{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T21:54:40Z","timestamp":1787262880818,"version":"build-2736575974"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011665","name":"Deanship of Scientific Research, King Saud University","doi-asserted-by":"publisher","award":["RGP 1441-007"],"award-info":[{"award-number":["RGP 1441-007"]}],"id":[{"id":"10.13039\/501100011665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray\u2013Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included <jats:italic>Human polyomavirus 2<\/jats:italic>, <jats:italic>Enterobacteria phage mEpX1<\/jats:italic>, and <jats:italic>Enterobacteria phage mEpX2<\/jats:italic>; whereas less abundant species included <jats:italic>Lactococcus phages ul36 and Streptococcus phage Abc2<\/jats:italic>. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray\u2013Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.<\/jats:p>","DOI":"10.1371\/journal.pone.0262108","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T19:31:57Z","timestamp":1642188717000},"page":"e0262108","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Viral dysbiosis in children with new-onset celiac disease"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8699-3143","authenticated-orcid":true,"given":"Mohammad","family":"El Mouzan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaad","family":"Assiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al 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Hamzeh-Mivehroud Mahmoudpour","year":"2008","journal-title":"Eur J Pharm Biopharm"},{"key":"pone.0262108.ref005","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.cell.2010.05.009","article-title":"Virus-plus-susceptibility gene interaction determines Crohn\u2019s disease gene Atg16L1 phenotypes in intestine","volume":"141","author":"K Cadwell","year":"2010","journal-title":"Cell"},{"key":"pone.0262108.ref006","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.immuni.2016.03.009","article-title":"Enteric viruses ameliorate gut inflammation via toll-like receptor 3 and toll-like receptor 7- mediated interferon-b production","volume":"44","author":"J-Y Yang","year":"2016","journal-title":"Immunity"},{"key":"pone.0262108.ref007","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.cell.2015.01.002","article-title":"Disease-specific alterations in the enteric virome in inflammatory bowel disease","volume":"160","author":"JM 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Sci"},{"key":"pone.0262108.ref022","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.aah5298","article-title":"Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease","volume":"356","author":"R Bouziat","year":"2017","journal-title":"Science"},{"key":"pone.0262108.ref023","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/MPG.0b013e31821a23d0","article-title":"European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease","volume":"54","author":"S Husby","year":"2012","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"pone.0262108.ref024","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1097\/MPG.0000000000001681","article-title":"Mass screening for celiac disease among school-aged children: toward exploring celiac iceberg in Saudi Arabia","volume":"65","author":"A Al-Hussaini","year":"2017","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"pone.0262108.ref025","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s12866-016-0894-1","article-title":"Enrichment dynamics of Listeria monocytogenes and the associated microbiome from naturally contaminated ice cream linked to a listeriosis outbreak","volume":"16","author":"A Ottesen","year":"2016","journal-title":"BMC Microbiol"},{"key":"pone.0262108.ref026","doi-asserted-by":"crossref","first-page":"e97699","DOI":"10.1371\/journal.pone.0097699","article-title":"Microbial community profiling of human saliva using shotgun metagenomic sequencing","volume":"9","author":"NA Hasan","year":"2014","journal-title":"PLOS ONE"},{"key":"pone.0262108.ref027","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1126\/science.1254529","article-title":"Longitudinal analysis of microbial interaction between humans and the indoor environment","volume":"345","author":"S Lax","year":"2014","journal-title":"Science"},{"key":"pone.0262108.ref028","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1073\/pnas.1523817113","article-title":"Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed infection leading to necrotizing fasciitis","volume":"113","author":"D Ponnusamy","year":"2016","journal-title":"PNAS"},{"key":"pone.0262108.ref029","doi-asserted-by":"crossref","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","article-title":"phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"PJ McMurdie","year":"2013","journal-title":"PloS one"},{"key":"pone.0262108.ref030","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"pone.0262108.ref031","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"N Segata","year":"2011","journal-title":"Genome Biol"},{"key":"pone.0262108.ref032","unstructured":"Oksanen J, Blanchet FG, Friendly M, Kindt R, Legendre P, McGlinn D, et al. vegan: Community Ecology Package. 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Available from: https:\/\/CRAN.R-project.org\/package=ggpubr."},{"key":"pone.0262108.ref036","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1111\/apt.14280","article-title":"Review article: the human intestinal virome in health and disease","volume":"46","author":"SR Carding","year":"2017","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0262108.ref037","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13073-016-0287-y","article-title":"The virome: A missing component of biological interaction networks in health and disease","volume":"8","author":"SA Handley","year":"2016","journal-title":"Genome Med"},{"key":"pone.0262108.ref038","doi-asserted-by":"crossref","first-page":"895","DOI":"10.15537\/smj.2017.9.20808","article-title":"Celiac disease in Saudi children. Evaluation of clinical features and diagnosis","volume":"38","author":"A Saeed","year":"2017","journal-title":"Saudi Med J"},{"key":"pone.0262108.ref039","doi-asserted-by":"crossref","first-page":"268","DOI":"10.4103\/sjg.SJG_551_17","article-title":"Genetic susceptibility for celiac disease is highly prevalent in the Saudi population","volume":"24","author":"A Al-Hussaini","year":"2018","journal-title":"Saudi J Gastroenterol"},{"key":"pone.0262108.ref040","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/WCO.0000000000000201","article-title":"Novel syndromes associated with JC virus infection of neurons and meningeal cells: no longer a gray area","volume":"28","author":"DP Miskin","year":"2015","journal-title":"Curr Opin Neurol"},{"key":"pone.0262108.ref041","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s00018-005-5454-z","article-title":"The human polyomaviruses","volume":"63","author":"S Easha","year":"2006","journal-title":"Cell. Mol. 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