{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:09:48Z","timestamp":1783087788574,"version":"3.54.6"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004846","name":"Beijing University of Chinese Medicine","doi-asserted-by":"publisher","award":["2180072120049"],"award-info":[{"award-number":["2180072120049"]}],"id":[{"id":"10.13039\/501100004846","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074246"],"award-info":[{"award-number":["82074246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Ankylosing spondylitis (AS), a chronic autoimmune disease, has been linked to the gut bacteriome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the characteristics of the gut virome in AS, we profiled the gut viral community of 193 AS patients and 59 healthy subjects based on a metagenome-wide analysis of fecal metagenomes from two publicly available datasets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AS patients revealed a significant decrease in gut viral richness and a considerable alteration of the overall viral structure. At the family level, AS patients had an increased abundance of <jats:italic>Gratiaviridae<\/jats:italic> and <jats:italic>Quimbyviridae<\/jats:italic> and a decreased abundance of <jats:italic>Drexlerviridae<\/jats:italic> and <jats:italic>Schitoviridae<\/jats:italic>. We identified 1,004 differentially abundant viral operational taxonomic units (vOTUs) between patients and controls, including a higher proportion of AS-enriched <jats:italic>Myoviridae<\/jats:italic> viruses and control-enriched <jats:italic>Siphoviridae<\/jats:italic> viruses. Moreover, the AS-enriched vOTUs were more likely to infect bacteria such as <jats:italic>Flavonifractor<\/jats:italic>, <jats:italic>Achromobacter<\/jats:italic>, and <jats:italic>Eggerthellaceae<\/jats:italic>, whereas the control-enriched vOTUs were more likely to be <jats:italic>Blautia<\/jats:italic>, <jats:italic>Ruminococcus<\/jats:italic>, <jats:italic>Collinsella<\/jats:italic>, <jats:italic>Prevotella<\/jats:italic>, and <jats:italic>Faecalibacterium<\/jats:italic> bacteriophages. Additionally, some viral functional orthologs differed significantly in frequency between the AS-enriched and control-enriched vOTUs, suggesting the functional role of these AS-associated viruses. Moreover, we trained classification models based on gut viral signatures to discriminate AS patients from healthy controls, with an optimal area under the receiver operator characteristic curve (AUC) up to 0.936, suggesting the clinical potential of the gut virome for diagnosing AS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This work provides novel insight into the AS gut virome, and the findings may guide future mechanistic and therapeutic studies for other autoimmune diseases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1154380","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T05:30:57Z","timestamp":1680154257000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Alterations in the gut virome in patients with ankylosing spondylitis"],"prefix":"10.3389","volume":"14","author":[{"given":"Chen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiulong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruochun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhisong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1005111","DOI":"10.1155\/2022\/1005111","article-title":"Gut microbiota and inflammatory cytokine changes in patients with ankylosing spondylitis","volume":"2022","author":"Liu","year":"2022","journal-title":"BioMed Res Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-020-04537-0","article-title":"Prevalence of ankylosing spondylitis in a Chinese population: a systematic review and meta-analysis","volume":"40","author":"Zhao","year":"2020","journal-title":"Rheumatol Int"},{"key":"B3","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0140-6736(16)31591-4","article-title":"Axial spondyloarthritis","volume":"390","author":"Sieper","year":"2017","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez119","article-title":"Comorbidity burden in axial spondyloarthritis: a cluster analysis","volume":"58","author":"Zhao","year":"2019","journal-title":"Rheumatol (Oxford)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nrrheum.2015.133","article-title":"Genetics of ankylosing spondylitis\u2013insights into pathogenesis","volume":"12","author":"Brown","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122126","article-title":"A possible role of intestinal microbiota in the pathogenesis of ankylosing spondylitis","volume":"17","author":"Yang","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/art.22812","article-title":"A common genetic background for inflammatory bowel disease and ankylosing spondylitis: a genealogic study in Iceland","volume":"56","author":"Thjodleifsson","year":"2007","journal-title":"Arthritis Rheum"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2022.2041338","article-title":"Patients with ankylosing spondylitis have high risk of irritable bowel syndrome: a long-term nationwide population-based cohort study","volume":"134","author":"Feng","year":"2022","journal-title":"Postgraduate Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature18847","article-title":"The microbiome and innate immunity","volume":"535","author":"Thaiss","year":"2016","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"16008","DOI":"10.1038\/npjgenmed.2016.8","article-title":"Exome-wide study of ankylosing spondylitis demonstrates additional shared genetic background with inflammatory bowel disease","volume":"1","author":"Robinson","year":"2016","journal-title":"NPJ Genom Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13059-017-1271-6","article-title":"Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis","volume":"18","author":"Wen","year":"2017","journal-title":"Genome Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00176-18","article-title":"Altered bacterial-fungal interkingdom networks in the guts of ankylosing spondylitis patients","volume":"4","author":"Li","year":"2019","journal-title":"mSystems"},{"key":"B13","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.chom.2019.10.009","article-title":"Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease","volume":"26","author":"Clooney","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221267","article-title":"Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease","volume":"81","author":"Tomofuji","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s40168-018-0410-y","article-title":"A human gut phage catalog correlates the gut phageome with type 2 diabetes","volume":"6","author":"Ma","year":"2018","journal-title":"Microbiome"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201044","article-title":"The dark side of the gut: Virome-host interactions in intestinal homeostasis and disease","volume":"218","author":"Li","year":"2021","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2018.05.009","article-title":"Close encounters of three kinds: Bacteriophages, commensal bacteria, and host immunity","volume":"26","author":"Keen","year":"2018","journal-title":"Trends Microbiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1101\/2022.12.27.522048","article-title":"Cataloguing and profiling of the gut virome in Chinese populations uncover extensive viral signatures across common diseases","author":"Li","year":"2022","journal-title":"bioRxiv"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1887719","article-title":"The gut virome in irritable bowel syndrome differs from that of controls","volume":"13","author":"Coughlan","year":"2021","journal-title":"Gut Microbes"},{"key":"B20","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.chom.2019.09.009","article-title":"The human gut virome is highly diverse, stable, and individual specific","volume":"26","author":"Shkoporov","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B21","doi-asserted-by":"publisher","first-page":"109132","DOI":"10.1016\/j.celrep.2021.109132","article-title":"Stability of the human gut virome and effect of gluten-free diet","volume":"35","author":"Garmaeva","year":"2021","journal-title":"Cell Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1099\/jmm.0.001107","article-title":"Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment","volume":"69","author":"Huang","year":"2020","journal-title":"J Med Microbiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"102360","DOI":"10.1016\/j.jaut.2019.102360","article-title":"Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis","volume":"107","author":"Zhou","year":"2020","journal-title":"J Autoimmun"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv033","article-title":"MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de bruijn graph","volume":"31","author":"Li","year":"2015","journal-title":"Bioinformatics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"104418","DOI":"10.1016\/j.isci.2022.104418","article-title":"A catalogue of 48,425 nonredundant viruses from oral metagenomes expands the horizon of the human oral virome","volume":"25","author":"Li","year":"2022","journal-title":"iScience"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00774-7","article-title":"CheckV assesses the quality and completeness of metagenome-assembled viral genomes","volume":"39","author":"Nayfach","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B29","unstructured":"R: A language and environment for statistical computing2020"},{"key":"B30","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.chom.2020.08.003","article-title":"The gut virome database reveals age-dependent patterns of virome diversity in the human gut","volume":"28","author":"Gregory","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00348-22","article-title":"Dysbiotic oral and gut viromes in untreated and treated rheumatoid arthritis patients","volume":"10","author":"Guo","year":"2022","journal-title":"Microbiol Spectr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"veab022","DOI":"10.1093\/ve\/veab022","article-title":"Characterization of the gut DNA and RNA viromes in a cohort of Chinese residents and visiting pakistanis","volume":"7","author":"Yan","year":"2021","journal-title":"Virus Evol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1097\/BOR.0000000000000239","article-title":"Subclinical gut inflammation in ankylosing spondylitis","volume":"28","author":"Ciccia","year":"2016","journal-title":"Curr Opin Rheumatol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1010572","article-title":"Role of the microbiome and its metabolites in ankylosing spondylitis","volume":"13","author":"Song","year":"2022","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.6.2969-2974.1999","article-title":"Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with bacteroides vulgatus or escherichia coli","volume":"67","author":"Rath","year":"1999","journal-title":"Infect Immun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000296","article-title":"Intestinal dysbiosis and innate immune responses in axial spondyloarthritis","volume":"28","author":"Ciccia","year":"2016","journal-title":"Curr Opin Rheumatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-051914-021944","article-title":"Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases","volume":"67","author":"Fragoulis","year":"2016","journal-title":"Annu Rev Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00760-7","article-title":"Molecular mimicry and ankylosing spondylitis: possible role of a novel sequence in pullulanase of klebsiella pneumoniae","volume":"369","author":"Fielder","year":"1995","journal-title":"FEBS Lett"},{"key":"B39","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s40168-021-01017-w","article-title":"Thousands of previously unknown phages discovered in whole-community human gut metagenomes","volume":"9","author":"Benler","year":"2021","journal-title":"Microbiome"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0257102","DOI":"10.1371\/journal.pone.0257102","article-title":"Novel drexlerviridae bacteriophage KMI8 with specific lytic activity against klebsiella michiganensis and its biofilms","volume":"16","author":"Ku","year":"2021","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S347110","article-title":"Characterization and genomic analysis of a novel drexlervirial bacteriophage IME268 with lytic activity against klebsiella pneumoniae","volume":"15","author":"Nazir","year":"2022","journal-title":"Infect Drug Resist"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9100663","article-title":"From orphan phage to a proposed new family-the diversity of N4-like viruses","volume":"9","author":"Wittmann","year":"2020","journal-title":"Antibiotics (Basel)"},{"key":"B43","doi-asserted-by":"publisher","first-page":"6757","DOI":"10.1038\/s41467-021-27112-y","article-title":"Dysbiosis of human gut microbiome in young-onset colorectal cancer","volume":"12","author":"Yang","year":"2021","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00379","article-title":"Oral administration of flavonifractor plautii strongly suppresses Th2 immune responses in mice","volume":"11","author":"Ogita","year":"2020","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1099\/ijsem.0.002800","article-title":"Lawsonibacter asaccharolyticus gen. nov., sp. nov., a butyrate-producing bacterium isolated from human faeces","volume":"68","author":"Sakamoto","year":"2018","journal-title":"Int J Syst Evol Microbiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"676","DOI":"10.3892\/etm.2021.10108","article-title":"Characteristics of the intestinal microbiome in ankylosing spondylitis","volume":"22","author":"Cardoneanu","year":"2021","journal-title":"Exp Ther Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.07.038","article-title":"Fecal microbiota in patients with ankylosing spondylitis: Correlation with dietary factors and disease activity","volume":"497","author":"Zhang","year":"2019","journal-title":"Clin Chim Acta"},{"key":"B48","doi-asserted-by":"publisher","first-page":"46","DOI":"10.15403\/jgld-2823","article-title":"Gut microbiota changes in inflammatory bowel diseases and ankylosing spondilytis","volume":"30","author":"Cardoneanu","year":"2021","journal-title":"J Gastrointestin Liver Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01703","article-title":"Alteration of fecal microbiota profiles in juvenile idiopathic arthritis. associations with HLA-B27 allele and disease status","volume":"7","author":"Di Paola","year":"2016","journal-title":"Front Microbiol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e34233","DOI":"10.1371\/journal.pone.0034233","article-title":"Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice","volume":"7","author":"Lam","year":"2012","journal-title":"PloS One"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s13312-019-1541-3","article-title":"Achromobacter xylosoxidans sepsis unveiling X-linked agammaglobulinemia masquerading as systemic-onset juvenile idiopathic arthritis","volume":"56","author":"Janarthanan","year":"2019","journal-title":"Indian Pediatr"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15885","article-title":"Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers","volume":"34","author":"Moreno-Arrones","year":"2020","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.541178","article-title":"Alterations of the gut microbiome composition and lipid metabolic profile in radiation enteritis","volume":"10","author":"Li","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/children9040569","article-title":"Impact of HLA-B27 and disease status on the gut microbiome of the offspring of ankylosing spondylitis patients","volume":"9","author":"Stoll","year":"2022","journal-title":"Children (Basel)"},{"key":"B55","doi-asserted-by":"publisher","first-page":"571","DOI":"10.21037\/atm.2019.09.41","article-title":"Variations in gut microbial profiles in ankylosing spondylitis: disease phenotype-related dysbiosis","volume":"7","author":"Chen","year":"2019","journal-title":"Ann Transl Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"2180913","DOI":"10.1155\/2020\/2180913","article-title":"miRNA-451a and miRNA-125a expression levels in ankylosing spondylitis: Impact on disease diagnosis, prognosis, and outcomes","volume":"2020","author":"Fotoh","year":"2020","journal-title":"J Immunol Res"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e54504","DOI":"10.1371\/journal.pone.0054504","article-title":"Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis","volume":"8","author":"Bay-Jensen","year":"2013","journal-title":"PloS One"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1154380\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T05:31:01Z","timestamp":1680154261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1154380\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,30]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2023.1154380"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1154380","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,30]]},"article-number":"1154380"}}