observed in overall viral diversity. However, compositional shifts at the vOTU level revealed 105 viruses enriched in NAFLD and 185 in non-NAFLD individuals. NAFLD-enriched viruses were mainly associated with Bacteroides, while non-NAFLD phages targeted beneficial genera such as Faecalibacterium and Oscillibacter. Functional analysis identified 65 differentially abundant KEGG orthologs, with metabolism-related viral genes notably depleted in NAFLD. Serum metabolomic analysis revealed nine differential metabolites, some of which were significantly correlated with vOTU abundances. A random forest classifier based on viral features achieved an AUC of 75.79% for distinguishing NAFLD status.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusion: Our findings demonstrate that the gut virome exhibits compositional and functional alterations in NAFLD, with potential implications for host metabolism. 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