{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:41:46Z","timestamp":1792885306706,"version":"4.5.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Louis-Hansens Foundation","award":["18-2B-2662"],"award-info":[{"award-number":["18-2B-2662"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["5042"],"award-info":[{"award-number":["5042"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The gut microbiome plays a crucial role in the pathogenesis and progression of inflammatory bowel disease (IBD). Understanding the dynamics of the gut microbiome in relation to treatment can provide valuable insights into disease management and therapy strategies. The aim of this study is to investigate if diversity and composition of the gut microbiome correlate with time since treatment and disease activity during maintenance infliximab (IFX) therapy among children with IBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data was collected from IBD patients aged 10\u201317 participating in an IFX-eHealth study. IFX infusions were administered in 4\u201312-week intervals based on weekly faecal calprotectin (FC) combined with symptom scores. Excess stool samples underwent microbiome profiling using 16S rRNA gene sequencing. Microbiome features, including alpha diversity and single taxa, were analysed for three key variables: 1) weeks-since-treatment, 2) FC, and 3) symptom score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 25 patients (median age 14.4 years) diagnosed with Crohn\u00b4s Disease (n = 16) or ulcerative colitis (n = 9), microbiota were analysed in 671 faecal samples collected across 15 treatment intervals.<\/jats:p>\n                    <jats:p>\n                      A significant decrease over time in Shannon diversity, following the initial increase within four weeks of treatment, was found across patients. FC levels showed no association with alpha diversity (\n                      <jats:italic>p<\/jats:italic>\n                      &gt;0.1), while symptom scores showed a negative association with Shannon and observed diversity in patients with UC. At the genus level, a lower abundance of the genera\n                      <jats:italic>Anaerostipes<\/jats:italic>\n                      and\n                      <jats:italic>Fusicatenibacter<\/jats:italic>\n                      (Firmicutes), and a greater abundance of the genus\n                      <jats:italic>Parasutterella<\/jats:italic>\n                      (Proteobacteria), were associated (\n                      <jats:italic>p<\/jats:italic>\n                      .adj&lt;0.05) with the time elapsed since last infusion in UC specifically, while only\n                      <jats:italic>Parasutterella<\/jats:italic>\n                      was associated across the full cohort (p.adj = 1e-10).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found a recurring reduction over time in alpha diversity following the initial increase in diversity after an IFX infusion. Changes in an individual\u2019s microbiome may be an early sign of increasing disease activity that precedes clinical symptoms and increased FC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0311604","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T13:33:02Z","timestamp":1734010382000},"page":"e0311604","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gut microbiota diversity repeatedly diminishes over time following maintenance infliximab infusions in paediatric IBD patients"],"prefix":"10.1371","volume":"19","author":[{"given":"Katrine","family":"Carlsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-4375","authenticated-orcid":true,"given":"Louise B.","family":"Thingholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Dempfle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6956-7676","authenticated-orcid":true,"given":"Mikkel","family":"Malham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Bang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibeke","family":"Wewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"issue":"2","key":"pone.0311604.ref001","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/ecco-jcc\/jjw148","article-title":"Inflammatory Bowel Disease Incidence is on the Continuous Rise Among All Paediatric Patients Except for the Very Young: A Nationwide Registry-based Study on 28-Year Follow-up","volume":"11","author":"LJ Virta","year":"2017","journal-title":"J Crohns Colitis"},{"issue":"7","key":"pone.0311604.ref002","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/ajg.2017.97","article-title":"Trends in Epidemiology of Pediatric Inflammatory Bowel Disease in Canada: Distributed Network Analysis of Multiple Population-Based Provincial Health Administrative Databases","volume":"112","author":"EI Benchimol","year":"2017","journal-title":"Am J Gastroenterol"},{"issue":"1","key":"pone.0311604.ref003","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1128\/CMR.15.1.79-94.2002","article-title":"Clinical aspects and pathophysiology of inflammatory bowel disease","volume":"15","author":"BA Hendrickson","year":"2002","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"pone.0311604.ref004","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mcna.2009.10.002","article-title":"Pediatric Inflammatory Bowel Disease: Highlighting Pediatric Differences in IBD","volume":"94","author":"CG Sauer","year":"2010","journal-title":"Medical Clinics of North America"},{"issue":"5","key":"pone.0311604.ref005","first-page":"1","article-title":"Metabolome\u2013microbiome crosstalk and human disease","volume":"10","author":"KA Lee-Sarwar","year":"2020","journal-title":"Metabolites"},{"key":"pone.0311604.ref006","first-page":"9","article-title":"Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review","author":"X Zhuang","year":"2021","journal-title":"Front Pediatr"},{"key":"pone.0311604.ref007","first-page":"1777","article-title":"Faecal Metabolomics in Paediatric Inflammatory Bowel Disease: A Systematic Review. 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