{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:00:16Z","timestamp":1787169616097,"version":"build-2736575974"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Gut microbiome imbalance is well established in ulcerative colitis (UC) in Western populations. Significantly less is known about the gut virome and whether geography impacts the UC-associated microbiome. The aim of this study was to characterize gut bacteriophage changes, as well as to identify phage-bacterial associations that can serve as potential biomarkers of UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Twenty children with UC and 20 healthy controls were enrolled in the study. Inclusion criteria included newly diagnosed treatment-na\u00efve children with UC with no antibiotic exposure for at least six months prior to sample collection. Deoxyribonucleic acid (DNA) was extracted from stool and rectal biopsies and was processed for shotgun metagenomic sequencing. Bioinformatics and statistical analyses were performed to assess phage diversity and their associations with gut bacteria. Candidate biomarkers were identified using the random forest classifier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In fecal samples, bacteriophage diversity was not significantly altered, but 72 species were significantly altered in UC, five of which (\n                      <jats:italic toggle=\"yes\">Salmonella_phage_SEN4<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">uncultured_crAssphage, Staphylococcus_phage_SPbeta-like<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Streptococcus_phage_YMC-2011<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Siphoviridae_u_s<\/jats:italic>\n                      ) were identified as candidate biomarker signatures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We found a significantly altered bacteriophage signature in children with new onset, treatment na\u00efve UC in Saudi children, a Middle Eastern population. These changes differed from previously reported Western UC cases, indicating that demographic bias needs to be considered when developing microbiota-based diagnostics and therapeutic applications for non-Western populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/sjg.sjg_24_25","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T06:00:13Z","timestamp":1744610413000},"page":"212-218","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Gut virome profile in new onset treatment na\u00efve Saudi children with ulcerative colitis"],"prefix":"10.4103","volume":"31","author":[{"given":"Mohammad","family":"El Mouzan","sequence":"first","affiliation":[{"name":"Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor C.","family":"Savidge","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Texas Children\u2019s Microbiome Center, Department of Pathology, Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al Sarkhy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Badu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Texas Children\u2019s Microbiome Center, Department of Pathology, Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badr","family":"Alsaleem","sequence":"additional","affiliation":[{"name":"The Children Hospital, Intestinal Failure Program, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Al Mofarreh","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Al Mofarreh Polyclinics, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Almasood","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaad","family":"Assiri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Gastroenterology Unit), College of Medicine, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"R1-20250724","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1053\/j.gastro.2011.10.001","article-title":"Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review","volume":"142","author":"Molodecky","year":"2012","journal-title":"Gastroenterology"},{"key":"R2-20250724","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/MPG.0b013e3181b99baa","article-title":"Rising incidence of inflammatory bowel disease among children: A 12-year study","volume":"50","author":"Malaty","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R3-20250724","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.gtc.2023.05.001","article-title":"Epidemiology of pediatric inflammatory bowel disease","volume":"52","author":"Khan","year":"2023","journal-title":"Gastroenterol Clin North Am"},{"key":"R4-20250724","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1093\/ibd\/izy085","article-title":"Determinants of IBD heritability: Genes, bugs, and more","volume":"24","author":"Turpin","year":"2018","journal-title":"Inflamm Bowel Dis"},{"key":"R5-20250724","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev-immunol-070119-115104","article-title":"Interaction between the microbiota, epithelia, and immune cells in the intestine","volume":"38","author":"Kayama","year":"2020","journal-title":"Annu Rev Immunol"},{"key":"R6-20250724","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrm.2016.80","article-title":"Tight junctions: From simple barriers to multifunctional molecular gates","volume":"17","author":"Zihni","year":"2016","journal-title":"Nat Rev Mol Cell Biol"},{"key":"R7-20250724","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12876-019-0930-3","article-title":"Role of colonic microbiota in the pathogenesis of ulcerative colitis","volume":"19","author":"Pei","year":"2019","journal-title":"BMC Gastroenterol"},{"key":"R8-20250724","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1128\/JCM.02574-12","article-title":"Longitudinal analyses of gut mucosal microbiotas in ulcerative colitis in relation to patient age and disease severity and duration","volume":"51","author":"Fite","year":"2013","journal-title":"J Clin Microbiol"},{"key":"R9-20250724","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4161\/gmic.22371","article-title":"Movers and shakers: Influence of bacteriophages in shaping the mammalian gut microbiota","volume":"4","author":"Mills","year":"2013","journal-title":"Gut Microbes"},{"key":"R10-20250724","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.tim.2014.02.010","article-title":"Exploiting gut bacteriophages for human health","volume":"22","author":"Dalmasso","year":"2014","journal-title":"Trends Microbiol"},{"key":"R11-20250724","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jviromet.2003.11.012","article-title":"Identification of peptide sequences that induce the transport of phage across the gastrointestinal mucosal barrier","volume":"116","author":"Duerr","year":"2004","journal-title":"J Virol Methods"},{"key":"R12-20250724","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.ejpb.2008.06.005","article-title":"Non-specific translocation of peptide displaying bacteriophage particles across the gastrointestinal barrier","volume":"70","author":"Hamzeh-Mivehroud","year":"2008","journal-title":"Eur J Pharm Biopharm"},{"key":"R13-20250724","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.cell.2010.05.009","article-title":"Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine","volume":"141","author":"Cadwell","year":"2010","journal-title":"Cell"},{"key":"R14-20250724","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-? production","volume":"44","author":"Yang","year":"2016","journal-title":"Immunity"},{"key":"R15-20250724","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":"Norman","year":"2015","journal-title":"Cell"},{"key":"R16-20250724","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1097\/MIB.0b013e318292477c","article-title":"Bacteriophages in gut samples from pediatric crohn's disease patients: Metagenomic analysis using 454 Pyrosequencing","volume":"19","author":"Wagner","year":"2013","journal-title":"Inflam Bowel Dis"},{"key":"R17-20250724","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1038\/ctg.2013.9","article-title":"Study of the viral and microbial communities associated with crohn's disease: A metagenomic approach","volume":"4","author":"P\u00e9rez-Brocal","year":"2013","journal-title":"Clin Transl Gastroenterol"},{"key":"R18-20250724","first-page":"1419","article-title":"Metagenomic analysis of microbiome in colon tissue from subjects with inflammatory bowel diseases reveals interplay of viruses and bacteria","volume":"21","author":"Wang","year":"2015","journal-title":"Inflam Bowel Dis"},{"key":"R19-20250724","first-page":"1085","article-title":"Incidence of pediatric inflammatory bowel disease in Saudi Arabia: A multicenter national study","volume":"20","author":"El Mouzan","year":"2014","journal-title":"Inflamm Bowel Dis"},{"key":"R20-20250724","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5144\/0256-4947.2015.19","article-title":"Characteristics of pediatric ulcerative colitis in Saudi Arabia: A multicenter national study","volume":"35","author":"AlSaleem","year":"2015","journal-title":"Ann Saudi Med"},{"key":"R21-20250724","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.2006.0030-1299.14714.x","article-title":"Entropy and diversity","volume":"113","author":"Jost","year":"2006","journal-title":"Oikos"},{"key":"R25-20250724","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/bioinformatics\/bty633","article-title":"ape 5.0: An environment for modern phylogenetics and evolutionary analyses in R","volume":"35","author":"Paradis","year":"2019","journal-title":"Bioinformatics"},{"key":"R26-20250724","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":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"R27-20250724","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i11","article-title":"Feature selection with the boruta package","volume":"36","author":"Kursa","year":"2010","journal-title":"J Stat Softw"},{"key":"R28-20250724","doi-asserted-by":"crossref","first-page":"e0170734","DOI":"10.1371\/journal.pone.0170734","article-title":"Novel temperate phages of salmonella enterica subsp. salamae and subsp. diarizonae and their activity against Pathogenic S. enterica subsp. enterica Isolates","volume":"12","author":"Mikalov\u00e1","year":"2017","journal-title":"PLoS One"},{"key":"R29-20250724","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1017\/S095026881600176X","article-title":"crAssphage is not associated with diarrhoea and has high genetic diversity","volume":"144","author":"Liang","year":"2016","journal-title":"Epidemiol Infect"},{"key":"R30-20250724","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.chom.2018.10.002","article-title":"Biology and taxonomy of crAss-like bacteriophages, the most abundant virus in the human gut","volume":"24","author":"Guerin","year":"2018","journal-title":"Cell Host Microbe"},{"key":"R31-20250724","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.1038\/s41467-022-31390-5","article-title":"Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome","volume":"13","author":"de Jonge","year":"2022","journal-title":"Nat Commun"},{"key":"R32-20250724","doi-asserted-by":"crossref","first-page":"657867","DOI":"10.3389\/fcimb.2021.657867","article-title":"Alterations, interactions, and diagnostic potential of gut bacteria and viruses in colorectal cancer","volume":"11","author":"Gao","year":"2021","journal-title":"Front Cell Infect Microbiol"}],"container-title":["Saudi Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_24_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:08:58Z","timestamp":1787166538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_24_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/sjg.sjg_24_25","relation":{},"ISSN":["1319-3767","1998-4049"],"issn-type":[{"value":"1319-3767","type":"print"},{"value":"1998-4049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]},"assertion":[{"value":"2025-01-20","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-14","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}