{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:13:26Z","timestamp":1784286806265,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative\/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of <jats:italic>Veillonella<\/jats:italic> and <jats:italic>Megasphaera<\/jats:italic> genera were increased depending on patients\u2019 age at diagnosis. <jats:italic>Veillonella<\/jats:italic> was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of <jats:italic>Veillonella<\/jats:italic> in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.<\/jats:p>","DOI":"10.3389\/fimmu.2020.598152","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T03:52:59Z","timestamp":1612669979000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis"],"prefix":"10.3389","volume":"11","author":[{"given":"Ramon V.","family":"Cortez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana N.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Padilha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana D.","family":"Bibas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo K.","family":"Toma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Porta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla R.","family":"Taddei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29204","article-title":"The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration","volume":"66","author":"Deneau","year":"2017","journal-title":"Hepatology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2004.09.003","article-title":"The immunobiology of primary sclerosing cholangitis","volume":"4","author":"Aoki","year":"2005","journal-title":"Autoimmun Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.3350","article-title":"Etiopathogenesis of primary sclerosing cholangitis","volume":"14","author":"Chapman","year":"2008","journal-title":"World J Gastroenterol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23294","article-title":"Diagnosis and management of primary sclerosing cholangitis","volume":"51","author":"Chapman","year":"2010","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310500","article-title":"The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls","volume":"66","author":"Kummen","year":"2017","journal-title":"Gut"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/2050640617717156","article-title":"Impact of age at diagnosis on disease progression in patients with primary sclerosing cholangitis","volume":"6","author":"Rupp","year":"2018","journal-title":"U Eur Gastroenterol J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001531","article-title":"Unique Inflammatory Bowel Disease Phenotype of Pediatric Primary Sclerosing Cholangitis: A Single-Center Study","volume":"65","author":"Shiau","year":"2017","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312533","article-title":"Characterisation of the faecal microbiota in Japanese patients with paediatric-onset primary sclerosing cholangitis","volume":"66","author":"Iwasawa","year":"2017","journal-title":"Gut"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60096-3","article-title":"Primary sclerosing cholangitis","volume":"382","author":"Hirschfield","year":"2013","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.pedneo.2018.09.007","article-title":"Characteristics and outcome of primary sclerosing cholangitis associated with inflammatory bowel disease in Asian children","volume":"60","author":"Lee","year":"2019","journal-title":"Pediatr Neonatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.065557","article-title":"Genetic basis for increased intestinal permeability in families with Crohn\u2019s disease: Role of CARD15 3020insC mutation","volume":"55","author":"Buhner","year":"2006","journal-title":"Gut"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2014.913189","article-title":"Primary sclerosing cholangitis and the microbiota: Current knowledge and perspectives on etiopathogenesis and emerging therapies","volume":"49","author":"Tabibian","year":"2014","journal-title":"Scand J Gastroenterol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12232","article-title":"Randomised clinical trial: Vancomycin or metronidazole in patients with primary sclerosing cholangitis - A pilot study","volume":"37","author":"Tabibian","year":"2013","journal-title":"Aliment Pharmacol Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02635.x","article-title":"Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis","volume":"31","author":"Mueller","year":"2011","journal-title":"Liver Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/00365520510023288","article-title":"Intestinal permeability and bacterial growth of the small bowel in patients with primary sclerosing cholangitis","volume":"40","author":"Bj\u00f6rnsson","year":"2005","journal-title":"Scand J Gastroenterol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000201480","article-title":"Lipopolysaccharides and beta-glucuronidase activity in choledochal bile in relation to choledocholithiasis","volume":"58","author":"Osnes","year":"1997","journal-title":"Digestion"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/MPG.0000000000000239","article-title":"The ESPGHAN Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents","volume":"58","author":"Levine","year":"2013","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.05.029","article-title":"Development, Validation, and Evaluation of a Pediatric Ulcerative Colitis Activity Index: A Prospective Multicenter Study","volume":"133","author":"Turner","year":"2007","journal-title":"Gastroenterology"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.soard.2018.07.021","article-title":"Shifts in intestinal microbiota after duodenal exclusion favor glycemic control and weight loss: a randomized controlled trial","volume":"14","author":"Cortez","year":"2018","journal-title":"Surg Obes Related Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat Methods"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME improves sensitivity and speed of chimera detection","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-842X.2006.00430.x","article-title":"Application of Laplace\u2019s Boundary-Mode Approximations to Estimate Species and Shared Species Richness","volume":"48","author":"Chao","year":"2006","journal-title":"Aust New Z J Stat"},{"key":"B24","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/j.1538-7305.1948.tb01338.x","article-title":"A Mathematical Theory of Communication","volume":"27","author":"Shannon","year":"1948","journal-title":"Bell System Tech J"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2014.08.018","article-title":"Data analysis for 16S microbial profiling from different benchtop sequencing platforms","volume":"107","author":"Pylro","year":"2014","journal-title":"J Microbiol Methods"},{"key":"B26","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/B978-0-12-407863-5.00019-8","article-title":"Advancing Our Understanding of the Human Microbiome Using QIIME","volume":"531","author":"Navas-Molina","year":"2013","journal-title":"Methods Enzymol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.71.12.8228-8235.2005","article-title":"UniFrac: a new phylogenetic method for comparing microbial communities","volume":"71","author":"Lozupone","year":"2005","journal-title":"Appl Environ Microbiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003531","article-title":"Waste Not, Want Not: Why Rarefying Microbiome Data Is Inadmissible","volume":"10","author":"McMurdie","year":"2014","journal-title":"PloS Comput Biol"},{"key":"B29","unstructured":"OksanenJ\n            BlanchetFG\n            FriendlyM\n            KindtR\n            LegendreP\n            McglinnD\n          Vegan: Community Ecology Package2952016"},{"key":"B30","first-page":"65","article-title":"Ggplot2: elegant graphics for data analysis","volume-title":"Media","author":"Wickham","year":"2009"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000604","article-title":"Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis","volume":"115","author":"Shah","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.3390\/nu12051474","article-title":"The Firmicutes\/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients","volume":"12","author":"Magne","year":"2020","journal-title":"Nutrients"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nature11552","article-title":"Functional interactions between the gut microbiota and host metabolism","volume":"489","author":"Tremaroli","year":"2012","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504978102","article-title":"Obesity alters gut microbial ecology","volume":"102","author":"Ley","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","article-title":"Inflammatory Bowel Disease","volume":"28","author":"Kaser","year":"2010","journal-title":"Annu Rev Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.03.022","article-title":"Inflammatory bowel diseases in pediatric and adolescent patients: Clinical, therapeutic, and psychosocial considerations","volume":"126","author":"Kim","year":"2004","journal-title":"Gastroenterology"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000329","article-title":"Very early-onset inflammatory bowel disease: Gaining insight through focused discovery","volume":"21","author":"Moran","year":"2015","journal-title":"Inflamm Bowel Dis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"5480","DOI":"10.1038\/s41598-018-23870-w","article-title":"Dysbiosis of the salivary microbiota in pediatric-onset primary sclerosing cholangitis and its potential as a biomarker","volume":"8","author":"Iwasawa","year":"2018","journal-title":"Sci Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312180","article-title":"Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis","volume":"66","author":"R\u00fchlemann","year":"2017","journal-title":"Gut"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1099\/ijs.0.059816-0","article-title":"Megasphaera indica sp. nov., an obligate anaerobic bacteria isolated from human faeces","volume":"64","author":"Lanjekar","year":"2014","journal-title":"Int J System Evol Microbiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00139","article-title":"Natural Competence is Common among Clinical Isolates of Veillonella parvula and Is Useful for Genetic Manipulation of This Key Member of the Oral Microbiome","volume":"7","author":"Knapp","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3201\/eid1107.041361","article-title":"Veillonella montpellierensis Endocarditis","volume":"11","author":"Rovery","year":"2005","journal-title":"Emerg Infect Dis"},{"key":"B43","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/s41564-018-0333-1","article-title":"Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis","volume":"4","author":"Nakamoto","year":"2019","journal-title":"Nat Microbiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-311915","article-title":"The gut-adherent microbiota of PSC-IBD is distinct to that of IBD","volume":"66","author":"Quraishi","year":"2017","journal-title":"Gut"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.598152\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T03:53:06Z","timestamp":1612669986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.598152\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2020.598152"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.598152","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]},"article-number":"598152"}}