Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis

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dc.contributor.authorKulecka, Mariaen
dc.contributor.authorO'Sullivan, Jillen
dc.contributor.authorFitzgerald, Rachelen
dc.contributor.authorVelikonja, Anaen
dc.contributor.authorHuseyin, Chloe E.en
dc.contributor.authorLaserna-Mendieta, Emilio J.en
dc.contributor.authorRuiz-Limón, Patriciaen
dc.contributor.authorEckenberger, Juliaen
dc.contributor.authorVidal-Marin, Miriamen
dc.contributor.authorTruppel, Bastian-Alexanderen
dc.contributor.authorSingh, Raminderen
dc.contributor.authorNaik, Sandhiaen
dc.contributor.authorCroft, Nicholas M.en
dc.contributor.authorTemko, Andriyen
dc.contributor.authorZomer, Alderten
dc.contributor.authorMelgar, Silviaen
dc.contributor.authorDeb, Protimaen
dc.contributor.authorSanderson, Ian R.en
dc.contributor.authorClaesson, Marcus J.en
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderCrohn’s and Colitis Foundation Litwin IBD Pioneers programen
dc.contributor.funderEuropean Commissionen
dc.contributor.funderInstituto de Salud Carlos IIIen
dc.date.accessioned2025-07-24T14:11:25Z
dc.date.available2025-07-24T14:11:25Z
dc.date.issued2025en
dc.description.abstractCurrent first-line treatments of paediatric ulcerative colitis (UC) maintain 6-month remission in only half of the patients. Relapse-prediction at diagnosis could enable earlier introduction of immunosuppressants. We collected intestinal biopsies from 56 treatment-naïve children, combining mucosal quantitative microbial profiling with host epigenomics, transcriptomics and genotyping, and in vitro and in vivo experiments on selected bacteria. Baseline bacterial diversity was lower in relapsing children, who had fewer butyrate-producers but more oral-associated bacteria, whereof Veilonella parvula induced inflammation in epithelial cell lines and IL10-/- mice. Microbiota had the strongest association with future relapse, followed by epigenome and transcriptome. Relapse-prediction from separate omics data was outperformed by a robust machine learning approach combining microbiomes and epigenomes. In summary, combinatory machine learning of host-microbe data, especially microbiome and epigenome, had prognostic potential in paediatric UC. Our translational findings also suggest that pro-inflammatory oral-associated colonizers can exploit reduced colonic bacterial diversity of relapsing children.en
dc.description.sponsorshipCrohn’s and Colitis Foundation Litwin IBD Pioneers program (Grant no. 510264)en
dc.description.statusPeer revieweden
dc.description.versionSubmitted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKulecka, M., O'Sullivan, J., Fitzgerald, R., Velikonja, A., Huseyin, C. E., Laserna-Mendieta, E. J., Ruiz-Limón, P., Eckenberger, J., Vidal-Marin, M., Truppel, B-A., Singh, R., Naik, S., Croft, N. M., Temko, A., Zomer, A., Melgar, S., Deb, P., Sanderson, I. R. and Claesson, M. J. (2025) 'Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis', Nature Communications, (40 pp).en
dc.identifier.eissn2041-1723en
dc.identifier.journaltitleNature Communicationsen
dc.identifier.urihttps://hdl.handle.net/10468/17755
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Research Centres Programme::Phase 2/12/RC/2273_P2/IE/APC_Phase 2/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Career Development Award/17/CDA/4765/IE/A translational ‘omics’ approach for predicting treatment outcome in newly-diagnosed children with ulcerative colitis/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Centres for Research Training (CRT) Programme/18/CRT/6214/IE/SFI Centre for Research Training in Genomics Data Science/en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-COFUND-FP/101034270/EU/INnovative Sustainable Development InterdisciPlinary Post-Doctoral Research Excellence/INSPIREen
dc.rights© the Authors 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectPaediatric ulcerative colitisen
dc.subjectMicrobiomeen
dc.subjectMachine learningen
dc.subjectMulti-omicsen
dc.subjectTreatment failureen
dc.subjectTreatment outcomeen
dc.titleCombining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitisen
dc.typeArticle (peer-reviewed)en
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